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DISEASE OF LYMPH VESSELS

Lymphedema Lecture Notes

Lymphedema (pronounced lim-fa-DEE-ma) is a chronic, progressive, and often debilitating condition characterized by localized tissue swelling and fluid retention, which occurs when the lymphatic system is impaired or damaged.

Breakdown of the key elements of this definition:
  1. Chronic and Progressive:
    • Chronic: It is a long-term condition that typically does not resolve on its own.
    • Progressive: If left untreated, the swelling tends to worsen over time, leading to more significant tissue changes.
  2. Localized Tissue Swelling and Fluid Retention:
    • The most visible and primary symptom is swelling, usually in one or more limbs (arms or legs), but it can also affect other body parts such as the trunk, head and neck, or genitalia.
    • The fluid that accumulates is rich in protein, which is a distinguishing feature from other types of edema.
  3. Impaired or Damaged Lymphatic System:
    • This is the defining characteristic. Lymphedema specifically results from a failure of the lymphatic system to adequately drain lymph fluid from a particular area of the body.
    • The lymphatic system is a network of vessels, nodes, and organs responsible for collecting excess interstitial fluid (lymph) from tissues, filtering it, and returning it to the bloodstream.
    • When this system is compromised, lymph fluid accumulates in the interstitial spaces, leading to swelling.
  4. Distinguishing from General Edema:
    • Edema is a general term for swelling caused by fluid accumulation. Many conditions can cause edema (e.g., heart failure, kidney disease, venous insufficiency).
    • Lymphedema is a specific type of edema characterized by:
      • High Protein Content: Unlike many other forms of edema where the fluid is mainly water and electrolytes, lymphedema fluid is rich in protein. This high protein content is crucial because it draws more water into the interstitial space, stimulates fibroblast activity, and contributes to tissue fibrosis (hardening/thickening of the skin and subcutaneous tissue).
      • Non-pitting (in later stages): While early lymphedema may be pitting (an indentation remains after pressure is applied), as the condition progresses and fibrosis occurs, the tissue becomes harder and the swelling becomes non-pitting.
      • Asymmetrical (often): Lymphedema often affects one limb or one side of the body, though it can be bilateral if the underlying cause affects both sides. Other systemic edemas are typically symmetrical.

In essence, lymphedema is the specific and chronic swelling that occurs when the body's natural drainage system for protein-rich fluid (the lymphatic system) is not working correctly.

Classification of Lymphedema

Lymphedema is broadly classified into two main types: primary lymphedema and secondary lymphedema. The distinction lies in whether the impairment of the lymphatic system is due to a congenital abnormality or an acquired damage/disruption.

I. Primary Lymphedema
  • Definition: Primary lymphedema results from an inherited or congenital abnormality or malformation of the lymphatic system itself. This means the lymphatic vessels or nodes are underdeveloped, malformed, or absent from birth, or develop abnormally later in life without an identifiable external cause.
  • Onset: Can be present at birth, develop during puberty, or even manifest in adulthood.
  • Causes (Congenital Malformations): These are structural abnormalities of the lymphatic system, often genetic in origin, leading to insufficient lymphatic transport capacity.
    • Aplasia: Complete absence of lymphatic vessels in a given area.
    • Hypoplasia: Underdevelopment or reduced number of lymphatic vessels, or vessels that are too small. This is the most common cause of primary lymphedema.
    • Hyperplasia (or Megalymphatics): Abnormally dilated and tortuous lymphatic vessels, often with incompetent valves, leading to reflux and inefficient drainage.
    • Lymphatic Dysfunction: Impaired function of otherwise normally structured vessels, e.g., due to impaired contractility.
  • Clinical Syndromes Associated with Primary Lymphedema:
    • Congenital Lymphedema (Milroy's Disease): Present at birth or develops within the first 2 years of life. Often affects one or both lower limbs. It is caused by mutations in the FLT4 gene (VEGFR3), leading to lymphatic hypoplasia.
    • Lymphedema Praecox (Meige's Disease): The most common form of primary lymphedema, usually developing around puberty or before age 35. Affects primarily females and typically the lower limbs. May be associated with mutations in the FOXC2 gene.
    • Lymphedema Tarda: Develops after age 35.
    • Other Genetic Syndromes: Primary lymphedema can also be a feature of certain genetic syndromes, such as Turner syndrome, Noonan syndrome, and yellow nail syndrome.
II. Secondary Lymphedema
  • Definition: Secondary lymphedema is much more common than primary lymphedema. It results from damage to or obstruction of a previously normal lymphatic system. The lymphatic system is acquiredly injured, leading to its inability to adequately drain lymph fluid.
  • Onset: Typically develops after an event that damages the lymphatic system, such as surgery, radiation, infection, or trauma.
  • Causes (Acquired Damage/Disruption):
    1. Cancer Treatment (Most Common Cause in Developed Countries):
      • Lymph Node Dissection/Removal: Surgical removal of lymph nodes (e.g., sentinel lymph node biopsy, axillary dissection for breast cancer, groin dissection for melanoma, pelvic dissection for gynecological cancers) is a major risk factor. This physically removes critical drainage pathways.
      • Radiation Therapy: Radiation used to treat cancer can damage lymphatic vessels and nodes, causing fibrosis and scarring that impede lymph flow.
    2. Infection (Most Common Cause Worldwide):
      • Filariasis (Elephantiasis): A parasitic infection (caused by filarial worms) transmitted by mosquitoes. The adult worms live in and block lymphatic vessels, causing severe damage and leading to massive lymphedema, particularly in the lower limbs and genitalia. This is a major cause of lymphedema in tropical and subtropical regions.
      • Cellulitis/Erysipelas: Recurrent severe bacterial infections of the skin and subcutaneous tissue can cause inflammation and scarring of lymphatic vessels, leading to damage.
    3. Trauma/Injury: Severe burns, crush injuries, or extensive wounds can directly damage or disrupt lymphatic vessels.
    4. Surgery (Non-Cancer Related): Any extensive surgery that involves large incisions or removal of tissue can inadvertently damage lymphatic pathways.
    5. Venous Insufficiency: Severe, chronic venous insufficiency can lead to an overload of the lymphatic system. While primarily venous edema, it can eventually lead to lymphatic damage and secondary lymphedema (phlebolymphedema).
    6. Obesity: Severe obesity can place mechanical stress on lymphatic vessels, impair lymphatic flow, and is increasingly recognized as a significant risk factor and contributor to lymphedema development and progression.
    7. Immobility/Lack of Muscle Pump: Prolonged immobility can reduce the effectiveness of the muscle pump, which aids lymphatic flow, exacerbating existing lymphatic issues or contributing to edema.
    8. Tumor Obstruction: Tumors themselves can grow and directly compress or invade lymphatic vessels and nodes, blocking lymph drainage.
Causes and Risk Factors

The development of lymphedema is a multifactorial process, influenced by a primary insult to the lymphatic system coupled with various risk factors that can exacerbate or trigger the condition.

I. General Risk Factors for Developing Lymphedema

These factors don't necessarily cause lymphatic damage themselves but increase the likelihood or severity of lymphedema when lymphatic damage is present or imminent.

  • Genetics/Family History: A family history of primary lymphedema increases risk.
  • Obesity: As mentioned, it's a significant risk factor for both onset and progression.
  • Increased Age: The lymphatic system may become less efficient with age.
  • Presence of Scar Tissue: Extensive scarring can obstruct lymphatic pathways.
  • Impaired Wound Healing: Can lead to chronic inflammation and further lymphatic damage.
  • Chronic Inflammation: Any condition causing persistent inflammation can contribute.
  • Female Sex: Women are more susceptible to certain cancers that involve lymph node dissection (e.g., breast cancer), increasing their risk of secondary lymphedema.
  • Severity of Initial Lymphatic Insult: More extensive surgery, higher doses of radiation, or severe infections increase the risk.
Pathophysiology of Lymphedema

Lymphedema originates from a fundamental imbalance between the production of interstitial fluid and its drainage by the lymphatic system. This leads to a vicious cycle of fluid accumulation, inflammation, and progressive tissue changes.

I. Initial Lymphatic Impairment and Fluid Accumulation
  1. Reduced Lymphatic Transport Capacity:
    • Primary Lymphedema: The lymphatic system is intrinsically deficient from birth. Its maximal transport capacity (MTC) is inherently lower than normal.
    • Secondary Lymphedema: A previously normal lymphatic system is damaged. This damage reduces the number and function of lymphatic vessels and nodes, thereby lowering the MTC.
    • The "Safety Factor": A healthy lymphatic system has a significant "safety factor," meaning it can handle a much higher volume of fluid (up to 10-20 times normal) than it typically drains without swelling. When the MTC drops below the actual lymphatic load, lymphedema begins.
  2. Accumulation of Protein-Rich Interstitial Fluid:
    • When the lymphatic system's capacity is overwhelmed or reduced, the interstitial fluid cannot be adequately drained.
    • Crucially, the lymphatic system is the only pathway for large proteins, cellular debris, and large molecules to be removed from the interstitial space.
    • Therefore, in lymphedema, there is a characteristic accumulation of protein-rich fluid in the affected tissues.
II. The Vicious Cycle: Inflammation, Fibrosis, and Tissue Remodeling

The accumulation of protein-rich fluid is not benign. The high protein concentration in the interstitial space acts as an osmotic force, drawing even more water from the capillaries into the tissue, thereby exacerbating the swelling. Furthermore, this protein-rich environment initiates a cascade of inflammatory and fibrotic changes:

  1. Inflammation and Immune Response:
    • Macrophage Activation: The stagnant, protein-rich lymph is an ideal medium for chronic low-grade inflammation. Macrophages are attracted to the area and activated.
    • Cytokine Release: Activated macrophages and other immune cells release pro-inflammatory cytokines (e.g., TNF-α, IL-1, IL-6) and growth factors (e.g., TGF-β, VEGF-C).
    • Impaired Local Immunity: The impaired lymphatic drainage also means that immune cells cannot effectively patrol and respond to local infections, making the lymphedematous limb more prone to recurrent infections (e.g., cellulitis), which in turn further damages the lymphatic system.
  2. Stimulation of Fibrosis (Connective Tissue Proliferation):
    • Fibroblast Activation: The high protein concentration and the persistent inflammatory mediators (especially TGF-β) stimulate fibroblasts in the subcutaneous tissue to produce and deposit excess collagen and other extracellular matrix components.
    • Adipose Tissue Accumulation: There is also a significant proliferation of adipocytes (fat cells) in the affected area. This is a characteristic feature of chronic lymphedema, contributing significantly to the increased limb volume and hardening.
    • Increased Tissue Viscosity: The deposition of collagen and fat leads to hardening and thickening of the subcutaneous tissue, making the limb feel firm and eventually non-pitting. This is known as fibrosis or sclerosis.
  3. Further Compromise of Lymphatic Function:
    • The chronic inflammation and fibrosis within the tissues can further compress and destroy remaining functional lymphatic vessels, leading to a further reduction in MTC. This creates a self-perpetuating cycle where lymphatic insufficiency leads to fluid accumulation, which leads to inflammation and fibrosis, which then worsens lymphatic insufficiency.
III. Clinical Progression and Tissue Changes

This pathological process leads to the characteristic signs and symptoms of lymphedema, progressing through stages:

  • Initial Stages (Stage 0, Stage 1):
    • Pitting Edema: Early lymphedema is often characterized by pitting edema (an indentation remains after pressure is applied), as the tissue is still relatively soft.
    • Reversible Swelling: The swelling may partially or fully resolve with elevation or overnight rest.
  • Later Stages (Stage 2, Stage 3):
    • Non-pitting Edema: As fibrosis and fat deposition increase, the tissue becomes firmer, and the swelling becomes non-pitting.
    • Skin Changes: The skin becomes thickened, hardened, and takes on an "orange peel" appearance (peau d'orange). There may be hyperkeratosis (thickening of the outer layer of the skin), papillomatosis (wart-like growths), and skin folds deepen.
    • Loss of Function: The increased limb volume and tissue changes can lead to pain, discomfort, reduced range of motion, and impaired mobility.
    • Increased Susceptibility to Infection: Due to impaired local immunity and stagnant fluid, recurrent episodes of cellulitis are common, further damaging the lymphatic system.
    • Lymphangiectasia/Dermal Backflow: In severe cases, lymphatic vessels in the skin may dilate, sometimes leaking lymph (lymphorrhea).
Signs and Symptoms / Clinical Presentation

The clinical presentation of lymphedema can vary based on its cause, location, and severity, but there are characteristic signs and symptoms that guide diagnosis.

I. General Signs and Symptoms
  1. Swelling (Edema):
    • Primary Symptom: The most obvious sign. Can affect arms, legs, trunk, head/neck, or genitalia.
    • Onset: Often gradual, but can be sudden, especially after an inciting event (e.g., surgery).
    • Location: Usually asymmetrical (affecting one limb or side), though bilateral involvement is possible.
    • Feeling of Heaviness/Fullness: The affected limb feels heavy, full, or tight, even before visible swelling is pronounced.
    • "Stocking/Glove" Pattern: Swelling often starts distally (in the hand or foot) and progresses proximally up the limb, though this is not always the case.
    • Reduced Pitting: Early on, the swelling may "pit." As the condition progresses and fibrosis occurs, it becomes less pitting or non-pitting.
  2. Skin Changes:
    • Thickening and Hardening (Fibrosis): The skin and subcutaneous tissue become firm, tough, and rubbery.
    • Peau d'Orange: The skin may take on an "orange peel" texture due to pitting around hair follicles.
    • Hyperkeratosis: Thickening of the outer layer of the skin, leading to a rough, scaly, or wart-like appearance.
    • Papillomatosis: Formation of small, wart-like growths on the skin surface.
    • Skin Folds: Deepening of natural skin folds or the formation of new folds.
    • Dryness and Cracking: The skin can become dry, flaky, and prone to cracking, increasing the risk of infection.
    • Discoloration: The skin may appear pale, reddish, or brownish (hyperpigmentation) due to chronic inflammation or hemosiderin deposition.
  3. Discomfort and Functional Impairment:
    • Pain/Aching: While often not severely painful, dull aching or discomfort is common, particularly in later stages or during inflammatory episodes.
    • Tightness/Tension: A constant feeling of pressure or tightness in the affected area.
    • Restricted Range of Motion: Swelling and tissue thickening can limit movement in joints.
    • Difficulty with Clothing/Jewelry: Rings, watches, or clothing become tight or no longer fit.
    • Impaired Function: Reduced ability to perform daily activities due to the size, weight, and stiffness of the limb.
    • Numbness/Tingling: May occur due to nerve compression from swelling.
  4. Increased Susceptibility to Infection:
    • Cellulitis: Recurrent bacterial infections (e.g., cellulitis, erysipelas) are a hallmark of lymphedema. Symptoms include redness, warmth, increased swelling, intense pain, fever, and malaise.
    • Fungal Infections: The moist environment in skin folds makes fungal infections more common.
  5. Stemmer's Sign (Diagnostic Feature):
    • A positive Stemmer's sign is often considered a hallmark of lymphedema in the toes or fingers. It is present when the skin at the base of the second toe (or middle finger) cannot be lifted into a fold. This indicates thickening and fibrosis of the skin and subcutaneous tissue. A negative Stemmer's sign (skin can be lifted) does not rule out lymphedema elsewhere in the limb.
II. Stages of Lymphedema (ISL Staging)
  • Stage 0 (Latency or Subclinical Lymphedema):
    • Description: The lymphatic system is damaged, but there is no visible or palpable swelling. The transport capacity of the lymphatic system is impaired, but it can still manage the lymphatic load.
    • Symptoms: Patients may report vague symptoms like occasional feelings of heaviness, fullness, or mild aching.
    • Reversible: Potentially reversible with early intervention, or can remain at this stage for years.
  • Stage 1 (Spontaneously Reversible Lymphedema):
    • Description: Visible swelling is present. The edema is typically soft and pitting.
    • Symptoms: Limb volume may increase. The swelling often reduces with limb elevation or overnight rest. Stemmer's sign may be negative or positive.
    • Reversible: At this stage, the condition is largely reversible if effectively treated, as significant fibrotic changes have not yet occurred.
  • Stage 2 (Spontaneously Irreversible Lymphedema):
    • Description: The swelling is persistent and does not significantly reduce with elevation. The tissue texture begins to change, becoming firmer or "brawny" due to the accumulation of protein and the onset of fibrosis.
    • Symptoms: The edema is less pitting or non-pitting. Stemmer's sign is typically positive. Skin changes (e.g., thickening, hyperkeratosis) may begin to appear.
    • Irreversible: While the volume can be managed, the fibrotic changes make the tissue irreversible to complete normal appearance.
  • Stage 3 (Lymphostatic Elephantiasis):
    • Description: This is the most advanced and severe stage, characterized by significant and irreversible swelling, often referred to as "elephantiasis."
    • Symptoms: Extreme increase in limb volume, gross tissue changes, extensive fibrosis, severe hyperkeratosis, papillomatosis, deep skin folds, and often impaired mobility. Recurrent infections (cellulitis) are common. Lymphorrhea (leaking lymph fluid) may occur from skin lesions.
    • Irreversible: Severe and debilitating, often with significant impact on quality of life.
Diagnostic Methods of Lymphedema

The diagnosis of lymphedema is primarily clinical, based on a thorough history and physical examination. Imaging studies are often used to confirm the diagnosis, differentiate lymphedema from other edemas, and identify the underlying cause and lymphatic anatomy.

