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GI 5 > Drug Toxicity > Flashcards

Drug Toxicity Flashcards

1
Q

on target effects

A
  • exaggeration of desired pharmacologic action due to alteration in exposure to drug
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2
Q

off target effects

A
  • adverse effects that occur when a drug interacts with unintended target (multiple receptors)
  • enantiomers of drugs can cause off target effects
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3
Q

pharmacokinetic interactions

A
  • one drug changes absorption, distribution, metabolism, or excretion of another drug
  • P450 isozyme system is central to this concept, especially CYP3A4
  • displacement of a drug from plasma proteins (albumin) via a second drug may increase bioavailability of displaced drug especially in liver failure, malnutrition or nephrotic syndrome
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4
Q

pharmacodynamic interactions

A
  • one drug changes the response of target or nontarget tissues to another drug
  • toxic interactions occur when two drugs activate complementary pathways leading to exaggerated effect (viagra and nitroglycerin)
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5
Q

type 1 hypersensitivity

A
  • immediate response or anaphylaxis results from production of IgE after exposure to foreign protein or hapten modified endogenous protein
  • subsequent exposure results in IgE cross link of antigen causing mast cell degranulation releasing inflammatory mediators promoting vasodilation, bronchoconstriction, and inflammation - wheal and flare reaction in skin, conjunctivitis, and rhinitis in upper respiratory tract
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6
Q

type II hypersensitivity

A
  • antibody dependent cytotoxic response occurs when drug binds to cells (usually RBCs) which are then recognized by antibodies (usually IgG) resulting in complement fixation, phagocytosis, or cytolysis by cytotoxic T cells
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7
Q

type III hypersensitivity

A
  • immune complex mediated occurs when antibodies (usually IgG or IgM) are formed against soluble antigens
  • antigen/antibody complexes are deposited in tissues such as kidneys, joints and lungs
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8
Q

type IV hypersensivity

A
  • delayed response that results from the activation of TH1 and cytotoxic T cells
  • no response with first exposure but subsequent dermal exposure activates Langerhans cells which migrate to regional lymph nodes and activate T cells which return to site and initiate immune response
  • poison ivy and latex allergy are well known examples
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9
Q

autoimmune reaction caused by methyldopa

A
  • hemolytic anemia by eliciting autoimmune reaction against Rh factors
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10
Q

drugs that can lupus like symptoms

A
  • hydralizine, isoniazid, and procainamide can cause lupus like syndrome by inducing antibodies to myeloperoxidase (hydralazine, isoniazid) and DNA (procainamide)
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11
Q

cause of red man syndrome

A
  • vancomycin
  • direct effect on mast cells causing degranulation
  • wheals and urticaria relatively localized to neck, arms and upper trunk
  • management involves antihistamines and slowing infusion
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12
Q

common causes of Steven Johnsons

A
  • barbiturates, sulfonamides, antiepileptics (phenytoin, carbamazepine), NSAIDs (ibuprofen, celecoxib) and allopurinol
  • skin eruptions and skin sloughs off
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13
Q

drug induced hepatotoxicity

A
  • tylenol depletes glutathione stores

- administration of N-acetylcysteine replenishes glutathione stores

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14
Q

drugs associated with renal toxicity

A
  • ACE inhibitors
  • NSAIDs
  • progressive increase in serum creatinine is hallmark
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15
Q

drugs associated with neurotoxicity

A
  • chemotherapeutic medicines
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16
Q

drugs associated with skeletal muscle toxicity

A
  • HMG-CoA reductase (statins)
  • corticosteroids (dexamethasone, hydrocortisone)
  • zidovudine
17
Q

three major mechanisms of drug induced cardiotoxicity

A
  • cardiac potassium channel blockade leading to prolonged QTc
  • direct toxicity to cardiac myocytes
  • toxicity to heart valves
18
Q

drugs associated with cardiotoxicity

A
  • fenfluramine

- causes proliferation of valvular fibroblasts that form myxoid plaques on AV valves

19
Q

drugs associated with pulmonary toxicity

20
Q

carcinogenesis due to drug therapy

21
Q

drugs associated with increased risk of serious infection

A
  • rituximab targets CD20+ B cells which are involved in non-Hodgkin’s lymphoma and rheumatoid arthritis
  • potentially adverse effects are progressive multifocal leukoencephalopathy, infection from polyomavirus, the JC virus, and hepatitis B reactivation with fulminant hepatitis
22
Q

Hy’s rule of drug induced hepatotoxicity

A
  • ALT greater than 3X upper limit combined with bilirubin 2X upper limit associated with mortality rate of at least 10%

GI 5 (22 decks)

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