Antituberculosis Flashcards
TB?
Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis (M-TB), an acid-fast aerobic bacteria that can grow on gram stain as either gram-positive or gram-negative.
TB treatment schedule-drugs and duration ?
Intensive Phase
-Isoniazid, Rifampicin,
Pyrazinamide,
Ethabutamol (HRZE)
-2 months
Continuation phase
-Isoniazid & Rifampicin (HR)
-4 months
What is the most potent TB regime?
Isoniazid & Rifampicin
(HR) and hence taken throughout the course of treatment
Ethambutol Potency?
Low potency
Ethambutol resistance against drugs?
↓ development of drug resistance other agents
First line of drugs for the management of TB?
RIPE
- Isoniazid (INH)
- Rifampicin/ Rifabutin
- Ethambutol
- Pyrazinamide
Second line of drugs for the management of TB?
Group A-BLL
Bedaquiline
Linezolid
Levofloxacin/Moxifloxacin
Group B-CT
Clofazimine
Terizidone/Cycloserine
Group C-PIEDAEM
Pyrazinamide
High dose INH
Ethambutol
Delamanid
p-amino-salicylic acid
Amikacin/Streptomycin
Ethionamide
Meropenem
Isoniazid synonyms?
H OR INH
Isoniazid MOA and activation?
MOA:
Inhibits mycolic acid synthesis (Mycobacterial cell wall synthesis)
Activation:
Activated by Kat G (peroxidase)
What is the most virulent component of the mycobacterium bacteria?
Mycolic acid
Normal pathway synthesis of mycolic acid and the pharmacology pathway with INH?
Normal Pathway:
InhA →FAS-II →Mycolic → Cell wall synthesis
Pharmacotherapy-admin INH:
INH admin →INH activated by Kat G →ING inhibits InhA →Inhibits FAS-II synthesis →Inhibits Mycolic acid synthesis → Inhibits cell wall synthesis
Isoniazid bacteria MOA, type of bacteria and onset?
Bactericidal-rapid & intermediate growing bacilli
Within 24hrs
Isoniazid site of action and implication?
Intracellular & Extraceullar
INH metabolism ?
First pass metabolism-Acetylation
INH metabolism pathway?
INH →(N-actyltransferase) →Acetyl INH
INH differing acetylates?
Slow acetylators=Neuropathy
Fast acetylators=Hepatoxic
INH Acetyl-INH accumulation?
It is hepatotoxic
INH Neuropathy reversal?
Pyrudoxine
INH resistance-2?
- KAT G mutations-won’t be able activate INH
- InhA mutation-INH won’t be able to bind to InhA to exert effects
INH CYP450 and antacids?
CYP450 Inhibitor
Antacids ↓ absorption
Rifampicin CYP450?
CYP450 Inducer
Rifampicin MOA and binding site?
Inhibits RNA synthesis
Binds to β-unit of DNA-dependent RNA polymerase
Rifampicin resistance?
rpoβ mutations
Rifampicin & protease inhibitors and solution-substantation?
Rifampicin(CYP450) ↓ concentration of protease inhibitors(M in liver)
Replace in HIV Immunotherapy with Rifabutin since it is a less CYP450 inducer then Rifampicin
Rifampicin bacteria MOA ans site?
Bactericidal(intracelluar & extracellular)
Which antituberculosis drug is the most sterilising agent and why?
Rifampicin since it works within an hour
Rifampicin S/E?
-Red-orange discolouration of body fluids(urine, sweat, tears)
-Hepatitis
-Hypersensitivity
Rifabutin CYP450 intensity?
-CYP450 Inducer
-Less potent inducer than Rifampicin
-Less effect on protease inhibitors ∴ Preffered in TB-HIV co-infectionj
Rifabutin DOA and comparison?
Longer-acting than Rifampicin
Ethambutol & CNS?
Crosses BBB in meningitis
Ethambutol MOA?
Inhibits arabinosyl transferase
(Mycobacterial cell wall component synthesis enzyme)
Ethambutol arabinosyl cell wall synthesis?
Arabinosyl transferase →Arabinogalactan synthesis → cell wall synthesis
Addition of Ethambutol:
Ethambutol→ ┴ Arabinosyl transferase →┴ Arabinogalactan synthesis → ┴ cell wall synthesis
Ethambutol S/E?
Eyes-Ocular toxicity(optic neuritis)
Hyperuricemia & joint pain(Arthralgia)
Ethambutol S/E?
Eyes-Ocular toxicity(optic neuritis)
Hyperuricemia & joint pain(Arthralgia)
Ethambutol DI?
Diuretics ( ↑ uric acid)
Neurotoxic agents
Pyrazinamide and CNS?
Distributed into the meninges
Pyrazinamide pro-drug?
Pyrazinamide is the pro-drug ∴ converted into Pyrazinoic acid by mycobacterial pyrazinomidase
Pyrazinamide MOA?
Inhibits cell wall synthesis
Pyrazinamide bacteria MOA, site and pH?
Bactericidal , Intracellular & acidic medium
Pyrazinamide S/E?
-Hepatotoxicty
-Hyperuricemia & joint paint
Pyrazinamide DI?
PAD
-Probenecid(↑ t1/2)
-Allopurinol
-Diuretics
Drug-induced hepatitis and TDM?
R.I.P-toxicity ↑
RIfampicin
Isoniazid
Pyrazinamide
monitor liver function every three days
TB Chemoprophylaxis:
-Drug
-Duration
-Indications
Drug:
Isoniazid Prevention Therapy(IPT)
Duration:
6 months
Indication:
Children < 5yrs
HIV +ve children
HIV +ve & immunocompromised adults
TB-HIV Co-infection
-Initiation of treatment
-ART
-Solution when CD4<50
-Prophylaxis
-Protease Inhibitors and solution
-Initiation of treatment:
TB treatment intiated first
ART:
ART within 8 weeks
Solution when CD4<50:
If CD4<50, START art WITHIN 2 weeks
Prophylaxis:
Co-trimoxazole prophylaxis
Protease Inhibitors:
Rifampicin interacts with protease inhibitors therefore use Rifabutin
TB Pregnancy
-Regime
-Line of drugs
-Vaccine and admission
-Dosage during pregnancy
-Regime:
The standard daily 6-month
regime
-Line of drugs:
1st line drugs freely cross
the placenta & excreted in
breast milk
-Vaccine and admission:
BCG Vaccine-48hrs after completing treatment
-Dosage during pregnancy:
TB agents can be used
during pregnancy and
lactation, but maximum
doses should not be exceded
Bedaquiline MOA?
Inhibits mycobacterial ATP synthetase
Bedaquiline S/E?
-QT-polongation
-Hepatotoxicty
-Arthralgia
Delamanid MOA and usage in children 6-12 years?
Inhibits mycolic acid synthesis
Alternative in children 6-12 years
Delamanid S/E?
-QT prolongation
-Peripheral neuropathyon
Levofloxacin QT effect and intensity comparison?
↓ effect on QT interval than moxifloxacin
What is the drug of choice that accomapnies Bedaquiline?
Levofloxacin
Linezolid S/E?
Myelosuppression
Clofazimine tolerance?
Well-tolerated
Clofazimine S/E?
Red-brown discolouration of skin
Conjunctiva
Retina
Urine
Terizidone S/E?
Neurological & Psychiatric disturbances (CNS)
Peripheral neuropathy
p-amino-salicylic acid?
-Hypothyroidism
-Hepatitis
Ethionamide S/E?
Hepatitis
Hypothrodism
CNS side effects