I. Clinical History
  1. Onset and Progression of Swelling: When did it start? Sudden or gradual? Unilateral or bilateral? Does it fluctuate? How has it changed?
  2. Medical History:
    • Cancer Treatment: History of cancer, lymph node dissection, radiation therapy.
    • Infections: History of recurrent cellulitis/erysipelas or parasitic infections.
    • Trauma/Surgery: Previous injury or surgery to the affected region.
    • Venous Disease: DVT or chronic venous insufficiency.
    • Genetic Conditions: Family history.
  3. Symptoms: Heaviness, tightness, aching, skin changes, difficulty with clothing.
II. Physical Examination
  1. Inspection: Asymmetry, Skin Changes (erythema, hyperpigmentation, hyperkeratosis), Hair Distribution (reduced/absent), Venous Patterns.
  2. Palpation: Temperature, Consistency (soft, pitting, firm, brawny), Stemmer's Sign.
  3. Measurements: Circumference Measurements, Volume Measurement (perometry, water displacement), Bioimpedance Spectroscopy (BIS).
III. Diagnostic Imaging
Modality Procedure / Use Findings in Lymphedema
1. Lymphoscintigraphy (Radionuclide Lymphangioscintigraphy)
  • Gold Standard (Functional Assessment).
  • Radioactive tracer injected into web space of toes/fingers. Images taken over time to visualize vessels/nodes and tracer transport.
 Delayed or absent lymphatic uptake, visualization of collateral channels, dermal backflow (tracer remaining in skin), absence of lymph node visualization.
2. Indocyanine Green (ICG) Lymphography Fluorescent dye (ICG) injected intradermally and illuminated with near-infrared light. Visualizes superficial vessels. Shows "dermal backflow," abnormal patterns ("splashes," "stardust"), and areas of obstruction. Useful for surgical planning.
3. Magnetic Resonance Lymphangiography (MRL) Uses MRI (with/without contrast) to visualize deeper lymphatic vessels and nodes. Identifies vessel abnormalities, lymph node status, and differentiates lymphedema from other conditions.
4. Ultrasonography (Ultrasound) Primarily used to rule out DVT or cysts, and assess tissue thickness. Increased subcutaneous tissue thickness, "honeycomb" patterns (dilated channels), thickening of dermis.
5. CT Scan & MRI Assess tumor involvement, quantify limb volume, differentiate from lipedema. Show characteristic patterns of subcutaneous edema and thickening.
IV. Differential Diagnosis
  • Chronic Venous Insufficiency (CVI): Often bilateral, varicose veins, skin discoloration (brawny), ulcers.
  • Cardiac Edema (CHF): Bilateral, symmetrical, pitting, shortness of breath, JVD.
  • Renal Edema: Bilateral, symmetrical, pitting, facial puffiness.
  • Hepatic Edema: Ascites, jaundice, bilateral pitting edema.
  • Hypothyroidism (Myxedema): Non-pitting edema.
  • Lipedema: Chronic adipose disorder (mostly women), symmetrical, painful fat accumulation, feet spared, Stemmer's sign negative.
  • Deep Vein Thrombosis (DVT): Acute, unilateral, painful, warmth, redness.
Management and Treatment Options

The goal is to reduce swelling, prevent progression, manage symptoms, and improve quality of life. Treatment is primarily conservative.

I. Conservative Management: Complete Decongestive Therapy (CDT)

The cornerstone of treatment. A two-phase program.

Phase I: Intensive Treatment (Decongestion Phase)
  1. Manual Lymphatic Drainage (MLD):
    • Description: Gentle, rhythmic massage to stimulate flow and reroute lymph.
    • Mechanism: Promotes lymphangiomotoricity and opens alternative pathways.
  2. Compression Bandaging:
    • Description: Multiple layers of short-stretch bandages applied to the limb.
    • Mechanism: Provides external pressure to reduce swelling, improve muscle pump efficiency, and break down fibrotic tissue. Worn 24 hours/day.
  3. Skin Care:
    • Description: Meticulous hygiene and moisturizing.
    • Mechanism: Prevents infection (cellulitis) in compromised skin.
  4. Decongestive Exercises:
    • Description: Low-impact exercises worn with compression.
    • Mechanism: Activates muscle pump to move fluid.
  5. Education: Self-care techniques and infection prevention.
Phase II: Maintenance Treatment (Self-Management Phase)
  1. Compression Garments: Custom-fitted or ready-to-wear garments worn daily. Replace bandages once volume is stabilized.
  2. Self-MLD: Patients taught simplified techniques.
  3. Self-Bandaging: Applied at night or during flare-ups.
  4. Regular Exercise & Lifelong Skin Care.
  5. Regular Follow-ups.
II. Additional Conservative Modalities
  • Pneumatic Compression Pumps: Devices applying sequential pressure. Adjunct to CDT.
  • Weight Management: Crucial for obese patients to reduce mechanical compression on vessels.
III. Surgical Interventions
A. Reconstructive/Physiologic Procedures (Aim to improve function):
  1. Lymphaticovenous Anastomosis (LVA) / Bypass (LVB):
    • Description: Microsurgical connection of lymphatic vessels to small veins.
    • Mechanism: Bypasses obstruction by draining into venous system.
    • Indication: Early to moderate lymphedema.
  2. Vascularized Lymph Node Transfer (VLNT):
    • Description: Transplantation of healthy lymph nodes to the affected area.
    • Mechanism: Provides new drainage pathways and growth factors.
B. Excisional/Ablative Procedures (Aim to reduce volume):
  1. Direct Excision/Debulking: Surgical removal of excess fibrotic tissue. For very advanced/disfigured limbs.
  2. Liposuction (Suction-Assisted Lipectomy):
    • Description: Removal of excess adipose tissue.
    • Indication: Chronic Stage 2 or 3 where maximal decongestion is achieved but fat remains. Requires lifelong compression post-op.
NURSING DIAGNOSES AND INTERVENTIONS
A. Impaired Tissue Integrity
  • Related to: Edema, altered circulation, chronic inflammation, skin changes.
  • As evidenced by: Swelling, thickened skin, discoloration, fissures, positive Stemmer's sign.
  • Interventions:
    • Assess skin integrity daily: Inspect for redness, warmth, cracks, blisters, signs of infection.
    • Provide meticulous skin care: Wash daily with mild soap, pat dry (especially folds). Apply low pH, non-perfumed moisturizer.
    • Protect skin from injury: Wear gloves for chores, use electric razor, avoid tight clothing/jewelry.
    • Elevate affected limb when resting.
    • Implement wound care protocols for breakdown.
    • Ensure proper fit of compression garments to prevent irritation.
B. Risk for Infection
  • Related to: Accumulation of protein-rich fluid (bacterial medium), altered skin integrity, decreased local immune response.
  • Interventions:
    • Educate on signs of infection: Redness, warmth, increased swelling, pain, fever, streaks. Report immediately.
    • Emphasize strict skin care regimen.
    • Advise on avoiding trauma: Prevent cuts, insect bites, sunburns, needle sticks (no blood draws/BP in affected limb).
    • Discuss prophylactic antibiotics if history of recurrent cellulitis.
    • Encourage prompt treatment of minor cuts with antiseptic.
C. Chronic Pain
  • Related to: Tissue distension, nerve compression, fibrosis, heavy limb.
  • Interventions:
    • Assess pain characteristics.
    • Administer prescribed analgesics.
    • Implement non-pharmacological strategies: Elevation, cold/warm packs (caution with sensation), gentle massage, relaxation.
    • Ensure proper fit of compression garments to avoid constriction.
    • Encourage gentle exercises to reduce stiffness.
D. Impaired Physical Mobility
  • Related to: Increased limb size/weight, stiffness, fear of injury.
  • Interventions:
    • Assess mobility and ROM.
    • Encourage gentle active/passive ROM exercises.
    • Collaborate with PT/OT for tailored programs.
    • Instruct on proper body mechanics.
E. Disrupted Body Image
  • Related to: Limb disfigurement, clothing difficulties.
  • Interventions:
    • Provide safe environment to express feelings.
    • Listen actively and empathetically.
    • Focus on functional improvements rather than just cosmetic.
    • Suggest coping strategies: Clothing choices, support groups, counseling.
F. Inadequate Health Knowledge / Ineffective Health Maintenance
  • Related to: Complexity of treatment, lack of information, barriers to adherence.
  • Interventions:
    • Assess current knowledge and learning style.
    • Provide clear education on: MLD, compression, skin care, infection prevention, signs of complications.
    • Use teach-back method.
    • Provide written materials/videos.
    • Address barriers (cost, time).
    • Refer to Certified Lymphedema Therapist (CLT).
III. Collaborative Interventions
  • Certified Lymphedema Therapist (CLT): Essential for CDT implementation.
  • Physician/Specialist: Diagnosis and medical management.
  • PT/OT: Functional adaptations.
  • Dietitian: Weight management.
  • Social Worker/Psychologist: Emotional support.

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anatomy and physiology of the lymphatic system

Anatomy and Physiology of the Lymphatic System

Anatomy and Physiology of Lymphatic System

The lymphatic system is part of the circulatory system which begins with very small close ended vessels called lymphatic capillaries which is in contact with the surrounding tissues and interstitial fluid. The lymphatic system is almost a parallel system to the blood circulatory system.

It consists of:
  • Lymph
  • Lymph vessel
  • Lymph nodes
  • Diffuse lymphoid tissue
  • Bone marrow
Lymph

Lymph is a clear, watery fluid that circulates throughout the lymphatic system. It is essentially an ultrafiltrate of blood plasma that has left the capillaries and entered the interstitial spaces, eventually being collected by the lymphatic vessels. Understanding its origin and contents is key to grasping its physiological roles.

I. Definition of Lymph
  • A clear, yellowish or whitish fluid that flows through the lymphatic vessels.
  • It is derived from interstitial fluid (tissue fluid) that surrounds the cells, which in turn is formed from blood plasma that filters out of blood capillaries.
  • It is identical to interstitial fluid in its composition.
II. Composition of Lymph

The composition of lymph is very similar to blood plasma, but with some key differences, primarily a lower concentration of large proteins.

  1. Water: The primary component, providing the solvent for all other substances.
  2. Electrolytes: Ions such as sodium (Na+), potassium (K+), chloride (Cl-), bicarbonate (HCO3-), etc., are present in similar concentrations to plasma.
  3. Nutrients: Glucose, amino acids, fatty acids, and vitamins, which have filtered out of the blood capillaries and are essential for cellular metabolism.
  4. Metabolic Waste Products: Urea, creatinine, and other cellular waste products.
  5. Proteins:
    • Lower concentration than plasma: While most large plasma proteins are too big to easily exit blood capillaries, some do leak out into the interstitial fluid. Lymph serves to return these leaked proteins to the bloodstream.
    • Plasma proteins: Albumin, globulins (including antibodies), and clotting factors are present in smaller amounts.
  6. Cells:
    • Lymphocytes: These are the most abundant cells in lymph, especially after it has passed through lymph nodes. Lymphocytes are crucial for immune responses.
    • Macrophages: Phagocytic cells that engulf foreign particles, cellular debris, and pathogens.
    • Other immune cells: Neutrophils may be present, particularly during infection.
    • Erythrocytes (Red Blood Cells): Generally absent in lymph unless there is trauma or pathology.
  7. Fats (Chylomicrons): After a fatty meal, specialized lymphatic vessels in the small intestine (lacteals) absorb dietary fats, which are then transported as chylomicrons in the lymph (giving it a milky appearance, especially after a meal).
  8. Bacteria, Viruses, Cellular Debris, Damaged Tissues: These are also transported within the lymph to the lymph nodes for filtration and immune processing.
  9. Antibodies: Carried by lymphocytes and dissolved in the fluid component, providing immune protection.
III. Formation of Lymph

Lymph formation is a direct consequence of fluid exchange between blood capillaries and the interstitial spaces:

  1. Filtration at Capillary Ends: Due to the relatively high hydrostatic pressure within blood capillaries, a significant amount of fluid, along with dissolved substances (but not large proteins or blood cells), is forced out of the capillaries and into the interstitial spaces, becoming interstitial fluid.
  2. Absorption at Venule Ends: Most of this interstitial fluid (about 85-90%) is reabsorbed back into the capillaries at the venule end, where hydrostatic pressure is lower and osmotic pressure is higher.
  3. Lymphatic Drainage: However, about 10-15% of the interstitial fluid, along with any leaked plasma proteins and cellular debris, remains in the interstitial spaces. This fluid is collected by the blind-ended lymphatic capillaries, at which point it is officially called lymph. The unique structure of lymphatic capillaries allows large molecules to enter easily.
  4. Volume: Approximately 2-4 liters of lymph are formed and returned to the bloodstream each day. This represents about 1-3% of the body's total weight.
IV. Functions of Lymph

The composition of lymph directly supports its critical functions within the body:

  1. Fluid Balance:
    • Return of Excess Interstitial Fluid: Lymph collects excess fluid from the interstitial spaces and returns it to the bloodstream. This prevents edema (swelling) and maintains fluid homeostasis. Without this function, interstitial fluid would accumulate rapidly, leading to death within approximately 24 hours.
    • Transport of Proteins: It returns plasma proteins that have leaked out of blood capillaries into the interstitial fluid back to the circulation. This is crucial because if these proteins remained in the interstitial fluid, they would increase its osmotic pressure, drawing more fluid out of the capillaries and causing persistent edema.
  2. Immune Surveillance and Defense:
    • Transport of Pathogens to Lymph Nodes: Lymph effectively "sweeps up" bacteria, viruses, cellular debris, and foreign particles from tissues and transports them to regional lymph nodes.
    • Antigen Presentation: Within the lymph nodes, these pathogens and antigens are presented to lymphocytes (T and B cells) and macrophages, initiating specific immune responses.
    • Distribution of Immune Cells: Lymph circulates lymphocytes and antibodies throughout the body, providing a means for immune cells to patrol tissues and quickly respond to infections.
  3. Fat Absorption and Transport:
    • Transport of Dietary Lipids: In the small intestine, specialized lymphatic capillaries called lacteals absorb dietary fats (in the form of chylomicrons), cholesterol, and fat-soluble vitamins (A, D, E, K).
    • Bypassing Liver (Initially): This lymphatic pathway allows these absorbed fats to bypass initial processing by the liver and enter the systemic circulation directly via the thoracic duct.
Lymph Vessels (Lymphatics) and Lymph Capillaries

The lymphatic system begins with tiny, blind-ended capillaries that merge to form progressively larger vessels, eventually returning lymph to the bloodstream. These vessels have unique structural features that facilitate the collection and transport of lymph.

