Ivermectin indication
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ivermectin indications clinical use
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Here is a complete, textbook-sourced summary of ivermectin indications:
Ivermectin - Indications
Drug Overview
Ivermectin (22,23-dihydroavermectin) is a macrocyclic lactone derivative of avermectin, produced by the soil actinomycete Streptomyces avermitilis. It is active at low doses against a wide range of helminths and ectoparasites.
Approved / Drug-of-Choice Indications
| Indication | Notes |
|---|---|
| Onchocerciasis (River Blindness) | Drug of choice; suppresses microfilariae but not curative (no macrofilaricidal activity against adult worms) |
| Strongyloidiasis | Drug of choice; for disseminated disease, treat for ≥14 days after negative fecal exams |
| Scabies | Drug of choice (oral); topical form also available |
| Cutaneous larva migrans | Drug of choice |
| Lymphatic filariasis | Used in mass drug administration (MDA) programs; active against microfilariae but NOT adult worms - combined with DEC or albendazole for synergy |
| Pediculosis capitis (Head lice) | 0.5% topical ivermectin lotion (Sklice) - FDA-approved 2012 for patients ≥6 months; also kills permethrin-resistant lice |
Additional Active (Variably Effective) Uses
- Ascariasis (Ascaris lumbricoides) - active
- Enterobiasis (Enterobius vermicularis / pinworm) - active
- Trichuriasis (whipworm) - only variably effective
- Hookworm - NOT effective
Mechanism of Action
Ivermectin opens glutamate-gated chloride channels in invertebrate nerve/muscle membranes, causing chloride influx, hyperpolarization, and muscle paralysis - especially of the nematode pharynx, blocking nutrient ingestion. These chloride channels exist only in invertebrates, so paralysis is parasite-specific.
Important Pharmacology Points
- Dose: 150-200 mcg/kg as a single oral dose
- Food interaction: Both food and beer significantly increase bioavailability
- Distribution: Highly protein-bound; concentrates in adipose tissue and liver; minimal CNS penetration (important safety margin)
- Excretion: Almost completely via feces
Key Adverse Effects
- In filarial infections: fever, myalgia, malaise, lightheadedness, postural hypotension (Mazzotti-like reaction proportional to parasite burden)
- In onchocerciasis: skin edema, pruritus, mild eye irritation
- Loa loa encephalopathy - serious risk if used in patients with Loa loa microfilaremia ≥30,000 microfilariae/mL; ivermectin is contraindicated in this situation
NOT Effective Against
- Cestodes (tapeworms)
- Trematodes (flukes) - lack high-affinity ivermectin receptors
- Fascioliasis (triclabendazole is the only option)
- Adult filarial worms (macrofilaricidal activity absent)
Sources: Harrison's Principles of Internal Medicine 22E, Goodman & Gilman's Pharmacological Basis of Therapeutics, Lippincott Illustrated Reviews Pharmacology, Katzung's Basic and Clinical Pharmacology 16th Ed., Dermatology 2-Volume Set 5e, Goldman-Cecil Medicine
Diabetes from harrison
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Diabetes Mellitus - Harrison's Principles of Internal Medicine 22E (2025)
1. Etiologic Classification
Type I - Type 1 DM
Immune-mediated beta cell destruction leading to absolute insulin deficiency.
Type II - Type 2 DM
Ranges from predominantly insulin resistance with relative insulin deficiency to a predominantly insulin secretory defect with insulin resistance.
