Pharmacology chapters
Antituberculous, antifungal, antiviral and antimalarial drugs
The first-line TB drugs and their side effects, the standard 6-month regimen and drug-resistant TB; antifungals (azoles, amphotericin B, echinocandins, nystatin, griseofulvin, terbinafine); antivirals (aciclovir, oseltamivir, hepatitis B and C drugs, HIV antiretrovirals); and antimalarials (chloroquine, primaquine, artemisinins, quinine), with weight-based dosing worked out by hand.
- First-line TB drugs: isoniazid (peripheral neuropathy → give pyridoxine; hepatitis), rifampicin (orange-red urine and tears, hepatitis, powerful enzyme inducer), pyrazinamide (hepatotoxicity, gout) and ethambutol (optic neuritis: red-green colour vision); the standard regimen is 2 months HRZE then 4 months HR, given under supervision (DOTS).
- Antifungals: amphotericin B binds ergosterol (serious systemic fungal infections; nephrotoxicity, infusion reactions, hypokalaemia); azoles block ergosterol synthesis (fluconazole: candida, cryptococcus; CYP inhibition); echinocandins (caspofungin) block the cell wall; nystatin is topical/oral only; griseofulvin and terbinafine treat dermatophytes (nails).
- Antivirals: aciclovir (herpes simplex, varicella; activated by viral thymidine kinase), ganciclovir (CMV; marrow toxicity), oseltamivir (influenza, neuraminidase), tenofovir/entecavir (hepatitis B), sofosbuvir-based combinations (hepatitis C); antimalarials: chloroquine (P. vivax blood stage) + primaquine (kills liver hypnozoites: radical cure; check G6PD), artemisinin combinations (artemether-lumefantrine) for falciparum, IV artesunate for severe malaria.
On this page
Antituberculous drugs
TB is treated with combinations to prevent resistance, for a long time because mycobacteria grow slowly and some lie dormant.
First-line drugs
| Drug (letter) | Mechanism | Key adverse effects |
|---|---|---|
| Isoniazid (H) | Inhibits mycolic acid synthesis; bactericidal for dividing bacilli | Peripheral neuropathy (pyridoxine deficiency; prevent with pyridoxine, especially in malnutrition, HIV, diabetes, alcohol use, pregnancy), hepatitis (more with age and alcohol), drug-induced lupus, seizures in overdose; slow acetylators at higher risk of neuropathy; inhibits CYP (phenytoin levels rise) |
| Rifampicin (R) | Inhibits bacterial DNA-dependent RNA polymerase; bactericidal; kills slowly dividing bacilli | Orange-red urine, tears and sweat (stains contact lenses), hepatitis, flu-like syndrome, thrombocytopenia; potent enzyme inducer → reduces oral contraceptives, warfarin, steroids, antiretrovirals, antiepileptics |
| Pyrazinamide (Z) | Active in acid environments (inside macrophages); sterilising | Hepatotoxicity (most hepatotoxic of the first-line drugs), hyperuricaemia and gout, arthralgia |
| Ethambutol (E) | Inhibits arabinosyl transferase (cell wall); bacteriostatic | Optic neuritis: reduced acuity and red-green colour blindness (check vision; reduce dose in kidney impairment) |
| Streptomycin (S) | Aminoglycoside (30S) | Ototoxicity (vestibular), nephrotoxicity; injection; now mainly second-line |
H = neuropathy (pyridoxine), R = red secretions and inducer, Z = liver and gout, E = eyes.
Hepatotoxicity: H, R and Z can all cause hepatitis; ethambutol does not. Check liver tests in at-risk patients; stop drugs if jaundice or large enzyme rises, then reintroduce one at a time.
Regimen for drug-sensitive TB
2HRZE / 4HR: an intensive phase of 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol, then a continuation phase of 4 months of isoniazid and rifampicin, given as fixed-dose combinations, with supervision of treatment (DOTS) as used by Pakistan's National TB Control Programme. Longer courses are used for TB meningitis (with steroids) and bone TB.
Isoniazid 5 mg/kg (max 300 mg)
Rifampicin 10 mg/kg (max 600 mg)
Pyrazinamide 25 mg/kg
Ethambutol 15 mg/kg
50 kg adult:
H = 5 × 50 = 250 mg
R = 10 × 50 = 500 mg
Z = 25 × 50 = 1250 mg
E = 15 × 50 = 750 mg
In practice, fixed-dose combination tablets are given by weight band.
Doses follow WHO adult guidance; follow the national programme's weight-band tables.
Drug-resistant TB and prevention
- MDR-TB: resistant to isoniazid and rifampicin; detected rapidly by GeneXpert (rifampicin resistance). Treated with second-line regimens (for example bedaquiline, linezolid, levofloxacin or moxifloxacin, clofazimine, delamanid) under specialist programmes.