I. Lymph Capillaries
  1. Structure:
    • Blind-ended: Unlike blood capillaries which form a continuous loop, lymphatic capillaries originate as blind-ended tubules in the interstitial spaces. This "closed" end is crucial for initiating lymph flow.
    • Single Layer of Endothelial Cells: They are composed of a single layer of flattened endothelial cells, similar to blood capillaries.
    • No Basement Membrane: A key distinguishing feature is the absence or incomplete presence of a continuous basement membrane beneath the endothelial cells. This lack of structural support makes them more permeable.
    • Overlapping Endothelial Cells (Mini-Valves): The endothelial cells significantly overlap each other. These overlaps are loosely attached and form one-way flap-like mini-valves. When interstitial fluid pressure is high, these flaps open inwards, allowing fluid, proteins, bacteria, and larger particles to enter the capillary. When pressure inside the capillary is high, the flaps close, preventing lymph from leaking back into the interstitial space.
    • Anchoring Filaments: Fine collagen filaments (anchoring filaments) extend from the endothelial cells into the surrounding connective tissue. These filaments anchor the capillaries to the tissue, ensuring that when tissue fluid volume increases, the capillaries are pulled open, preventing collapse and facilitating fluid entry.
  2. Permeability:
    • Lymph capillaries are much more permeable than blood capillaries. This high permeability allows them to absorb not only excess interstitial fluid but also large molecules like plasma proteins (which have leaked out of blood capillaries), cell debris, bacteria, and even whole cancer cells. This ability to absorb large particles is vital for their immune and fluid balance functions.
  3. Distribution:
    • Lymph capillaries are extensive networks found almost everywhere blood capillaries are present. They permeate nearly all body tissues, forming dense plexuses within the interstitial spaces.
    • Exceptions: They are generally not found in certain areas, including:
      • Brain and Spinal Cord: The central nervous system has its own fluid drainage system (cerebrospinal fluid).
      • Bone Marrow: While lymphoid tissue is in bone marrow, it doesn't have lymphatic capillaries in the same way.
      • Avascular tissues: Like cartilage, epidermis of the skin, and the cornea of the eye.
      • Spleen: The spleen is a lymphoid organ, not a site of fluid collection from the interstitium via capillaries.
II. Lymph Vessels (Lymphatics)

Lymph capillaries merge to form progressively larger collecting vessels, which are collectively known as lymphatics. These vessels share structural similarities with veins but also have distinct features.

  1. Structure:
    • Similar to Veins, but Thinner Walls: Lymphatic vessels are structurally similar to veins, possessing three tunics (intima, media, externa), but their walls are generally much thinner and more delicate.
    • More Valves: A distinguishing feature of lymphatic vessels is the presence of an even greater number of valves than in veins. These numerous one-way valves are crucial for preventing the backflow of lymph and ensuring its unidirectional flow towards the heart. The presence of these valves gives the lymphatic vessels a characteristic beaded or segmented appearance.
    • Lymphangions: The segment of a lymphatic vessel between two consecutive valves is called a lymphangion. These lymphangions have smooth muscle in their walls, which contract rhythmically to propel lymph forward.
    • Afferent and Efferent Vessels: Lymphatic vessels entering a lymph node are called afferent lymphatic vessels, while those leaving a lymph node are efferent lymphatic vessels.
  2. Types of Lymphatic Vessels (in increasing size):
    • Lymphatic Capillaries: The starting point, blind-ended, highly permeable.
    • Collecting Lymphatic Vessels: Formed by the union of capillaries, these often travel alongside arteries and veins, having numerous valves.
    • Lymphatic Trunks: Formed by the convergence of collecting vessels. There are typically five major lymphatic trunks:
      • Lumbar trunks: Drain lymph from the lower limbs, pelvic organs, and anterior abdominal wall.
      • Bronchomediastinal trunks: Drain lymph from the thoracic viscera and chest wall.
      • Subclavian trunks: Drain lymph from the upper limbs.
      • Jugular trunks: Drain lymph from the head and neck.
      • Intestinal trunk (unpaired): Drains lymph from the digestive organs.
Lymphatic Ducts:

The two largest lymphatic vessels in the body, which ultimately return lymph to the venous circulation.

  • Thoracic Duct (Left Lymphatic Duct):
    • Origin: Begins in the abdomen as a dilated sac called the cisterna chyli (located anterior to the L1 and L2 vertebrae). The cisterna chyli receives lymph from the lumbar trunks and the intestinal trunk, meaning it drains the lower limbs, pelvic and abdominal organs.
    • Course: Ascends through the thoracic cavity, collecting lymph from the left broncho-mediastinal trunk, left subclavian trunk, and left jugular trunk.
    • Drainage Area: Drains lymph from the entire lower half of the body (both legs, pelvis, abdomen), the left side of the thorax, the left upper limb, and the left side of the head and neck.
    • Termination: Empties into the venous system at the junction of the left internal jugular vein and the left subclavian vein in the root of the neck.
  • Right Lymphatic Duct:
    • Origin: A much shorter vessel (about 1-2 cm long).
    • Drainage Area: Drains lymph from the right upper limb, the right side of the thorax, and the right side of the head and neck (from the right jugular, right subclavian, and right broncho-mediastinal trunks).
    • Termination: Empties into the venous system at the junction of the right internal jugular vein and the right subclavian vein in the root of the neck.
III. Overall Distribution

The lymphatic system is a vast, one-way network of vessels that transports lymph from peripheral tissues back to the cardiovascular system. It essentially runs parallel to the venous system, collecting fluid that cannot be reabsorbed by blood capillaries and filtering it before returning it to the blood.

Lymph Circulation

Lymph circulation is a one-way street, beginning in the peripheral tissues and ending back in the bloodstream. This accessory route is vital for maintaining fluid balance, transporting absorbed nutrients, and facilitating immune responses.

I. Path of Lymph Circulation
  1. Interstitial Fluid: Fluid (plasma minus large proteins) filters out of blood capillaries into the interstitial spaces, becoming interstitial fluid. This fluid surrounds tissue cells.
  2. Lymphatic Capillaries: The blind-ended, highly permeable lymphatic capillaries collect excess interstitial fluid, leaked proteins, cellular debris, and pathogens from the interstitial spaces. Once inside these capillaries, the fluid is called lymph.
  3. Collecting Lymphatic Vessels: Lymphatic capillaries merge to form larger collecting vessels. These vessels have numerous one-way valves, giving them a beaded appearance, and often travel alongside blood vessels.
  4. Lymph Nodes: Lymphatic vessels typically pass through one or more (often 8-10) lymph nodes. Lymph flows into a node via afferent lymphatic vessels, is filtered as it passes through the node, and then exits via efferent lymphatic vessels. This filtration process allows immune cells within the node to monitor the lymph for foreign substances.
  5. Lymphatic Trunks: Efferent vessels eventually converge to form larger lymphatic trunks. There are several major trunks throughout the body (e.g., lumbar, intestinal, broncho-mediastinal, subclavian, jugular).
  6. Lymphatic Ducts: The lymphatic trunks drain into one of two large lymphatic ducts:
    • Thoracic Duct:
      • Receives lymph from the cisterna chyli (which collects lymph from the lumbar trunks and intestinal trunk).
      • Also receives lymph from the left jugular, left subclavian, and left broncho-mediastinal trunks.
      • Drains: The entire lower body, left upper limb, left side of the thorax, and left side of the head and neck.
      • Terminates: Empties into the venous circulation at the junction of the left internal jugular vein and the left subclavian vein.
    • Right Lymphatic Duct:
      • Receives lymph from the right jugular, right subclavian, and right broncho-mediastinal trunks.
      • Drains: The right upper limb, right side of the thorax, and right side of the head and neck.
      • Terminates: Empties into the venous circulation at the junction of the right internal jugular vein and the right subclavian vein.
  7. Subclavian Veins: Once lymph enters the subclavian veins, it mixes with blood plasma and becomes part of the general venous circulation, eventually returning to the heart.
II. Factors Aiding Lymph Flow (The Lymphatic Pump)

Unlike the cardiovascular system, which has the heart as a central pump, the lymphatic system relies on extrinsic and intrinsic mechanisms to propel lymph against gravity and low pressure. These mechanisms collectively form what is sometimes called the "lymphatic pump."

  1. Skeletal Muscle Pump:
    • Mechanism: Contraction and relaxation of skeletal muscles surrounding lymphatic vessels compress the vessels. This compression pushes lymph forward through the one-way valves.
    • Importance: This is a major driving force, especially in the limbs. Increased physical activity (exercise) significantly enhances lymph flow by increasing muscle contractions. Conversely, prolonged inactivity leads to sluggish lymph flow.
  2. Respiratory Pump (Pressure Changes during Breathing):
    • Mechanism: During inhalation, the diaphragm descends, increasing intra-abdominal pressure and decreasing intrathoracic pressure. This pressure gradient compresses abdominal lymphatic vessels (including the cisterna chyli) and draws lymph into the thoracic duct, which is in the lower-pressure thoracic cavity. During exhalation, the reverse occurs, helping to maintain flow.
  3. Rhythmic Contraction of Smooth Muscle in Lymphatic Vessels (Intrinsic Lymphatic Pump):
    • Mechanism: The walls of larger lymphatic vessels (collecting vessels, trunks, ducts) contain smooth muscle cells, particularly in the segments between valves (lymphangions). These smooth muscles undergo slow, rhythmic, spontaneous contractions.
    • Importance: This intrinsic peristaltic-like action helps to actively propel lymph forward, especially when other external pumps are less active.
  4. Pulsations of Adjacent Arteries:
    • Mechanism: Lymphatic vessels often run in close proximity to arteries. The pulsations (throbbing) of these arteries, due to each heartbeat, can compress the lymphatic vessels and gently massage lymph along.
  5. One-Way Valves:
    • Mechanism: These numerous valves are crucial structural components within lymphatic vessels that ensure unidirectional flow. They prevent lymph from flowing backward due to gravity or pressure fluctuations.
  6. Compression of Tissues by External Objects:
    • Mechanism: External compression, such as massage, compression garments, or simply leaning on an object, can also temporarily increase pressure on lymphatic vessels and aid lymph flow.
  7. Hydrostatic Pressure in Interstitial Fluid:
    • Mechanism: The initial entry of interstitial fluid into lymphatic capillaries is driven by a pressure gradient. When interstitial fluid pressure is higher than the pressure inside the lymphatic capillary, the mini-valves open, allowing fluid to enter.
III. Significance of Lymph Circulation
  • Essential for Life: The continuous return of fluid and proteins from the interstitial spaces to the blood prevents fatal edema and hypovolemia (low blood volume).
  • Immune System Function: It allows immune cells and antigens to be circulated and processed in lymph nodes, initiating vital immune responses.
  • Nutrient Transport: Especially important for the absorption and transport of dietary fats.
Lymph Nodes

Lymph nodes are small, encapsulated organs that are strategically distributed throughout the body along the lymphatic vessels. They serve as primary sites for immune surveillance.

I. Structure of a Lymph Node

Lymph nodes are typically oval or bean-shaped, ranging in size from 1 mm to 25 mm (about 1 inch) in diameter.

  1. Capsule:
    • Each lymph node is enclosed by a dense fibrous capsule made of connective tissue.
    • Trabeculae: Extensions of the capsule, called trabeculae, extend inwards into the interior of the node, dividing it into compartments and providing structural support.
  2. Cortex and Medulla:
    • Cortex (Outer Region): The outer part of the lymph node. It contains:
      • Lymphoid Follicles (Nodules): Spherical clusters of lymphocytes.
      • Primary Follicles: Densely packed with small, inactive B lymphocytes.
      • Secondary Follicles: Develop in response to an antigen. They have a lighter-staining central area called a germinal center, which contains rapidly proliferating B cells, plasma cells (antibody-producing cells), and follicular dendritic cells.
      • Paracortex (Deep Cortex): The region between the follicles and the medulla. This area is rich in T lymphocytes and high endothelial venules (HEVs), through which lymphocytes can enter the node from the bloodstream. Dendritic cells, which present antigens to T cells, are also abundant here.
    • Medulla (Inner Region): The central part of the lymph node. It consists of:
      • Medullary Cords: Branching cords of lymphatic tissue that extend inward from the cortex. They contain B lymphocytes, plasma cells, and macrophages.
      • Medullary Sinuses: Large lymphatic capillaries that separate the medullary cords. Lymph flows through these sinuses.
  3. Lymphatic Sinuses (Channels for Lymph Flow):
    • These are a network of irregular channels lined by reticular cells and macrophages, forming a labyrinth through which lymph percolates.
    • Subcapsular Sinus (Marginal Sinus): Located immediately beneath the capsule, where afferent lymphatic vessels first empty.
    • Cortical Sinuses (Trabecular Sinuses): Extend from the subcapsular sinus, along the trabeculae.
    • Medullary Sinuses: Located in the medulla.
    • Flow Path: Lymph enters the subcapsular sinus, flows through cortical and medullary sinuses, and eventually collects in the efferent lymphatic vessels.
  4. Blood Supply:
    • Lymph nodes receive arterial blood and drain venous blood. High Endothelial Venules (HEVs) in the paracortex are particularly important, allowing lymphocytes to enter the node directly from the blood circulation.
  5. Afferent and Efferent Lymphatic Vessels:
    • Afferent Lymphatic Vessels: Several (typically 4-5) afferent vessels pierce the convex surface of the capsule, bringing lymph into the node. These vessels have valves that direct lymph inward.
    • Efferent Lymphatic Vessels: Fewer (typically 1-2) efferent vessels emerge from the hilum (the indented region) of the lymph node, carrying filtered lymph out of the node. These also have valves to prevent backflow.
II. Location and Distribution

Lymph nodes are found throughout the body, often clustered in strategic locations where they can effectively filter lymph from large regions. They are typically arranged in deep and superficial groups. Key large groups include:

  1. Cervical Lymph Nodes:
    • Location: In the neck, both superficial (along the sternocleidomastoid muscle) and deep (around the internal jugular vein).
    • Drainage: Head and neck.
    • Clinical Significance: Often swell during throat infections, colds, and ear infections.
  2. Axillary Lymph Nodes:
    • Location: In the armpits (axilla).
    • Drainage: Upper limbs, pectoral region, and the mammary glands.
    • Clinical Significance: Crucial in the staging of breast cancer, as cancer cells often metastasize via lymphatic drainage to these nodes.
  3. Inguinal Lymph Nodes:
    • Location: In the groin region.
    • Drainage: Lower limbs, external genitalia, and superficial abdominal wall.
    • Clinical Significance: May swell with infections or cancers of the lower extremities or pelvic area.
  4. Popliteal Lymph Nodes:
    • Location: Behind the knee.
    • Drainage: Superficial leg and foot.
  5. Thoracic Lymph Nodes:
    • Location: Within the mediastinum and around the hila of the lungs (hilar nodes), along the aorta (aortic nodes), and sternum (sternal nodes).
    • Drainage: Thoracic organs (lungs, heart, esophagus, mediastinum).
    • Clinical Significance: Involved in lung infections (e.g., tuberculosis) and lung cancer.
  6. Abdominal and Pelvic Lymph Nodes:
    • Location: Along the aorta (e.g., para-aortic nodes), iliac vessels, and within the mesentery of the intestines (e.g., mesenteric nodes).
    • Drainage: Abdominal and pelvic organs (e.g., gastrointestinal tract, kidneys, reproductive organs).
    • Clinical Significance: Involved in cancers of the digestive system and urogenital system.
  7. Cisterna Chyli: While not a true lymph node, this is a dilated sac that collects lymph from the lumbar and intestinal trunks, located in front of L1 & L2 vertebrae.
III. Functions of Lymph Nodes

Lymph nodes perform two primary, interconnected functions:

  1. Filtration of Lymph:
    • Mechanism: As lymph slowly flows through the intricate network of sinuses within the node, macrophages and reticular cells lining these sinuses phagocytose (engulf) debris, foreign particles, bacteria, viruses, dead cells, and cancer cells.
    • Importance: This cleansing action prevents harmful substances from reaching the bloodstream, effectively "purifying" the lymph before it is returned to the circulation. Lymph typically passes through around 8-10 nodes before returning to the blood, ensuring thorough filtration.
  2. Immune Surveillance and Activation:
    • Antigen Presentation: Lymph nodes are packed with lymphocytes (T cells and B cells) and antigen-presenting cells (APCs) like dendritic cells and macrophages. When pathogens or their antigens are carried into the node via lymph, APCs capture and present these antigens to lymphocytes.
    • Lymphocyte Proliferation: This antigen presentation triggers the activation and rapid proliferation (clonal expansion) of specific T and B lymphocytes that recognize the antigen.
    • Antibody Production: Activated B cells transform into plasma cells, which produce and secrete large quantities of antibodies into the lymph and eventually into the blood, targeting the invading pathogens.
    • Cell-Mediated Immunity: Activated T cells differentiate into various effector T cells (e.g., cytotoxic T cells that directly kill infected cells) and memory T cells.
    • Importance: Lymph nodes are the key sites where adaptive immune responses are initiated and amplified, leading to the eradication of infections and the development of immunological memory.
Lymphoid Tissues (e.g., tonsils, Peyer's patches)

Lymphoid tissue is a specialized connective tissue containing large numbers of lymphocytes and macrophages, forming the structural and functional basis of the immune system. It can be categorized into primary lymphoid organs (where lymphocytes mature) and secondary lymphoid organs/tissues (where lymphocytes become activated). For this objective, we'll focus on the more "diffuse" or "aggregated" lymphoid tissues.

