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53 Cards in this Set
- Front
- Back
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How do you calculate therapeutic index?
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LD50/ED50
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How do you calculate margin of safety?
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LD1/ED99
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What is the LD50?
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dose that causes death in 50% of a group of animals
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What is the therapeutic window?
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how big of a range of doses you can give within the margin of safety
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What are the ways a drug can cause toxicity?
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too much of a "good" thing, interference with normal physiological functions, direct physiochemical injury, reactive intermediates, immunologic injury
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Which drugs interfere with normal physio functions?
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strychnine, arsenic, lead
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How can a drug cause direct physiochemical injury?
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mucosal injury or solvent effects
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Which drugs injure the mucosal lining of the esophagus?
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tetracycline, quinidine, NSAIDS
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Which drugs lead to acute toxicity via reactive intermediates?
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acetaminophen and CCl4
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How do mutagens cause injury?
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bioactivation to become reactive electrophiles, form adducts with DNA, overwhelm repair mechanisms
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How do you calculate therapeutic index?
|
LD50/ED50
|
|
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How do you calculate margin of safety?
|
LD1/ED99
|
|
|
What is the LD50?
|
dose that causes death in 50% of a group of animals
|
|
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What is the therapeutic window?
|
how big of a range of doses you can give within the margin of safety
|
|
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What are the ways a drug can cause toxicity?
|
too much of a "good" thing, interference with normal physiological functions, direct physiochemical injury, reactive intermediates, immunologic injury
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Which drugs interfere with normal physio functions?
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strychnine, arsenic, lead
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How can a drug cause direct physiochemical injury?
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mucosal injury or solvent effects
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Which drugs injure the mucosal lining of the esophagus?
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tetracycline, quinidine, NSAIDS
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Which drugs lead to acute toxicity via reactive intermediates?
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acetaminophen and CCl4
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How do mutagens cause injury?
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bioactivation to become reactive electrophiles, form adducts with DNA, overwhelm repair mechanisms
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How do promoters cause chronic toxicity?
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potentiate the effects of genotoxic carcinogens, facilitate growth and development of dormant or latent tumor cells
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What are the immediate hypersensitivity immune toxicities of a drug?
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rash, asthma, rhinitis, laryngeal edema
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What mediates immediate hypersensitivity reactions?
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IgE
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What drug causes immediate hypersensitivity reactions?
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penicillin
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What reactions are caused by antibodies activating complement?
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autoimmune hemolytic anemia, thrombocytopenic purpura, granulocytopenia, systemic lupus erythematosus
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What complement mediated reaction do you get with penicillin?
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hemolytic anemia
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Which complement-mediated reaction do you get with methyldopa?
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methyldopa-induced autoimmune hemolytic anemia
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Which complement-mediated reaction do you get with quinidine?
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quinidine-induced thrombocytopenic purpura
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What complement-mediated reaction do you get with sulfonamide?
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sulfonamide-induced granulocytopenia
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What complement-mediated reaction do you get with hydralazine?
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hydralazine-induced systemic lupus erythematosus
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How is acetaminophen normally metabolized?
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phase II reactions: glucuronidation and sulfation
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Which enzyme does Phase I metabolization of acetaminophen?
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CYP 2E1
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What induces acetominophen toxicity?
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ethanol and isonizid
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What inhibits CYP 2E1?
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cimeditidne
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What is the antidote to acetominophen overdose?
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N-acetyl cysteine
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What does N-acetyl cysteine do?
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source of cystein for hepatic glutathionie synthesis for detox of NAPQI
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When do you see hepatic toxicity with acetaminophen?
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12-24 hours
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What is the prognosis for acetaminophen injury?
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will recover with good care, liver can regenerate
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How much acetaminophen do you give with liver disease?
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limit to 2-4g/day
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What metabolizes CCl4?
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CYP2E1 and CYP2B1/2
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What happens to the liver with CCl4?
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initiates lipid peroxidation, reversible liver damage
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What is halothane?
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anesthetic
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What increases incidence of liver toxicity with INH?
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alcohol or rifampin use
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What increases severity of liver toxicity with INH?
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pyrazinamide
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Who gets more liver toxicity with INH?
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older people, slow acetylators
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What is associated with cholestatic reactions?
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elevated bilirubin, alkaline phosphatase, pruritis
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What drugs can cause cholestatic reactions?
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estradiol, phenothiazines, erythromycins, sulfonamides, captorpil, anabolic steroids
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What is the prognosis of cholestatic reactions?
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can be fatal or take a while to resolve
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What can cause alergic hepatitis?
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phenytoin, carbamazepine
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What are the systemic symptoms of granulomatous reactions?
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fever, malaise, fatigue
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What causes drug-induced chronic hepatitis?
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alpha-methyldopa, sulfasalazine, nitrofurantoin
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What causes microvesicular steatohepatitis?
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tetracycline, valproic acid, aspirin, fialuridine, AZT
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What should you rule out with drug-induced hepatotoxicity?
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alcohol, viral hepatitis, idiopathic autoimmune, genetic/metabolic disease, occupational exposure, steatohepatitis
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