What is BCG also used for?
To treat bladder cancer
What are the risk factors for TB?
- Prison (crowded conditions)
- Immigrant from high burden country
- Debilitating illness
- Certain diseases: DM, Hodgkin lymphoma, CKD, malnutrition, immunosuppression
1. RA on TNF alpha antagonists
What are the basic TB tx regimens (chart: preferred and alternatives)?
- Summary: 2-4 drugs taken for at least 26 weeks on different dosing schedules
- NOTE: a continuation phase of once-weekly INH/RPT can be used for HIV- patients who do NOT have cavities on chest film AND who have (-) acid-fast bacilli (AFB) smears at the completion of the initial phase
What is this?
- MTB acid-fast stain
- Acid fast bacillus, obligate aerobe
1. Ability to retain carbolfuchsin stain due to high lipid content in waxy cell wall (mycolic acid)
2. Grows very slowly (doubling time of 18 hours)
- Cultures held for 6-8 weeks before being finalized
- Stained poorly by the dyes used in gram stain
What are the 2 main side effects for INH?
- Neuropathy for slow acetylators
- Hepatotoxicity for fast acetylators
What is the MOA of Ethambutol?
- Inhibition of RNA synthesis
- Disrupts cell wall synthesis: INH arabinosyl transferase -> mycolic acids usually attach to 5'-hydroxyl groups of D-arabinose residues of arabinogalactan and form mycolyl-arabinogalactyl-peptidoglycan complex in cell wall
1. Disrupts arabinogalactan synthesis (necessary for synthesis of peptidoglycan units of cell wall)
2. Results in increased cell wall permeability
- Static effect: possible -cidal at high levels
- Bacilli must be actively dividing
- Slow devo of resistance; no cross resistance
What are the first-line and alternative agents for treating TB?
1. Isoniazid (INH) + Rifampin (RIF) + Pyrazinamide (PZA) + Ethambutol (EMB) or Streptomycin
1. Ofloxacin; cycloserine; capreomycin; kanamycin; amikacin; ethionamide; clofazimine; para-aminosalicyclic acid
- NOTE: in HIV+, Rifabutin (instead of Rifampin) can DEC drug interaxns w/PI's and NNRTI's
Why is the IGRA test important?
- IFN-gamma assay (IGRA) can be used for diagnosis of TB, and is specific only to MTB
- Will also not get a false (+) for people who have received the BCG vaccine
What is the difference between TB infection and active disease?
- Most infections acquired from active case to susceptible host – this is primary infection
- In most cases, primary infections are asymptomatic (only 5% develop clinically significant disease -> peeps with impaired cell-mediated immunity)
1. Only evidence of infection is fibrocalcific nodule at site of infection
2. Viable organisms can remain dormant for years and reactivate to produce 2o infection (active disease)
3. 2o infection usually involves apices of lungs -> cavitation occurs frequently
4. Erosion of cavities into airway is source of infection –> person is expectorating organisms
What are some of the new TB drugs in devo (image)?
Probably don't need to know these
How is TB related to HIV?
- All stages of HIV associated w/INC risk of TB, even with HAART -> but, low CD4 count important risk factor
- Variable pulmonary manifestations (see attached image; others with bilateral infiltrates, pleural effusion)
1. Increased frequency of false negative sputum smears, absence of granulomas in tissues -> may see TB infection in the lower lobes of the lungs
- Cavitation/bronchial damage more severe in immuno-competent individuals due to robust immune response
1. With reduced immune response as in HIV, there is no bronchial damage and few AFB in sputum
What are the AE's of Isoniazid?
- Peripheral neuropathy: dose-relsated burning, prickling sensation in hands and feet (stocking-glove)
1. Competition bt INH and pyridoxal phosphate -> corrected w/Vit. B6 supplementation (10-50mg daily)
2. More freq. in malnourished, diabetics, and alcoholics
- Hepatotoxicity: dose-related
1. Major toxic rxn (hepatitis) in 2% due to toxic metabolite from acetylation of INH
2. INC liver enzymes in up to 20% of pts (caution if admin w/other hepatotoxic drugs, like RIF)
- Allergic rxns: not dose-related
Why is TB difficult to diagnose in HIV+ patients?
- Not as much expectoration of bacteria (can’t rely as much on these tests)
- PPD may be (-) because the patient’s immune system is so compromised
Briefly describe the MOA's of the 4 first-line anti-TB drugs (image).
