1
Q
The most prevalent communicable infectious disease on earth and remains a leading infectious killer globally
A
Tuberculosis (TB)
2
Q
Is mycobacteria fast or slow growing?
A
Slow growing
3
Q
A
4
Q
A
5
Q
Once infected w/ M. tuberculosis, a person’s lifetime risk of active TB is approximately ___%
A
10
6
Q
- What are the 2 most important drugs in tx of TB?
- Which age groups have a 2-5X greater risk for active disease compared w/ other age groups?
A
- Isoniazid & Rifampin
- <2y/o and >65y/o
7
Q
____ should be used whenever possible to reduce tx failures and the selection of drug-resistant isolates
A
Directly Observed Treatment (DOT)
8
Q
TB is more common in which 5 groups of people?
A
- Prison inmates
- IV drug abusers
- Immigrants
- HIV infected pts*
- Young minority adults
9
Q
Sxs of TB
A
General ROS:
- Fatigue
- Fever
- Weight loss
- Night sweats
- Productive cough
10
Q
- 2 or more antimicrobials are used in the tx of _____.
- Generally, __ drugs are given at the outset of tx
- Which 2 drugs are the best for preventing drug resistance
A
Active tuberculosis
4
Rifampin & Isoniazid
11
Q
What are the 4 drugs used in Tx of Active TB in order of preference?
A
- Isoniazid
- Rifampin
- Pyrazinamide
- Ethambutol
(IRPE)
12
Q
- Monotherapy can be used only for infected pts who _____.
- Combination therapy is required for treating ____.
A
- do not have active TB (latent infection)
- Active TB (at least 2 drugs)
13
Q
Regimens for treating TB:
- Intensive phase is ___months
- Continuation phase of either ___ or ___ months
(total of __ to ____ months of tx)
A
- 2
- 4 - 7
- 6 - 9
14
Q
Which 2 TB meds are weight based?
A
- Pyrazinamide
- Ethambutol
15
Q
Drugs given in:
- Initial Phase:
- Continuation Phase:
A
- Initial: all 4 - Isoniazid, Rifampin, pyrazinamide, ethambutol
- Continuation: Isoniazid & Rifampin
(Have best results in HIV patients + or -)
16
Q
Which 2 drugs need to be adjusted for renal function? Why?
A
- Pyrazinamide
- Ethambutol
(they are weight based)
17
Q
What is the tx for Latent TB?
Is latent or active more common?
A
- Isoniazid (6 or 9 months)
- Isoniazid & Rifampin (3 months)
- Rifampin (4 months)
Latent
18
Q
- Does a pt w/ latent TB have active disease and are able to trasmit it to others?
- In what type of pt does latent TB become active?
A
- no!
- Immunocompromised
19
Q
Which TB drug?
- Inhibits cell wall synthesis
A
- Isoniazid
- Ethambutol
20
Q
Which TB drug?
- Inhibits RNA synthesis
A
Rifampin
21
Q
Which TB drug?
- Exact target is unclear
- Disrupts Plasma Membrane
- Disrupts Energy Metabolism
A
Pyrazinamide
22
Q
What is the 1st line tx for Active AND Latent TB?
A
Isoniazid
23
Q
Which drug?
- Inhibits synthesis of mycolic acids, an essential component of mycobacterial cell walls
- First-line for active and latent TB
- PK: Hepatic clearance
A
Isoniazid
(1st line for active/latent TB)
24
Q
What are the 2 ADEs of Isoniazid?
A
- Hepatic toxicity
- Peripheral neuropathy : VIt B6-pyridoxine
25
**Which drug?**
* Turns body fluids orange
* Inhibits DNA-dependent RNA polymerase (Blocking production of RNA)
* First-line for active and latent TB
Rifampin
26
Rifampin can be used for what other 3 infections?
* Atypical mycobacterial infections
* eradication of meningococcal colonization
* Staphylococcal infections
27
**Which drug?**
* **PK:** hepatic clearance & CYP inducer
* **ADEs:**
* turns body fluids orange color\*\*
* Cholestasis (hepatitis\*\*)
* Rash
* Flu like syndrome w/ intermittent dosing
* Thrombocytopenia (bruising/bleeding)
* Nephritis\*\*
Rifampin
28
**Which drug?**
* Used for disseminated M. avium infection in AIDS pts and is quite active against M. tuberculosis
* Most rifampin resistant organisms are resistant to this drug
* Less potent enzyme inducer than rifampin, it may be used for pts who are receiving protease inhibitors
* For HIV-positive pts, the ATS/CDC recommends regimens with 3 or more doses of the TB drugs / week
Rifabutin
29
**Which drug?**
* A long-acting rifamycin that can be used once weekly in the continuation phase of treatment (after the first 2 months) in carefully selected HIV-negative patients
* Approximately as potent an enzyme inducer as rifampin
similar drug interactions are likely
Rifapentine
30
**Which drug?**
* a sterilizing agent prescribed during the first 2 months of therapy
* Mechanism not fully understood
* Possibly disrupts plasma membrane
* Possibly energy metabolism
* _Because it is a "sterilizing" agent the total duration of therapy for TB to be shortened to 6 months\*\*_
Pyrazinamide
31
**Which drug?**
* Hepatic clearance, metabolites renally cleared-reduced dose if \<30mlmin clearance
* **ADE:**
* hepatotoxicity
* hyperuricemia\*\*\*
* rash
* GI disturbance
* arthralgias (don't give acetaminophen bc/ hepatotoxic.)