I. Diffuse Lymphoid Tissue

This refers to collections of lymphocytes and macrophages that are loosely scattered within the connective tissue of mucous membranes, particularly those lining the gastrointestinal, respiratory, urinary, and reproductive tracts. It is the most common form of lymphoid tissue and lacks a distinct capsule. Its primary role is to protect these open passages from invading pathogens.

II. Aggregated Lymphoid Follicles (Nodules) - MALT

When lymphoid tissue is organized into dense, spherical clusters, it forms lymphoid follicles or nodules. These are typically unencapsulated. Many of these are part of Mucosa-Associated Lymphoid Tissue (MALT), which collectively guards the body's mucous membranes.

  1. Tonsils:
    • Description: Ring-like arrangements of lymphoid tissue located in the pharynx (throat) region, forming a protective circle at the entrance to the digestive and respiratory tracts. They are covered by epithelium that invaginates to form blind-ended crypts, which trap bacteria and particulate matter, allowing immune cells to destroy them.
    • Types:
      • Palatine Tonsils: Located at the posterior end of the oral cavity (the "tonsils" commonly removed). They are the largest and most often infected.
      • Lingual Tonsil: Located at the base of the tongue.
      • Pharyngeal Tonsil (Adenoids): Located on the posterior wall of the nasopharynx. When enlarged, they can obstruct breathing and are often referred to as "adenoids."
    • Significance: Act as the first line of defense against inhaled and ingested pathogens, initiating immune responses locally.
  2. Aggregated Lymphoid Follicles (Peyer's Patches):
    • Description: Large, oval or elongated clusters of lymphoid follicles found in the wall of the distal part of the small intestine (ileum). They are strategically positioned to monitor the bacterial flora of the gut and prevent the growth of pathogenic bacteria.
    • Significance: Crucial for immune surveillance in the intestine. They contain B cells that can differentiate into IgA-producing plasma cells, which secrete IgA antibodies into the gut lumen to neutralize pathogens. They also contain specialized M (microfold) cells that sample antigens from the gut lumen and present them to underlying immune cells.
  3. Appendix (Vermiform Appendix):
    • Description: A small, finger-like projection extending from the large intestine (cecum). Its wall contains a high concentration of lymphoid follicles.
    • Significance: Thought to be a lymphoid organ that plays a role in gut immunity, possibly serving as a "safe house" for beneficial gut bacteria or a site for immune cell maturation. Its exact functions are still being fully elucidated, but its lymphoid tissue indicates an immune role.
III. Other Locations of Lymphoid Tissue
  • Bone Marrow: Not just a site for hematopoiesis (blood cell formation), but also a primary lymphoid organ where B lymphocytes mature and where all lymphocytes originate.
  • Spleen: The largest lymphoid organ, it contains vast amounts of lymphoid tissue (white pulp) for filtering blood and initiating immune responses.
  • Thymus Gland: A primary lymphoid organ where T lymphocytes mature and are "educated."
  • Liver and Lungs: While not considered primary lymphoid organs, they contain significant populations of immune cells (e.g., Kupffer cells in the liver, alveolar macrophages in the lungs) and diffuse lymphoid tissue that contribute to local immunity.
IV. General Significance of Lymphoid Tissue
  • Pathogen Surveillance: They constantly monitor for pathogens entering through various portals of entry (e.g., respiratory, digestive).
  • Immune Response Initiation: They provide sites where lymphocytes can encounter antigens, proliferate, and differentiate into effector cells (e.g., plasma cells, cytotoxic T cells) to combat infections.
  • Immunological Memory: They contribute to the development of immunological memory, allowing for a faster and stronger response upon subsequent exposure to the same pathogen.
The Spleen

The spleen is a soft, blood-rich organ that is unique among lymphoid organs because it filters blood, not lymph. Its complex internal structure allows it to perform diverse immunological and hematological functions.

I. Anatomy and Location
  1. Location:
    • The spleen is located in the upper left quadrant of the abdominal cavity, nestled inferior to the diaphragm, posterior to the stomach, and superior to the left kidney.
    • It is typically between the 9th and 11th ribs. Its posterior surface is related to the diaphragm, and its medial surface to the stomach, left kidney, and tail of the pancreas.
    • It is intraperitoneal, meaning it is almost entirely surrounded by peritoneum.
  2. Size and Shape:
    • Typically about 12 cm (5 inches) long, 7 cm (3 inches) wide, and 3-4 cm (1.5 inches) thick. It weighs about 150-200 grams in adults.
    • It is oval-shaped, dark red-purple, and has a soft, friable (easily torn) consistency.
  3. Capsule and Trabeculae:
    • The spleen is enclosed by a thin, but relatively tough, fibrous capsule made of dense irregular connective tissue. This capsule also contains some smooth muscle cells, which can contract to help expel blood.
    • Trabeculae extend inward from the capsule, dividing the spleen into compartments and providing structural support. They also carry blood vessels into the splenic pulp.
  4. Hilum:
    • The medial surface of the spleen has an indentation called the hilum, where the splenic artery (bringing blood to the spleen) and splenic vein (draining blood from the spleen) enter and exit, respectively. Lymphatic vessels and nerves also pass through the hilum.
  5. Splenic Pulp:
    • The internal substance of the spleen is called the splenic pulp, which is highly vascularized and consists of two main components:
      • White Pulp:
        • Description: Consists of spherical clusters of lymphoid tissue, primarily lymphocytes (T and B cells) surrounding central arteries. It appears as "white" spots on a gross section.
        • Composition:
          • Periarteriolar Lymphoid Sheath (PALS): Concentric rings of T lymphocytes surrounding a central arteriole.
          • Splenic Follicles: Nodules of B lymphocytes, often with germinal centers, located within the PALS.
        • Function: Involved in immune responses. It is the site where immunological reactions to blood-borne antigens occur.
      • Red Pulp:
        • Description: Surrounds the white pulp and makes up the bulk of the spleen. It is rich in blood, giving it a deep red color.
        • Composition:
          • Splenic Cords (Cords of Billroth): Networks of reticular connective tissue containing macrophages, lymphocytes, plasma cells, and red blood cells.
          • Splenic Sinuses (Sinusoids): Wide, leaky capillaries that separate the splenic cords. These sinusoids have a discontinuous basement membrane, allowing blood cells to easily move between the cords and sinuses.
        • Function: Primarily involved in filtering blood, removing old/damaged red blood cells and platelets, and storing blood.
II. Key Functions of the Spleen
  1. Blood Filtration and Cleansing (Hematological Functions):
    • Removal of Old/Damaged Red Blood Cells: As red blood cells age (typically after 120 days), they become less flexible and are unable to navigate the narrow splenic sinusoids and cords. Macrophages in the red pulp recognize and phagocytose these senescent or damaged red blood cells, breaking down hemoglobin and recycling iron. This is often called the "graveyard of red blood cells."
    • Removal of Platelets: Similarly, old or damaged platelets are removed from circulation by macrophages in the spleen.
    • Removal of Other Blood-borne Debris: Phagocytic cells in the spleen also remove cellular debris, microorganisms, and other particulate matter from the blood.
  2. Immune Surveillance and Response (Immunological Functions):
    • Immune Response to Blood-borne Pathogens: The white pulp of the spleen is analogous to a very large lymph node, but it filters blood instead of lymph. It provides a site for lymphocytes (T and B cells) and antigen-presenting cells to encounter blood-borne antigens (e.g., bacteria, viruses) and initiate specific immune responses.
    • Antigen Presentation: Dendritic cells and macrophages in the white pulp present antigens to lymphocytes, leading to their activation.
    • Lymphocyte Proliferation: Activated B and T cells proliferate in the white pulp, generating an army of immune cells.
    • Antibody Production: Plasma cells generated in the spleen produce antibodies that are released into the bloodstream to target pathogens.
  3. Blood Storage:
    • Red Blood Cells and Platelets: The red pulp acts as a reservoir for blood. In some animals, the spleen can contract to release a significant volume of blood into circulation during hemorrhage or increased activity (though this function is less pronounced in humans). It also stores a considerable amount of platelets (up to 30-40% of the body's total platelet count).
    • Monocytes: The spleen serves as a large reservoir for monocytes, which can be rapidly deployed to sites of tissue injury or infection.
  4. Hematopoiesis (Fetal Life):
    • Fetal Blood Cell Production: During fetal development, the spleen is an important site of hematopoiesis (blood cell formation).
    • Adult Life (Pathological Conditions): In adults, the spleen generally does not produce red or white blood cells under normal conditions. However, in certain pathological conditions (e.g., severe anemia, myelofibrosis), it can resume its hematopoietic function (extramedullary hematopoiesis).
III. Clinical Significance
  • Splenomegaly: Enlargement of the spleen, often indicative of an underlying condition such as infection (e.g., mononucleosis), liver disease, or certain blood cancers.
  • Splenectomy: Surgical removal of the spleen. While individuals can live without a spleen, they become more susceptible to certain bacterial infections (particularly encapsulated bacteria like Streptococcus pneumoniae, Haemophilus influenzae type B, and Neisseria meningitidis) because the spleen is crucial for filtering these bacteria from the blood and initiating an early immune response.
Bone Marrow in the Lymphatic and Immune Systems

Bone marrow is a primary lymphoid organ, alongside the thymus, meaning it is where lymphocytes originate and mature. It is a highly vascular, soft, spongy tissue found in the medullary cavities of bones.

I. Anatomy and Location
  1. Location:
    • Found within the spongy (cancellous) bone and medullary cavities of long bones.
    • In adults, red bone marrow (the active, hematopoietic type) is primarily found in the flat bones (sternum, ribs, vertebrae, pelvic bones, skull) and the epiphyses (ends) of long bones (femur, humerus).
    • Yellow bone marrow (composed mostly of fat cells) replaces red marrow in the shafts of long bones during adolescence, though it can convert back to red marrow if needed (e.g., severe hemorrhage).
  2. Composition:
    • The primary cellular components are hematopoietic stem cells (HSCs), which are multipotent cells capable of differentiating into all types of blood cells, including immune cells.
    • It also contains stromal cells (fibroblasts, adipocytes, endothelial cells, macrophages) that create the microenvironment (bone marrow niche) necessary for hematopoiesis and lymphocyte development.
II. Key Roles in the Lymphatic and Immune Systems

Bone marrow performs two fundamental and indispensable roles:

  1. Site of Hematopoiesis (Origin of All Immune Cells):
    • All Lymphocytes and Other Leukocytes Originate Here: Hematopoietic stem cells (HSCs) in the red bone marrow are the progenitors for all blood cells, including:
      • Lymphoid Stem Cells: These differentiate into B lymphocytes, T lymphocytes (though T cells leave the bone marrow to mature in the thymus), and Natural Killer (NK) cells.
      • Myeloid Stem Cells: These differentiate into all other white blood cells (leukocytes) that are crucial for innate immunity (Neutrophils, Eosinophils, Basophils, Monocytes) and Erythrocytes/Platelets.
    • Continuous Production: The bone marrow continuously produces billions of new blood cells daily, ensuring a constant supply of immune cells to maintain the body's defense.
  2. Site of B Lymphocyte Maturation:
    • Primary Lymphoid Organ for B Cells: Unlike T cells, B lymphocytes undergo their entire maturation process (from lymphoid stem cell to immunocompetent, naive B cell) within the bone marrow.
    • Development and Selection: During this process, B cells acquire their unique B cell receptors (BCRs) and undergo rigorous selection to ensure that they are functional and, crucially, self-tolerant (i.e., do not react against the body's own tissues).
    • Release of Naive B Cells: Once mature, naive (antigen-inexperienced) B cells are released from the bone marrow into the bloodstream and lymphatic circulation, ready to encounter antigens in secondary lymphoid organs (like lymph nodes or the spleen).
  3. Site of Long-Lived Plasma Cells and Memory B Cells:
    • After an immune response, activated B cells can differentiate into long-lived plasma cells and memory B cells. A significant proportion of these long-lived cells migrate back to the bone marrow, where they reside for years or even decades.
    • Long-Lived Plasma Cells: Continuously produce antibodies, providing long-term humoral immunity.
    • Memory B Cells: Provide a rapid and robust secondary immune response upon re-exposure to the same antigen. The bone marrow acts as a crucial niche for the survival of these essential memory cells.
III. Clinical Significance
  • Bone Marrow Transplants: Used to treat various hematological disorders and cancers (e.g., leukemia, lymphoma) by replacing diseased or damaged bone marrow with healthy hematopoietic stem cells.
  • Immune Deficiencies: Dysfunction of the bone marrow can lead to severe immune deficiencies due to a lack of mature lymphocytes and other immune cells.
  • Autoimmune Diseases: Problems with B cell selection in the bone marrow can contribute to autoimmune diseases where B cells produce antibodies against self-antigens.
The Thymus Gland

The thymus is a primary lymphoid organ because it is the site of T-cell maturation and education. It is particularly active during childhood and adolescence, undergoing a process of involution (shrinkage) after puberty.

I. Structure and Location
  1. Location:
    • Located in the superior mediastinum, posterior to the sternum and anterior to the great vessels of the heart and the trachea.
    • It partially overlies the superior part of the heart and its great vessels.
  2. Size and Development:
    • It is relatively large in infants and children, continuing to grow until puberty.
    • After puberty, it begins to atrophy (shrink), a process called involution, where much of its lymphoid tissue is replaced by adipose (fat) tissue. While it becomes smaller, it remains functionally active throughout life, albeit at a reduced capacity.
  3. Gross Anatomy:
    • Typically bilobed (two lobes), connected by an isthmus.
    • Enclosed by a fibrous capsule.
    • The capsule sends trabeculae (septa) into the interior, dividing the lobes into numerous smaller compartments called lobules.
  4. Microscopic Anatomy (within each lobule): Each lobule has two distinct regions:
    • Cortex (Outer Region):
      • Composition: Densely packed with rapidly dividing T lymphocytes (thymocytes), macrophages, and specialized epithelial cells called thymic epithelial cells (TECs).
      • Function: This is the primary site for the initial stages of T-cell maturation and the first round of T-cell selection (positive selection).
    • Medulla (Inner Region):
      • Composition: Less densely packed with thymocytes. It contains more mature T cells, dendritic cells, macrophages, and characteristic structures called thymic (Hassall's) corpuscles.
      • Thymic Corpuscles: Concentric layers of flattened, keratinized epithelial cells. Their exact function is not fully understood, but they may be involved in the final stages of T-cell maturation and the production of specific cytokines.
      • Function: This is where the crucial second round of T-cell selection (negative selection) occurs, and where mature, naive T cells exit the thymus.
II. Key Functions of the Thymus Gland

The thymus's primary function is the education and maturation of T lymphocytes (T cells). This process ensures that T cells are both functional and self-tolerant.