- Isoniazid: inhibits cell wall synthesis
- Ethambutol: inhibits cell wall synthesis
- Pyrazinimide: exact target unclear, but 1) disrupts plasma membrane and 2) disrupts energy metabolism
- Rifampin: inhibits RNA synthesis
What is the critical cytokine for the control of TB?
- TNF from macros is critical to help control TB infection (this is why RA pts on TNF-alpha inhibitors are at an increased risk)
- TNF is important to keep granulomas from falling apart
1. IFN-gamma also critical because if you have mutations in this receptor, you won't form granulomas at all
What are the treatment options for latent TB infection? Which tx is more frequently completed?
- 3-mo tx with INH-RPT with DOT is effective and more frequently completed than US standard of INH w/o DOT
- NOTE: due to reports of severe liver injury and death, the CDC recommends that the combo of RIF and PZA should generally NOT be offered for tx of latent TB infection
What are the MOA, resistance, and spectrum of Rifampin?
- MOA: inhibition of RNA synthesis via binding of beta subunit of the Mb RNA polymerase (mammalian RNA polymerase not as sensitive, so unaffected except at supra-clinical doses)
- Resistance: DNA-dependent RNA polymerase does not bind drug (becoming widespread)
1. Never give as a single agent bc resistance emerges rapidly
- Spectrum: IC and EC mycobacteria
- NOTE: RIF is the most commonly used of the Rafamycins
What is resistant TB? What is the main risk factor?
- MDR TB: resistance to INH and RIF most common -> AIDS patients
- XDR TB: resistance to INH, RIF, flouroquinolone, at least one additional drug
1. Emerged in 2005 in south Africa.
- Noncompliance is risk factor for devo of resistance
1. Directly observed therapy (DOT) is used in Shelby County and many other places to prevent this
What should you do before treating patients for latent TB?
Make sure patients do not have active disease -> get a CXR
What are some of the clinical manifestations of miliary/disseminated TB? CXR?
- Lymphohematogenous dissemination following 1o inf can result in miliary/disseminated TB (HIV patients at high risk)
- CXR can look like a bunch of seeds all over (millet seeds)
1. Dyspnea, cough
- Other organ involvement: liver (RUQ pain, nausea and vomiting), bone marrow, spleen
1. Meningitis, Pott’s disease (vertebral osteomyelitis), GI (nausea/vomiting/diarrha), urinary tract (sterile pyuria, hematuria, proteinuria)
2. Adrenal insufficiency, epididymitis (highly convoluted duct behind the testis, along which sperm passes to the vas deferens), prostatitis
How is Isoniazid absorbed, distributed, metabolized, and excreted?
- Absorption: rapidly from GI tract with oral dose, or IM
- Distribution: all tissues and fluids
1. W/inflamed meninges, therapeutic levels in CSF
2. Crosses placenta; distributed in breast milk
- Metabolism: acetylated via N-acetyl transferase
1. 2-3x lower plasma conc in fast acetylators vs. slow (half-lives vary from 1-4 hours)
2. Chronic liver disease affects metabolism (DEC dose)
3. Induces CYP -> can influence concurrent CYP substrate therapy
- Excretion: drug, inactive metabolites (75%) out in urine
How do you diagnose latent TB?
- PPD (purified protein derivative): intradermal injection of tuberculin material stimulates delayed-type hypersensitivity rxn mediated by T lymphos -> induration in 48-72 hours
1. BCG immunization can cause false (+) test -> wanes over time and clinically ignore the fact that someone got the BCG (adults at least; up to 20% will still be (+) 10 yrs or more from time of vaccination)
2. Infection with nontuberculous mycobacteria can also cause false positive results
- IGRA (Quantiferon gold, Quan-TB, T-spot): blood cells from the pt exposed to Ags from MTB -> amt of IFN-gamma released from cells is measured
1. No false positives with BCG or NTM infections
- HIV+ patients: false negatives in both tests can occur due to lack of immune response, sometimes called anergy
How are Rifabutine and RPT related to RIF?
- Rifabutine and RPT are derivatives of RIF
1. Rifabutine: 2. RPT: longer half-life than Rifabutine and RIF, so it can be given only once weekly (intermediate to RIF and Rifabutine as a CYP inducer)
2. RPT: longer half-life than Rifabutine and RIF, so it can be given only once weekly (intermediate to RIF and Rifabutine as a CYP inducer)
What is the main toxicity associated with Ethambutol?