Type III - Other specific types:
- A. Monogenic/MODY - Mutations in HNF-4α, Glucokinase, HNF-1α, IPF-1, HNF-1β, NeuroD1, KLF11, PAX4, BLK, GATA4/6, GLUT2, GLIS3
- B. Neonatal diabetes (onset <6 months) - mutations in ATP-sensitive K+ channel subunits, RFX6, insulin gene
- C. Transient neonatal diabetes
- D. Exocrine pancreas disease - pancreatitis, pancreatectomy, neoplasia, cystic fibrosis, hemochromatosis, fibrocalculous pancreatopathy
- E. Genetic defects in insulin action - type A insulin resistance, leprechaunism, Rabson-Mendenhall syndrome, lipodystrophy
- F. Endocrinopathies - acromegaly, Cushing's syndrome, glucagonoma, pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma
- G. Drug/chemical-induced - glucocorticoids, calcineurin/mTOR inhibitors, pentamidine, nicotinic acid, statins, HIV therapies, diazoxide, β-agonists, thiazides, PCSK9 inhibitors, atypical antipsychotics
- H. Infections - congenital rubella, CMV, coxsackievirus
- I. Uncommon immune-mediated - stiff-person syndrome, anti-insulin receptor antibodies, immune checkpoint inhibitor therapy
- J. Other genetic syndromes - Wolfram, Down, Klinefelter, Turner, Friedreich's ataxia, Huntington's, Prader-Willi, myotonic dystrophy
Type IV - Gestational DM (GDM)
Glucose intolerance developing in the 2nd or 3rd trimester; insulin resistance driven by pregnancy hormones. Affects ~16% of pregnancies worldwide (IDF 2021). 35-60% risk of developing DM within 10-20 years post-partum.
2. Diagnostic Criteria
| Test | Normal | Prediabetes | Diabetes |
|---|---|---|---|
| HbA1c | <5.6% (<41 mmol/mol) | 5.7-6.4% (42-47 mmol/mol) | ≥6.5% (≥48 mmol/mol) |
| FPG | <5.6 mmol/L (<100 mg/dL) | 5.6-6.9 mmol/L (100-125 mg/dL) | ≥7.0 mmol/L (≥126 mg/dL) |
| 2-h PG (OGTT) | <7.8 mmol/L (<140 mg/dL) | 7.8-11.0 mmol/L (140-199 mg/dL) | ≥11.1 mmol/L (≥200 mg/dL) |
| Random glucose + symptoms | - | - | ≥11.1 mmol/L (≥200 mg/dL) |
3. Symptoms of Hyperglycemia
Polyuria, polydipsia, weight loss, fatigue, weakness, blurry vision (reversible lens water content change), frequent superficial infections (vaginitis, fungal skin infections), slow wound healing. Metabolic derangements relate to osmotic diuresis and catabolic state.
4. Physical Examination Focus
- Weight/BMI, orthostatic BP
- Retinal examination
- Foot exam: pedal pulses, vibratory sensation (128-Hz tuning fork at great toe base), 10-g monofilament, pinprick, ankle reflexes, nail care
- Look for: hammer/claw toes, Charcot foot, sites of potential ulceration
- Periodontal examination (more frequent in DM)
5. Glycemic Targets (HbA1c)
| Population | Target HbA1c |
|---|---|
| Most adults | <7% |
| Tight control (young, no hypoglycemia risk) | ≤6.5% |
| Elderly/cognitive impairment/limited lifespan | <7.5-8% |
| Pre-conception (women of childbearing age) | <6.5% |
| Priority is avoidance of hypoglycemia (<3.0 mmol/L / <54 mg/dL) |
Key trials: DCCT (Type 1), UKPDS, ACCORD, ADVANCE, VADT (Type 2). Improved glycemic control consistently reduces microvascular complications. Early control in Type 1 DM reduces cardiovascular events decades later.
6. Pharmacologic Treatment
Type 1 DM - Insulin Regimens
Goal: mimic physiologic insulin secretion (basal + prandial).
| Insulin | Onset | Peak | Duration |
|---|---|---|---|
| Rapid-acting (aspart, glulisine, lispro) | <0.25 h | 0.5-1.5 h | 3-5 h |
| Short-acting (Regular) | 0.5-1.0 h | 2-3 h | 4-8 h |
| Inhaled human insulin | <0.25 h | 1-2 h | 3 h |
| Intermediate (NPH) | 2-4 h | 4-10 h | 10-16 h |
| Long-acting (degludec, glargine, detemir) | 1-9 h | Flat/peakless | 16-42 h |
Delivery systems: MDI (multiple daily injections), CSII (insulin pump), sensor-augmented pump, or Automated Insulin Delivery (AID) - uses pump + CGM + algorithm to adjust basal in real-time.
Emerging: Teplizumab (anti-CD3 monoclonal antibody) - FDA-approved to delay onset of clinical Type 1 DM (Stage 3) in patients ≥8 years with preclinical (Stage 2) disease.
