Antivirals and antifungals
Antivirals, Antifungals, Antimalarials, Antiprotozoals and Anthelmintics: FCPS Part 1
Antiviral, antiretroviral, hepatitis, antifungal, antimalarial, antiprotozoal and anthelmintic drugs for FCPS Part 1, organised by mechanism. Covers aciclovir crystal nephropathy, oseltamivir, ribavirin haemolysis, artesunate, primaquine and G6PD, mefloquine, praziquantel, pyrantel and scabies.
Antiviral principles
Viruses replicate inside host cells, so most antivirals target a virus-specific enzyme (DNA polymerase, reverse transcriptase, protease, integrase, neuraminidase) and many are nucleoside analogues that interrupt viral nucleic acid synthesis.
Herpesvirus drugs
| Drug | Mechanism | Use | Toxicity |
|---|---|---|---|
| Aciclovir, valaciclovir | Guanosine analogue first phosphorylated by viral thymidine kinase (so only infected cells activate it), then inhibits viral DNA polymerase and terminates the chain | HSV (including 2% eye ointment for keratitis), VZV, IV for HSV encephalitis | Crystal nephropathy, neurotoxicity in renal failure |
| Ganciclovir, valganciclovir | Activated by CMV UL97 kinase | CMV | Myelosuppression: monitor the full blood count |
| Foscarnet | Pyrophosphate analogue; needs no activation | Resistant HSV or CMV; when marrow cannot tolerate ganciclovir | Nephrotoxicity, low calcium and magnesium |
- Aciclovir nephropathy: aciclovir is poorly soluble in urine; high IV doses with dehydration let crystals deposit in the renal tubules (obstructive AKI). Hydrate well, infuse slowly, adjust for GFR.
- Shingles: start oral antiviral within 72 hours of rash onset (later if new lesions or immunocompromised): it shortens illness and reduces acute pain.
Influenza
- Oseltamivir (oral) and zanamivir (inhaled) inhibit neuraminidase, which cleaves sialic acid to free new virions; blocking it traps virions on the cell surface and blocks release. Start within 48 hours, though severely ill patients benefit later. Amantadine (M2) is obsolete because of resistance.
HIV antiretrovirals
| Class | Examples | Key toxicity |
|---|---|---|
| NRTIs | Tenofovir (renal tubular damage, bone loss), lamivudine, emtricitabine, abacavir (hypersensitivity with HLA-B*57:01), zidovudine (anaemia, myopathy), didanosine, stavudine (painful peripheral neuropathy, pancreatitis, lactic acidosis) | Mitochondrial toxicity with older drugs |
| NNRTIs | Efavirenz (vivid dreams), nevirapine (hepatotoxicity, SJS) | Enzyme induction |
| Integrase inhibitors | Dolutegravir (first line), bictegravir | Weight gain, insomnia |
| Protease inhibitors | Darunavir, atazanavir (unconjugated hyperbilirubinaemia), indinavir (crystalluria and kidney stones), ritonavir boosting | Dyslipidaemia, interactions |
- First line: tenofovir, lamivudine and dolutegravir. Start ART as soon as possible after diagnosis, including in pregnancy, where dolutegravir-based therapy is now preferred (the early neural tube defect concern was not confirmed). Delay briefly only in cryptococcal or TB meningitis.
- PEP within 72 hours for 28 days; PrEP with tenofovir–emtricitabine; co-trimoxazole prophylaxis when CD4 is below 200.
Hepatitis B and C
- Chronic hepatitis B: long-term tenofovir or entecavir (high barrier to resistance), or pegylated interferon. Give prophylaxis before rituximab or chemotherapy.
- Hepatitis C: direct-acting antivirals (sofosbuvir, an NS5B polymerase inhibitor, with velpatasvir, an NS5A inhibitor) cure over 95% in 8–12 weeks. Sofosbuvir with amiodarone causes bradycardia.
- Ribavirin is concentrated and trapped in red cells as phosphorylated forms that deplete ATP, causing oxidative haemolytic anaemia (falling Hb, reticulocytosis, high unconjugated bilirubin, low haptoglobin). It is teratogenic in both sexes; contraception continues for months after stopping.
