anticoagulation; inhibits vitamin K in liver
What enzyme metabolizes warfarin?
What secondary enzyme also metabolizes warfarin (other than CYP)?
VKORC1 (vitamin K epoxide reductase complex protein 1)
What 3 drugs are great examples of genes affecting response to drugs (pharmacogenomics)?
warfarin atomoxetine (strattera for ADHD) irinotecan (anticancer)
Which enzyme metabolizes atomoxetine (strattera)?
Which drug has 15 different alleles in the encoding gene for metabolism?
What is the the indication of Irinotecan?
What is the indication of atomoxetine?
What is the MOA of Irinotecan?
What enzyme metabolizes irinotecan?
Which drug has a decreased activity in 10% of cancer patients leading to a 5-fold increase in side effects because they do not have the enzyme?
irinotecan don't have UDP-glucuronyltransferase 1A1
What anticoag drugs are inhibited by CYP2B6?
Ticlopidine Clopidogrel Thiolactone metabolite of Prasugrel
What are some drugs that enhance metabolism (enzyme induction)?
phenobarb other barbiturates glutethimide phenylbutazone meprobamate ethanol phenytoin rifampin griseofulvin carbamazepine
What is the indication of Glutethimide?
piperidine based sedative hypnotic
What sedative hypnotic undergoes selective hydroxylation to create 2 different enantiomers in a mixture?
Which anti-seizure drug is metabolized into 10% 'R' enantiomer and 90% 'S' enantiomer?
Which smooth muscle relaxant/peripheral vasodilator undergoes regioselective metabolism by demethylation?
What is the indication of Papaverine (Pavabid)?
smooth muscle relaxant used as a peripheral vasodilator
Which two drugs can create metabolites that are active and toxic?
Nevirapine (AIDS) Procainamide (anti-arrythmic)
What specific metabolite created from Paroxetine can inactivate CYP2D6?
What drug does the metabolite carbene come from?
How many CYP enzymes does the human genome code for?
at least 57
What enzyme metabolizes more than 50% of drugs?
Which local anesthetic is de-ethylated (oxidative dealkylation) during the first-pass effect into acetylaldehyde? Also classified as a tertiary aliphatic/alicyclic amine oxidation...
What is the indication of Lidocaine?
local anesthetic ventricular arrythmias during acute MI or cardiac sx post-herpatic neuralgia caused by herpes zoster infection
What drug cannot be given oral for ventricular arrythmias and why?
Lidocaine b/c first pass effect deactivates the metabolites
What drug has metabolites that can cause neurotoxicity/seizure and must be closely monitored during an IV?
Which drug undergoes a series of metabolic steps prior to urine excretion, can be found in the urine 60-90 days after use, and 6 months after use in hair?
9THC (marijuana, tetrahydrocannabinol)
Which ant-seizure (anti-epileptic) drug undergoes oxidation via an intermediate arene oxide (epoxide) and a hydride shift?
Which three drugs undergo selective oxidation?
Diazepam 17-alpha-ethinylestradiol Bromobenzene
What is the indication of Diazepam(Valium)?
anti-seizure muscle relaxant
___ is a terrible liver toxin because the epoxide it creates reacts with DNA and RNA? Was used during WWII. Attaches to either water or GSH
Metabolism of this can lead to a carcinogen b/c of the epoxide it creates in the liver?
benzo[a]pyrene polyaromatic hydrocarbons (charcobroil!)
What is an example of a drug that creates an epoxide that can be isolated from the urine and has even been found in drinking water in CA? In this case, the epoxide metabolite is the ACTIVE drug. Oxidation of C=C olefin.
What is the indication of carbamazepine (tegretol)?
partial and clonic-tonic seizures (anticonvulsant)
What is another drug that undergoes olefinic oxidation via an intermediate epoxide?
What is the indication of secobarbitol?
short duration anesthetic
What are two drugs that undergo benzylic oxidations?
What is the indication of metoprolol?
What is the indication of tolmetin?