Type 2 DM - Glucose-Lowering Agents
| Class | Mechanism | Key Drug(s) | Notes |
|---|---|---|---|
| Biguanides | ↓ hepatic glucose production | Metformin | First-line; avoid if GFR <30, acidosis, unstable CHF, liver disease |
| Sulfonylureas | ↑ insulin secretion (K+ channel) | Glimepiride, glipizide, glyburide | Prefer glimepiride/glipizide over glyburide in elderly |
| Meglitinides | ↑ insulin secretion (K+ channel, short-acting) | Repaglinide, nateglinide | Taken with meals |
| GLP-1 RAs | ↑ insulin secretion, ↓ glucagon, delay gastric emptying | Semaglutide, liraglutide, dulaglutide | Cardiovascular benefit; caution: may worsen retinopathy with rapid glucose correction |
| SGLT-2 inhibitors | ↑ urinary glucose excretion | Empagliflozin, canagliflozin, dapagliflozin | Cardiovascular + renal protection |
| DPP-4 inhibitors | ↑ GLP-1/GIP levels | Sitagliptin, saxagliptin | Weight-neutral |
| Thiazolidinediones | ↑ insulin sensitivity (PPAR-γ) | Pioglitazone | Weight gain, edema, fracture risk |
| Alpha-glucosidase inhibitors | ↓ GI carbohydrate digestion | Acarbose, miglitol | GI side effects |
| Amylin analog | ↓ glucagon, slow gastric emptying | Pramlintide | Used with insulin |
| Insulin | Direct glucose lowering | Various | Used if severe hyperglycemia or catabolic state |
7. Complications
Microvascular (diabetes-specific)
Retinopathy (leading cause of new blindness age 20-74 in the US)
- Nonproliferative: microaneurysms, blot hemorrhages, cotton-wool spots - appears in 2nd decade of hyperglycemia
- Proliferative: neovascularization (hallmark), vitreous hemorrhage, fibrosis, retinal detachment
- Treatment: laser photocoagulation, anti-VEGF agents, vitrectomy; prevention via glycemic + BP control
Nephropathy
- Albuminuria + declining renal function
- Annual screening: urine albumin-to-creatinine ratio + eGFR
Neuropathy
- Distal symmetric polyneuropathy (most common): stockings-and-gloves sensory loss
- Autonomic neuropathy: gastroparesis, orthostatic hypotension, sexual dysfunction, sudomotor dysfunction
- Mononeuropathy: CN III palsy, carpal tunnel syndrome
- Charcot neuroarthropathy
Macrovascular
- Coronary heart disease (leading cause of mortality in Type 2 DM)
- Peripheral arterial disease
- Cerebrovascular disease
- Heart failure
Other Complications
Gastroparesis, genitourinary dysfunction, dermatologic manifestations, cataracts, glaucoma, cheiroarthropathy (thickened skin, reduced joint mobility), periodontal disease, hearing loss, infections, increased fracture risk, cognitive impairment/dementia, depression, obstructive sleep apnea, metabolic-associated steatotic liver disease.
8. Other Therapies
- Metabolic/bariatric surgery - consider if Type 2 DM + BMI >30 kg/m² with inadequate glycemic control on optimal medical therapy; can produce dramatic DM resolution
- Very-low-calorie diet (800-1000 kcal/day) - can dramatically improve or resolve recent-onset Type 2 DM
- Pancreas transplantation - normalizes glucose in Type 1 DM; declining due to success of CGM/AID technology
- Islet cell transplantation - FDA-approved islet product; less invasive; requires immunosuppression
9. Comprehensive Diabetes Care (Ongoing Monitoring)
- HbA1c: 2-4 times/year
- Annual eye exam (earlier if retinopathy present)
- Annual foot exam (1-2x/year by provider)
- Annual neuropathy screen (Type 1: 5 years post-diagnosis; Type 2: at diagnosis)
- Annual kidney disease testing (urine albumin + eGFR)
- BP assessment 2-4x/year; lipids 1-2x/year
- Immunizations: influenza, pneumococcal, hepatitis B, COVID-19, RSV (>60 yrs)
- Psychosocial care: screen for depression, anxiety, diabetes distress
Source: Harrison's Principles of Internal Medicine 22E (2025), Chapters 415, 416, 417
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