Pharmacology · Short notes

Antimicrobial Agents: Short Notes & Cheat Sheet

Mechanisms, spectra and signature toxicities of antibacterial, anti-TB, antifungal, antiviral, antimalarial and anthelmintic drugs.

Short notes

Read these before you attempt the topic's MCQs.

Group antibiotics by their target: learn the target once and the mechanism MCQs for the whole class follow.

β-lactams bind penicillin-binding proteins (transpeptidases) and are bactericidal. Clavulanic acid, sulbactam and tazobactam protect them from β-lactamases.
Penicillin G is given IV because stomach acid destroys it; penicillin V is taken orally. Benzathine penicillin treats syphilis and prevents recurrence of rheumatic fever.
Cloxacillin, dicloxacillin and nafcillin resist penicillinase and are used for staphylococci. Amoxicillin causes a rash in infectious mononucleosis. Piperacillin covers Pseudomonas.
Probenecid prolongs penicillin's action by blocking its tubular secretion.
Cephalosporins by generation: 1st cefazolin (surgical prophylaxis); 3rd ceftriaxone (meningitis, gonorrhoea, typhoid), ceftazidime (Pseudomonas) and cefixime (oral); 4th cefepime; 5th ceftaroline (MRSA). None of them cover enterococci or Listeria.
Imipenem is given with cilastatin (which blocks renal dehydropeptidase) and can cause seizures. Ertapenem does not cover Pseudomonas. Aztreonam covers only Gram-negatives and is safe in penicillin allergy.
Vancomycin binds D-Ala-D-Ala. It is used for MRSA, and orally for C. difficile. Infusing it too fast causes red man syndrome. It is nephrotoxic and ototoxic, so trough levels are monitored.

Aminoglycosides (gentamicin, amikacin, streptomycin) bind the 30S subunit and are bactericidal and concentration-dependent, with a post-antibiotic effect. They cause kidney damage, irreversible ototoxicity and neuromuscular blockade, and do not work against anaerobes.
Tetracyclines (doxycycline) bind the 30S subunit. They chelate calcium, iron and antacids, stain teeth, and are avoided in children under 8 and in pregnancy. They cause photosensitivity.
Macrolides bind the 50S subunit. Erythromycin inhibits CYP3A4, prolongs QT and stimulates gut motility. Azithromycin has a long half-life and few interactions. Clarithromycin is used for H. pylori.
Chloramphenicol can cause grey baby syndrome and aplastic anaemia.
Clindamycin covers anaerobes and carries the highest risk of C. difficile colitis.
Linezolid is used for VRE and MRSA. It is a weak MAO inhibitor (serotonin syndrome risk) and causes thrombocytopenia.

Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) inhibit DNA gyrase and topoisomerase IV. They can cause tendon rupture, prolong QT, and are avoided in children and pregnancy. Ciprofloxacin raises theophylline levels.
Metronidazole treats anaerobes, Giardia, amoebiasis, Trichomonas and C. difficile. It causes a metallic taste and a disulfiram-like reaction with alcohol.
Sulfonamides block dihydropteroate synthase; trimethoprim blocks dihydrofolate reductase. Together (co-trimoxazole) they are used to treat and prevent Pneumocystis pneumonia and for UTIs.
Sulfonamides cause SJS, crystalluria, haemolysis in G6PD deficiency, and kernicterus in newborns.