What are three drugs that undergo allylic oxidation?
Pentazocine (Talwin) Quinidine Hexobarbitol
What is the indication of Pentazocine (Talwin)
narcotic used for pain used for pre- or post op anesthesia
Quinidex Extendtabs Quinaglute Dura Tabs Quinalan Cardioquin
What is the indication of quinidine?
Which quinidine brand causes GI upset?
Quinidex Extendtabs (sulfate salt)
Which form of quinidine cause much less GI upset?
the sugar salts (compared to the sulfate salt)
What is the indication of glutethimide?
insomnia (use for 3-7 days)
What are two drugs that are oxidated at an alpha carbon next to carbonyl or an imine?
What is Diastat?
rectal diazepam gel anticonvulsant
Why would you use Diastat?
if you have N/V and you can't keep your oral anticonvulsant down also for anxiety, skeletal muscle relaxant
What drug does the metabolite Oxazepam stem from?
What is Oxazepam used for?
anxiety for detoxing an alcoholic
What are two drugs that undergo aliphatic oxidation?
Ibuprofen Chlorpropamide (Diabinese)
What is the indication for Chlorpropamide?
oral anti-diabetic sulfonylurea
What are two drugs that undergo oxidation at alicyclic carbons?
Acetohexamide (dymelor) Minoxidil (Loniten, Rogaine)
What is the indication of Acetohexamide (Dymelor)?
oral antidiabetic sulfonylurea
What is minoxidil indicated for (two things)?
severe unresponsive hypertension (loniten) male pattern baldness (rogaine)
What are 4 examples of tertiary aliphatic and alicyclic amine oxidations?
Chlorpromazine (Thorazine) Nicotine Lidocaine Tamoxifen Citrate (Nolvadex)
What is the indication of Chlorpromazine (Thorazine) and Phenothiazine?
antiemetic antivertigo antipsychotic tab, cap, supp, syrup, injection
What drug cause the thorazine shuffle?
chlorpromazine (thorazine) or phenothiazine it is neurotoxic
What is the the #1 drug for treating breast cancer?
tamoxifen citrate (nolvadex)
What are 4 examples of oxidations of primary and secondary amines?
Propanolol (Inderal) Methylphenidate (Ritalin) Phentermine (Ionamin, Adipex-P, Zantryl, Fastin) (dl)-Amphetamine sulfate
What is propranolol indicated for?
beta blocker (non-selective) test anxiety/stage fright
What is the indication of Methylphenidate?
Fastin Zantryl Adipex-P Ionamin
What is phentermine indicated for?
appetite suppressant managing obesity used to study hardcore
What is (dl)-Amphetamine sulfate indicated for?
What drug makes metabolites like an imine, an oxime and phenylacetone, which can be found in the urine of meth users?
What are two drugs that undergo oxidation of nitrogen heterocycles?
Trimethoprim (Trimpex, Proloprim, Bactrim, Septra, Cotrim) Nicotine
What is trimethoprim indicated for?
dihydrofolate reductase inhibitor (antibiotic) in combo to make Septra, used for UTIs and pcp (HIV pneumonia)
What 2 drugs undergo oxidation of an amide?
Diazepam ---> DesmethylDiazepam Cyclophosphamide (Cytoxan, Neosar)
What is the indication of cyclophosphamide?
alkylating agent (anticancer)
Which drug has to be a prodrug in order to be active and the metabolite it creates can cause hemorrhagic cystitis? What is the name of the metabolite?
Cyclophosphamide= drug Phosphoramide Mustard= active prodrug Metabolite= Acrolein
Which drugs undergo oxidation of a carbon-oxygen system (O-dealkylation)?
codeine----> morphine trimethoprim metoprolol prazosin indomethacin
T/F: codeine is active in itself.
What prodrug arises from codeine and is actually the active form of the drug, which some people do not ever get to experience if they are slow metabolizers?
morphine comes from codeine
Which drug undergoes desulfurization?
What is Thiopental indicated for?
induces anesthesia to get you through stage 1 of anesthesia so you don't vomit
Which drug undergoes sulfur oxidation?