  1. Site of T Lymphocyte Maturation:
    • "Boot Camp" for T Cells: T cell precursors (pro-thymocytes) originate in the bone marrow and migrate to the thymus. Here, they are called thymocytes.
    • Acquisition of T Cell Receptors (TCRs): Within the thymus, thymocytes undergo gene rearrangement to develop unique T cell receptors (TCRs) on their surface, which allow them to recognize specific antigens presented by other cells.
    • Immunocompetence: The process by which T cells become able to recognize and bind to antigens presented by MHC (Major Histocompatibility Complex) molecules.
  2. T-Cell Selection (Thymic Education):
    • This is a highly rigorous and critical process, often described as "survival of the fittest," ensuring that the body's T-cell repertoire is effective but not harmful. Over 95% of thymocytes die during this process.
    • Positive Selection (in Cortex):
      • Purpose: Ensures that T cells are capable of recognizing self-MHC molecules (MHC restriction).
      • Process: Thymocytes must successfully bind to MHC molecules presented by cortical thymic epithelial cells. T cells that bind too weakly or not at all undergo apoptosis (programmed cell death). This ensures the T cell will be able to interact with antigen-presenting cells later.
    • Negative Selection (in Medulla):
      • Purpose: Ensures that T cells do not react too strongly against self-antigens presented by self-MHC molecules (self-tolerance). This prevents autoimmune reactions.
      • Process: Thymocytes that bind too strongly to self-peptide-MHC complexes presented by medullary thymic epithelial cells or dendritic cells undergo apoptosis. This eliminates potentially autoreactive T cells.
      • AIRE (Autoimmune Regulator) Gene: Medullary TECs express the AIRE gene, which allows them to present a wide array of "self" proteins from other parts of the body, thus educating T cells about self-antigens they might encounter elsewhere.
  3. Hormone Production:
    • Thymic epithelial cells produce several hormones, such as thymosin, thymopoietin, and thymulin, which are essential for the maturation and differentiation of T cells within the thymus.
  4. Release of Naive T Cells:
    • Only about 2-5% of the original thymocytes successfully pass both positive and negative selection. These "survivors" are mature, immunocompetent, and self-tolerant naive T cells.
    • These mature T cells exit the thymus and populate secondary lymphoid organs (like lymph nodes and spleen), ready to encounter their specific antigens and participate in immune responses.
III. Clinical Significance
  • DiGeorge Syndrome: A congenital disorder where the thymus fails to develop, leading to a severe deficiency of T cells and profound immunodeficiency, making individuals highly susceptible to infections.
  • Thymoma: A tumor of the thymic epithelial cells. It can sometimes be associated with autoimmune diseases like myasthenia gravis.
  • Involution: While it shrinks, the thymus remains functionally important throughout life, continually supplying T cells, though at a reduced rate. Loss of thymic function early in life (e.g., due to disease or surgical removal) can significantly compromise the immune system.

Anatomy and Physiology of the Lymphatic System Read More »

benign prostatic hyperplasia bph

Benign Prostatic Hyperplasia (BPH)

BPH 

BPH-Benign prostatic hyperplasia is the enlargement, or hypertrophy, of the prostate gland.

 BPH is common in elderly men over 60 years and above

Common causes of BPH and Pathophysiology

The outcome of BPH depends on two major factors i.e.

  1. Anatomical factors:   These involve enlargement of the Prostate gland which produces a physical blockage at the neck of the bladder against urinary flow.  This results in increased responsiveness of the prostate gland to androgens and estrogens. 
  2.  Dynamic factors; These result from excessive sympathetic stimulation via alpha-1 receptors in the prostate gland leading to increased tone at the sphincters of urinary bladder and the prostate.

The pathophysiology of BPH is as follows:

  • Resistance. BPH is a result of complex interactions involving resistance in the prostatic urethra to mechanical and spastic effects.
  • Obstruction. The hypertrophied lobes of the prostate may obstruct the bladder neck or urethra, causing incomplete emptying of the bladder and urinary retention.
  • Dilation. Gradual dilation of the ureters and kidneys can occur.

Resulting symptoms of BPH.

  • Urinary frequency. Frequent trips to the bathroom to urinate may be an early sign of a developing BPH.
  • Urinary urgency. This is the sudden and immediate urge to urinate.
  • Nocturia. Urinating frequently at night is called nocturia.
  • Weak urinary stream. Decreased and intermittent force of stream is a sign of BPH.
  • Dribbling urine. Urine dribbles out after urination.
  • Straining. There is presence of abdominal straining upon urination.
  • Urinary retention
  • Decrease in force of urinary out put
  • Intermittency during urination

Investigations and Diagnosis of BPH

  • Digital rectal examination (DRE). A DRE often reveals a large, rubbery, and nontender prostate gland.

bph dre

  • Urinalysis. A urinalysis to screen for hematuria and UTI is recommended.
  • Prostate specific antigen levels. A PSA level is obtained if the patient has at least a 10-year life expectancy and for whom knowledge of the presence of prostate cancer would change management.
  • Urinalysis: Color: Yellow, dark brown, dark or bright red (bloody); appearance may be cloudy. pH 7 or greater (suggests infection); bacteria, WBCs, RBCs may be present microscopically.
  • Urine culture: May reveal Staphylococcus aureus, Proteus, Klebsiella, Pseudomonas, or Escherichia coli.
  • Urine cytology: To rule out bladder cancer.
  • BUN/Cr: Elevated if renal function is compromised.
  • Prostate-specific antigen (PSA): Glycoprotein contained in the cytoplasm of prostatic epithelial cells, detected in the blood of adult men. Level is greatly increased in prostatic cancer but can also be elevated in BPH. Note: Research suggests elevated PSA levels with a low percentage of free PSA are more likely associated with prostate cancer than with a benign prostate condition.
  • WBC: May be more than 11,000/mm3, indicating infection if patient is not immunosuppressed.
  • Uroflowmetry: Assesses degree of bladder obstruction.
  • IVP with post voiding film: Shows delayed emptying of bladder, varying degrees of urinary tract obstruction, and presence of prostatic enlargement, bladder diverticula, and abnormal thickening of bladder muscle.
  • Voiding cystourethrography: May be used instead of IVP to visualize bladder and urethra because it uses local dyes.
  • Cystometrogram: Measures pressure and volume in the bladder to identify bladder dysfunction unrelated to BPH.
  • Cystourethroscopy: To view degree of prostatic enlargement and bladder-wall changes (bladder diverticulum).
  • Cystometry: Evaluates detrusor muscle function and tone.
  • Transrectal prostatic ultrasound: Measures size of prostate and amount of residual urine; locates lesions unrelated to BPH.

Classification of drugs for BPH

They are classified into 3 major groups;

  1. 5 alpha-reductase inhibitors
  2. Alpha-1 selective blockers
  3. Combined therapies

5 alpha-reductase inhibitors  

They inhibit an enzyme 5 alpha – reductase in the prostate thus preventing the conversion of testosterone into active form thus suppressing the activity of androgens in the prostate. The overall effect is decreased growth of the prostate gland.

N.B the effects of these drugs is not prompt and don’t relieve urine retention.

  • Finasteride 5mg o.d.
  • Dutasteride 0.5mg o.d

Both are administered orally

Alpha – 1 selective blockers

They block alpha I receptors in the prostate and bladder leading to relaxation of sphincter and so improved urine flows.

These are grouped into two;

  • Short acting agent e.g. Prazosin, Indamine, and Alfuzosin.
  • Long acting agents e.g. Tamucurosin, Doxazocin and Terazosin.

Doses;

  • Prazosin 0.5-1mg o.d given at bed time after few days orally then maintained  at 1mg b.d * 3/7
  • Terazosin 2-10mg o.d
  • Doxazocin  1mg o.d.
  • Tamucurosin 0.4 mg once daily given with meals orally.

 NB:  Tamucurocin is a long acting member best indicated since doesn’t interfere with blood pressure

Trazocin should be given at a lower dose then maintained later this is to avoid hypotension while standing

Their effects are faster thus usually combined with Finasteride

Adverse effects:

  • Postural hypotension
  • Tachycardia reflex

Others rarely used members include; Phentolamine and phenoxybenzamine

Medical Management

The goals of medical management of BPH are to improve the quality of life and treatment depends on the severity of symptoms.

  • Catheterization. If a patient is admitted on an emergency basis because he is unable to void, he is immediately catheterized.
  • Cystostomy. An incision into the bladder may be needed to provide urinary drainage.

Pharmacologic Management

  • Alpha-adrenergic blockers (eg, alfuzosin, terazosin), which relax the smooth muscle of the bladder neck and prostate, and 5alpha reductase inhibitors.
  • Hormonal manipulation with antiandrogen agents (finasteride [Proscar]) decreases the size of the prostate and prevents the conversion of testosterone to dihydrotestosterone (DHT).
  • Use of phytotherapeutic agents and other dietary supplements (Serenoa repens [saw palmetto berry] and Pygeum africanum [African plum]) are not recommended, although they are commonly used.
  • One herbal medication effective against BPH is Saw Palmetto.
Saw Palmetto bph
Saw Palmetto

Surgical Management

Other treatment options include minimally invasive procedures and resection of the prostate gland.

  • Transurethral microwave heat treatment. This therapy involves the application of heat to prostatic tissue.
  • Transurethral needle ablation (TUNA). TUNA uses low-level radio frequencies delivered by thin needles placed in the prostate gland to produce localized heat that destroys prostate tissue while sparing other tissues.
  • Transurethral resection of the prostate (TURP). TURP involves the surgical removal of the inner portion of the prostate through an endoscope inserted through the urethra.
  • Open prostatectomy. Open prostatectomy involves the surgical removal of the inner portion of the prostate via a suprapubic, retropubic, or perineal approach for large prostate glands.

Benign Prostatic Hyperplasia (BPH) Read More »

Erectile dysfunction medications

Erectile Dysfunction Medications

Erectile Dysfunction

Erectile dysfunction, ED is the inability of the male to attain and maintain an erection sufficient to permit satisfactory sexual intercourse.

Penile erectile dysfunction is a condition in which the corpus cavernosum does not fill with blood to allow for penile erection. This can result from the aging process and in vascular and neurological conditions.

So, what is impotence?

Impotence, a term often used synonymously with ED, many involve a total inability to achieve erection, an inconsistent ability to achieve or ability to sustain only brief erections.

Physiology of an Erection

This begins with stimulus such as sight and touch. This stimulates the parasympathetic nervous division that transmits nerve impulses to the erectile tissue of the penis (corpus carvernosum). The nerve endings release nitric oxide(NO) which binds on muscle cells in the penis leading to generation of cyclic GMP (Cyclic Guanosine monophosphate) which relaxes the muscle cells in the corpus cavernosum leading to creation of larger intracellular spaces and sinusoids. More blood flows into the erectile tissues, the tissue expands compresses the veins leaving the penis, thus increased blood volume in the organ and one erects.

      Erection is continuously maintained during sexual intercourse by the release of NO, and prostaglandin E1 (PGE1).

Termination of erection( Detumescence ) is brought about by 2 events i.e.

  • Activity of enzyme phosphodiesterase type 5 enzyme (PDE-5) which catalyzes the breakdown of GMP into inactive form.
  • Stimulation of sympathetic nervous division to bring about the contraction of the penile muscles terminating ejaculation.

 

Pharmacology application of the above;

  • Erection relies on the penile blood flow thus an event that interferes with penile blood flow results into penile dysfunction.
  • Any factor which interferes with neuro-transmitters such as acetylcholine may end with Erectile Dysfunction.
  • Psychological factors e.g. stress may as well interfere initiation of erection.

Classification of Erectile Dysfunction.

Primary Erectile Dysfunction; is where a man has never  been able to attain and maintain an erection for sexual intercourse

Secondary Erectile Dysfunction: is where impotence occurs in a man who has past history of satisfactory sexual performance.

Causes of Erectile Dysfunction

  • Erectile Dysfunction mainly occurs past middle age and is common after the age of 65 years.

A variety of vascular, Neurological, hormonal or endocrinal, pharmacological or psychological and genetic causes may underly the disorder, i.e.

  • Vascular diseases: Blood supply to the penis can become blocked or narrowed as a result of vascular disease such as atherosclerosis (hardening of the arteries).
  • Neurological disorders (such as multiple sclerosis): Nerves that send impulses to the penis can become damaged from stroke, diabetes, or other causes.
  • Psychological states: These include stress, depression, lack of stimulus from the brain and performance anxiety.
  • Trauma: An injury could contribute to symptoms of Erectile Dysfunction.
  • Cancer treatments;  near the pelvis can affect the penis’ functionality.
    Surgery and or radiation for cancers in the lower abdomen or pelvis can cause Erectile dysfunction. Treating prostate, colon-rectal or bladder cancer often leaves men with Erectile dysfunction.
  • Drugs;  used to treat other health problems can negatively impact erections such as Cimetidine (Tagamet), Ranitidine (Zantac)

Classification of Drugs used to treat Erectile Dysfunction.

There are divided into 4 groups;

  • Central inhibitors
  • Peripheral inhibitors
  • Central conditioners
  • Peripheral conditioners

PDE 5 Inhibitors/Peripheral Inhibitors.

These are agents which act in the penile tissue to maintain the environment of erection. They include phosphodiesterase-5 inhibitors e.g. sildenafil, tadalafil, and vardenafil are selective PDE-5 inhibitors developed drugs in the past decade and found effective in a majority of patients with Erectile Dysfunction.

SILDENAFIL:

 It is an orally active drug

Classification:

Therapeutic– ED agent, vasodilator

Pharmacological– phosphodiesterase type 5 inhibitor

Brand names:
  • Kamagra
  • Penegra
  • viagra
  • Caverta
  • Edegra 25, 50, 100mg tablets
Indications:         
  • Erectile Dysfunction
  • Pulmonary Hypertension.
Mechanism of action;

 Sildenafil acts by selectively inhibiting an enzyme phosphodiesterase-5 and enhancing nitric oxide action in corpus cavernosum thus preventing the breakdown of GMP produces smooth muscle relaxation of the corpus cavernosum which in turn promotes increased blood flow and subsequent erection hence sex intercourse and exercise tolerance is improved but it has no effect on penile (swelling) tumescence in the absence of sexual activity. It doesn’t cause priapism in most patient.

 Dosage:

  It is recommended in the dose of

  • 50mg for men less than 65 years,
  • elderly 25mg if not effective then 100mg 1 hour by intercourse.

Duration and degree of penile erection is increased in 74-82% of men with Erectile Dysfunction including diabetic Neuropathy cases.

However, Sildenafil is effective in men who have lost libido or when ED is due to spinal cord injury or damaged Nervic eregantis since Nitric Oxide is an important regulator of pulmonary vascular resistance, PDE-5 inhibitor lower pulmonary circulation than vardenafil and is only PDE-5 inhibitor shown to improve arterial   oxygenation in pulmonary Hypertension. It has now become the drug of choice for this condition

N.B.; it should be given once a day.  

Adverse effects/ side effects:

These are mainly due to preservation of nitric oxide which causes vasodilatation in the brain.

  • Dizziness and headache
  • Nasal congestion
  • Hypotension and palpitation
  • Loose emotion
  • A feeling of dependency/ addiction
  • Flushing
  • Tachycardia
  • Muscle pain
  • Diarrhoea
  • Sildenafil in addiction, weakly inhibits the isoenzyme PDE-5 which is involved in photoreceptor transduction in the retina. As such impairment of colour vision especially, blue-green discrimination occurs in some recipients.
  • Hormones and related drug neuropathy among users of PDE-5 inhibitors have be reported.
Contraindications:
  • In patients with coronary heart diseases.
  • Those taking nitrates. Though sildenafil remains effective for less than 2hours, it is advised that nitrates should be avoided for 24hours
  • Presence of liver or kidney disorder
  • Peptic ulcer, bleeding disorder
  • Patients of leukemia, sickle cell anemia, myocardial infarction etc.
Drug interactions:
  •  Sildenafil markedly potentiates the vasodilator action of nitrates, precipitates fall in Blood Pressure and myocardial infarction may occur.
  • Inhibitors of CYP3A4 like erythromycin, Ketoconazote, cemetidine may potentiate its action i.e. may increase Sildenafil plasma concentration.
  • Vitamin k antagonist may increase the risk of bleeding.
  • Concomitant use with alpha- blockers may lead to hypotension.

