Pharmacology of drugs used in the management of tuberculosis

Question 1

Describe when first line agents are used

Answer 1

Used in intensive phase. The aim is to rapidly kill tubercle bacilli. Infectious patients become less infectious within 10-14 days.

Continuation phase is to prevent relapse.

Question 2

Describe First Line Agents and which ones are used for Intensive and COntinuation phase

Answer 2

First-line agents
[HER-Z]
H-Isoniazid
R-Rifampicin
E-Ethambutol
Z-Pyraxinamide
Intensive Phase: HER-Z for 2 months
Continuation Phase: HR for 4 months

Daily dosing

Question 3

Describe Adult TB drug dosages

Answer 3

Isoniazid(H)- 5mg/kg
Rifampicin(R)-10mg/kg
Ethambutol(E)-15mg/kg
Pyrazinamide(Z)-25mg/kg

Question 4

Describe Children TB drug dosages

Answer 4

Isoniazid(H)-10mg/kg and max of 300
Rifampicin(R)-15mg/kg and max of 600
Ethambutol(E)-20mg/kg and max of 1200
Pyrazinamide(Z)-35mg/kg and max of 2000

Question 5

Describe what extrapulmonary TB is and its treatment duration.

Answer 5

TB meningitis, TB bones/jooints and Military TB

May need to increase continuation pahse to 7 months

Question 6

Describe the mech. of action of Isoniazid(H), Rifampicin(R), Ethambutol(E) and Pyrazinamide(Z)

Answer 6

Isoniazid(H)-Inhibits cell wall synthesis

Rifampicin(R)-Inhibits RNA synthesis

Ethambutol(E)-Inhibits cell wall synthesis

Pyrazinamide(Z)- Inhibtis cell wall synthesis

Question 7

Describe the target bacilli of essential TB drugs (HER-Z)

Answer 7

Isoniazid(H)- Rapid and intermediate growing bacilli
Rifampicin(R)-All populations
Ethambutol(E)-ALL populations
Pyrazinamide(Z)-Slow growing Bacilli

Question 8

Describe the adverse effects and their management of Isoniazid

Answer 8

Adverse Effects
1.Peripheral neuropathy
2.Hepatitis

Management
1. Give 50-75 pyridoxine daily to treat peripheral neuropathy

Question 9

Describe the adverse effects and their management of ***Rifampicin.

Answer 9

Adverse Effects and (-Management)
1. GIT disturbances- (Anti-emetic or Antacids)
2. Rash, Hypersensitivity reactions- (Antihistamine, check platelet count in petechial rash).
3. Red-orange colour of tears, urine and sweat- (will resolve when the drug is stopped)

Question 10

Describe the adverse effects and their management of Ethambutol

Answer 10

Ocular Toxicity: Optic Neuritis- Stop immediately

Hyperuricaemia, Joint Pain- treat symptomatically with NSAIDs.

Ethambutol is Contraindicated in pre-existing optic neuritis

Question 11

Describe the adverse effects and their management of pyrazinamide

Answer 11

1. Hepatoxicity
2. Hyperuricaemia, Joint pain- treat symptomatically with NSAIDs.

Question 12

Describe the Pharmacokinetics, Clinical uses and Drug interactions of Rifampicin.

Answer 12

Pharmacokinetics
1. Oral bioavialbitlity reduced by food
Indications
1. M. tuberculosis
2. Leprosy
3. Brucellosis
4. Resistant staphylococcal infections
Drug Interactions
Inducer of cyt p450, so the efficacy of the following drugs in decreased
1. Protease inhibitors(Lopinavir, Ritonavir, Atanazavir)
2. NNRTIs
3. Warfin
4. Combined oral contraceptive pill
5. Phenytoin
6. Floconazole
7. Oral Hypoglucaemics
8. Theophylline
9. Digoxin

Question 13

Describe the Indications of Rifabutin

this drug is related to Rifampicin

Answer 13

Related to Rifampicin

Indications
1. Used in patients co-infected with HIV on ART regimen receiving protease inhibitors
2. Prophylaxis in MAC

Question 14

Describe the Indications, Pharmacokineitcs and Drug interactions of Ethambutol.

Answer 14

Indications
Only used in Mycobacterial Infections
Pharmacokinetics
1. Crosses BBB in meningitis
Drugs Interactions
1. Diuretics
2. Neurotoxic Agents

Question 15

Describe the pahrmacokinetics and drug interactions of **Pyrazinamide

*pyrazinamide is a prodrug of pyrazinoic acid

Answer 15

Pharmacokinetics
1. Half-life: 9-10 hours
Drug Interactions
1. Inhibits Urate Clearance (elevations of serum urate)
2. Allopurinol
3. Probenecid
4. Diuretics

Question 16

Describe the clinical uses, MOA, rug interactions and resistance to the drug of Isoniazid

Answer 16

Clinical Uses
1. Mycobacterium Tuberculosis
2. Non-TB mycobacteria
3. Chemoprophylaxis TB

Mech. Of Action
Inhibits mycolic acid synthesis

Drug Interactions
Antacids decrease absoprtion
Inhibits cytochrome P450

Resistance
1. KatG
2. InhA mutations

Question 17

Describe management of TB and HIV co-infection.

Answer 17

ART should be started in all TB patients with HIV irregardless of their CD4 count
TB treatment is initiated first
co-trimoxazole prophylaxis
Rifampicin interacts with protease inhibitors
Either double dose the protease inhibitors or give rifabutin.

Question 18

Second Line Agents

Descrube the MOA, Adverse Effects and Metabolism of Bedaquiline

Answer 18

Mech. Of Action
Inhibits mycobacterial ATP synthase
Adverse Effects
1. QT prolongation
2. Nausea
3. Headachr
4. Arthralgia

Question 19

Second-line agents

Describe the MOA, Adverse Effects of Delaminid

Answer 19

Mech. Of Action
Inhibits Mycolic Acid Synthesis
Adverse Effects
1. QT prolongation
2. Peripheral Neuropathy

Question 20

Describe the side effects of second line agents

Answer 20

Levofloxacin: has less Qt interval effect than moxifloxacin
Linezolid: Has a risk of bone marrow suppression
Clofazimine: Well tolerated but sometimes causes skin to acquire a red-brown hue
Terizidone: A/E include neuropsychiatric side effects and peripheral neuropathy.
Ethionamide: Hepatitis, Hypothyroidism, CNS effects (seizures and depression)

Question 21

Believe in yourself

Answer 21

Believe in Yourself