Antimicrobial mechanisms & toxicity — MRCP Part 1 flashcards

Question 1

Aminoglycosides and tetracyclines bind the ______ ribosomal subunit, whereas macrolides, clindamycin, linezolid and chloramphenicol bind the 50S subunit.

Accepted Answer

30S — Aminoglycosides cause misreading of mRNA (bactericidal); tetracyclines block aminoacyl-tRNA binding; macrolides and clindamycin block translocation; chloramphenicol inhibits peptidyl transferase.

Question 2

Aminoglycosides and tetracyclines bind the 30S ribosomal subunit, whereas macrolides, clindamycin, linezolid and chloramphenicol bind the ______ subunit.

Accepted Answer

50S — Aminoglycosides cause misreading of mRNA (bactericidal); tetracyclines block aminoacyl-tRNA binding; macrolides and clindamycin block translocation; chloramphenicol inhibits peptidyl transferase.

Question 3

What is the mechanism of action of quinolones such as ciprofloxacin?

Accepted Answer

Inhibition of bacterial DNA gyrase (topoisomerase II) and topoisomerase IV. — This stops bacterial DNA from being supercoiled and replicated.

Question 4

What is the mechanism of action of rifampicin?

Accepted Answer

Inhibits bacterial DNA-dependent RNA polymerase. — It blocks transcription. It is also a potent CYP450 inducer and turns urine and tears orange.

Question 5

Sulphonamides block bacterial folate synthesis by competing with ______, while trimethoprim inhibits dihydrofolate reductase.

Accepted Answer

PABA — Using both (co-trimoxazole) blocks two steps in the same pathway.

Question 6

Sulphonamides block bacterial folate synthesis by competing with PABA, while trimethoprim inhibits ______.

Accepted Answer

dihydrofolate reductase — Using both (co-trimoxazole) blocks two steps in the same pathway.

Question 7

What is the mechanism of action of vancomycin?

Accepted Answer

It binds the D-Ala-D-Ala terminus of cell wall precursors, inhibiting peptidoglycan (cell wall) synthesis. — It is a glycopeptide active against Gram-positive organisms, including MRSA.

Question 8

Name the two main dose-related toxicities of gentamicin.

Accepted Answer

Nephrotoxicity and ototoxicity (cochlear and vestibular). — Both relate to drug accumulation, which is why levels are monitored, especially in renal impairment.

Question 9

Which serious haematological adverse effect is associated with chloramphenicol?

Accepted Answer

Aplastic anaemia (bone marrow aplasia). — This is why systemic chloramphenicol is reserved for serious infections; eye drops are widely used.

Question 10

Which antibiotic is classically most associated with Clostridioides difficile diarrhoea?

Accepted Answer

Clindamycin. — Clindamycin disrupts the normal colonic flora; cephalosporins, quinolones and co-amoxiclav are also high-risk.

Question 11

Name two important adverse effects of erythromycin and clarithromycin.

Accepted Answer

QT prolongation and CYP450 (CYP3A4) inhibition, causing drug interactions (also GI upset). — Macrolides interact with statins, theophylline and warfarin. Azithromycin inhibits CYP3A4 much less.

Question 12

What important musculoskeletal adverse effect did the MHRA highlight for fluoroquinolones?

Accepted Answer

Tendinitis and tendon rupture (especially in older people and those taking corticosteroids). — Quinolones also lower the seizure threshold and prolong the QT interval; the MHRA warns of rare long-lasting, disabling effects.

Question 13

Why is aciclovir selectively active in virus-infected cells?

Accepted Answer

It must first be phosphorylated by viral thymidine kinase; the active form then inhibits viral DNA polymerase. — Uninfected cells do not activate it. Its main toxicity is nephrotoxicity (crystal nephropathy), so keep patients well hydrated.

Question 14

The main toxicity of ganciclovir is ______, whereas the main toxicity of foscarnet is nephrotoxicity.

Accepted Answer

myelosuppression — Both treat CMV. Foscarnet does not need viral kinase activation, so it works in aciclovir-resistant HSV; it can also cause seizures (via low calcium/magnesium).

Question 15

The main toxicity of ganciclovir is myelosuppression, whereas the main toxicity of foscarnet is ______.

Accepted Answer

nephrotoxicity — Both treat CMV. Foscarnet does not need viral kinase activation, so it works in aciclovir-resistant HSV; it can also cause seizures (via low calcium/magnesium).

Question 16

What is the main dose-related adverse effect of ribavirin?

Accepted Answer

Haemolytic anaemia. — Ribavirin accumulates in red cells. It is also teratogenic, so contraception is needed in both partners.

Question 17

What is the mechanism of action of oseltamivir?

Accepted Answer

Neuraminidase inhibitor — it stops release of new influenza virions from infected cells. — It is most effective when started within 48 hours of symptom onset; in severe or hospitalised influenza UKHSA still advises treatment after 48 hours (off-label).

Question 18

What is the mechanism of action of azole antifungals?

Accepted Answer

They inhibit ergosterol synthesis (fungal lanosterol 14-alpha-demethylase, a CYP450 enzyme). — Because they inhibit CYP450, azoles cause interactions (e.g. with warfarin, statins) and can cause hepatotoxicity.

Question 19

Name the electrolyte disturbances caused by amphotericin B.

Accepted Answer

Hypokalaemia and hypomagnesaemia (from renal tubular toxicity). — Amphotericin binds ergosterol in fungal membranes but also damages renal tubules; lipid formulations are less nephrotoxic.

Question 20

Terbinafine inhibits ______, whereas caspofungin (an echinocandin) inhibits beta-glucan synthesis in the fungal cell wall.

Accepted Answer

squalene epoxidase — Terbinafine is used for fungal nail infection; echinocandins are used for invasive Candida and Aspergillus.

Question 21

Terbinafine inhibits squalene epoxidase, whereas caspofungin (an echinocandin) inhibits ______ synthesis in the fungal cell wall.

Accepted Answer

beta-glucan — Terbinafine is used for fungal nail infection; echinocandins are used for invasive Candida and Aspergillus.

Antimicrobial mechanisms & toxicity flashcards

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