N.B: men even without Erectile Dysfunction are going for it to enhance sexual satisfaction.

Nursing implications:
  • Determine Erectile Dysfunction before administration.
  • Monitor hemodynamic parameters and exercise before and after therapy
Patient/ family teaching:
  • Instruct the patient to take drugs at least 1 hour before sexual activity
  • Not more than once a day.
  • Instruct the patient that sexual stimulation is required for erection to occur.
  • Advise the patient that the drug is not indicated for women.
  • Advise the patient not to concurrently take the drug with nitrates or alpha-adrenergic blockers
  • Instruct the patient if chest pain occurs after taking the drug to report to the PHC practioners immediately.
  • Advise the patient to avoid excess alcohol intake in combination with PDE-5 since it can increase the risk of orthostatic hypotension
TADALAFIL:
  Brand names;
  • Megalis,
  • Tadarich,
  • Tadalis,
  • Cialis and Apcalis 10, 20mg tablets

            It is a more potent and longer acting congener of Sildenafil, duration of action is 24-36 hours. It is claimed to act faster, though peak plasma levels are attained between 30-120minutes.

Indication;
  • Erectile Dysfunction
Mechanism of action
  • As for Sildenafil

Side effects, risks, contraindications and drug interactions are similar to Sildenafil

  • Because of its longer lasting action, nitrates are contraindicated for 36-48hours after Tadalafil.
  • Due to its lower affinity for PDE-6, visual disturbances occur less frequently
Dosage:
  •  10mg o.d. at least 30minutes before sexual intercourse (max 20mg)

Peripheral Initiators of Erection

They include Alprostadil administered intra cavernously (injected) directly into the corpus cavernosum using a fine needle or introduced into the urethra as a small pellet, produces erection in few hours to permit intercourse  .  It is more used in patients taking anti-hypertensive drugs, those with cardiac diseases e.g Coronary artery disease and patients who do not respond to PDE-5 inhibitors.

Mode of Action

It is a prostaglandin E1 analog thus relaxes the penile muscles bringing about erection.

Contraindications
  1.  Presence of any anatomical obstruction or condition that might predispose to priapism. The risk could be exacerbated by these drugs.
  2.  Penile implants.
  3.  Bleeding disorders, CV diseases, optic neuropathy, severe hepatic and renal disorders.
Adverse effects
  • Priapism
  • Thrombo-embolism
  • Local tenderness
  • Penile fibrosis

Central initiators:

 These initiate neuronal path ways for erection e.g.

  • Apomorphine administered orally
Mechanism of action:

Apomorphine is a dopamine agonist  which acts centrally to stimulate an erectile neuronal path way.

It is also for known for Parkinsonism and induction of vomiting thus rarely used for this indication

Adverse effect:
  • Nausea and vomiting
  • Head ache and dizziness
  • Decreased milk production if taken by lactating mothers for another use

Central conditioners:

These provide a central mood condition of erection. They include;

(a). Trazodone which is a CNS anti-depressant due to massive adverse effects

(b). Androgens: e.g. testosterone

Click here to read more about Androgens.

Erectile Dysfunction Medications Read More »

androgens

Androgens

Androgens

Androgens are male sex hormones

Androgens include Testosterone, which is produced in the testes, and the Androgens, which are produced in the Adrenal glands.

Androgens are chiefly produced in the testes and small amounts in adrenal cortex. In female, small amounts are produced in the ovary and adrenal cortex.

        Testosterone is the most important natural androgen and in adult male, 8-10mg is produced daily. Its secretion is regulated by gonadotropins and gonadotrophic releasing Hormone (GnRH).  Inadequate production of androgens is due to pituitary malfunction or atrophy, injury to or removal of testicles. Androgens stimulate the development of male characteristics.

Naturally occurring androgens hormones are;

  • Testosterone, the principal androgenic hormone produced by the leydig cells of the testes.
  • Dehydroepiandrosterone (DHEA) produced by adrenal cortex.

Common Terms

Anabolic steroids: androgens developed with more anabolic or protein-building effects than androgenic effects.
Androgenic effects: effects associated with development of male sexual characteristics and secondary characteristics (e.g., deepening of voice, hair distribution, genital development, acne)
Androgens: male sex hormones, primarily testosterone; produced in the testes and adrenal glands
Hirsutism: hair distribution associated with male secondary sex characteristics (e.g., increased hair on trunk, arms, legs, face)
Hypogonadism: underdevelopment of the gonads (testes in the male)
Penile Erectile Dysfunction: condition in which the corpus cavernosum does not fill with blood to allow for penile erection; can be related to aging or to neurological or vascular conditions

Examples of Androgens

Drug NameUsual DosageUsual Indications
danazol (Danocrine)100–600 mg/d PO, depending on use and responsePrevent ovulation for treatment of endometriosis; prevention of hereditary angioedema
fluoxymesterone (Androxy)5–20 mg/d PO for replacement therapy; 10–40 mg/d PO for certain breast cancersTreatment of delayed puberty in male patients and certain breast cancers in postmenopausal women
testosterone (Androderm, Depo-testosterone)50–400 mg IM every 2–4 weeks, dose varies with preparation (check more below)Replacement therapy in hypogonadism (check more below)
methyltestosterone (Testred, Virilon)Males: 10–50 mg/d PO Females: 50–200 mg/d POReplacement therapy in hypogonadism; treatment of delayed puberty in male patients and certain breast cancers in postmenopausal women

TESTOSTERONE (depo-testerone, androderm) 

Classification:

Therapeutic: Hormone

Pharmacological: Androgen

Pregnancy; Category-x

Schedule: III controlled substance.

Dosage: 50–400 mg IM every 2–4 weeks, dose varies with preparation; some long-acting depository forms are available; dermatological patch 4–6 mg/day, replace patch daily.

Effects of Testosterones.

Anabolic Effects (Growth and Metabolic Functions)

  • Maintains bone density.
  • Regulates fat distribution.
  • Helps in Red Blood Cell production.
  • Supports muscle growth, strength and body mass.
  • Speeds up recovery from injury.
  • They act to increase the retention of nitrogen, sodium, potassium, and phosphorus.
  • They decrease the urinary excretion of calcium.
  • Testosterones increase protein anabolism and
    decrease protein catabolism (breakdown).

Androgenic Effects ( Sexual Characteristics and Functions)

  • Enhances sex drive and libido.
  • Increases aggression.
  • Acne.
  • Beard and body hair.
  • Male pattern boldness.
  • Development and maintenance of male sex organs.
  • Spermatogenesis.
  • Increased size of the prostate.

Control of Testosterone Secretion.

Hypothalamus releases GnRH, which stimulates the Anterior Pituitary gland to secrete FSH an LH which in turn stimulate the Leydig cells to secrete testosterone. High levels of serum testosterone exerts a negative feedback i.e.

  • APG suppresses secretion of LH.
  • Hypothalamus suppresses the GnRH.

Indications of Testosterone.

  1. Hypogonadism and impotence in males due to testicular/pituitary/hypothalamic deficiency.
  2. Testosterone deficiency .
  3. Breast cancer treatment in post menopausal women, who cant be operated.
  4. Treatment of delayed male puberty.
  5. Prevention of postpartum breast engorgement.
  6. Illegally, sportsmen often use anabolic steroids for promoting their musculature and sporting abilities.
  7. Blockage of follicle-stimulating hormone and luteinizing
    response hormone release in women to prevent ovulation for
    treatment of endometriosis.
  8. Prevention of hereditary angioedema

Contraindications of Testosterone.

  •  Allergy to androgens or other ingredients in the drug. Prevent hypersensitivity reactions.
  •  Pregnancy, lactation. Potential adverse effects on the neonate. It is not clear whether androgens enter breast milk.
  •  Presence or history of prostate or breast cancer . Aggravated by the testosterone effects of the drug.
  •  Liver dysfunction, Cardiovascular disease. Can be exacerbated by the effects of the hormones.
  •  Topical forms of testosterone have a Black Box Warning alerting user to the risk of virilization (Female develops male characteristics) in children who come in contact with the drug.
  •  Danazol has Black Box warning regarding the risk of thromboembolic events, fetal abnormalities, hepatitis, and intracranial hypertension.
  • For use with caution in patients with Diabetes Mellitus, BPH and Sleep apnea.

Side Effects and Adverse Effects of Testosterone

                      In men,

  • Administration of an androgen may result in breast enlargement
  • (gynecomastia),
  • testicular atrophy,
  • inhibition of testicular function,
  • impotence,
  • enlargement of the penis,
  • nausea and vomiting,
  • jaundice,
  • headache,
  • anxiety,
  • male pattern baldness,
  • acne and depression,
  • fatigue,
  • abdominal cramps,
  • confusion,
  • deepening of the voice,
  • edema,
  • drug-induced hepatitis,
  • gingivitis.
  • hirsutism (increased hair distribution)

                         In women,

  • receiving an androgen preparation for breast carcinoma the most common adverse reactions are;
  • amenorrhea and virilization (acquisition of male sexual characteristics such as changes in body and facial hair, a deepening voice, acne, menstrual irregularities and enlargement of the clitoris).
Drug Interactions

  1. May increase action of warfarin (anti-coagulants),  oral hypoglycemic agents and insulin.

  2.  Concurrent use with corticosteroids may increase the risk of edema formation.

Nursing intervention/ involvement:

  •  If the androgen is to be administered as a buccal tablet, the nurse demonstrates the placement of the tablet and warns the patient not to swallow the tablet but to allow it to dissolve in the mouth.
  • The nurse reminds the patient not to smoke or drink water until the tablets is dissolved. Oral and parenteral androgens are often taken or given by injection outpatient basis.
  • When given by injection, the injection is administered deep I.M into the gluteus muscle.
  •   Oral testosterone is given with or before meal to decrease gastric upset.
  • When testosterone Trans -dermal system testostederm is prescribed, the nurse places the system on clean, dry scrotal skin. Optimal skin contact of the Trans dermal system is achieved by shaving scrotal hair before placing the system.
  • Monitor fluid input and output
  • Weigh the patient twice a week
  • Assess for edema and report
  • Monitor secondary sexual characteristics in men
  •  Monitor menstrual irregularities, deepening of the voice, in females.
  • Monitor Hemoglobin and hematocrit periodically
  • Monitor urine and serum calcium levels
Patient/family teaching:
  1.  Advise the patient to report signs of priapism, difficulty in urinating, hypercalcemia, edema, unexpected weight gain, swelling of the fee, hepatitis, unusual bleeding.
  2. Explain rationale for prohibiting use of testosterone for increasing athletic performance
  3.   Notify Doctor of pregnancy.
  4.   DM patients to monitor blood sugar.
  5. Regular follow up, laboratory tests and physical examination
  6.  For ladies to notify doctor if signs of body hair distribution, deepening of voice menstrual irregularities occur.

ANABOLIC STEROIDS

 These are agents that are not easily converted to the potent androgen 5 alpha o-dihydrotestosterone (DHT) hence their effects on sex are less but their anabolic effect are high.

Drugs commonly used by athletes include; nandolone, stanozolol, and mithenelone. All of this drugs are regulated as controlled substances, making their use by athletes illegal.

Clinical uses/indications of anabolic steroids.

  • Osteoporosis
  • Appetite improves and there is a feeling of well being.
  • To counteract osteoporosis seen in chronic glucocorticosteroid therapy.
  • Stimulates linear growth in prepubertal boys (height).
  • Used in renal diseases.
NANDROLONE

      This is another steroid naturally produced by body, it is often synthesized and sold under the trade names Deca- Durabolin and Durbolin.

Professional athletes like Berry Bonds and Roger Clemens alleged used nandrolone to illegally enhance their performance.

STANOZOLOL:

       This synthetic steroid goes by the brand name Winstrol. This steroid is unusual in that it can be taken orally. Base ball players like Rafael. Palmeiro have tested positive for illegal use of stanozolol and strength athletes often use it illegally to quickly get stronger.

OXANDROLONE:

          Is a synthetic steroid retailed as the drug Anavar, which is approved for use in osteoporosis. Body builders use this steroid illegally to create greater muscle.

Contraindications:

  • Male patients with cancer of the breast or with known or suspected carcinoma of the prostate.
  • Carcinoma of the breast in female with hypercalcemia; androgenic anabolic steroids may stimulate osteolytic resorption of bones.
  • Pregnant because of masculinization of the fetus.
  • Nephrosis or the nephritic phase of nephritis.

Side effects of anabolic steroids:

  • Severe acne, oily skin and hair – hair loss.(virilization)
  • Liver diseases resulting into complications such as heart attack and stroke.
  • Altered mood, irritability, increased aggression, depression or suicidal tendencies.
  • Alteration in cholesterol and other blood lipids
  • High blood pressure
  • Gynecomastia- abnormal development of mammary glands in men causing breast enlargement.
  • Shrinking of testicles.
  • Azoospermia (absence of sperm in semen)
  • Menstrual irregularities in women
  • Infertility
  • Excess facial or body hair, deeper voice in women.
  • Stunted growth and heat in teens
    risk of viral or bacterial un function due to unsterile injections
  • Edema
  • Prostate cancer
  • Injury from skin-to-skin transfer of topical testosterone

 

Drug interactions:

  • Anti-coagulants. Anabolic steroids may increase sensitivity to oral anti-coagulants. Dosage of the anti-coagulants may have to be decreased in order to maintain the prothrombin time at the desired therapeutic level. Patients receiving oral anti-coagulant therapy require close monitoring, especially when anabolic steroids are started or stopped.

Patient’s information:

  • The physician should instruct patients to report any of the following effects of androgenic anabolic steroids,
  • hoarseness,
  • acne,
  • changes in menstrual periods,
  • more hair on the face,
  • Nausea and vomiting,
  • changes in skin colour or ankle swelling.

ANTI ANDROGENS

Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens  from mediating their biological effects in the body.

They act by blocking the androgen receptor and/or inhibiting or suppressing androgen production. They include:

  • Danzol
  • Finasteride
  • Spironolactone
  • Flutamide
  • Cyproterone
  • Ketoconazote
  • Bicalutamide and Nilutamide

Finasteride

Available preparations:      Tablets 5mg

Available brands:                 Finest, Proscar

           The androgen hormone inhibitor finasteride is a synthetic drug that inhibits the conversion of testosterone into the  androgen 5 alpha o-dihydrotestosterone (DHT). The development of the prostate glands is dependent on DHT. The lowering of serum levels of DHT reduces the effect of this hormone on the prostate gland, resulting in decrease in the size of the gland and this synthesis associated with prostate gland enlargement.

Indications;

  • Benign Prostatic Hyperplasia(BPH)
  • Androgenetic alopecia (male pattern baldness) in men only

Mechanism of action:

 It inhibits the enzyme 5-alpha-reductase which is responsible for converting testosterone to its potent metabolite 5-alpha dihydrotestosterone in prostate, liver and skin since 5-alphs dihydrotestosterone is partially responsible for prostatic hyperpiesia and hair loss.

Dose:

  • In BPH 5mg o.d
  • Alopecia 1mg/day for 3 months or more. Available in tablets of mg and 5mg

Side effects;

  • Decreased libido
  • Decreased volume of ejaculation
  • Erectile dysfunction/impotence
  • Breast tenderness and enlargement
  • Testicular pain

Contraindications/precautions;

  • Known hypersensitivity to finasteride
  • Use with caution on hepatic impairment

Nursing implications:

  •   Assess for symptoms of prostatic hyperplasia e.g. feeling of incomplete bladder emptying, interruption of the urinary stream
  •   Digital rectal examination should be done before and periodically during BPH therapy.
  •   Laboratory tests of prostate specific antigen cancer concentration which is used to screen for cancer of prostate.
  • Take this drug without regard to meals.