Antifungals
| Drug | Mechanism | Use | Toxicity |
|---|---|---|---|
| Amphotericin B | Binds ergosterol, forming membrane pores | Cryptococcal meningitis (with flucytosine), mucormycosis, invasive fungal infection, visceral leishmaniasis (liposomal) | Nephrotoxicity, hypokalaemia, hypomagnesaemia, infusion reactions |
| Azoles | Inhibit lanosterol 14α-demethylase (CYP51), blocking ergosterol synthesis | Fluconazole: candida; voriconazole: aspergillosis | CYP inhibition (warfarin, statins), hepatotoxicity, QT |
| Echinocandins (caspofungin) | Inhibit β-glucan cell wall synthesis | Candidaemia first line | Few |
| Flucytosine | Converted to 5-FU in fungi | With amphotericin | Marrow suppression |
| Terbinafine | Squalene epoxidase inhibitor | Dermatophytes, onychomycosis | Hepatotoxicity |
| Griseofulvin | Binds fungal microtubules; deposited in new keratin | Tinea capitis | Teratogenic, enzyme inducer |
- Tinea capitis needs oral griseofulvin or terbinafine because the fungus lives inside the hair shaft and follicle, which topical agents cannot reach. A kerion is an inflammatory reaction, not an abscess; do not incise.
Antimalarials
| Drug | Mechanism and use | Toxicity |
|---|---|---|
| Artemisinins (artesunate, artemether) | Haem iron cleaves the endoperoxide bridge, releasing free radicals that damage parasite proteins; fastest parasite clearance; IV artesunate first line for severe malaria | Post-artesunate delayed haemolysis |
| Lumefantrine (partner) | Long half-life | Take with fatty food |
| Chloroquine | Inhibits haem polymerisation in the food vacuole; vivax, ovale, malariae | Bull's eye maculopathy and corneal deposits with long-term use (lupus, RA), pruritus, QT; hydroxychloroquine causes skin hyperpigmentation |
| Primaquine | Kills liver hypnozoites (radical cure of vivax and ovale) and gametocytes | Haemolysis in G6PD deficiency (dark urine, back pain, bite cells): test G6PD first |
| Quinine | Severe malaria if artesunate unavailable | Cinchonism, hypoglycaemia (insulin release), QT |
| Halofantrine | Rarely used | Highest QT and torsades risk; never after mefloquine |
| Mefloquine | Prophylaxis | Neuropsychiatric: lowers seizure threshold, depression, psychosis; long half-life, effects last weeks |
| Atovaquone–proguanil, doxycycline | Prophylaxis |
- Artemisinin combination therapy: artemether has a short half-life; it removes most parasites within days, and the long-acting partner (lumefantrine) clears the remaining parasites and protects against resistance. Artemisinins do not kill hypnozoites.
- Post-artesunate delayed haemolysis 1–3 weeks later, with no parasites and a negative Coombs test: red cells whose parasites were removed in the spleen ("pitted" cells) return to circulation and are then cleared early. Not treatment failure.
- Vivax relapse months after chloroquine means hypnozoites were not cleared: add primaquine after a G6PD test. Falciparum has no hypnozoites. Chloroquine-resistant falciparum is treated with an ACT.
- Pakistan: vivax predominates; falciparum is treated with ACT.
Antiprotozoals
- Metronidazole: amoebiasis (followed by a luminal agent such as diloxanide), giardiasis, trichomoniasis. Adverse effects: metallic taste, disulfiram-like reaction with alcohol, neuropathy, raised INR.
- Visceral leishmaniasis: liposomal amphotericin, antimonials, miltefosine. Toxoplasmosis: pyrimethamine, sulfadiazine, folinic acid. Pneumocystis: co-trimoxazole.
