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Respiratory Block: Pharmacology > Treatment of TB > Flashcards

Treatment of TB Flashcards

(98 cards)

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1
Q

What are the 4 first line agents in the treatment of TB?

A
  1. Rifampicin - R
  2. Isoniazid - H
  3. Ethambutol - E
  4. Pyrazinamide - Z
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2
Q

What is considered the intensive phase of first line TB treatment?

A

Rifampicin + Isoniazid + Ethambutol + Pyrazinamide for 2 months

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3
Q

What is considered the continuation phase of first line TB treatment?

A

Isoniazid + Rifampicin for 4 months

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4
Q

What occurs during the intensive phase of treatment?

A

The intensive phase is to rapidly kill tubercle bacilli
Infectious patients become less infectious within 10-14 days
- Majority will become smear negative within 2 months

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5
Q

Who is first line TB treatment given to?

A

New patients that haven’t come into contact with resistant TB patients

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6
Q

What are the 2 main principles of TB treatment?

A
  1. Multi-drug therapy

2. Daily dosing

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7
Q

What are some of the extra-pulmonary TB types commonly seen?

A

TB meningitis, TB bones / joints, miliary TB

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8
Q

What is considered the intensive phase of extra-pulmonary TB treatment?

A

Rifampicin + Isoniazid + Ethambutol + Pyrazinamide for 2 months

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9
Q

What is considered the continuation phase of extra-pulmonary TB treatment?

A

Isoniazid + Rifampicin for 7 months

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10
Q

What is the mechanism of action of Isoniazid?

A

Inhibits cell wall synthesis - inhibits mycolic acid synthesis (mycobacterial cell wall component)

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11
Q

What is the mechanism of action of Ethambutol?

A

Inhibits cell wall synthesis - inhibits formation of mycobacterial cell wall by inhibiting arabinosyl transferase

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12
Q

What is the mechanism of action of Rifampicin?

A

Inhibits RNA synthesis - binds to the beta-unit of DNA dependent RNA polymerase

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13
Q

What is the mechanism of action of Pyrazinamide?

A

Exact target unclear (no known MOA)

  • disrupts plasma membranes
  • disrupts energy metabolism
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14
Q

How are doses calculated?

A

By weight

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15
Q

What is the main drug property of Isoniazid?

A

Bactericidal after 24 hours

- high potency: kills >90% bacilli in the first few days of treatment

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16
Q

What is the main drug property of Rifampicin?

A

Bactericidal within 1 hour

- high potency

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17
Q

What is the main drug property of Pyrazinamide?

A

Bactericidal with a low potency.

- Achieves its sterilizing action within 2-3 months

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18
Q

What is the main drug property of Ethambutol?

A

Bacteriostatic, low potency

- Minimizes the emergence of drug resistance

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19
Q

What are the target bacilli of Isoniazid?

A

Rapid and intermediate growing bacilli

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20
Q

What are the target bacilli of Rifampicin?

A

All populations including dormant bacilli

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21
Q

What are the target bacilli of Pyrazinamide?

A

Slow growing bacilli

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22
Q

What are the target bacilli of Ethambutol?

A

All bacterial populations

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23
Q

In what pH does Isoniazid work?

A

Alkaline and acid media

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24
Q

In what pH does Rifampicin work?