Patient/ family teaching;

  1. Finasteride possesses risk to male fetus; tell males not to have sex with pregnant women to avoid the risk of absorption
  2. Inform the Doctor immediately if sexual partner is or may become pregnant because additional measures such as discontinuing the drug or use of condom may be necessary.

Androgens Read More »

Uterine Relaxants

Uterine Relaxants

Uterine Relaxants

Uterine Relaxants are drugs which inhibit uterine motility by decreasing the frequency and strength of contractions.

Uterine Relaxants are drugs that inhibit uterine contractions and prolong pregnancy to allow the fetus develop more fully, thereby increasing the chances of neonatal survival.

These drugs prevent premature labor. It can succeed if only the cervical dilatation is less than 4cm.
They include;

  • Salbutamol
  • Magnesium Sulphate
  • Nifedipine
  • Indomethacin
  • Terbutaline

SALBUTAMOL

Legal class; class B controlled drugs
Medical class; tocolysis
Form; tabs , sterile solution for injection
Dosage :tabs 4mg
Soluton for injection 50mg/ ml

Indications
  • Uncomplicated premature labour between 24 to 33 weeks of gestation
  • Asthma
Contraindications
  •  Cardiac diseases
  • APH
  • Intra uterine fetal death.
  • Intra uterine infections
  • Raptured membranes
  • Eclampsia and pre-eclampsia
  • 1st an 2nd trimester of pregnancy
Dose
  • For premature labour, intravenous, infusion 10mcg/ min, gradually increase according to response at 10 minutes intervals until contractions diminish, then increase rate until contractions have ceased, max dose : 45mcg/min
  • Maintain rate for 1hr then gradually reduce by intravenous or intramuscular injection 100-250mg repeated according to response, then orally 4mg every 6-8hrs
    Do not use for more than 48minutes
Side effects
  •  Hypoglycemia
  • Vomiting and nausea
  • Sweating
  • Tremors
  • Hypotension
  • Pulmonary oedema
  • Maternal and fetal tachycardia
  • Headache
  • Palpitations
  • Urticaria

Magnesium Sulphate ( MgSO4)

Legal class; class B controlled drugs
Medical class; tocolytic and anticonvulsant
Form; sterile solution for injection
Strength/dosage; 50% of 5 grams/10ml

uterine relaxants magnesium sulphate

Dosage
Loading dose (14g)

4g of MgSO are given slowly intravenously for over 15 to 20 minutes and is prepared as follows

  1. Take a 20ml syringe and draw 8 mils if 50% MgSO4 (4g)
  2. Add 12 mils of water for injection to make 20% of the solution
  3. Give intravenously slowly over 15 minutes.

Immediately this is followed by 10g intramuscular and  is  prepared as follows;

  1. Take 20mils syringe, draw 10mils of 50% MgSO4 (undiluted) which is equivalent to 5g in each syringe
  2. Then add one mil of 2% lignocaine in each syringe to reduce pain
  3. Give deep intramuscular on each buttock
Maintenance Dose

Give 5g of 50% MgSO4 deep intramuscular on alternate buttocks every 4hrs prepare as below.

  1. Take 10ml syringe and draw 10ml of 50% of MgSO4 (5g).
  2. Add 1ml of lignocaine 2% in a syringe and give deep intramuscular.
    The dose can be repeated after every 4hrs of alternate buttock.
  3. The treatment is continued for 24hrs from the time of starting treatment or last fit.
    >  Incase the mother gets fit before 4hours, she is given 2g slowly intravenous.
Useful Effects of MgSO4:
  • Prevent seizures which are associated with pre eclampsia and eclampsia
  • Reduces cerebral oedema
  • Relieves constipation by retaining some water in the lumen
Indications
  •  Severe eclampsia and pre eclampsia
  • Patients with hypomagnesemia
  • Patients with severe asthma
  • Used in short term treatment of constipation
  • Patients with myocardial infarction
Contraindications
  •  Patients with hypermagnesemia
  • Patients who are hypersensitive to MgSO4
  • Renal impairment
  • Hepatic failure
  • Hypotensive patients
  • Patients with epilepsy
Side effects
  •  Drop in blood pressure
  • Flushing of the skin
  •  Dizziness
  •  Confusion
  •  Muscle weakness
  •  Loss of knee jack reflex
  •  Prolonged bleeding time
  •  Excessive bowel activity
Adverse effects
  •  Shock in hypertensive patients
  • Hypermagnesemia
  • Respiratory depression and coma

NIFIDIPINE

Legal class; class B controlled drugs
Medical class; tocolytic and antihypertensive
Form; tablet


Dosage
  •  20mg and the dose is repeated after 30minutes if contractions persists.
  • If contractions continue after 3hrs give 20mg every 3-8hrs until ceased and the maximum dose is 160mg/day

Indications
  •  Threatened abortion
  • Preterm labour less than 34wks of pregnancy
  • Hypertension

Contraindications
  •  Maternal conditions like cardiac diseases
  •  Hypertension
  •  Intrauterine infections
  •  Any condition that make pregnancy to prolong
  •  Fetal death

Side effects
  •  Dizziness
  • Headache
  • Flushing
  • Oedema
  • Fatigue

Quick Links

  1.  Female Sex Hormones
  2. Estrogen Receptor Modulators
  3. Fertility Drugs/gonadotropins
  4. Drugs used in labor
  5. Abortifacients

Uterine Relaxants Read More »

Drugs used in labor

Drugs used in Labor

Drugs used in Labour

Drugs used in labour can be grouped according to the effect they have on the uterus.

  1. Uterine Stimulants/Uterine Mortility drugs. (Oxytocics)
  2. Uterine relaxants (Tocolytics)

Uterine Stimulants/Uterine Motility Drugs(Oxytocics)

Uterine motility drugs stimulate uterine contractions to assist labor (oxytocics) or induce abortion (abortifacients). 

Oxytocics

Oxytocics stimulate contraction of the uterus, much like the action of the hypothalamic hormone oxytocin, which is stored in the posterior pituitary. These drugs include

  • Ergonovine (Ergotrate)
  • Methylergonovine (Methergine)
  • Oxytocin (Pitocin, Syntocinon).

Oxytocin

Legal class; class B controlled drugs
Medical class; oxytocic drugs
Form; sterile solution for injection
Strength; 10 IV per ampule.

Indications of Oxytocin
  1.  Induction of labor
  2.  Cases of inter-uterine fetal death.
  3.  Hypotonic uterine contractions
  4.  Mothers with hypertension
  5.  After delivery to control bleeding
  6. Pre-eclampsia and eclampsia
  7.  Congestive cardiac failure
  8.  Post term
  9. Prevent PPH
  10. Incomplete or missed abortion.
  11. Active management of third stage of labor.

Contraindications of Oxytocin
  •  Hypertonic uterine
  •  Fetal and maternal distress
  •  Multiple pregnancy
  •  Trial of labor
  •  Mal presentation like breech, brow
  •  Cephalo pelvic disproportion
  •  Low blood pressure
Dose
  1. Induction/argumentation of labour;  5 I.U into 500mls of solution for infusion, initially, 5 drops per min.
  2. Preventing of PPH after delivery of the placenta; Slow I.V, 5 I.U, increase rate during 3rd stage.

Route
  •  Intramuscular
  • Intravenously when mixed with normal saline or dextrose

Side Effects
  •  Dizziness
  • Nausea and vomiting
  • Rashes
  • Fetal brandy cardia
  • Hypotension

Adverse Effects
  •  Lead to ruptured uterus
  • Hypotension
  • Tachycardia
  • Intra uterine fetal anoxia and hypoxia to the fetus leading to birth asphyxia.
Pharmacokinetics
  •  Absorption is immediate following IV injections
  • Drug is distributed throughout the extracellular fluid. Some amount enters the fetal circulation.
  • It is metabolized rapidly in kidney and liver in small amount and are excreted in urine

Abortifacients

Abortifacients are used to evacuate uterine contents via intense uterine contractions. These drugs include;

  • Misoprostol
  • Carboprost (Hemabate)
  • Dinoprostone (Cervidil, Prepidil Gel, Prostin E2)
  • Mifepristone ( Mifeprex). 

Misoprostol

Legal class; class B controlled drugs
Medical class; oxytocic drugs/ cervical, rippening agent
Form; tablet
Strength; 200mcg/ 100mcg tablet

Indications
  •  Induction of labour
  • Control post partum hemorrhage due to uterine atony
  • Before cervical dilatation
  • Intra-uterine fetal death
  • Gastric and deudenal ulcerations
Contraindications
  •  Mal presentation
  • Placeta previa grade 3 and 4
  • Multiparous mothers
  • Cephalo pelvic disproportion
  • Hypersensitivity to misoprostol
Dose
  • Induction of labour; 100mcg vaginally every after 12hrs
  • NSAID ulcerations; 200mcg 4 times a day
Route
  • Sublingually
  • Rectally
  • Vaginally
Side Effects
  • Headache
  • Dizziness
  • Fever
  • Shivering
  • Vomiting
  • Uterine rupture
  • Fetal distress.
  • Constipation
Pharmacokinetics.

Absorbed in the GIT and distributed widely through out the body metabolised in the liver and is excreted in urine.

DINOPROSTOL

Available preparation – 3mg tab
Available brand – Prostin

Pharmacokinetics

Following vaginal insertion, it diffused slowly into the maternal blood.
There is also some local absorption into the uterus through the cervix
It is distributed widely in the molter, metabolized in the lungs, liver, kidney, spleen and other maternal tissues and excreted in urine with small amount in faeces.

Indications
  • Induction of labor
  • Missed abortion
Contraindications
  •  Active cardiac diseases
  • Multiple pregnancy
  • Hypersentivity to dinoprostol
  • Untreated pelvic infection
  • Caesarian section

Dose :  3 mg vaginally

Side Effects
  •  Abdominal pain
  • Nausea and vomiting
  • Hypotension
  • Shivering
  • Back pain
  • Rapid cervical dilatation

SYNTOMETRINE

Legal class; class B controlled drugs
Medical class; oxytocic drug
Form; sterile solution for injection
Strength; combination of ergometrine and Pitocin ( ergometrine 0.5 mg + Pitocin 5 IU) –It exists in an ampules of 1 mill

Dose
  • I ml as single dose but can be repeated where necessary if bleeding is not controlled
Route
  •    Intramuscular
  •    Intravenous
Indications
  1.  Give to multi gravidas after delivery
  2.   Mothers with a history of post partum hemorrhage
  3. Multiple or twin delivery because of large placental site
  4. Mothers with heavy lochia
  5. Abortion when fundal height is less than 12 weeks
Contraindications

Mothers with cardiac disease, pre eclampsia, eclampsia and hypertension.

Adverse Effects
  •  Retained placenta
  •  IUFD in undiagnosed second twin
  • Lead to retained 2nd twin
  • Uterine rapture if given in abortion, above 20 weeks of gestation products of conception are not fully out.
  • Causes hypoxia and anoxia
Side Effects
  • Nausea and vomiting
  • Headache
  • Hypotension
  • Dyspnea
  • Muscle pain

ERGOMETRINE

Legal class; class B controlled drugs
Medical class; oxytocic drug
Form; tablet and sterile solution
Strength/dosage; tabs 0.25 to 0.5mg tab
Injection 200mcg/ml
0.5mg/ml
EFFECTS
It causes sudden prolonged intermittent uterine contraction
INDICATION
Contra indications
Side effects
Dangers
(Are the same as for syntometrine)

UTERINE RELAXANTS

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Fertility Drugs/ Gonadotropin Drugs drugs

Fertility Drugs/Gonadotropin Drugs

Fertility Drugs

Fertility drugs are drugs that stimulate the female reproductive system.

Examples of Fertility drugs;

  • Cetrorelix (Cetrotide)
  • Chorionic gonadotropin (Chorex, Profasi, Pregnyl).
  • Chorionic gonadotropin alpha (Ovidrel).
  • Clomiphene (Clomid)
  • Menotropins
    (Pergonal, Humegon).

Therapeutic Actions and Indications.

Women without primary ovarian failure who cannot get pregnant after 1 year of trying may be candidates for the use of fertility drugs. Fertility drugs work either directly to stimulate follicles and ovulation or stimulate the hypothalamus to increase FSH and LH levels, leading to ovarian follicular development and maturation of ova.

Indications

  1. Given in sequence with human chorionic gonadotropin (HCG) to maintain the follicle and hormone production, these drugs are used to treat infertility in women with functioning ovaries whose partners are fertile.
  2. Fertility drugs also may be used to stimulate multiple follicle development for the harvesting of ova for in vitro fertilization.
  3. Menotropins also stimulate spermatogenesis in men with low sperm counts and otherwise normally functioning testes.
  4. Cetrorelix inhibits premature LH surges in women undergoing controlled ovarian stimulation by acting as a GnRH antagonist.
  5. Chorionic gonadotropin is used to stimulate ovulation by acting like GnRH and affecting FSH and LH release.

Contraindications of fertility drugs

  1. Allergy to fertility drug:  Prevent hypersensitivity.
  2.  Primary ovarian failure: These drugs only work to stimulate functioning ovaries
  3. Thyroid or adrenal dysfunction. Drugs have effects on the hypothalamic-pituitary axis.
  4. Ovarian cysts: Can be stimulated by the drugs and can become larger
  5. Pregnancy: Due to the potential for serious fetal effects
  6. Idiopathic uterine bleeding: Can represent an underlying problem that could be exacerbated by the stimulatory effects of these drugs.
  7. Lactation: Risk of adverse effects on the baby
  8. Thromboembolic disease. Increased risk of thrombus formation
  9. Women with respiratory diseases: Alterations in fluid volume and blood flow can overtax the respiratory system.

Adverse effects of fertility drugs

  • Greatly increased risk of multiple births and birth defects
  • Ovarian overstimulation: abdominal plain, distention, ascites, pleural effusion
  • Headache
  • Fluid retention
  • Nausea
  • Bloating
  • Uterine bleeding
  • Ovarian enlargement
  • Gynecomastia
  • Febrile reactions possibly due to stimulation of progesterone release.

Fertility Drugs

DrugIndicationDose
Clomifene Anovulatory infertility50mg daily for 5 days, starting within 5 days of onset of menstruation (preferably on the second day) or at any time if cycles have ceased
Bromocriptine Hyper prolactanaemic, infertility, Suppression of lactation, Hypogonadism, Galactorrhoea syndrome, Benign breast diseaseInitially 1.25mg at bed time increased gradually to the usual dose of 2.5mg 3 times a day with food increased if necessary to a max. dose 30mgdaily

Nursing Diagnosis

  • Acute pain related to headache, fluid retention, or GI upset
  • Sexual dysfunction related to alterations in normal hormone control
  • Disturbed body image related to drug treatment and diagnosis
  • Deficient Knowledge regarding drug therapy
  •  Risk for Impaired Tissue Perfusion (Cardiopulmonary, Peripheral) related to increased risk for thrombus formation
  •  Situational Low Self-Esteem related to the need for fertility drugs.

Drugs used in labor

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Estrogen Receptor Modulators

Estrogen Receptor Modulators

Estrogen Receptor Modulators

Estrogen Receptor Modulators are agents that either stimulate or block specific estrogen receptor sites.

They are used to stimulate specific estrogen receptors to achieve therapeutic effects of increased bone mass without stimulating the endometrium and causing other less desirable effects i.e. these drugs stimulate the estrogen receptors in the body so as to produce estrogen as needed by the body.

Examples of Estrogen Receptor Modulators.

Two available estrogen receptor modulators are raloxifene (Evista) and toremifene (Fareston).

Raloxifene

Dose : 60 mg/day Orally.

Indications : –Used therapeutically to stimulate specific estrogen receptor sites, which results in an increase in bone mineral density without stimulating the endometrium in women; – reduces risk of invasive breast cancer in  postmenopausal women with osteoporosis who are at
high risk for invasive breast cancer

Toremifene

Dose : 60 mg/day orally until disease progression occurs.