Pyrazinamide
32
\_\_\_\_\_ is given until drug sensitivities are known
* **Inhibits** mycobacterial arabinosyl transferases, which are involved in the polymerization rxn of arabinoglycan, an essential component of the **mycobacterial cell wall**
Ethambutol
33
**Which drug?**
* Given in four drug initial combination therapy for tuberculosis until drug sensitivities are known
* Hepatic & Renal clearance, dose reduction in renal failure
Ethambutol
34
What are the ADEs of Ethambutol?\*\*
* Retrobulbar neuritis (reversible if drug stopped)
35
**Multiple Drug Resistant - TB**
* Caused by organisms that are resistant to at least ___ of the best anti-TB drugs: Isoniazid & Rifampin
2
36
**Which drug?**
* The first drug in a new class of anti-TB meds to be approved in more than 40 yrs
* Inhibits the proton transfer chain of mycobacterial ATP synthase required for energy generation of M. tuberculosis
* **Box warning:**
* increased mortality
* QT prolongation \>500ms (get EKG before giving this drug)
Bedaquiniline
37
MDR TB (multiple drug resistant) can take up to __ months to cure.
24
38
**Bedaquiline monitoring:**
* How often should you monitor for sxs: N, HA, hemoptysis, CP, joint pain, rash
* ECG before start of tx and repeat when?
* Monitor for ___ related adverse drug rxns w/ serum transaminases
* ____ drug monitoring should be considered in pts w/ severe renal impairment & when given w/ other drugs that induce/suppress the cytochrome P450 system
* once a week
* 2, 12, and 24 weeks after tx started
* liver-related
* Therapeutic drug monitoring
39
5 second line TB meds
* Streptomycin
* Capreomycin
* Amikacin/kanamycin
* Moxifloxacin
* p-Aminosalicylic acid
(SCAMP)
40
**Which "other" med?**
## Footnote
* Injectable agent given intramuscularly in doses of 15–30 mg/kg/day (maximal dose 1 g)
* Major toxicities include ototoxicity (both vestibular and cochlear) and nephrotoxicity
* If the medication must be used in older patients, the dose should not exceed 750 mg
•Capreomycin
41
**Which "other" med?**
## Footnote
* A phenazine dye used in the treatment of leprosy
* Active in vitro against M avium complex and Mycobacterium tuberculosis
* Given orally as a single daily dose of 100 mg for treatment of M avium complex disease
* Clinical efficacy for the therapy of tuberculosis has not been established.
* Adverse effects include nausea, vomiting, abdominal pain, and skin discoloration
•Clofazimine
42
**Which "other" med?**
## Footnote
* A bacteriostatic agent, is given in doses of 15–20 mg/kg (not to exceed 1 g) orally
* Used in re-treatment regimens and for primary therapy of highly resistant M tuberculosis
* Can induce a variety of central nervous system dysfunctions and psychotic reactions.
•Cycloserine
43
**Which "other" med?**
## Footnote
* Like cycloserine, bacteriostatic, given orally in a dose of 15–20 mg/kg (maximal dose 1 g)
* Used in combination therapy but is poorly tolerated with marked gastric irritation
•Ethionamide
44
**Which "other" med?**
## Footnote
* Particularly moxifloxacin
* Active in vitro against M tuberculosis, with MICs of 0.25–2 mcg/mL
* These medications demonstrated to be efficacious in treating tuberculosis in patients unable to take isoniazid, rifampin, and pyrazinamide
* Rapid emergence of resistance has been described in some series
* Combination of 6 months of the long-acting rifamycin, rifapentine, in combination with moxifloxacin, is as effective as standard therapy in the treatment of tuberculosis
•Fluoroquinolones
45
**Which "other" med?**
## Footnote
* effective in achieving culture conversion in patients with treatment-refractory, highly resistant pulmonary tuberculosis
* Long-term use of this agent for tuberculosis is associated with significant side effects, particularly the 600 mg daily dose
•Linezolid
46
**ADE of which drug?**
* Asymptomatic elevation of aminotransferases
* Clinical hepatitis / Fatal hepatitis
* Peripheral neurotoxicity / CNS effects
* Lupus-like syndrome
* Hypersensitivity
* Monoamine poisoning
* Diarrhea
Isoniazid
47
**ADE of which drug?**
* Cutaneous rxns
* GI rxns (N, anorexia, abd pain)
* Flu-like syndrome
* Hepatotoxicity
* Severe immunologic rxns
* Orange discoloration of bodily fluids (sputum, urine, sweat, tears)
* Drug interactions due to induction of hepatic microsomal enzymes
Rifampin
48
**ADE of which drug?**
* Hepatotoxicity
* GI sxs (N/V)
* Non-gouty polyarthralgia
* Asymptomatic hyperuricemia
* Acute gouty arthritis
* Transient morbilliform rash
* Dermatitis
Pyrazinamide
49
**ADE of which drug?**
* Retrobulbar neuritis
* Peripheral neuritis
* Cutaneous rxns
Ethambutol
50
**Monitoring of which drug?**
* LFT monthly in patients who have preexisting liver disease or who develop abnormal liver function that does not require discontinuation of drug; dosage adjustments may be necessary in patients receiving anticonvulsants or warfarin
Isoniazid
51
**Monitoring of which drug?**
* Liver enzymes and interacting drugs as needed (eg, warfarin)
Rifampin
52
**Monitoring of which drug?**
* Serum uric acid can serve as a surrogate marker for adherence; LFTs in patients with underlying liver disease
Pyrazinamide
53
**Monitoring of which drug?**
* Baseline visual acuity testing and testing of color discrimination; monthly testing of visual acuity and color discrimination in patients taking \>15–20 mg/kg, having renal insufficiency, or receiving the drug for \>2 months
Ethambutol
