Ectoparasiticides — Mechanism and kdr Resistance
Agent Selection — Scabies and Pediculosis
| Agent |
Mechanism |
kdr Resistance |
Key Point |
| Permethrin |
Na+ channel prolonged opening |
Affected — treatment may fail |
First-line scabies; avoid in high-kdr lice settings |
| Malathion |
Acetylcholinesterase inhibitor |
Not affected |
Flammable — no flames during application |
| Spinosad |
nAChR + GluCl activation |
Not affected |
Ovicidal — single application usually sufficient |
| Benzyl alcohol |
Spiracle asphyxiation (physical) |
No resistance risk |
No neurotoxic mechanism |
| Ivermectin (oral) |
GluCl channel opening |
Not affected |
Preferred for institutional scabies outbreaks |
| Benzyl benzoate |
Direct mite neurotoxicity |
Not affected |
Resource-limited settings; more irritating than permethrin |
Crusted Scabies
Topical permethrin alone fails — mite burden too high, crust blocks penetration. Combine: oral ivermectin + topical permethrin + keratolytics. Highly contagious — treat all close contacts simultaneously. Post-treatment itch: normal for 2–4 weeks (hypersensitivity to dead mites) — do not retreat without confirming live mites.
Pyrethroid Mechanism and Knockdown Resistance (kdr)
Normal Action
Voltage-Gated Na+ Channel
- Pyrethroid binds open Na+ channel
- Prevents channel inactivation
- Sustained Na+ influx → repetitive firing
- Low dermal absorption in humans at therapeutic doses
- Cats: lack hepatic esterase metabolism → severe toxicity from dog products
Resistance Mechanism
kdr — Target Site Mutation
- Point mutation in voltage-gated Na+ channel gene
- Reduces pyrethroid binding affinity
- Normal channel function preserved
- Cross-resistance to ALL pyrethroids (entire class)
- Dose increase does not overcome kdr
- Piperonyl butoxide: inhibits esterase metabolism — does NOT overcome kdr
Antiparasitic Therapy in Pregnancy
Generally Safe / Recommended
Use When Indicated
- Malaria treatment: never withhold — artemisinin-based combination therapy (2nd/3rd trimester); quinine + clindamycin (1st trimester)
- Chloroquine: safe throughout all trimesters (prophylaxis)
- Praziquantel: WHO recommends throughout pregnancy
- Albendazole / Mebendazole: single dose from 2nd trimester (WHO)
- Permethrin 5%: preferred scabies agent — low absorption
- Spiramycin: reduces vertical toxoplasma transmission
Avoid / Contraindicated
Do Not Use in Pregnancy
- Lindane: contraindicated — CNS toxicity from dermal absorption; banned many countries
- Diethylcarbamazine: contraindicated throughout pregnancy
- Doxycycline: contraindicated (bone and tooth development)
- Ivermectin: avoid elective use (limited safety data)
- Malathion: avoid (organophosphate precaution)
- Benznidazole / Nifurtimox: teratogenic — contraindicated
- Miltefosine: teratogenic — contraindicated
Key Drug Interactions Across Antiparasitic Classes
High-Yield Interactions
Rifampicin + praziquantel: CYP3A4 induction dramatically lowers praziquantel levels — never co-administer. Metronidazole + warfarin: CYP2C9 inhibition — monitor INR. Metronidazole + alcohol: disulfiram-like reaction (acetaldehyde accumulation). Ivermectin + P-glycoprotein inhibitors (ritonavir, verapamil): increased CNS penetration. Corticosteroids + praziquantel: reduced cerebrospinal fluid penetration — use albendazole in neurocysticercosis. Pyrimethamine + other myelosuppressants: additive bone marrow suppression. Artemether-lumefantrine: prolongs corrected QT — avoid other corrected QT-prolonging agents. Lindane: GABA-A antagonist — CNS toxicity in children; contraindicated.