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104 Cards in this Set
- Front
- Back
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Characteristics of Latent TB
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No signs or symptoms
Patient feels normal TB cannot spread Positive skin or blood test Normal CXR Need tx to prevent progression |
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Characteristics of active TB
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Cough, fever, weight loss, night sweats
Patient feels ill Contagious Positive skin or blood test Abnormal CXR Need tx to cure disease |
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When can monotherapy be considered for TB tx?
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Only in latent dz
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Preferred agents for tx of latent TB
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Izoniazid (INH)- most preferred
Rifampin (RIF; Rifadin) Rifabutin (Micobutin) |
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MOA of Isoniazid
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Not clearly defined; thought to interfere with mycolic acid synthesis
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INH regimen for latent TB
(regimens given for other drugs but only need to know INH for quiz and test) |
Given Daily for 9 mo
(minimum doses: 270) *Preferred for all patients, should be used for HIV + patients, patients with fibrotic lesions on CXR, and children |
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Adverse drug reactions of Isoniazid
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Hepatotoxicity
Peripheral neuropathy CNS effects Lupus-like shyndrome Hypersensitivity |
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Drug interactions with isoniazid
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phenytoin,
carbamazepine, primidone, warfarin |
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Give pyridoxine 10-50 mg daily w/ isoniazid in what pts?
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pregnant, alcoholic, diabetic, and malnourished patients to decrease neuropathy
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MOA for Rifampin (RIF; Rifadin)
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Binds to DNA-dependent bacterial RNA polymerase, blocking RNA transcription and protein synthesis
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Rifampin adverse reactions
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Rash, GI, increased LFTs, CBC alterations, red-orange discoloration of urine, feces, saliva, sweat, tears, and CSF (universal effect).
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Drug interactions with Rifampin
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Drug interactions: Extensive; RIF is a potent CYP3A4 inducer (decreases concentration of many drugs,
including oral contraceptives and warfarin). |
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What do pts need to be aware of with Rifampin tx for latent tb?
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Patients should not wear soft contact lenses during therapy to avoid permanent discoloration
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MOA of Rifabutin
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Similar to Rifampin
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What is unique about Rifabutin
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less potent inducer of CYP3A4 and can be substituted in patients with significant drug interactions
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how often should HIV+ pts take latent tb meds?
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no less than every day
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When can RIF tx be used for Latent TB?
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INH resistsance or intolerance
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When should pts on latent TB tx be monitored?
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Monthly
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What are we monitoring for?
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adherence
s/sxs of possible adverse effects s/sxs of active dz |
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Close monitoring should be done on what pts? (pts with highest risk for adverse events and drug interactions)
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HIV+
Pregnant women Early post-partum women Pts with chronic liver dz who use alochol regularly |
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What tests should be done on pts most at risk for adverse events?
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Monthly liver function and bilirubin on pts with abnormal baseline transaminases
Pregnant pts Pts with a concern for liver damage (alcoholic pts) |
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When should discontinuation of INH be considered?
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If transaminases are 3-5x normal limit
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What do all pts receive for active TB? and why?
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multiple agents to combat resistance
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Who should be notified and involved in tx of all TB cases?
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Health Department
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Nonpharmacologic therapy for TB
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-prevention of TB spread
-replenishment of patient to normal weight and health -surgery to remove damaged tissue and lesions -infection control (i.e. isolation, respirators, and negative pressure rooms). |
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Goals of tx for Active TB
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Cure pt as quickly as possible
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How is the goal achieved?
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starting the patient on specific antimycobacterial treatment quickly,
resolving signs and symptoms, achieving a noninfectious state |
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What is required for goals to be reached?
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Pt adherence to the medication regimen
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Preferred agents for tx of active TB
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INH
RIF Pyrazinamide (PZA) Ethambutol (EMB) |
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MOA of Pyrazinamide (PZA)
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Exact mechanism not elucidated; greatest activity against dormant or semidormant organisms within macrophages or caseous foci
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Administration of PZA
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with or without food
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Adverse reactions w/ PZA
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GI, arthralgias (up to 40%), uric acid elevations, hepatotoxicity, photosensitive dermatitis
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Drug interactions w/ PZA
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few
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PZA contraindicated in what pts?
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Pts with gout
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MOA of Ethambutol
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Inhibits arabinosyl transferase leading to impaired mycobacterial cell wall synthesis
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Administration of Ethambutol
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with or without food
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Adverse reactions to Ethambutol (EMB)
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Retrobulbar neuritis – change in visual acuity, inability to see the color green
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Drug interactions with EMB
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no significant interactions
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All inital regimens for active TB tx have how many agents? and are use for how long?
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4
8 weeks |
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What is used to guide treatment selection?
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drug susceptibility testing on initial isolates
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If isolate is susceptible to INH, RIF, and PZA, what can be stopped and when?
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EMB can be stopped at any time
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Continuation phase of active TB tx begins when?
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after the initial 8 weeks of tx
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How many agents are usually used in continuation tx for active TB?
