Antimycobacterials Flashcards
List the relevant/important antimycobacterials
Rifamycins (antibacterials) = rifampicin, rifabutin
Other = ethambutol, isoniazid, pyrazinamide, streptomycin
What does isoniazid target?
Targets mycolic acid
What does ethambutol target?
Arabinogalactan
What does pyrazinamide target?
short chain fatty acid precursors
What does Rifampicin target?
RNA polymerase (beta subunit)
What is the MOA of Rifampicin?
Inhibits DNA-dependent RNA polymerase –> inhibiting transcription of single stranded RNA into DNA
Reserved for MRSA and mycobacterial infections (also meningitis and epiglottitis
What are some ADRs of Rifamycin?
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
What are some allergic reactions to Rifampicin?
Rash, flu-like symptoms, haemolytic anaemia
Haemoglobulinaemia, acute renal failure
Risk = taking irregularly/intermittently, if restarted after interval w/out
What drugs interact w/ Rifampicin?
Induces CYP450
Reduces levels of = warfarin, theophylline, itraconazole, steroids, opioids, phenytoin, verapamil, contraception
Rifabutin has less interactions than rifampicin
What is the MOA of isoniazid?
Bacteriostatic against static bacteria
Bactericidal against actively dividing M/ tuberculosis
MOA: Reduces catalase-peroxidase –> inhibits synthesis of mycolic acid component of cell wall
What are the ADRs of isoniazid?
Hepatitis due to acetyl-hydrazine metabolite = fast or slow acetylation phenotypes
Peripheral neuropathy due to pyridoxine (B6) deficiency –> INH inactivates this vitamin
What drugs interact isoniazid?
Alcohol and rifampicin = inc risk of hepatotoxicity
Carbamazepine and phenytoin levels inc = INH is an enzyme inhibitor
Aluminium salts = INH is absorbed by them
What is the MOA/activity of pyrazinamide?
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
What are the ADRs of pyrazinamide?
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
Name some C/I for pyrazinamide use
Significant liver disease
Porphyria
What are some precautions for pyrazinamide use?
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
What are some signs of asymptomatic pyrazinamide hepatotoxicity?
syndrome of fever
anorexia
malaise
liver tenderness
hepatomegaly
splenomegaly
What are some signs of serious reaction associated with pyrazinamide?
Clinical jaundice
Massive hepatic necrosis
When should someone on pyrazinamide see a doctor?
Continuous nausea
Vomiting
unusual tiredness
yellowing of skin or sclera
dark urine
pale faeces
What class does ethambutol belong to and outline its indications?
Class = synthetic butanol derivative
Indication = mycobacterium tuberculosis, M. avium-intracellulare infections
What is the MOA and target of ethambutol?
Bacteriostatic against mycobacteria
Inhibit RNA synthesis, targeting arabinogalactan
Why is ethambutol not typically used in children?
Has a common side effect of optic neuritis
Children aren’t always able to voice changes in eye sight/vision
List some ADRs for ethambutol
Optic neuritis
headache, confusion, disorientation, hallucination, malaise, N/V, anorexia, abdominal pain
Jaundice, peripheral neuritis, hyperuricaemia, acute gout, neutropenia, renal failure, other blood dyscrasias
Describe the characteristics of ethambutol induced optic neuritis
Decreased visual acuity = usually reversible (if caught early)
Scotoma = blind spots in otherwise normal vision
Colour blindness