What are some of the possible clinical manifestations of TB (image)?
How do you treat TB?
- Secondary/primary pulmonary TB
1. If suspicion is high, don't wait for confirmed dx -> start treatment
2. 4-drug treatment required initially:
a. INH, Rifampin, Pyrazinimide, Ethambutol (RIPE)
b. Once susceptibility is known, and if susceptible, can stop Ethambutol
c. After 2 months of RIPE/RIP, can stop PZA and continue INH/Rifampin for 4-7 more months to complete 6-9 months of therapy
- Miliary TB: 9-12 months -> all 4 drugs
What are the first-line and alternative treatments for M. Avium complex?
- First-line: Clarithromycin + Ethambutol or Clofazimine or Ciprofloxacin or Amikacin
- Alternative: Rifabutin; Rifampin (RIF); Ethionamide; Cycloserine; Imipenem; Azithromycin
What are the most common symptoms with primary TB infection?
In most cases, primary infection is asymptomatic
What is the resistance to Isoniazid?
- When used alone, resistant organisms rapidly emerge, so used in combo (1 in 106 orgs have naturally occurring resistance to INH -> about 100 orgs on day 1 of tx -> about the same for PZA and EMB; 1 in 108 for RIF)
- Resistance mechanisms:
1. Inability to take up the drug
2. Alteration in the target enzyme
3. Overproduction of the target enzyme
What is the treatment for latent TB?
- Isoniazid for 9 months
- Isoniazid and Rifapentine for 3 months
What is the MOA of Pyrazinomide?
- Exact MOA unkown
- Bacilli convert pyrazinomide to pyrazinoic acid (POA)
- DEC pH below threshold for growth
- Resistant strains may lack the pyrazinamidase
- Cidal or static depending on conc in infected site
- Most active against tubercle bacilli in acid envo of lysosome and macro -> IC site w/slow replication
What is the likelihood of getting TB on a plane?
- Likelihood of other passengers on plane getting TB actually very low due to the high rate of air exchange on the plane
1. Passed more by contact than aerosol transmission on a plane
What is PknG?
- MTB can grow intracellularly in macros -> effective means of evading the immune system
1. Ab's and complement are ineffective
- Once MTB is phagocytosed, it can inhibit phagosome-lysosome fusion via the protein PknG (see attached image)
How do you diagnose TB?
- Acid fast stain on sputum initial test (see attached image) -> culture should be done at the same time
1. Lowenstein-Jensen agar required -> substances to enrich growth and inhibit other flora
2. 3-6 wks to grow on solid agar (doubling time 18 hrs)
3. Will not grow on blood agar
- Culture in liquid media can show results in 2 weeks
- PCR, or nucleic acid amplification even more rapid
1. Better on smear-positive specimens (initially sputum will come back smear-positive or negative)
When is Cycloserine used? What is its MOA?
- Broad spectrum, second-line agent
1. Active pulm and extra-pulm TB -> only used when others fail, and in re-treatment (i.e., MDR-TB)
2. Used for M. Avium complex when others don't work
3. UTI's (seldom used clinically)
- MOA: structural analog of D-alanine; blocks cell wall syn
1. Can block enzymes (via competitive INH) required for D-alanine incorporation into pentapeptide of peptidoglycan strands (give wall rigid mech stability): L-alanine racemase and D-alanine synthetase
2. Based on conc at site (and bac susceptibility), will be static or cidal
3. Effective in resistant orgs -> NO cross resistance
What is latent TB infection?
- MTB infection is contained initially and infection remains in a prolonged, suppressed state of “latency"
- Latent infection has the potential to develop into active infection at any time -> identification and treatment of LTBI protects the health of the individual and the public
- Overall, w/o treatment, about 5 to 10% of infected persons will develop TB disease at some time in their lives
1. About half of those people who develop TB will do so in the first two years of infection
2. For persons whose immune systems are weak, esp. those with HIV infection, risk of devo TB disease is considerably higher than for peeps with normal immune systems
What can't you have when you are on INH?
Can’t drink alcohol when you are on INH
Sorry, no shots of tequila
How can we prevent TB?
- Prompt ID and adequate treatment immediately
- Use masks and respiratory isolation
- Treat latent converters
- Screen: HIV infected, close contacts of pt with TB, low-income populations, alcoholics and IVDU, prison inmates, foreign born from countries with high incidence
What is this?