- Isoniazid preventive therapy (or rifapentine-based short courses) for close contacts (children under 5) and people with HIV and latent TB.
- BCG vaccine at birth protects children against severe forms (TB meningitis, miliary TB).
Leprosy: multidrug therapy with dapsone, rifampicin and clofazimine (red-brown skin discolouration). Dapsone causes haemolysis in G6PD deficiency.
Antifungal drugs
| Drug | Mechanism | Uses | Adverse effects |
|---|---|---|---|
| Amphotericin B | Binds ergosterol in fungal membranes → pores | Serious systemic fungal infections: cryptococcal meningitis (with flucytosine), invasive candidiasis and aspergillosis, mucormycosis, visceral leishmaniasis | Nephrotoxicity (reduced with lipid formulations and saline loading), hypokalaemia, hypomagnesaemia, fever and rigors during infusion, anaemia, thrombophlebitis |
| Azoles: fluconazole, itraconazole, voriconazole, posaconazole; topical clotrimazole, miconazole; ketoconazole (topical now) | Inhibit fungal cytochrome P450 (14α-demethylase) → less ergosterol synthesis | Fluconazole: candidiasis, cryptococcal maintenance; itraconazole: dermatophytes, histoplasmosis; voriconazole: aspergillosis | CYP inhibition (raise warfarin, statins, ciclosporin), liver toxicity, QT; ketoconazole: gynaecomastia and adrenal suppression (blocks steroid synthesis); voriconazole: visual disturbance |
| Echinocandins: caspofungin, micafungin | Inhibit β-glucan synthesis (cell wall) | Invasive candidiasis, aspergillosis (salvage) | Well tolerated; IV only |
| Nystatin | Polyene (like amphotericin); not absorbed | Oral and gut candidiasis (topical/oral suspension) | Minimal |
| Flucytosine | Converted to 5-fluorouracil in fungi | With amphotericin for cryptococcal meningitis | Marrow suppression |
| Griseofulvin | Binds microtubules; deposited in keratin | Dermatophyte infections of hair (tinea capitis) and skin | Enzyme inducer, headache, photosensitivity, teratogenic |
| Terbinafine | Inhibits squalene epoxidase | Onychomycosis (nail fungus), tinea | Liver toxicity, taste disturbance |
Antiviral drugs
| Drug | Mechanism | Uses | Adverse effects |
|---|---|---|---|
| Aciclovir, valaciclovir | Guanosine analogue; activated by viral thymidine kinase → inhibits viral DNA polymerase | Herpes simplex (encephalitis: IV), varicella-zoster (chickenpox, shingles) | Crystal nephropathy (hydrate), neurotoxicity; resistance through thymidine kinase loss |
| Ganciclovir, valganciclovir | Activated by viral kinase (UL97) | CMV (retinitis, transplant) | Marrow suppression (neutropenia) |
| Foscarnet | Directly inhibits viral DNA polymerase (no activation) | Resistant CMV and HSV | Nephrotoxicity, electrolyte disturbance (low calcium, magnesium) |
| Oseltamivir, zanamivir | Neuraminidase inhibitors (block release of new virions) | Influenza A and B; best within 48 hours of symptoms | Nausea; zanamivir: bronchospasm |
| Tenofovir, entecavir | Nucleos(t)ide analogues (reverse transcriptase/polymerase) | Chronic hepatitis B (tenofovir also HIV) | Tenofovir: kidney injury, bone loss |
| Sofosbuvir (+ daclatasvir or velpatasvir) | NS5B polymerase inhibitor (direct-acting antivirals) | Hepatitis C (cures most cases in 12 weeks); widely used in Pakistan's hepatitis C programmes | Bradycardia with amiodarone |
| Interferon-α | Immune modulation | Formerly hepatitis B and C | Flu-like illness, depression, marrow suppression |
Antiretroviral therapy (HIV)
Combination of three drugs (usually two NRTIs + an integrase inhibitor), started as soon as possible after diagnosis.
| Class | Examples | Notable adverse effects |
|---|---|---|
| NRTIs (nucleoside reverse transcriptase inhibitors) | Tenofovir, lamivudine, emtricitabine, zidovudine, abacavir | Zidovudine: anaemia, marrow suppression; abacavir: hypersensitivity (HLA-B*5701); lactic acidosis (older drugs) |
| NNRTIs | Efavirenz, nevirapine | Efavirenz: vivid dreams, CNS effects; nevirapine: rash, hepatotoxicity |
| Integrase inhibitors | Dolutegravir, raltegravir | Insomnia, weight gain; dolutegravir is in preferred first-line regimens (TLD: tenofovir, lamivudine, dolutegravir) |
| Protease inhibitors | Lopinavir/ritonavir, atazanavir, darunavir | Metabolic effects, CYP3A4 inhibition (ritonavir used as a booster); atazanavir: jaundice |
| Entry inhibitors | Maraviroc (CCR5), enfuvirtide | (none commonly tested) |
Prevention: post-exposure prophylaxis (within 72 hours), prevention of mother-to-child transmission, pre-exposure prophylaxis.
