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Pharmacology > Antituberculosis > Flashcards

Antituberculosis Flashcards

1
Q

TB?

A

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.

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2
Q

TB treatment schedule-drugs and duration ?

A

Intensive Phase
-Isoniazid, Rifampicin,
Pyrazinamide,
Ethabutamol (HRZE)
-2 months

Continuation phase
-Isoniazid & Rifampicin (HR)
-4 months

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3
Q

What is the most potent TB regime?

A

Isoniazid & Rifampicin
(HR) and hence taken throughout the course of treatment

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4
Q

Ethambutol Potency?

A

Low potency

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5
Q

Ethambutol resistance against drugs?

A

↓ development of drug resistance other agents

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6
Q

First line of drugs for the management of TB?

A

RIPE

  1. Isoniazid (INH)
  2. Rifampicin/ Rifabutin
  3. Ethambutol
  4. Pyrazinamide
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7
Q

Second line of drugs for the management of TB?

A

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

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8
Q

Isoniazid synonyms?

A

H OR INH

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9
Q

Isoniazid MOA and activation?

A

MOA:
Inhibits mycolic acid synthesis (Mycobacterial cell wall synthesis)

Activation:
Activated by Kat G (peroxidase)

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10
Q

What is the most virulent component of the mycobacterium bacteria?

A

Mycolic acid

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11
Q

Normal pathway synthesis of mycolic acid and the pharmacology pathway with INH?

A

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

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12
Q

Isoniazid bacteria MOA, type of bacteria and onset?

A

Bactericidal-rapid & intermediate growing bacilli

Within 24hrs

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13
Q

Isoniazid site of action and implication?

A

Intracellular & Extraceullar

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14
Q

INH metabolism ?

A

First pass metabolism-Acetylation

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15
Q

INH metabolism pathway?

A

INH →(N-actyltransferase) →Acetyl INH

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16
Q

INH differing acetylates?

A

Slow acetylators=Neuropathy

Fast acetylators=Hepatoxic

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17
Q

INH Acetyl-INH accumulation?

A

It is hepatotoxic

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18
Q

INH Neuropathy reversal?

A

Pyrudoxine

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19
Q

INH resistance-2?

A
  1. KAT G mutations-won’t be able activate INH
  2. InhA mutation-INH won’t be able to bind to InhA to exert effects
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20
Q

INH CYP450 and antacids?

A

CYP450 Inhibitor
Antacids ↓ absorption

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21
Q

Rifampicin CYP450?

A

CYP450 Inducer

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22
Q

Rifampicin MOA and binding site?

A

Inhibits RNA synthesis

Binds to β-unit of DNA-dependent RNA polymerase

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23
Q

Rifampicin resistance?

A

rpoβ mutations

24
Q

Rifampicin & protease inhibitors and solution-substantation?

A

Rifampicin(CYP450) ↓ concentration of protease inhibitors(M in liver)

Replace in HIV Immunotherapy with Rifabutin since it is a less CYP450 inducer then Rifampicin

25
Q

Rifampicin bacteria MOA ans site?

A

Bactericidal(intracelluar & extracellular)

26
Q

Which antituberculosis drug is the most sterilising agent and why?

A

Rifampicin since it works within an hour

27
Q

Rifampicin S/E?

A

-Red-orange discolouration of body fluids(urine, sweat, tears)

-Hepatitis

-Hypersensitivity

28
Q

Rifabutin CYP450 intensity?

A

-CYP450 Inducer
-Less potent inducer than Rifampicin
-Less effect on protease inhibitors ∴ Preffered in TB-HIV co-infectionj

29
Q

Rifabutin DOA and comparison?

A

Longer-acting than Rifampicin

30
Q

Ethambutol & CNS?

A

Crosses BBB in meningitis

31
Q

Ethambutol MOA?

A

Inhibits arabinosyl transferase
(Mycobacterial cell wall component synthesis enzyme)

32
Q

Ethambutol arabinosyl cell wall synthesis?

A

Arabinosyl transferase →Arabinogalactan synthesis → cell wall synthesis

Addition of Ethambutol:

Ethambutol→ ┴ Arabinosyl transferase →┴ Arabinogalactan synthesis → ┴ cell wall synthesis

33
Q

Ethambutol S/E?

A

Eyes-Ocular toxicity(optic neuritis)

Hyperuricemia & joint pain(Arthralgia)

33
Q

Ethambutol S/E?

A

Eyes-Ocular toxicity(optic neuritis)

Hyperuricemia & joint pain(Arthralgia)

34
Q

Ethambutol DI?

A

Diuretics ( ↑ uric acid)

Neurotoxic agents

35
Q

Pyrazinamide and CNS?

A

Distributed into the meninges

36
Q

Pyrazinamide pro-drug?

A

Pyrazinamide is the pro-drug ∴ converted into Pyrazinoic acid by mycobacterial pyrazinomidase

37
Q

Pyrazinamide MOA?

A

Inhibits cell wall synthesis

38
Q

Pyrazinamide bacteria MOA, site and pH?

A

Bactericidal , Intracellular & acidic medium

39
Q

Pyrazinamide S/E?

A

-Hepatotoxicty
-Hyperuricemia & joint paint

40
Q

Pyrazinamide DI?

A

PAD

-Probenecid(↑ t1/2)
-Allopurinol
-Diuretics

41
Q

Drug-induced hepatitis and TDM?

A

R.I.P-toxicity ↑

RIfampicin
Isoniazid
Pyrazinamide

monitor liver function every three days

42
Q

TB Chemoprophylaxis:

-Drug
-Duration
-Indications

A

Drug:
Isoniazid Prevention Therapy(IPT)

Duration:
6 months

Indication:
Children < 5yrs
HIV +ve children
HIV +ve & immunocompromised adults

43
Q

TB-HIV Co-infection

-Initiation of treatment
-ART
-Solution when CD4<50
-Prophylaxis
-Protease Inhibitors and solution

A

-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

44
Q

TB Pregnancy

-Regime
-Line of drugs
-Vaccine and admission
-Dosage during pregnancy

A

-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

45
Q

Bedaquiline MOA?

A

Inhibits mycobacterial ATP synthetase

46
Q

Bedaquiline S/E?

A

-QT-polongation
-Hepatotoxicty
-Arthralgia

47
Q

Delamanid MOA and usage in children 6-12 years?

A

Inhibits mycolic acid synthesis

Alternative in children 6-12 years

48
Q

Delamanid S/E?

A

-QT prolongation
-Peripheral neuropathyon

49
Q

Levofloxacin QT effect and intensity comparison?

A

↓ effect on QT interval than moxifloxacin

50
Q

What is the drug of choice that accomapnies Bedaquiline?

A

Levofloxacin

51
Q

Linezolid S/E?

A

Myelosuppression

52
Q

Clofazimine tolerance?

A

Well-tolerated

53
Q

Clofazimine S/E?

A

Red-brown discolouration of skin

Conjunctiva

Retina

Urine

54
Q

Terizidone S/E?

A

Neurological & Psychiatric disturbances (CNS)

Peripheral neuropathy

55
Q

p-amino-salicylic acid?

A

-Hypothyroidism
-Hepatitis

56
Q

Ethionamide S/E?

A

Hepatitis
Hypothrodism
CNS side effects

Pharmacology (44 decks)

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