What should you give with INH? Why?
- Add B6 to INH
- To prevent peripheral neuropathy
What is the ADME of Cycloserine?
- Absorption: administered orally w/good absorption
- Distribution: distributed widely and NOT protein bound
1. Lungs, pleural, and synovial fluid
2. CSF conc uninflamed meninges: 50-80% (with inflamed, 80-100% of serum conc)
3. Rapidly crosses placenta; distributed in amniotic fluid and breast milk
- Excretion: excreted unchanged by renal mech; dose adjustment required for renal impairment
What is the MOA of Isoniazid?
- Interferes with mycolic acid synthesis -> disrupts cell wall synthesis
1. Cidal for rapidly dividing bacilli -> EC cavitary lesions
2. Static for slow-growing -> closed caseous lesions and macros
- Penetrates host cells, so effective for IC bacilli
What is the ADME of Pyrazinamide?
- Absorption: well absorbed from GI tract after oral admin, and peak serum levels w/in 2 hours
- Distribution: widely distributed -> therapeutic in CSF w/inflamed meninges
1. Distributes into breast milk, but unknown if crosses into placenta
- Metabolism: hydrolyzed in the liver to pyrazinoic acid, its major metabolite, then to hydroxyl-pyrazinoic acid, the main excretory compound
- Excretion: Pyrazinamide and its metabolites are excreted in the urine (70%), primarily via glomerular filtration -> dose adjustment is recommended in severe renal dysfunction
What is MDR-TB? What are the possible effective treatments?
- MDR TB is a form of drug-resistant TB in which TB bacteria can no longer be killed by at least the two best antibiotics, isoniazid (INH) and rifampin (RIF), most commonly used to cure TB
- As a result, this form of the disease is more difficult to treat than ordinary TB and requires up to 2 additional drugs?
What are the AE's of Cycloserine?
- Involve CNS: usually reversible w/discontinued therapy
1. Headache, tremor, vertigo, confusion, psychotic states w/suicidal tendencies, paranoid reactions, seizures
2. Contraindicated in peeps w/history of epilepsy
- Symptoms generally appear w/in first 2 weeks of therapy
- Large doses, or concurrent alcohol use INC risk of seizures
- Use w/caution in pts w/history of depression, as risk of suicide may increase
What are the therapeutic uses of Rifampin?
- First-line against M. TB -> effective for both rapidly (EC cavitary lesions and slowly dividing (closed caseous lesions and macros) cells (but NOT as a single agent)
- Not only for TB:
1. MRSA and S. epididermis (in combo w/Vanc or Gentimicin -> NOT effective as a single agent)
2. Prophylactically for household members exposed to meningitis caused by meningococci or H. flu
3. Eradication of Staph in nasal carriers
4. Most active anti-leprosy drug at present
What is the most important determinant of whether over MTB disease occurs?
Adequacy of the host’s cell-mediated immune response
What is XDR-TB? What are some tx options?
- Less common form of MDR-TB in which TB bac have changed enough to circumvent the 2 best AB's, INH and RIF, as well as most of the alternative drugs for MDR-TB
1. These second-line drugs incl. any fluoroquinolone, and at least one of the other three injectable anti-TB drugs: amikacin or kanamycin (aminoglycosides), or capreomycin
- As a result, XDR TB needs up to 2 years of extensive drug treatment, and is the most challenging to treat.
Describe the drug interaxns of RIF.
- Induction of CYP 450: most enzymes, except 2D6 (incl. 1A2, 2C9, 2C19, and 3A4)
1. Reduces half-lives of drugs metabolized by P450: prednisone, propanodol, sulfonamides, dapsone, ketoconazole, HIV protease inhibitors, NNRTI's, etc.
- Oral anticoags and contraceptives less effective
1. Significant DEC in efficacy of coumadin-type anticoags
2. Reports of reduced plasma estrogen concs
3. Alternative contraceptive means should be used while taking RIF
- Probenecid INC serum levels of RIF when taken concurrently
- NOTE: Rifabutin has less effect on metabolism of HIV PI's; polymyalgia, pseudo-jaundice, and anterior uveitis (inflam of middle layer of the eye) unique to Rifabutin
What are the clinical manifestations of secondary/reactivated TB?