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2
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When INH and RIF cannot be used, how long is tx duration
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2 years
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Regimen 1 initial phase agents, interval and doses
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INH, RIF, PZA, & EMB
7 days/wk x 56 doses (8 wks) OR 5 days/wk x 40 doses (8 wks) |
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Regimen 1a continuation phase agents, interval and doses
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INH & RIF
7 days/wk x 126 doses (18 wks) OR 5 days/wk x 90 doses (18 wks) |
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Total # of doses with Regimen 1 and 1a
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Total doses: 130-182 (26wks)
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Regimen 1b agents, interval and doses
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INH & RIF
Twice weekly x 36 doses (18 wks) |
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Total doses with Regimen 1 and 1b
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76-92 (26wks)
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Initial phase Regimen 2 agents, interval and doses
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INH, RIF, PZA & EMB
7 days/wk x 14 doses (2 wks) then twice weekly x 12 doses (6 wks) OR 5 days/wk x 10 doses (2 wks) then twice weekly x 12 doses (6wks) |
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Continuation phase regiment 2a agents, interval and doses
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INH & RIF
Twice weekly x 36 doses (18 wks) |
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Total doses with active TB tx regiment 2 and 2a
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58-62 (26wks)
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When should regimens 1b and 2a be used in HIV+ pts?
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if CD4>100 cells/µL
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What regimens should be administered via DOT and which are always DOT?
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should be: 2-3 x weekly regimens
always: 5 day weekly regimens |
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A 7 mo continuation phase is required in what pts?
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1) Patients with cavitary pulmonary TB whose 2 month sputum culture is still positive
2) Patients treated with once-weekly INH and rifapentine whose 2 month sputum culture is still positive 3) Those who receive an initial phase consisting of RIF, INH, and EMB (no PZA) |
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2nd line agents used for resistant and multiple-drug resistant forms of TB
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1) Rifapentine (RPT). This is a once-weekly agent similar to RIF. It’s only appropriate in HIV negative patients, those without cavitary disease on initial CXR, those who have a 2 month sputum smear negative for AFB, and those with pulmonary disease.
2) Fluoroquinolones – levofloxacin, moxifloxacin 3) Aminoglycosides – streptomycin, kanamycin, amikacin 4) Cycloserine 5) Ethionamide 6) Capreomycin 7) P-aminosalicylic acid (PAS) |
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How to manage GI upset due to tx
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Take with food and/or at bedtime
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Mangement of minor ruritic rash due to tx
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antihistamines
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Petichial rash can indicate what?
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A petechial rash can indicate thrombocytopenia secondary to RIF.
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Generalized erythematous rash management due to tx
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If the patient experiences a generalized erythematous rash, especially with fever or mucous membrane involvement, all meds should be stopped and re-started sequentially to identify offending agent.
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Management of hepatitis due to tx
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Monitor LFTs; the patient may require treatment interruption if >3x ULN. Also watch for signs/symptoms of hepatitis (elevated LFTs or T. bili, fatigue, weakness, anorexia, nausea, jaundice).
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Patients no longer considered infectious if they meet ALL of the following criteria:
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1) Are on adequate therapy
2) Have had significant clinical response 3) Have had 3 consecutive negative sputum smears |
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Monitoring for active TB tx
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1) Smears and cultures
2) CMP/LFT/CBC at baseline and periodically throughout treatment 3) Audiometric testing at baseline and monthly for streptomycin patients 4) Vision testing on those receiving EMB 5) Test for HIV 6) Therapeutic drug monitoring for those suspected of drug absorption problems, MDR-TB, or drug interaction issues 7) MONITOR ADHERENCE AT EVERY CONTACT WITH PATIENT |
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For pts with AFB positive smears, whe should it be repeated? and for how long?
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For patients with AFB positive smears, the smear should be repeated every 1-2 weeks until there are 2 consecutive negative results.
-If they are still positive after 2 months of therapy, repeat susceptibility. -Once the patient is on maintenance therapy, cultures should be performed monthly until 2 negative cultures (2-3 months). |
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What to monitor for pts with negative pretreatment smears
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For patients with negative pretreatment smears, monitor chest x-ray.
If no improvement after 3 months, it is considered strong evidence that any abnormality seen was remnant of old (inactive) TB or other process. |
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What can you not use in HIV+ pts if CD4 counts <100
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twice-weekly therapy
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What continuation phase regimen is contraindicated in HIV+ pts?
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once weekly
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For those patients currently being treated with antiretrovirals, what should be used?
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rifabutin, a less potent inhibitor of CYP450, should be used in place of rifampin to decrease risk of virologic failure
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If pt is diagnosed with HIV and TB simultaneously, which tx should be initiated first? and why?
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TB should be initiated first, with the antiretroviral regimen beginning 2-4 weeks later
-This will prevent the patient from starting up to eight medications at once, with difficulty distinguishing causes of adverse events and drug interactions. |
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Tx regimen often extended to 9 mo in what populations?
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children and pregnant women
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Which first line agents are contraindicated in children?
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RPT and ethambutol
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Initial regimen for tx in pregnancy should include what drugs?