What is thioridazine indicated for?
What is a metabolite of Thioridazine (mellaril) that is not as toxic and is a good antipsychotic?
What is a drug that undergoes oxidative dehalogenation?
What is halothane indicated for?
What is the huge problem with Halothane, which is metabolized by oxidative dehalogenation?
it causes severe liver damage because it creates a fluorocarbon and HCl (10,000 times more acidic than vinegar)
Name a drug that undergoes oxidative aromatization.
Name a drug that undergoes stereospecific ketone reduction.
R (+) Warfarin
What are two drugs that undergo reduction of a nitro or azo compounds?
Dantrolene (Dantrium) Sulfasalazine (Azulfidine)
What is Dantrolene indicated for?
direct acting skeletal muscle relaxant used in spasticity, malignant hyperthermia with seizures
What is sulfasalazine indicated for?
sulfonamide antibiotic and antiinflammatory used to treat ulcerative colitis and rheumatoid arthritis
What are two drug that undergo miscellaneous reductions?
Disulfiram (Antabuse) Sulindac (Clinoril)
What is disulfiram indicated for?
What is sulindac indicated for?
Which drug undergoes a reduction in the liver (which is rare) and begins with a sulfoxide prodrug?
Which drug undergoes ester hydrolysis?
What are two other examples of hydrolysis of esters or amides? (reduction section)
Clofibrate (Atromid-S) Prazosin (Minipress)
What is the indication of Clofibrate?
What is the indication of Prazosin?
antihypertensive alpha 1 blocker
Which are harder to hydrolyze in the body, amides or esters?
Many prodrugs are _____? Hint: easily hydrolyzed in the body
What is an -enol drug that undergoes oxygen glucuronidase conjugation (phase II)?
Which alcohol hydroxyl drug undergoes glucuronidation?
What is the indication of Chloramphenicol?
serious infections, monitor for blood dyscrasias
What is a phenol hydroxyl drug that undergoes glucuronidation?
What is a carboxylate hydroxyl example of glucuronidation?
What is the indication of Fenoprofen?
What is an example of N-hydroxyl glucuronidation?
What is Dapsone indicated for?
txt of brown recluse spider bites leprosy pcp (pneumocystitis carinni pneumonia)
What are two drugs that undergo sulfate conjugations (phase II)?
Alpha-Methyldopa (Aldomet) Albuterol (Proventil, Ventolin, Airet)
What is aldomet indicated for?
What is albuterol indicated for?
bronchospasms in COPD
What is a drug that is conjugated with glycine?
Isoniazid (Laniazid, Nydrazid)
What is Isoniazid indicated for?
What are two drugs that undergo Glutathione (GSH) nucleophilic displacement conjugation?
Nitroglycerin Azathioprine (Imuran)
What is Nitroglycerin indicated for?
nitrate vasodilator for treatment and prophylaxis of angina
What is azathioprine indicated for?
immunosuppressant used to txt transplantation and rheumatoid arthritis
What drug leads to the active immunosuppressant mercaptopurine?
What are two drugs that undergo GSH Michael Addition phase II conjugation?
APAP Ethacrynic Acid (Edecrin)
What is Ethacrynic acid indicated for?
loop diuretic used to rid edema in CHF, renal and liver diseases= lots of urine produced to rid edema
What toxic metabolite does APAP generate when undergoing phase II Michael addition GSH conjugation?
iminoquinone = liver failure *reason why you should not drink alcohol and take APAP with or for hangover
What are two drugs that undergo N-acetylation?
Clonazepam (Clonipin) Hydralazine (Apresoline)
What is clonazepam indicated for?
What is hydralazine indicated for?
Which antihypertensive vasodilator has ~20 metabolites?
Which drug shows treatment failure because of fast acetylators?
Which drug can have covalent binding in liver cell macromolecules leading to liver damage?
Norepinephrine, dopamine, serotonin, and histamine are all biogenic amines that are inactivated by what 2 methylation molecules?