Antimalarial drugs
The malaria parasite has liver (including dormant hypnozoites in P. vivax and P. ovale) and blood stages. P. vivax is the commonest species in Pakistan; P. falciparum causes most severe disease.
| Drug | Acts on | Uses | Adverse effects |
|---|---|---|---|
| Chloroquine | Blood schizonts; blocks haem polymerisation in the parasite | P. vivax, P. ovale, P. malariae, sensitive falciparum (resistance widespread); also lupus and rheumatoid arthritis (hydroxychloroquine) | Itch (common in dark skin), gut upset, retinopathy (long-term), QT prolongation; dangerous in overdose |
| Primaquine (tafenoquine) | Liver hypnozoites and gametocytes | Radical cure of P. vivax/ovale (prevents relapse); single low dose to block falciparum transmission | Haemolysis in G6PD deficiency (test first), methaemoglobinaemia; avoid in pregnancy |
| Artemisinins (artemether, artesunate) | Blood schizonts (fast-acting; free radicals) | ACT (artemisinin-based combination therapy) such as artemether-lumefantrine for uncomplicated falciparum; IV artesunate for severe malaria (first choice) | Generally well tolerated; delayed haemolysis after IV artesunate |
| Quinine | Blood schizonts | Severe malaria if artesunate unavailable (with doxycycline or clindamycin) | Cinchonism (tinnitus, deafness, headache, blurred vision), hypoglycaemia (insulin release), QT prolongation, blackwater fever |
| Mefloquine | Blood schizonts | Prophylaxis and treatment | Neuropsychiatric effects (vivid dreams, psychosis) |
| Atovaquone-proguanil | Blood and liver schizonts | Prophylaxis and treatment | Gut upset |
| Doxycycline | Blood schizonts | Prophylaxis; adjunct to quinine | Photosensitivity, oesophagitis |
| Sulfadoxine-pyrimethamine | Folate synthesis | With artesunate in some ACTs; intermittent preventive treatment in pregnancy in Africa | SJS, folate deficiency |
Standard daily dose = 0.25 mg/kg (base) for 14 days
(0.5 mg/kg/day for 7 days in some regimens)
60 kg adult: 0.25 × 60 = 15 mg base daily × 14 days
Total course = 15 × 14 = 210 mg
Check G6PD first. In G6PD deficiency, a weekly regimen
of 0.75 mg/kg for 8 weeks may be used under supervision:
0.75 × 60 = 45 mg once weekly
Doses follow WHO malaria guidance; check the current national treatment guideline.
Expect: first-line TB drugs with mechanism and signature adverse effects (H neuropathy and pyridoxine, R orange secretions and enzyme induction, Z gout, E optic neuritis), 2HRZE/4HR, MDR-TB definition, amphotericin B mechanism and nephrotoxicity, azole interactions, griseofulvin and terbinafine for dermatophytes, aciclovir activation by thymidine kinase, ganciclovir for CMV, oseltamivir, hepatitis B and C drugs, antiretroviral classes, chloroquine for vivax, primaquine for radical cure and G6PD, ACT for falciparum, IV artesunate for severe malaria, quinine cinchonism and hypoglycaemia.
Quick revision
- H neuropathy (pyridoxine), R red secretions and inducer, Z liver and gout, E eyes.
- TB: 2HRZE/4HR; MDR-TB = H + R resistance.
- Amphotericin B: ergosterol pores; nephrotoxic. Azoles: block ergosterol synthesis; CYP inhibitors.
- Aciclovir: HSV, VZV. Ganciclovir: CMV. Oseltamivir: influenza.
- HBV: tenofovir, entecavir. HCV: sofosbuvir combinations.
- Vivax: chloroquine + primaquine (G6PD check). Falciparum: ACT. Severe: IV artesunate.
- Quinine: cinchonism, hypoglycaemia.
Written by The House Job from standard pharmacology and microbiology references (Katzung's Basic and Clinical Pharmacology; Levinson's Review of Medical Microbiology).
FAQ
Which anti-TB drug causes optic neuritis?
Ethambutol, which affects visual acuity and red-green colour vision.
Why is pyridoxine given with isoniazid?
Isoniazid causes pyridoxine (vitamin B6) deficiency, which leads to peripheral neuropathy; pyridoxine prevents it.
What is the role of primaquine in vivax malaria?
It kills the dormant liver hypnozoites, preventing relapses (radical cure); G6PD status must be checked first.
What is the main adverse effect of amphotericin B?
Kidney damage, along with low potassium and fever and rigors during infusion.