Anthelmintics and ectoparasiticides
| Drug | Mechanism | Uses |
|---|---|---|
| Albendazole, mebendazole | Bind β-tubulin, blocking glucose uptake | Roundworm, hookworm, pinworm, hydatid, neurocysticercosis |
| Praziquantel | Increases calcium influx across the worm tegument: spastic paralysis and tegument damage within minutes | Schistosomiasis, tapeworms, flukes |
| Pyrantel pamoate | Nicotinic agonist: persistent depolarisation of worm muscle, spastic paralysis; live immobile worms are passed | Ascaris, hookworm, pinworm |
| Piperazine | GABA agonist: flaccid paralysis | Ascaris (antagonises pyrantel) |
| Ivermectin | Opens glutamate-gated Cl- channels | Strongyloides, onchocerciasis, crusted scabies |
| Permethrin 5% | Na+ channel toxin in arthropods | Scabies: treat the patient and all household contacts at once, repeat in 7 days |
- Neurocysticercosis: killing viable cysts provokes inflammation, so give corticosteroids and an antiepileptic with albendazole; examine the eyes first (intraocular cysts).
Remember Activated by viral kinase, aciclovir spares uninfected cells; trapped in red cells, ribavirin destroys them.
Exam trap Primaquine without a G6PD test can cause life-threatening haemolysis.
How FCPS asks about this
- Rising creatinine on IV aciclovir: crystals deposit in the tubules; hydrate.
- Ganciclovir monitoring: full blood count (myelosuppression).
- Oseltamivir: neuraminidase inhibition blocks virion release.
- Before primaquine: G6PD test; blurred vision on long-term chloroquine is bull's eye maculopathy.
- Artesunate mechanism and ACT logic: haem iron cleaves the endoperoxide bridge; long-acting partner clears the rest.
- Praziquantel and pyrantel: calcium influx across the tegument; persistent depolarisation.
- Indinavir; didanosine: kidney stones; painful neuropathy and pancreatitis.
Test yourself on this topic
5 of the 67 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
For uncomplicated falciparum malaria, artemether is always given together with lumefantrine for 3 days. Which of the following best explains why?
Answer: The long-acting partner clears the remaining parasites
Artemisinins reduce the parasite load very quickly but have a half-life of only about an hour. A 3-day course alone leaves some parasites alive, and the infection recrudesces. Lumefantrine has a half-life of several days, so it removes the parasites that survive and protects the artemisinin from developing resistance, while the artemisinin protects the partner by cutting the number of parasites it must clear. This is the basis of all artemisinin-based combination therapies (ACTs).
ACT principle
- Artemisinin: fast, short-lived
- Partner: slow, long-lived
- Partner clears residual parasites
- Each protects the other from resistance
Remember Fast drug to knock down, slow drug to mop up.
Exam trap Lumefantrine absorption needs fat, so it should be taken with food or milk.
Why the other options are wrong
- Lumefantrine slows artemether's breakdown in the liver There is no such useful interaction.
- Artemether alone causes severe haemolysis Monotherapy is avoided because of recrudescence and resistance, not haemolysis.
- Lumefantrine kills dormant liver hypnozoites Neither drug kills hypnozoites.
- Artemether alone does not act on ring forms Artemisinins are active against rings, unlike many older drugs.
A man with falciparum malaria is given artesunate. How does it kill the parasite?
Answer: Haem iron cleaves its endoperoxide bridge
Artemisinins contain an endoperoxide bridge. Inside the infected red cell, iron from haem released by the parasite's digestion of haemoglobin cleaves this bridge, producing carbon-centred free radicals that alkylate and damage many parasite proteins. This gives very rapid killing of all blood stages, including young rings. Chloroquine instead blocks haem polymerisation, and artemisinins do not kill liver hypnozoites.
Artemisinins
- Endoperoxide bridge
- Activated by haem iron
- Free radicals damage parasite proteins
- Fastest killing; short half-life
Remember The parasite's own haem switches the drug on.
Exam trap Artemisinins do not prevent vivax relapse; primaquine is still needed for hypnozoites.
Why the other options are wrong
- Blocks haem polymerisation to haemozoin That is chloroquine and quinine.
- Inhibits parasite dihydrofolate reductase That is pyrimethamine and proguanil.
