AE of drugs_classic examples Flashcards
Discolors children’s teeth
Tetracyclcine
A drug used to treat epilepsy and is a well known inducer of cytochrome P450 metabolizing enzymes
Phenobarbital
A number of agents can INDUCE different cytochrome P450 enzymes.
Some important examples are: Carbamazepine Phenobarbital Phenytoin Primidone Polycylic aromatics found in environment and cigarette smoke Glucocorticoids Chronic alcohol St. John's wort
A drug that INACTIVATES its target by forming a covalent bond resulting in carbamylation of its target
Neostigmine
Neostigmine is a carbamate that forms a covalent bond
with the serine hydroxyl group of acetylcholine esterase,
thus carbamylating the enzyme.
Other examples of chemicals that form covalent bonds with their targets are:
- Paraoxon–phosphorylates acetylcholine esterase
- Phenoxybenzamine–alkylates the alpha receptor
- Cyclophosphamide–alkylates DNA
- Omeprazole– alkylates the H+/K+ - ATPase proton pump in parietal cells
A drug that is a very strong inhibitor of the anionic (acid) renal tubular secretion systems?
Probenicid
Probenecid is a strong inhibitor of renal tubular secretion of drugs.
It markedly prolongs the action of penicillins and many cephalosporins.
It also has uricosuric effects by blocking the active reabsorption of uric acid in the kidneys.
A drug used to INDUCE glucuronyltransferase in the newborn
Phenobarbital
Glucuronyltransferase deficiency (Type II),
Crigler-Najjer Syndrome
may persist in adult life
and may benefit from treatment
with phenobarbital.
A drug obtained Over-the-Counter (OTC) to LOWER stomach acid but it causes numerous drug-drug interactions by BLOCKING microsomal metabolizing enzymes
Cemetidine
Inhibitors of microsomal cytochrome P450 enzymes include:
Cimetidine Ketoconazole Chloramphenicol Disulfiram Erythromycin Acute alcohol Grapefruit juice
Used to measure renal plasma flow?
Para-aminohippuric acid (PAH)
Para-aminohippuric acid is actively secreted by the anionic (acid) transport system in the kidney and is almost entirely cleared by a single pass through the kidney and therefore, can be used to measure renal plasma flow (ca. 660 mL/min).
An endogenous substance produced by endothelial cells that activates guanylyl-cyclase via a paracrine action on vascular smooth muscle
NO
When muscarinic receptors (M-3) are activated on endothelial cells, there is an increase in intracellular Ca2+, which through calmodulin, activate nitric oxide synthase which in turn converts arginine to
citrulline and NO.
NO diffuses to the epithelial cell where it activates quanylyl cyclase to convert GTP to cGMP which then activates
protein kinase G which then activates a phosphatase resulting in vasodilation.
A drug known to cause porphyria in patients with abnormal heme synthesis
Phenobarbital
The barbituric acid mimics the heme structure which is a repressor of ALA synthase.
Slow acetylators of this drug may have a HIGHER propensity to experience peripheral neuropathy
Isoniazid
“Slow” acetylators of isoniazid
may have a greater incidence of peripheral neuropathy than “fast” acetylators.
This can be minimized by co-administration of pyridoxine.
The acetylated product of isoniazid gives rise to reactive intermediates that may lead to hepatotoxicity.
However, age of the patient is
more important than acetylator phenotype.
Isoniazid should be used with extreme caution in patients above 35 years of age and not at all in patients over 50 years old.
A drug well recognized for causing drug-induced autoimmune hemolytic anemia
Alpha-methyl-DOPA
Alpha-methyl-DOPA alters the cell membrane in such a fashion that in some individuals autoantibodies are formed against the red cell membrane.
This is in contrast to penicillin-induced acute hemolytic anemia where antibodies
are directed towards penicillin conjugated to the red cell membrane to function as a hapten.
An antimalarial drug that may cause acute hemolytic anemia in patients DEFICIENT in glucose-6-phosphate dehydrogenase (G-6-PDH)
Primaquine
Individuals deficient in glucose-6-phosphate dehydrogenase (G-6-PDH) are incapable of maintaining NADPH levels. The erythrocytes of these individuals are much more susceptible to oxidative lysis
and methemoglobin formation.
These individuals are sensitive to many drugs such as: Primaquine Probenecid Sulfonamides Nitrofurantoin
A sedative hypnotic drug introduced into Western Germany in 1957 was responsible for many cases of phocomelia (seal limbs) due to its teratogenic effects
Thalidomide
Definite and probable human teratogens include:
Alkylating agents (e.g. cyclophosphamide)
Antimetabolites (e.g. mercaptopurine)
Retinoids (e.g. etretinate, isotretinoin)
Heavy metals (e.g. lead, cadmium, mercury)
Antifolates (e.g. methotrexate)
Anticonvulsants (e.g. phenytoin, valproate, carbamazepine)
Thalidomide
Ethanol (Fetal alcohol syndrome)
A widely used drug which DECREASES brain activity by binding to the GABA/chloride ionophore complex and acts as an allosteric activator of the chloride channel
Diazepam
An antiarrythmic drug well recognized for causing thrombocytopenic purpura
Quinidine
This is a Type II hypersensitivity reaction.
