Organ directed toxicity: GI
Aspirin
Organ directed toxicity: Kidneys
Aminoglycosides
Organ directed toxicity: Liver
Acetominophen
Organ directed toxicity: Heart
Doxorubicin
Fetal toxicity directly toxic effects: sulfonamide
induced kernicterus
Fetal toxicity directly toxic effects: Chloramphenicol
Gray baby syndrome
Fetal toxicity that are directly toxic: Bone growth
Tetracycline
Fetal toxicity: teratogens
Thalidomide Antifolates Phenytoin Warfarin Isotretinoin Lithium Valproic Acid Fetal alcohol syndrome
Drug Allergies: Hypersensivity. Most drugs are not by themselves immunogenic. When they bind covalently to a macromolecule or alter structure of macromolecule to become an immunogenic ______
hapten
Drug toxicity hypersensitivities target organs type I
GI
Skin
Lung
Vasculature
Drug toxicity hypersensitivities target organs type II
Circulating Blood cells
Drug toxicity hypersensitivities target organs type III
Blood Vessels
Skin
Joints
Kidney
Drug toxicity hypersensitivities target organs type IV
Skin
Lungs
Central Nervous System
(Stevens-Johnson Syndrome)
Hypersensitivity reaction type I involves IgE that release
histamine, leukotrienes, prostaglandins
Drugs associated with Type I reactions
Beta-lactam anti-bacterials
Neuromuscular blockers
Quinolones
Platinum-basid cytotoxic drugs (cis-platin)
Foreign Proteins
Drugs associated with Type I reactions
Beta-lactam anti-bacterials
Neuromuscular blockers
Quinolones
Platinum-basid cytotoxic drugs (cis-platin)
Foreign Proteins
Drugs associated with hemolytic anemia and thrombocytopenia
Beta-lactam
NSAID
Quinine-quinidine
drugs associated w/ thrombocytopenia
Beta-lactam
NSAID
Quinine-quinidine
Heparin Abciximab Sulfonamides Carbamazepine Propylthiouracil
Type III hypersensitivity require longer or short exposure?
Longer (high dose, and/or long duration therapy)
Type IV cell-mediated or delayed hypersensitivity caused by
Topical drugs, also metals and jewelry, poison ivy
Stevens-Johnson from sulfonamides, lamotrigine, allopurinol
Interstitial nephritis from acetominophen, NSAIDs, PPIs, Anti-bacterials, anti-virals
drug-induced hepatitis from Acetominophen, NSAIDs, steroids (anabolic, BCP), statins
Drug idiosyncrasies: Abnormal serum cholinesterase develop ______ when given normal doses of succinylcholine
apnea
Drug idiosyncrasies: Abnormal serum cholinesterase develop apnea when given normal doses of ________
succinylcholine
Isoniazid involves genetic aberrations related to
fast and slow acetylation
Glucose-6-phosphate dehydrogenase elicits hemolytic anemia elicited by ________
Primaquine
Sulfonamide
Nitrofurantoin
Barbiturates can cause porphyria because it mimics part of the heme structure and in some people is can block the portion of the heme site that regulates what enzyme that converts succinyl to porphobilinogen
ALA synthetase
Alkalinization of urine via sodium bicarbonate will enhance the excretion of
weak organic acids
Acidification of the urin via ammonium chloride enhances the excretion of
weak organic bases
What drug blocks tubular secretion of for example
Probenicid
Valium and ethanol have a ______effect on one another
synergistic
Propanolol and isoproterenol have ______ effects as well as nalaxone and morphine
opposing
Animal testing is done in how many species to confirm efficacy, selectivity, and mechanism? This leads to IND judgement
2 species
Clinical testing involves 3 phases, which phases tests whether a drug works, involves 1000-6000 patients (multicenter testing) and is tested in a double-blind trial
Phase 3
IND stands for
Investigational new drug. Follow animal testing
NDA occurs after the 3 phases of clinical trials and stands for
New drug application
Phase 4 occurs after NDA and involves
postmarketing surveillance; is after the drug is on the market
Animal testing--> IND--> Clinical trial Phases 1-3--> NDA --->Phase 4 post market surveillance
general set up for drug testing
Phase ___finds the maximum tolerated dose, characterizes adverse effects, and defines the pharmacokinetics and is never double blind
1
Phase ___ attempts to determine clinical effectiveness of test agent
2
Phase ___ is extensive testing of a drug’s efficacy and toxicity and is usually carried out by physicians in private practice
Phase 3
Informed consent is required for Phases 1-3 but only needs to be in writing for phases ____
1 and 2