- Disrupts parasite mitochondrial transport That is atovaquone.
- Kills dormant liver hypnozoites That is primaquine and tafenoquine.
A young man has pale, scaly macules on his chest and back that became obvious after sun exposure. KOH shows 'spaghetti and meatballs'. What is the first-line treatment?
Answer: Topical ketoconazole shampoo
Pityriasis versicolor is caused by Malassezia furfur, a lipophilic yeast; azelaic acid production inhibits melanocytes, so patches look pale on tanned skin. KOH shows short hyphae with spores (spaghetti and meatballs), and lesions may fluoresce yellow-green under Wood's lamp. Topical ketoconazole shampoo or selenium sulfide is first line; oral itraconazole or fluconazole for extensive disease. Pigment takes months to return; recurrence is common.
Pityriasis versicolor
- Malassezia yeast
- Pale patches after tanning
- KOH: spaghetti and meatballs
- Treat: ketoconazole, selenium sulfide
- Recurrence common
Remember Pale spots on a tanned back: Malassezia.
Exam trap Oral terbinafine does not work for Malassezia.
Why the other options are wrong
- Oral griseofulvin course Used for tinea capitis.
- Potent topical steroid Worsens fungal infection.
- Oral amoxicillin course Not a bacterial infection.
- Oral terbinafine course Works poorly orally for Malassezia.
A man with advanced HIV has painful swallowing and white plaques in the mouth. Endoscopy shows white plaques along the oesophagus. What is the treatment?
Answer: Oral fluconazole
Oesophageal candidiasis is an AIDS-defining illness, usually with a CD4 count under 200 cells/µL. Painful swallowing with oral thrush is enough to treat. Systemic therapy is needed: oral fluconazole for 2–3 weeks. Topical agents cannot reach the oesophagus well. Antiretroviral therapy should be started or optimised.
Oesophageal candidiasis
- AIDS-defining
- Odynophagia with oral thrush
- Treat with oral fluconazole
- Start ART
Remember Thrush plus painful swallowing: treat the oesophagus systemically.
Exam trap Failure to improve on fluconazole needs endoscopy for HSV, CMV or resistant Candida.
Why the other options are wrong
- Topical nystatin only Not enough for oesophageal disease.
- Oral aciclovir For herpes oesophagitis.
- Oral metronidazole Not antifungal.
- IV amphotericin as first choice Reserved for resistant or severe cases.
A hotel cook has no symptoms, but stool microscopy during a screening programme shows Entamoeba histolytica cysts. Which of the following is the most appropriate treatment?
Answer: Paromomycin
Metronidazole and tinidazole are absorbed in the upper gut, so they kill invasive trophozoites in the wall and liver but leave cysts in the lumen. A poorly absorbed luminal agent such as paromomycin or diloxanide furoate is needed to clear cysts and stop the person passing infection to others. Asymptomatic cyst passers should be treated, especially food handlers, and treatment of invasive disease is always completed with a luminal drug.
Amoebiasis drugs
- Metronidazole: invasive (tissue) disease
- Paromomycin/diloxanide: luminal cysts
- Always follow tissue treatment with a luminal drug
- Treat cyst passers, especially food handlers
Remember Clear the lumen or the infection returns.
Exam trap Entamoeba dispar looks identical on microscopy but does not invade; antigen or PCR tests tell them apart.
Why the other options are wrong
- Intravenous metronidazole Tissue drug; it does not clear luminal cysts, and IV is unnecessary.
- Oral prednisolone Steroids would risk invasive disease.
- Albendazole Albendazole is for nematodes, not amoebae.
- No treatment is needed Cyst passers, especially food handlers, should be treated.
Where this sits in the CPSP syllabus
- Paper 1: Chemotherapy, Antivirals, antifungals, antimalarials, antiprotozoals and anthelmintics
- Medicine & Allied, Paper 2: Antimicrobials, Antimalarials, antiamoebics and anthelmintics
- Medicine & Allied, Paper 2: Antimicrobials, Antivirals and antifungals
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