Drug-sensitive TB is treated as 2HRZE/4HR (6 months). Rifampicin turns secretions orange and is a strong enzyme inducer. Isoniazid causes neuropathy (prevented with pyridoxine) and hepatitis. Pyrazinamide causes hyperuricaemia. Ethambutol causes optic neuritis and red-green colour blindness.
Amphotericin B binds ergosterol and forms pores. It is nephrotoxic, causes low K+ and Mg2+, and causes infusion reactions. The liposomal form is less toxic.
Azoles inhibit 14α-demethylase. Ketoconazole strongly inhibits CYP3A4 and causes gynaecomastia. Fluconazole reaches the CSF. Voriconazole is used for Aspergillus.
Other antifungals: caspofungin (β-glucan synthesis), terbinafine (squalene epoxidase; nail infections), griseofulvin (enzyme inducer, teratogen).
Acyclovir needs viral thymidine kinase to be activated and can crystallise in the kidneys. Ganciclovir treats CMV and suppresses bone marrow. Oseltamivir works best within 48 hours of flu symptoms.
Hepatitis C (common in Pakistan): sofosbuvir (NS5B polymerase inhibitor) combined with daclatasvir or velpatasvir (NS5A inhibitors). Hepatitis B: tenofovir or entecavir.
HIV: abacavir requires HLA-B*5701 screening first; zidovudine suppresses bone marrow; ritonavir is used as a CYP3A4-inhibiting booster; dolutegravir is an integrase inhibitor.

Chloroquine treats the blood stage of P. vivax. Long-term use causes retinopathy, and P. falciparum is widely resistant.
Primaquine kills the liver hypnozoites of vivax and ovale (radical cure). It causes haemolysis in G6PD deficiency, so test first.
Artemisinin-based combination therapy (e.g. artemether–lumefantrine) is first-line for uncomplicated falciparum malaria. IV artesunate treats severe malaria.
Quinine causes cinchonism and hypoglycaemia. Mefloquine causes neuropsychiatric effects.
Albendazole and mebendazole bind β-tubulin. Ivermectin treats strongyloides and scabies. Praziquantel treats tapeworms and schistosomiasis. Pyrantel causes spastic paralysis of worms. Diethylcarbamazine treats filariasis.

High-yield facts in one place. Cover the right-hand column and test yourself.

Target	Drugs
Cell wall (PBPs)	Penicillins, cephalosporins, carbapenems, aztreonam
Cell wall (D-Ala-D-Ala)	Vancomycin, teicoplanin
30S ribosome	Aminoglycosides, tetracyclines
50S ribosome	Macrolides, chloramphenicol, clindamycin, linezolid
DNA gyrase / topo IV	Fluoroquinolones
RNA polymerase	Rifampicin
Folate pathway	Sulfonamides, trimethoprim
Ergosterol (binds)	Amphotericin B, nystatin
Ergosterol synthesis	Azoles, terbinafine
Mycolic acid	Isoniazid

Drug	Remember
Aminoglycosides	Nephro- and ototoxicity, NM blockade
Vancomycin	Red man syndrome
Tetracyclines	Teeth staining, photosensitivity, chelation
Chloramphenicol	Grey baby, aplastic anaemia
Clindamycin	Pseudomembranous colitis
Fluoroquinolones	Tendon rupture, QT prolongation
Metronidazole	Disulfiram reaction, metallic taste
Isoniazid	Neuropathy (give B6), hepatitis
Ethambutol	Optic neuritis
Rifampicin	Orange secretions, enzyme induction
Amphotericin B	Nephrotoxicity, ↓K+ ↓Mg2+
Primaquine	Haemolysis in G6PD deficiency

Buy AT 30, CCEL at 50: 30S: Aminoglycosides, Tetracyclines. 50S: Chloramphenicol, Clindamycin, Erythromycin (macrolides), Linezolid.
RIPE: First-line TB drugs: Rifampicin, Isoniazid, Pyrazinamide, Ethambutol.
Cephalosporins miss LAME organisms: Listeria, Atypicals, MRSA (except ceftaroline), Enterococci.

Aminoglycosides need oxygen to enter bacteria, so they do not work against anaerobes.
Doxycycline is cleared mainly in the faeces, so it is the tetracycline that is safe in renal failure.
Ceftriaxone should not be given with calcium-containing IV fluids in neonates.
Ertapenem, unlike imipenem and meropenem, does not cover Pseudomonas.
Rifampicin reduces the effect of oral contraceptives, warfarin and many antiretrovirals.

Attempt the Antimicrobial Agents MCQs while the notes are fresh. Anything you get wrong is saved to your incorrect list for the next revision round.