Indications: Used as an antineoplastic agent because of its effects on estrogen receptor sites for treatment of advanced breast cancer in postmenopausal women with estrogen receptor–positive and estrogen
receptor–unknown tumors

Contraindications of Estrogen Receptor Modulators
  • Allergy to estrogen receptor modulators.
  • Contraindicated in pregnancy and lactation because of potential effects on the fetus or neonate. 
  •  History of venous thrombosis or smoking. Increased risk of blood clot formation if smoking and estrogen are combined.
Adverse Effects of Estrogen Receptor Modulators
  • Raloxifene has been associated with GI upset, nausea, and vomiting.
  • Changes in fluid balance may cause headache, dizziness, visual changes, and mental changes.
  • Specific estrogen receptor stimulation may cause hot flashes, skin rash, edema, and vaginal bleeding.
Clinically Important Drug–Drug Interactions
  •  Cholestyramine: reduced raloxifene absorption
  • Highly protein-bound drugs (e.g. diazepam, ibuprofen, indomethacin, naproxen): interference on binding sites
  • Warfarin: decreased prothrombin time if taken with raloxifene

Nursing Considerations

  1.  Assess for the mentioned cautions and contraindications (e.g. drug allergies, cardiovascular diseases, metabolic bone disease, history of thromboembolism, etc.) to prevent any complications.
  2. Perform a thorough physical assessment (e.g. bowel sounds, skin assessment, vital signs, mental status, etc.) to establish baseline data before drug therapy begins, to determine effectiveness of
    therapy, and to evaluate for occurrence of any adverse effects associated with drug therapy.
  3. Assist with pelvic and breast examinations. Ensure specimen collection for Pap smear and obtain a history of patient’s menstrual cycle to provide baseline data and to monitor for any adverse
    effects that could occur.
  4. Arrange for ophthalmic examination especially for patients who are wearing contact lenses because hormonal changes can alter the fluid in the eye and curvature of the cornea, which can
    change the fit of contact lenses and alter visual acuity.
  5. Monitor laboratory test results (e.g. urinalysis, renal and hepatic function tests, etc.) to determine possible need for a reduction in dose and evaluate for toxicity.

Nursing Diagnoses
  •  Ineffective tissue perfusion related to changes in the blood vessels brought about by drug therapy and risk of thromboemboli
  • Excess fluid volume related to fluid retention
  • Acute pain related to systemic side effects of gastrointestinal (GI) pain and headache


Implementation with Rationale
These are vital nursing interventions done in patients who are taking female sex hormones and estrogen receptor modulators:

  •  Administer drug with food to prevent GI upset.
  • Provide analgesic for relief of headache as appropriate.
  • Provide small, frequent meals to assist with nausea and vomiting.
  • Monitor for swelling and changes in vision or fit of contact lenses to monitor for fluid retention and fluid changes.
  • Provide comfort measures to help patient tolerate drug effects.
  • Provide safety measures (e.g. adequate lighting, raised side rails, etc.) to prevent injuries.
  • Educate client on drug therapy to promote understanding and compliance.


Evaluation

Here are aspects of care that should be evaluated to determine effectiveness of drug therapy:

  •  Monitor patient response to therapy (palliation of signs and symptoms of menopause, prevention of pregnancy, decreased risk factors for coronary artery disease, and palliation of certain cancers).
  • Monitor for adverse effects (e.g. GI upset, edema, changes in secondary sex characteristics, headaches, thromboembolic episodes, and breakthrough bleeding).
  • Evaluate patient understanding on drug therapy by asking patient to name the drug, its indication, and adverse effects to watch for.
  • Monitor patient compliance to drug therapy

Fertility Drugs/Gonadotropin Drugs

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Fertility Drugs/ Gonadotropin Drugs drugs

Gonadotropin drugs

GONADOTROPINS

Gonadotropins are fertility medications given by injection that contain follicle-stimulating hormone (FSH) alone or combined with luteinizing hormone (LH).

Gonadotropins are hormones that stimulate the gonads, which are the sex organs in the body. 

Gonadotropins are produced by the pituitary gland, which is a small gland located at the base of the brain. The release of gonadotropins is regulated by the hypothalamus.

 

In females, the gonads are the ovaries, and in males, they are the testes.

Gonadotropins are a class of medications used to treat infertility and disorders associated with reproductive functions.

Types of Gonadotropins

There are two main types of gonadotropins:

1. Follicle-stimulating hormone (FSH): This hormone stimulates the growth and development of follicles in the ovaries of females and sperm production in the testes of males.

Females

Males

– Normal Ovarian Function: FSH is useful for the development and maturation of follicles in the ovaries, which contain the eggs. This ensures regular ovulation and fertility.

– Estrogen Production: FSH stimulates the production of estrogen by the growing follicles. Estrogen is for the development of female secondary sexual characteristics, menstrual cycle regulation, and overall reproductive health.

– Improved Egg Quality: FSH contributes to the development of healthy eggs, increasing the chances of successful fertilization and pregnancy.

– Fertility Treatment: FSH is a key component of fertility treatments like in vitro fertilization (IVF) to stimulate multiple egg production.

– Sperm Production: FSH is essential for the production of sperm in the testes. It stimulates the Sertoli cells, which are responsible for nourishing and supporting sperm development.

– Improved Sperm Quality: FSH contributes to the production of healthy, motile sperm, increasing the chances of fertilization.

2. Luteinizing hormone (LH): This hormone triggers ovulation in females and testosterone production in males.

Females

Males

– Ovulation: LH triggers the release of the mature egg from the follicle (ovulation), which is essential for fertilization.

– Corpus Luteum Formation: After ovulation, LH stimulates the formation of the corpus luteum, which produces progesterone. Progesterone is for maintaining the uterine lining for potential pregnancy.

– Hormonal Balance: LH plays a role in regulating the production of estrogen and progesterone, contributing to hormonal balance in the female body.

– Fertility Treatment: LH is used in fertility treatments to trigger ovulation and support the development of the corpus luteum.

– Testosterone Production: LH stimulates the Leydig cells in the testes to produce testosterone. Testosterone is essential for male sexual development, sperm production, and overall health.

– Secondary Sexual Characteristics: LH-driven testosterone production is responsible for the development of male secondary sexual characteristics like facial hair, muscle mass, and deepening of the voice.

– Libido and Sexual Function: Testosterone, produced under the influence of LH, plays a crucial role in libido and sexual function.

GONADOTROPIN DRUGS (Fertility Drugs)

Gonadotropin Drugs/Fertility drugs are agents that stimulate the female reproductive system.

Fertility drugs are medications used to help women who are having trouble getting pregnant. They work by stimulating the ovaries to produce more eggs, increasing the chances of conception.

Indications for Fertility Drugs:

1. Treatment of infertility in women with functioning ovaries whose partners are fertile: This is a broad category encompassing various causes of infertility, including:

  • Anovulation: When a woman doesn’t ovulate regularly, fertility drugs can stimulate ovulation and increase the chances of pregnancy.
  • Polycystic Ovarian Syndrome (PCOS): PCOS often causes irregular ovulation. Fertility drugs can help regulate ovulation and improve fertility.
  • Endometriosis: This condition can affect ovulation and egg quality. Fertility drugs can help stimulate ovulation and improve chances of conception.
  • Premature Ovarian Failure: In some cases, women experience premature ovarian failure, leading to low egg reserves. Fertility drugs can help stimulate limited egg production.
  • Unexplained Infertility: When the cause of infertility is unknown, fertility drugs can be used to stimulate ovulation and see if it improves chances of pregnancy.

2. Used to stimulate multiple follicle development for harvesting of ova for in vitro fertilization (IVF): This is a crucial aspect of IVF, where multiple eggs are needed for fertilization and embryo transfer.

3. Menotropins are used to stimulate spermatogenesis in men with low sperm counts and otherwise normally functioning testes: While not directly related to female fertility, this highlights the broader application of fertility drugs in both men and women.

Contraindications for Fertility Drugs:
  1. Allergy to fertility drug: Prevent hypersensitivity reactions.
  2. Primary ovarian failure: These drugs only work to stimulate functioning ovaries.
  3. Ovarian cysts: Can be stimulated by the drugs and can become larger.
  4. Pregnancy: Due to the potential for serious fetal effects.
  5. Idiopathic uterine bleeding: Can represent an underlying problem that could be exacerbated by the stimulatory effects of these drugs.
  6. Lactation: Risk of adverse effects on the baby.
  7. Thromboembolic disease: Increased risk of thrombus formation.
  8. Women with respiratory diseases: Alterations in fluid volume and blood flow can overtax the respiratory system.
Adverse Effects:
  • Greatly increased risk of multiple births and birth defects.
  • Ovarian overstimulation: abdominal pain, distention, ascites, pleural effusion.
  • Others: headache, fluid retention, nausea, bloating, uterine bleeding, ovarian enlargement, gynecomastia, and febrile reactions possibly due to stimulation of progesterone release.

  • Fluid retention is a common side effect of fertility medications, because;

    Hormonal Changes: Fertility drugs increase estrogen levels, which can lead to fluid retention. Estrogen promotes sodium retention in the body, and sodium attracts water, causing fluid buildup.

    Increased Blood Flow: Fertility drugs increase blood flow to the ovaries and uterus, which can lead to fluid buildup in the pelvic area.

Drugs used in treatment of infertility

Name

Clinical uses and dosage

Contraindications

Clomifene


  • Available in tablet form of 50mg

  • Brand name Clomid

Infertility due to failure to ovulate.

Given 50 mg daily × 5/7

Starting from the 5th day of the cycle ,

Increase to 100mg ×5/7

From day 5-10 if no response.

Pregnancy.

Bromocriptine


  • Available in tablet form of 2.5mg

Female infertility associated with hyperprolactinemia

Dosage 1.25 – 2.5mg

Bid × 3-7 days with food.

Inhibition of lactation 2.5mg bid with meals × 14 days.

 

Severe ischemic heart disease

Uncontrolled hypertension

Pregnancy

Breast feeding.

FEMALE REPRODUCTIVE SYSTEM DRUGS

Drugs that affect the female reproductive system typically include hormones and hormonal-like agents.

These drug types include;

  1.  Female Sex Hormones
  2. Estrogen Receptor Modulators
  3. Fertility Drugs/gonadotropins
  4. Drugs used in labor
  5. Abortifacients
gonadotropin sites

Gonadotropin Sites of Action

Female Sex Hormones

The female sex hormones can be used to replace hormones that are missing or to act on the control mechanisms of the endocrine system to decrease the release of endogenous hormones.
Drugs that act like estrogen, particularly at specific estrogen receptors, are also used to stimulate the effects of estrogen in the body with fewer of the adverse effects.

Female sex hormones include;

  • Estrogens 
  • Progestins

Estrogens.

This hormone is naturally produced by the ovaries, placenta and adrenal glands. It stimulates the development of female sex characteristics, prepares the body for pregnancy, affects the release of FSH and LH, and is responsible for proliferation of the endometrial lining.

Low estrogen in the body is responsible for the signs and symptoms of menopause, in the uterus, vagina, breast and cervix.

Other Functions of estrogen include;

  1. Breast development.
  2. Increase cholesterol in bile, to prevent damaging effects of bile salts.
  3. Increases fat storage, such as in breast tissue.
  4. Maintains bone mineral density.
  5. Maintains muscle strength.
  6. Prevents atherosclerosis, by increasing HDL concentration and lowering LDL.
  7. Estrogen is responsible for maintaining libido, memory, and mental health. 
  8. It stimulates ovulation, maintains the uterine walls and is important in vaginal lubrication.
Indications of Estrogen Therapy.
  • Estrogens are used for hormone replacement therapy (HRT) when ovarian activity is blocked or absent.
  • Is used to control the signs and symptoms of menopause.
  • They can also be used in therapy for prostate cancer and inoperable breast cancer, also as palliative care.
  • Treatment of female hypogonadism(when the body produces little or no hormones).
  • Treat ovarian failure.
  • Oral contraceptives (estrogen and progestin)
  • Morning after pill (emergency pills)
  • Endometriosis
  • Dysmenorrhea, used with progestin.

Progestin/Progesterone.

This promotes maintenance of pregnancy and it is called a pregnancy hormone.

Its functions include;

  1. Transforms proliferative endometrium into secretory endometrium.
  2. Prevents follicle maturation, ovulation and uterine contractions.
  3. Used in contraceptives. It inhibits release of GnRH, FSH and LH, hence follicle development and ovulation are prevented.
Indications of Progestin.
  • Used as a contraceptive.
  • Maintains pregnancy and development of secondary sex characteristics.
  • Use to treat primary and secondary amenorrhea, and functional uterine bleeding.
  • Treatment of acne and premenstrual dysphoric disorder (PMDD).
  • For the relief of signs and symptoms of menopause .
Contraindications of Female Sex hormones.

Estrogen

  • Known allergies
  • Idiopathic vaginal bleeding.
  • Breast Cancer(Estrogen dependant cancer)
  • CVA since it increases clotting factor prodn.
  • Hepatic dysfunction.
  • Pregnancy.
  • Lactation.

Progestin/Progesterone

  • PID
  • STD
  • Endometriosis
  • Renal and hepatic disorders.
  • Epilepsy.
  • Asthma.
  • Migraine headaches
  • Cardiac Dysfunction —potential excerbation.
Adverse Effects.
  • Corneal Changes.
  • Photosensitivity.
  • Peripheral edema.
  • Chloasma ( patches on the face)
  • Hepatic adenoma.
  • Nausea
  • Vomiting.
  • Abdominal cramps.
  • Bloating.
  • Withdraw bleeding.
  • Changes in menstrual flow.

Important aspects/issues to remember.

  1.  Women receiving any of these drugs should receive an annual medical examination, including
    breast examination and Pap smear, to monitor for adverse effects and underlying medical
    conditions.
  2. Women taking estrogen should be advised not to smoke because of the increased risk of
    thrombotic events.
  3. Women who are receiving these drugs for fertility programs should receive a great deal of psychological support and comfort measures to cope with the many adverse effects associated
    with these drugs. The risk of multiple births should be explained.
  4. Drugs are used in treatment of specific cancers in males and they should be advised about the
    possibility of estrogenic effects.
  5. Not indicated during pregnancy or lactation because of potential for adverse effects on the fetus
    or neonate.
Examples of female sex hormones and dosages.

Estrogen

  1. Estradiol, 1–2 mg/day orally or  1–5 mg IM every 3–4 weeks or  2–4 g intravaginal cream daily.
  2. Estrogens, conjugated (C.E.S., Premarin), 0.3–1.25 mg/day orally.
  3. Estropipate (Ortho-Est, Ogen), 0.625–5 mg/day orally.

Progestin/Progesterone.

  1. Etonogestrel (Implanon) 68 mg implanted sub dermally for up to 3 yr, replaced or changed when needed.
  2. Medroxyprogesterone (Provera) 5–10 mg/day PO for 5–10 days for amenorrhea or 400–1000 mg/week IM for cancer therapy or 150 mg of deep IM every 3 months (13 weeks) for contraception.
Clinically important Drug Interactions

Estrogen

  •  Barbiturates, rifampin, tetracyclines, phenytoin: decreased serum estrogen levels
  • Corticosteroids: increased therapeutic and toxic effects of corticosteroids.
  • Nicotine: Increased risk of thrombi and emboli
  • Grapefruit juice: inhibition of metabolism of estradiols
  • St. John’s wort: can affect metabolism of estrogens and can make estrogen-containing
    contraceptives less effective.

Progestins

  •  Barbiturates, carbamazepine, phenytoin, griseofulvin, penicillin, tetracyclines, rifampin: reduced
    effectiveness of progestins
  • St. John’s wort: can affect the metabolism of progestins and can make progestin-containing
    contraceptives less effective..

Estrogen Receptor Modulators

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Quick Links.

  1.  Female Sex Hormones
  2. Estrogen Receptor Modulators
  3. Fertility Drugs/gonadotropins
  4. Drugs used in labor
  5. Abortifacients

Gonadotropin drugs Read More »

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