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INH, RIF, and EMB
There is little information about the safety of PZA during pregnancy. If resistance is likely, PZA use can be considered |
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When using INH in pregnancy, what else should be given?
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pyridoxine supplementation at a dose of 25 mg/day
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If necessary to use 2nd line agents in pregnancy, what should be avoided and why?
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aminoglycosides due to established fetal toxicity in studies with streptomycin; it can interfere with ear development and lead to congenital deafness
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exercise cautin in pregnancy with what drugs and why?
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ethionamide (premature delivery and congenital deformities) and fluoroquinolones (permanent cartilage damage in animals)
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Latent TB tx can be deferred until when in pregnancy?
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2nd trimester
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Are the antimycobacterial agents safe in breastfeeding?
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Yes. Most antimycobacterial agents are excreted in breast milk but appear to be safe.
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S/sx of hepatotoxicity from INH
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Abd pain, elevated LFTs, nausea, vomiting, loss of appetite, fatigue, dark colored urine
*Hepatotoxicity: AST > 3 times normal limit with symptoms or > 5 times normal limit without symptoms INH hepatotoxicty: 10-20% will have asymptomatic LFT increased, 1% will develop hepatitis • Pre-exisiting liver disease, elderly, post-partum, pregnant patients at increased risk, heavy alcohol use • Increased when combined with RIF • If baseline LFTs >6-8 times normal, INH should be avoided |
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s/sx of peripheral neuropathy from INH
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Tingling or burning in hands and feet, numbness, weakness
*** INH peripheral neuropathy - Dose related • Increased risk in patients predisposed to neuropathy, pyridoxine 25-50 mg/day recommended in these patients o DM o HIV o Renal failure o Alcoholism o Nutritional deficiency |
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s/sx of CNS effects from INH
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Difficulty speaking, irritability, seizures, dysphoria, and inability to concentrate
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s/sx of Lupus-like syndrome from INH and how common?
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Anti-nuclear antibodies, clinical lupus
20% develop antibodies, <1% develop clinical s/sx |
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s/sx of hypersensitivity to INH
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Fever, rash, Stevens-Johnson syndrome, hemolytic anemia
Rare |
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AEs of Rifampin
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Hepatotoxicity
Immunologic Reaction Flu-like Syndrome Red-orange Discoloration GI Skin Reactions |
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s/sx of Hepatotoxicity from RIF
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increased LFTs, hyperbilirubinemia, rare clinical hepatitis as above
*more common when used in combo (RIF+INH) |
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s/sx of immunologic reaction to RIF
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Thrombocytopenia, hemolytic anemia, acute renal failure
Rare |
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s/sx of Flu-like Syndrome with RIF and when is it more common?
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Fever, chills, sweats, aches
*More common with irregular administration |
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s/sx of Red-orange Discoloration with RIF
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Bodily fluids – sweat, tears, urine, sputum
Contact lenses can be permanently stained |
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GI s/sx with RIF
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Nausea, vomiting, diarrhea, loss of appetite, abd pain
Incidence variable |
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s/sx of Skin Reactions with RIF
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Pruritis, rash, hypersensitivity
Generally self-limiting, true hypersensitivity is rare |
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AEs of PZA
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Hepatotoxicity
GI Polyarthralgias Hyperuricemia Rash |
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s/sx of hepatotoxicity with PZA and when is it increased?
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Abd pain, increased LFTs, nausea, vomiting, loss of appetite, fatigue, dark colored urine
Increased at higher doses |
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GI s/sx with PZA and when is it increased?
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Nausea, vomiting, loss of appetite
Increased at higher doses |
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s/sx of polyarthralgias with PZA
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painful joints
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s/sx of hyperuricemia with PZA
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Usually asymptomatic, acute gouty arthritis
Acute gouty arthritis rare except in patients with preexisting gout (contraindication to use) |
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s/sx of rash with PZA
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Transient rash, photosensitivity
Generally self-limiting |
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AEs of ethambutol
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Retrobulbar Neuritis
Peripheral Neuritis Skin Reactions |
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s/s of retrobulbar neuritis with ethambutol and when is it increased?
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Decreased visual acuity, decreased red-green discrimination, blurred vision, eye pain
Increased at higher doses, increased with greater duration of therapy, unilateral or bilateral, not recommended in children unable to monitor |
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s/sx of peripheral neuritis with emthambutol
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Tingling or burning in hands and feet, numbness, weakness
Rare |
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s/sx of skin reactions with ethambutol
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rash
rare |
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AEs of Rifabutin
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Similar to Rifampin:
Polyarthralgias Hematologic Toxicity Uveitis |
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s/sx of polyarthralgias with rifabutin
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painful joints
1-2% of patients, increased with higher doses |
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s/sx of hematologic toxicity with rifabutin
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Neutropenia
Increased incidence with more frequent dosing |
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s/sx of uveitis with rifabutin and what increases risk?
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Hazy vision, floaters, decreased acuity
Increased risk with higher doses and when used in combination with macrolides |
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AEs of rifapentine
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similar to RIF
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