- Insidious onset
- Malaise, anorexia, low-grade fever, weight loss, night sweats, shortness of breath (SOB)
- Cough productive of blood-streaked and/or purulent sputum
- Some get pleuritic pain
What is the pathogenesis of TB?
- Doesn't have classic bacterial virulence factors, like toxins, capsules and fimbriae
- Cell wall contains many waxy-like substances that make it impermeable to many host defense systems: 1) mycolic acids, 2) glycolipids, 3) arabinogalactans, 4) free lipids
- Virulence factors:
1. Cord factor: virulent strains grow in characteristic cord-like pattern, avirulent strains do not -> inhibits macro maturation and induces TNF-alpha release
2. Sulfatides (surface glycolipids): once phagocytosed, inhibits phago-lysosomal fusion (protein PknG), allowing the bacteria to replicate
- Can grow IC in macros: effective means of evading the immune system -> Ab's and complement are ineffective
- IFN-γ: critical mediator allowing macros to contain the infection -> released by TH1 (after MTB enters macro via endocytosis)
1. Th1 response leads to granuloma formation and caseous necrosis (IL-12 released by macros to call Th1)
2. Activated macros secrete TNF and cytokines that recruit more monocytes
- TNF-α extremely important –> RA patients on antagonists at increased risk for TB
In which pts is 3-mo tx with INH-RPT for latent TB infection not recommended? Why?
- Children <2 y/o bc safety and pharmacokinetics of RPT have not been established for them
- HIV+ patients on ART bc drug interaxns have not been studied
- Pregnant women or women expecting to get pregnant during tx bc safety in pregnancy is unkown
- Pts who have LTBI w/presumed INH or RIF resistance
Why is TB hard to treat? Why is this important?
- Organism multiplies slowly
- Survives in protected IC location; may be dormant for long periods (resistant to AB's in this state)
- Propensity to devo resistance to antimicrobials
- Compliance issues
- Drug toxicity and interactions (esp. for HIV+)
- COMBINATION and PROLONGED COURSE OF THERAPY (can last up to 2 years)
What are the 2 fixed mycobacterium drug combos?
- Rifater: 120mg RIF, 50mg INH, 300mg PZA
- Rifamate: 600mg RIF, 300mg INH
What are some of the clinical manifestations of progressive primary TB?
- Tubercle can erode into a bronchus, spill its contents and infection spreads to other parts of the lung
- Resembles acute bacterial pneumonia
- CXR with infiltrates or lobar consolidation, hilar LAD, pleural effusion (variable)
- Difficult to diagnose
What are the AE's for RIF?
- Relatively low AE incidence (<4%)
- Discolors body fluids (tears, urine, saliva) -> turns them orange-red (wear glasses so contact lenses not stained)
- GI disturbances and nervous system complaints
- Fever, chills, and aches
- Hepatotoxicity (hepatitis/liver failure): jaundice with chronic liver disease, alcoholics, elderly, or pts receiving other hepatotoxics; more relevant in pts that are slow acetylators -> rare in pts w/normal liver function (RIF/INH generally safe in such pts)
What is a positive PPD?
- >15 mm: no known risk factors
- 10-15 mm: homeless, IVDU, nursing home resident, recent immigrant, children less than 4 years of age
- 5-10 mm: HIV, recent contact of someone with TB, person with fibrotic changes on CXR consistent with prior TB, organ transplants, immunosuppressed (prednisone, TNF alpha antagonists)
What is Capreomycin?
- MOA: unknown, but bacteriostatic
1. Strains of TB resistant to Streptomycin or Amikacin (both aminoglycosides) usually susceptible
- IM admin
- AE's: nephrotoxicity (incl. acute tubular necrosis, ATN), ototoxicity (3% detectable, 11% sub-clinical), eosinophilia, elevated serum BUN
1. Serious AE's incl. ATN, electrolyte disturbances, and acoustic N injury -> toxicity reduced if given 2-3x wkly after initial response to daily dosing
- Reserved as last line agent due to admin route and AE profile: adjunct (parenteral) agent in combo w/at least one other -> resistance develops when used alone
- Effective in MDR therapy; also used in tx of other mycobacterial diseases
What factor makes TB virulent?
Why is a long course of therapy required for TB?
- Organism grows very slowly
- There are metabolically inactive lesions in the lesion
- Organism is located intracellularly
- Caseous material blocks penetration by drugs
What is the ADME of Ethambutol?