A

Alkaline and acid media

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25
In what pH does Pyrazinamide work?
Acid medium
26
In what pH does Ethambutol work?
Alkaline and acid media
27
What is the site of action of Isoniazid?
Intracellular and extracellular
28
What is the site of action of Rifampicin?
Intracellular and extracellular
29
What is the site of action of Pyrazinamide?
Intracellular bacilli only macrophage
30
What is the site of action of Ethambutol?
Intracellular and extracellular
31
What form is Isoniazid given?
It is a given as a pro-drug and activated by mycobacterial KatG
32
What are the clinical uses of Isoniazid?
- Mycobacterium Tuberculosis treatment - Non-tuberculosis mycobacteria - Chemoprophylaxis of TB
33
What are the pharmacokinetics of isoniazid?
Undergoes first pass metabolism largely by acetylation
34
What drug interactions are seen with Isoniazid?
- antacids decrease absorption | - inhibits cytochrome P450 (increases plasma concentration of phenytoin / carbamazepine, warfarin)
35
How does resistance to Isoniazid develop?
KatG / InhA mutations
36
What are the pharmacokinetics of Rifampicin?
- highly protein bound - half life: 2-5 hours - rapid metabolism in liver (autoinduction, enterohepatic circulation)
37
What are the clinical uses of Rifampicin?
- Mycobacterium tuberculosis - Non-tuberculosis mycobacteria - Leprosy, brucellosis, resistant staphylococcal infections
38
How does Rifampicin resistance develop?
Mutations in rpoB (beta subunit of RNA polymerase)
39
What drug interactions are seen with Rifampicin?
Inducer of CYTP450 enzymes: protease inhibitors, NNRTIs, warfarin, combined oral contraceptive, phenytoin, fluconazole, oral hypoglycaemics, theophylline, digoxin = decreased efficacy of these drugs
40
What is important about the drug interactions with Rifampicin in HIV positive patients?
Rifampicin is a CYP450 inducer | = must exclude protease inhibitors if haven't yet started ARVs
41
What is Rifabutin?
Related to Rifampicin, but a less potent inducer of CYTP450
42
What is Rifabutin used for?
Used in patients co-infected with HIV on ART regimen receiving protease inhibitors - also used as prophylaxis in MAC
43
What is ethambutol used for?
Only used in mycobacterial infections | - crosses BBB in meningitis
44
What conversion of Pyrazinamide takes place?
Converted to pyrazinoic acid by mycobacterium pyrazinamidase
45
What is the action of Pyrazinamide on mycobacterium?
Bactericidal for intracellular mycobacterium in acidic medium
46
What is Pyrazinamide used for?
Used for the treatment of Mycobacterium infections (TB) | - distributed widely, including meninges
47
What are the common adverse effects of Isoniazid?
- peripheral neuropathy | - hepatitis
48
How is Isoniazid peripheral neuropathy managed?
Give 10-25mg pyridoxine daily
49
How is Isoniazid hepatitis managed?
Stop treatment | Do liver function tests
50
What are the common adverse effects of Rifampicin?
- GIT disturbances - Rash, hypersensitivity reactions - Hepatitis - Red / orange color of fluids - tears, urine, sweat
51
How can Rifampicin GIT disturbances be managed?
Give anti-emetic, antacid (time antacid with isoniazid so as not to prevent absorption)
52
What is the hepatotoxicity of Rifampicin?
Least hepatotoxic of the TB medications | - hepatotoxicity uncommon unless alcoholic or history of liver disease
53
What are the common adverse effects of Ethambutol?
- ocular toxicity: optic neuritis | - hyperuricaemia, joint pain
54
In what condition is Ethambutol contraindicated?
C/I: in pre-existing optic neuritis
55
What are the common adverse effects of Pyrazinamide?
- Hepatotoxicity (hepatitis, liver damage) | - Hyperuricaemia, joint pain
56
What is the hepatotoxicity of Pyrazinamide?
Most hepatotoxic
57
How should Pyrazinamide hepatotoxicity be managed?
Stop treatment | Do liver function tests - ALT
58
Which first line agents cause drug induced hepatitis?
Pyrazinamide, Isoniazid, Rifampicin
59
Which second line agents cause drug induced hepatitis?
Ethionamide / prothionamide, PAS
60
When should drug induced hepatitis be suspected?
Suspected when: 1. ALT >3 times the upper limit of normal (with symptoms) OR 2. ALT >5 times the upper limit of normal (no symptoms)
61
