Drug Toxicity Flashcards
What are the four categories of Adverse Drug Reactions?
- Drug binding to intended receptor but at inappropriate concentration
- Drug binding to a target/receptor not intended
- Mediated by the immune system
- Idiosyncratic responses (unknown mechanism)
What is a Type I hypersensitivity reaction?
Immediate hypersensitivity (results from production of IgE after exposure to an antigen); Antigen may be a foreign protein or an endogenous protein modified by a hapten to become immunogenic
What is a Type II hypersensitivity reaction?
Antibody-dependent cytotoxic reaction; drug recognized by immune system (usually IgG)
What is a Type III hypersensitivity reaction?
Immune-complex mediated reaction; antibodies formed against soluble antigens (A-A complex deposits in tissue leading to serum sickness or imflammation of the tissues)
What is a Type IV hypersensitivity reaction?
Delayed-type reactions; Activation of cytotoxic T-cells
What four drugs mentioned can intiate autoimmune reactions? What reactions might they cause?
Hemolytic anemia: Methyldopa
Lupus-like reaction: Hydralazine, Isoniazid, Procainamide
What are common skin rashes to occur from ADRs?
- Erythema multiforme
- Stevens-Johnson syndrome
What drugs are reported to cause Stevens-Johnson syndrome?
- Barbituates
- Sulfonamides
- Phenytoin
- Penicillins
- Carbamazepine
- Allopurinol
- NSAIDs
T or F: Stevens-Johnson syndrome is a fully understood pathology.
F
What immune toxicities are presented with cytotoxic agents?
- Routinely damages proliferating nml cells
- INC’d risk of infection (cytotoxic to WBC)
T or F: Immunotherapies that target specific cell types are associated with INC’d risk of infection.
T
What is the most frequent reason for drug withdrawals from market in the US?
Hepatotoxicity
What may metabolites cause? Example?
Liver damage; Acetaminophen (oxidized to N-acetyl-p-benzoquioneimine)
What are possible manifestations of renal toxicity?
- Renal hemodynamic
- Tubular damage
- Tubular obstruction
- Glomerular nephropathy
- Interstital nephritis
What are drugs that may cause progressive renal failure?
- Anti-neoplastic (cancer) agents
- Contrast media
- Amphotericin B
- Gentamicin
- ACE Inhibitors
- Immunomodulators
- NSAIDs
“A/C AGAIN”
T or F: Renal tubular injury caused by Gentamicin is reversible upon cessation
T
T or F: Amphoterican B has a high frequency of injury.
T; Mechanism for efficacy is shared by the mechanism responsible for toxicity
T or F: Contrast media has a DOSE-RELATED nephrotoxicity
T
What are the three major mechanisms of Cardiovascular toxicity?
- Interact with cardiac potassium channels (cause QTc prolongation, delayed repolarization and cardiac arrythmias)
- Directly cytotoxic to myocytes
- Toxic to heart valves
What drugs interact with cardiac potassium channels cause QTc prolongation?
- Antipsychotics
- Anti-emetics
What drugs are directly toxic to myocytes?
Doxorubicin (produces reactive oxygen species)
How can drug toxicity affect pulmonary function?
Toxicity might cause anything from acute reversible exacerbations to chronic remodeling (i.e. pulmonary fibrosis)
What drugs may cause pulmonary fibrosis?
- Bleomycin
- Amiodarone
What is a teratogen?
Substance that may induce defects in the developing fetus (TORCH)
How does the timing of the drug administered affect the pregnancy?
< 3 weeks: usually results in death
3-8 weeks: organogenesis is being greatly affected
How do you TX drug toxicity?
- Reduce/eliminate exposure
- Provide supportive care
- Provide antidote