- Absorption: 75% of oral dose
- Distribution: widely, but concentrates in kidneys, lungs, and saliva
1. Therapeutic levels in CSF w/inflamed meninges
2. Crosses placenta -> levels 30% of maternal
3. Distributes into breast milk: no reports of AE's to fetus or infant
- Metabolism: partially metabolized in the liver
- Excretion: excreted in urine (50% as unchanged drug); T(1/2) of 3.5 hrs, but extends up to 15 hours w/renal disease -> REDUCE DOSE w/renal disease
What are the epi, transmission for MTB?
- Mycobacterium tuberculosis (MTB) causes more deaths than any other single microbial agent worldwide
1. 1.7 million people die each year
2. 9 million new infections occur each year
3. 500,000 are infected with a MDR strain of TB
- Humans are the natural reservoir, and disease is spread person-to-person
1. Most transmission via aerosols generated by coughing of people who have the disease
- 90% of people who become infected with MTB do not develop the disease
- Things are getting better -> mortality has decreased significantly in the last 25 years
Describe the ADME of RIF.
- A: well absorbed orally; impaired by food or para-aminosalicylic acid (TB AB: separate use by 8-12 hrs)
- D: penetrates all tissues well, incl. CSF; 75-85% protein bound
- M: deacetylated in liver (retains full AB activity, but not reabsorbed) -> half-life INC by hepatic dysfunction (auto-induction of hepatic microsomal enzymes in first 2 wks = shorter half-life)
- E: primarily in bile (30% unchanged -> undergoes hepatic recirculation); sm. amt. via renal tubular secretion
1. No adjustment needed for renal insufficiency
What are the AE's and drug interactions associated with Ethambutol?
- AE's: dose-related optic neuritis (<1%)-> DEC visual acuity, loss of color discrimination, constriction of visual fields monthly visual exams during therapy (bc duration relative to length of tx after sxs noticed), reversible weeks to months after end of therapy (unilateral or bilateral)
1. Allergic reactions
2. Increase in serum urate (hyperuricemia; w/ or w/o precipitation of gout) -> about 50% of pts, and possibly enhanced by INH and pyridoxine (Vit. B6)
- Drug interactions: Al++-containing acids reduce absorption -> allow 3-4 hrs after antacids b4 Etham dose
What are the AE's of Pyrazinamide?
- Dose-related hepatotoxicity: typically seen w/large doses for long periods (40-50mg/kg/d; most severe rxn)
1. Transient INC in serum aminotransferase also observed
- Mild, non-gouty arthralgias
- Hyperuricemia: due to INH of urate excretion; often asymptomatic, but if discontinue use if acute gout devos
1. Arthralgia (non-gouty) reported in about 40% of pts, and appears to be secondary to hyperuricemia
What is Ethionamide? What are its AE's?
- Inhibits peptide synthesis: structural analog of INH
1. Works via different mech, but result the same
2. Resistance can devo rapidly when used as a single agent; can induce low-level resistance to isoniazid
3. Inactive pro-drug activated by mycobac redux system
- Oral admin, and wide distribution, incl. CSF
- Extensive hepatic metabolism
- Static or cidal, depending on concentration
- Reserved as last-line agent due to toxicity: GI, hepatic, neurologic
1. About 50% of pts can't tolerate a single does above 500 mg bc of GI disturbance -> best taken w/meals in divided doses so GI disturbance is minimized
a. Most common GI effects are anorexia, nausea, gastric irritation
3. Neurologic effects: depression, asthenia (abnormal physical weakness or lack of energy), blurred vision, diplopia, dizziness, tremors and others -> relieved by pyroxidine (Vit. B6)
3. Signs and symptoms of hepatotoxicity resolve when treatment stopped -> hepatic function should be checked at regular intervals
What are the drug interactions with INH?
- Antacids (esp. w/aluminum salts): DEC drug absorption, possibly by gastric emptying (take at least 1 hr pre-INH)
- Levodopa: inhibits dopa decarboxylase, reducing effectiveness of tx and worsening Parkinson's symptoms
- Inhibits CYP's: that metabolize phenytoin (anti-convulsant), diazepam (anxiety, muscle spasms, seizures), fluoxetine (SSRI), nelfinavir (PI), and others, DEC efficacy
- Induces CYP2E1: worsening production of toxic metabolite of acetaminophen produced by this pathway