What should be done if drug induced hepatitis is suspected?
1. Exclude other causes: viral hepatitis, alcohol consumption, other drugs 2. Stop the hepatotoxic drugs 3. Monitor ALT levels
62
What should ALT levels be?
<100IU/l
63
How should re-introduction of drugs be done if drugs are stopped due to drug induced hepatitis?
Re-introduce: Rifampicin - Isoniazid - Ethambutol - Pyrazinamide - Monitor liver function (ALT every 3 days)
64
Which of the first line TB agents is not hepatotoxic?
Ethambutol
65
What is given for TB prophylaxis?
Isoniazid for 6 months
66
Who should Isoniazid prophylaxis be given to?
- Children <5 years - HIV positive children - Adults: HIV positive and immunocompromised
67
What are the ART guidelines for TB & HIV?
ART should be started in all TB patients living with HIV regardless of their CD4 count - TB treatment initiated first - ART within 8 weeks - If CD4 <50: start ART within 2 weeks
68
What is an important drug interaction in TB and HIV?
Rifampicin interacts with protease inhibitors
69
What additional prophylaxis should be given to TB & HIV patients?
Co-trimoxazole prophylaxis
70
What should be done for TB in pregnant women?
Should be treated promptly with standard daily 6 month regimen
71
What is the risk of TB drugs to the unborn fetus?
The first line drugs freely cross the placenta | Risk-benefit weigh up
72
What is the risk of hepatitis in pregnant women on TB treatment?
Risk of Isoniazid induced hepatitis is 2.5 times higher in pregnant women than non-pregnant
73
What should be done for breastfeeding mothers with TB?
Mothers should be encouraged to breastfeed | - if mother is infectious - use surgical masks
74
What is multi-drug resistant TB?
Resistant to Rifampicin and Isoniazid
75
What is extensively drug resistant TB?
MDR-TB + resistance to a fluoroquinolone + resistance to an injectable
76
What are the 4 groups of second line agents used in treating resistant TB?
1. Fluoroquinolones 2. Injectables 3. Other core 2nd line agents 4. Add-on agents
77
Which fluoroquinolone is the most commonly used in treating resistant TB?
Moxifloxacin
78
Which fluoroquinolone is the most commonly used in treating children with resistant TB?
Levofloxacin
79
How long is the course of treatment for MDR TB?
Shortened MDR TB regimen 9-12 months (vs. previously 18-24 months)
80
What is the intensive phase of MDR TB treatment?
4-6 months: | Km-Mfx-Eto-Cfz-Z-Hh-E
81
What is the continuation phase of MDR TB treatment?
5 months | Mfx-Cfz-Z-E
82
What should be tested for in treating MDR TB?
Test resistance / susceptibility to Fluoroquinolones & 2nd line injectables - If resistance: use conventional MDR-TB regimen (at least 5 drugs)
83
How should MDR TB be treated in pregnancy?
C/I: Ethionamide / pth & injectables
84
What are the two new TB drugs available?
1. Bedaquiline | 2. Delamanid
85
Who is Bedaquiline given to?
Only adult patients >18 years | - MDR / Pre-XDR TB / XDR
86
What is the half life of Bedaquiline?
Very long! = 5.5 months | - Only given for the first 24 weeks of treatment due to this
87
How is Bedaquiline metabolized?
Hepatically
88
What are the side effects of Bedaquiline?
QT prolongation, hepatotoxic
89
What is Delamanid used to treat?
MDR / XDR / patients with HIV (no D/I) | >18 years of age
90
What is the main adverse effect of Delamanid?
QT prolongation
91
What is the most common related SE of Bedaquiline?
QT prolongation
92
What is the most common related SE of Delamanid?
- QT prolongation | - Peripheral neuropathy
93
What is the most common related SE of Clofazimine?
Pink to brown discoloration of skin, cornea, retina, urine
94
What is the most common related SE of Cycloserine / Terizidone?
Neurological & psychiatric disturbances
95
What is the most common related SE of PAS?
- GIT disturbance | - Hypothyroidism
96
What is the most common related SE of Thioacetazone
- Steven-Johnson syndrome | - Toxic epidermal necrolysis (C:I HIV)
97
What is the most common related SE of Aminoglycosides?
Hearing loss, vestibular toxicity, nephrotoxicity, electrolyte disturbance
98
What is the most common related SE of Ethionamide / prothionamide?
Hepatitis / hypothyroidism

Respiratory Block: Pharmacology (8 decks)

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