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35 Cards in this Set

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what are the two pathways needed to produce NADPH for P450 reactions?
1. Embden-Meyerhof Pathway
2. PPP
What are the 5 mechanisms for drug metabolism?
1. Oxidative reactions
2. Glucuronidation
3. Esterases
4. MAO
5. Alcohol and aldehyde dehydrogenase
what amine is present in chese and wine?
tyramine
what is used in treatment of parkinsons?
MAOI
metabolism of thiopental
IV anesthetic --> pentobarbital (barbiturate)
metabolism of parathion
insecticide --> paraoxon (cholinesterase inhibitor)
metabolism of CCl4
dry cleaning --> free radical scavenger
metabolism of terfenadine
toxic antihitamine precursor --> histamine
metabolism of Norepi
Epi
metabolism of morphine
morphine-6-glucoronide
metabolism of sulfasalazine
5-ASA
metabolism of EtOH
acetaldehyde
metabolism of procainamide
NAPA
inducers of P450 enzymes
- cigarettes
- phenobarbital (barbituate)
- rifampin (inhibits mRNA polymerase)
- phenytoin (anti-epileptic)
- carbamazepine (anti-epileptic, induces own metabolism)
inhibitors of P450 enzymes
- cimetidine and ketoconazole
- disulfiram (aldehyde dehydrogenase)
- metronidazole -like disulfiram
- cimetidien
antifungals (ketoconazole, itraconazole)
- antibiotics (erythromycins, trolenadomycin, clarithromycin)
- HIV protease inhibhitors
- some SSRI, PPI, grapefruit juice
what prototypical drug displaces plasma binding of coadministered drugs?
warfarin
what are the genetics of G6PD deficiency?
sex linked
protective against malaria
what is the mechanism of G6PD toxicity?
Red cells don't make NADPH (part of the PPP)--> you can't make glutathione peroxidase --> cell is susceptible to oxidative damage --> hemolysis by H2O2 buildup
what drugs/compounds should be avoided in people with G6PD?
- primaquine (antimalarial)
- nitrofuratoin (antibiotic for UTIs)
- napththalene (moth balls)
- fava beans
what is the mechanism behind pseudocholinesterase deficiency toxicity?
pseudocholinesterase breaks down succinylcholine. Post-surgical paralysis is prolonged.
Tell me more about succinyl choline
has a high affinity for nicotinic receptors, but is resistant to AChE
- can induce a depolarizing blockade
what is prophyria?
problems with heme synthesis
- barbiturates induce d-ALA synthetase which leads to accumulation of heme precursors (d-ALA), which are neurotoxic
are fast acetylators autosomal dominant?
yes
what do you have to watch out for if you're a slow acetylator?
sulfonamide toxicity
what is the mechanism of sulfa drugs?
In bacteria, antibacterial sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthetase, DHPS. DHPS catalyses the conversion of PABA (para-aminobenzoate) to dihydropteroate, a key step in folate synthesis. Folate is necessary for the cell to synthesize nucleic acids
what is the mechanism of sulfonamide toxicity?
metabolite sulfapyridine gives toxitiy
what other drugs can cause toxicity in slow acetylators?
isoniazid
hydralazine
how do isoniazid and hydralazine cause toxity?
induces autoimmune reactions by inducing autoanitibodies aginast myeloperoxidase --> lupus like
which drugs are given as prodrugs?
- cyclophosphamide
- sulfasalazine
- enalapril
- terfenedine
what is cyclophosphamide used for?
chemotherapy for lymphomas
what is sulfasalazine used for?
anti-inflammatory agent in the treatment of IBD as well as for RA.
what is enalapril used for?
ACE inhibitor used for hypertension and CHF
what is terfenedine used for?
active ingredient in the antihistamines
which drugs/substances are made more toxic by drug metabolism?
- ethylene glycol
- CCl4
which drugs/substances show a carcinogenic effect after metabolism?
- aflatoxin
- polycyclic aromatic hydrocarbons (cigarettes)