SAM methyltransferase enzymes
Which enzyme is responsible for inactivating dopamine and norepinephrine?
What are two drugs that undergo methylation via COMT?
Levodopa (Larodopa, Dopar) Terbutaline (Berthaire, Brethine, Bricanyl): not really though b/c of 1,3 position
What is a resorcinol that is NOT a substrate for COMT because of the 1,3 position of hydroxyls?
What is Terbutaline indicated for?
What position do the hydroxyls have to be to be substrates for COMT?
What drug do you have to co-administer with Levodopa?
Brethine Bricanyl Berthaire
What are 2 drugs that undergo methylation via N-methyl transferase?
amantadine (symmetrel) nicotine
What is amantadine indicated for?
Parkinson's type A flu virus
What is a drug that undergoes methylation via S-methyl transferase?
What is propylthiouracil indicated for?
hyperthyroidism by preventing synthesis of T3 and T4
Why is grapefruit juice bad?
the flavenoids in it inhibit p-glycoproteins in the GI tract = no absorption of drug
Name 5 drugs that have been taken off the market due to DIs causing torsades depointes/QT elongation?
Terfenadine (Seldane): antihistamine Mibefradil (Posicor) Astemizole (Hismanal): antihistamine Grepafloxacin (Raxar): antibiotic Cisapride (Propulsid): caused GI problems
Which antibiotic can cause QT elongation problems?
When making an IV solution, what should you NEVER mix phenytoin with?
When making an IV, what should you never mix amphotericin with?
When making an IV, what should you NEVER mix with opiates?
What will physically and chemically react with the beta-lactam rings of penicillins, cephalosporins, and monobactams in an IV solution and cause decomposition?
gentamicin and other basic solution drugs like furosemide
What are some red flag hyperlipidemia drugs?
bile acid sequesterants statins
What are some red flag drugs for GERD/ulcers?
cimetidine cisapride sucralfate
What is a red flag drug for osteoporosis?
What are some red flag anticonvulsants?
carbamazepine phenobarbitol phenytoin
What is a red flag immunosuppressant?
What is a red flag drug for CHF?
What are some red flag drugs for TB?
What is a red flag anticoagulant?
What is a red flag asthma bronchodilator?
What is a red flag herbal product?
St. John's Wort
What is a red flag drug for UTI?
What are some red flag drugs for HIV/AIDS?
reverse transcriptase inhibitors protease inhibitors non-nucleoside reverse transcriptase inhibitors
What is a red flag women's product?
What is a red flag anti-depressant MAOI?
What is a red flag antibiotic?
erythromycin and other macrolides
What is a red flag manic-depressive drug?
What is a red flag anti-fungal drug?
What are "momma's little helpers"?
amphetamines and secobarbitol
What drugs are the main substrates for p-glycoprotein, ABC?
digoxin fexofenadine vincristine indinavir colchicine topotecan paclitaxel loperamide
What drugs inhibit p-glycoprotein ABC?
ritonavir cyclosporine verapamil erythromycin ketoconazole itraconazole quinidine azithromycin valspodar
What drugs induce p-glycoprotein?
Which drug is given to cancer patients to get a more effective absorption of anticancer drugs and inhibit p-glycoprotein?
What are some drugs that are substrates for organic cation transporters (OCTs) drug transporters?
cimetidine methotrexate zidovudine
What are some drugs that are inhibitors of the OCT transporters?
probenicid cefadroxil cefamandole cefazolin
Which (OCT) drug is given with penicillins/cephalosporins to increase their absorption when there is a severe infection?
Which drugs (inhibitors of OCT) can block their own elimination?
What are some known cardiovascular substrates for p-glycoprotein?
digoxin diltiazem nicardipine verapamil mostly calcium channel blockers
What are some known antineoplastic substrates for p-gycoprotein?
vinblastine vincristine etoposide paclitaxel
What are some known transplant substrates for p-glycoproteins?
What are some steroid substrates for p-glycoprotein?