Antimycobacterials

Question 1

List the relevant/important antimycobacterials

Answer 1

Rifamycins (antibacterials) = rifampicin, rifabutin

Other = ethambutol, isoniazid, pyrazinamide, streptomycin

Question 2

What does isoniazid target?

Answer 2

Targets mycolic acid

Question 3

What does ethambutol target?

Answer 3

Arabinogalactan

Question 4

What does pyrazinamide target?

Answer 4

short chain fatty acid precursors

Question 5

What does Rifampicin target?

Answer 5

RNA polymerase (beta subunit)

Question 6

What is the MOA of Rifampicin?

Answer 6

Inhibits DNA-dependent RNA polymerase –> inhibiting transcription of single stranded RNA into DNA

Reserved for MRSA and mycobacterial infections (also meningitis and epiglottitis

Question 7

What are some ADRs of Rifamycin?

Answer 7

Flushing, itching = self limiting
Orange/red discolouration of tears, urine, saliva, sweat, soft contact lenses

Wheeze, cholestatic jaundice, hepatotoxicity (common among TB drugs), blood dyscrasias

Neurological symptoms, pseudomembranous colitis

Question 8

What are some allergic reactions to Rifampicin?

Answer 8

Rash, flu-like symptoms, haemolytic anaemia

Haemoglobulinaemia, acute renal failure

Risk = taking irregularly/intermittently, if restarted after interval w/out

Question 9

What drugs interact w/ Rifampicin?

Answer 9

Induces CYP450

Reduces levels of = warfarin, theophylline, itraconazole, steroids, opioids, phenytoin, verapamil, contraception

Rifabutin has less interactions than rifampicin

Question 10

What is the MOA of isoniazid?

Answer 10

Bacteriostatic against static bacteria
Bactericidal against actively dividing M/ tuberculosis

MOA: Reduces catalase-peroxidase –> inhibits synthesis of mycolic acid component of cell wall

Question 11

What are the ADRs of isoniazid?

Answer 11

Hepatitis due to acetyl-hydrazine metabolite = fast or slow acetylation phenotypes

Peripheral neuropathy due to pyridoxine (B6) deficiency –> INH inactivates this vitamin

Question 11

What drugs interact isoniazid?

Answer 11

Alcohol and rifampicin = inc risk of hepatotoxicity

Carbamazepine and phenytoin levels inc = INH is an enzyme inhibitor

Aluminium salts = INH is absorbed by them

Question 12

What is the MOA/activity of pyrazinamide?

Answer 12

Targets short-chain fatty acid precursors

Active against bacteria within macrophages

Bactericidal against M. tuberculosis in acid pH

Activity declines with time = pH inc as inflammation dec

Question 13

What are the ADRs of pyrazinamide?

Answer 13

Hyperuricaemia (competes w/ uric acid at PCT), polyarthralgia, nausea

Urticaria, itch, dysuria, hepatotoxicity, rash, allergic reactions

thrombocytopenia, acute porphyria crisis (can’t handle haem), acute gout

Question 14

Name some C/I for pyrazinamide use

Answer 14

Significant liver disease

Porphyria

Question 15

What are some precautions for pyrazinamide use?

Answer 15

Gout = pyrazinamide inhibits renal excretion of urate –> raises uric acid levels

Renal impairment = avoid in moderate/severe impairment –> accumulation of uric acid crystals

Diabetes = management becomes difficult

Question 16

What are some signs of asymptomatic pyrazinamide hepatotoxicity?

Answer 16

syndrome of fever

anorexia

malaise

liver tenderness

hepatomegaly

splenomegaly

Question 17

What are some signs of serious reaction associated with pyrazinamide?

Answer 17

Clinical jaundice

Massive hepatic necrosis

Question 18

When should someone on pyrazinamide see a doctor?

Answer 18

Continuous nausea

Vomiting

unusual tiredness

yellowing of skin or sclera

dark urine

pale faeces

Question 19

What class does ethambutol belong to and outline its indications?

Answer 19

Class = synthetic butanol derivative

Indication = mycobacterium tuberculosis, M. avium-intracellulare infections

Question 20

What is the MOA and target of ethambutol?

Answer 20

Bacteriostatic against mycobacteria

Inhibit RNA synthesis, targeting arabinogalactan

Question 21

Why is ethambutol not typically used in children?

Answer 21

Has a common side effect of optic neuritis

Children aren’t always able to voice changes in eye sight/vision

Question 22

List some ADRs for ethambutol

Answer 22

Optic neuritis

headache, confusion, disorientation, hallucination, malaise, N/V, anorexia, abdominal pain

Jaundice, peripheral neuritis, hyperuricaemia, acute gout, neutropenia, renal failure, other blood dyscrasias

Question 23

Describe the characteristics of ethambutol induced optic neuritis

Answer 23

Decreased visual acuity = usually reversible (if caught early)

Scotoma = blind spots in otherwise normal vision

Colour blindness