Term
| CO binding affinity to Hb |
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Definition
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Term
|
Definition
| Accute (fire)-->carboxy Hb--> hypoxia-->headache, tachycardia, tachypnea, coma, convulsions, resp failure, tightness in temporal area, confusion, loss of vision, |
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Term
| CO chronic problems (smoking) |
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Definition
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Term
|
Definition
| O2: 100% initially, hyperbaric if severe |
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Term
|
Definition
| Industrial: fumigation of ships, sterilization of soil, metallurgy |
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Term
|
Definition
| plant seeds, silver polish, pesticides |
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Term
|
Definition
| metabolite of nitroprusside, a vasodilator for HTN |
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Term
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Definition
| binds to cytochrome oxidase, stops ETC, blocks O2 utilization, death is due to resp failure |
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Term
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Definition
| cellular hypoxia, no cyanosis, bright red venous blood, bitter almond breath, rapid coma |
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Term
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Definition
| amyl nitrite oxidizes limited Hb to methemoglobin, which competes with Cyt oxidase for CN and is eliminated, followed by IV sodium thiosulfate to accelerate detox via mitochondrial rhodanese. Last step is methylene blue to reduce methemoglobin to Hb. |
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Term
| Mito. rhodanese mechanism |
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Definition
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Term
|
Definition
| denatured alcohol, household products |
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Term
|
Definition
| alcohol dehydrogenase converts to formic acid, limited conversion to CO2 by folate dependent system, formic acid accumulates |
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Term
|
Definition
| irreversible blindness, metabolic acidosis, death |
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Term
| MeOH clinical presentation |
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Definition
| blurred vision, photophobia, papilledema, feeling of being in a snowfield", nausea, vomiting, abdominal pain |
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Term
|
Definition
| EtOH competitive inhibitor, 10-20x greater affinity, Bicarb for metabolic acidosis, hemodialysis to remove MeOH and formic acid, folate to increase conversion to CO2 |
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Term
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Definition
| antifreeze, industrial solvent |
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Term
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Definition
| metabolizes to oxalic acid, deposits in renal tubules and cuses kidney damage, calcium oxalate crystals appear in urine for diagnosis, metabolic acidosis, NOT BLINDNESS |
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Term
| Ethylene glycol treatment |
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Definition
| EtOH, bicarb, hemodialysis (same as MeOH) |
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Term
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Definition
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Term
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Definition
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Term
|
Definition
| GI irritation and bleeding, met. acidosis, hepatic failure, pulmonary edema |
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Term
|
Definition
| deferoxamine (desferal) if serum Fe greater than 400ug/ml |
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Term
|
Definition
| erythrocytes, soft tissues, bone |
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Term
| Lead halflife of elimination |
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Definition
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Term
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Definition
| hypochromic microcytic anemia due to inhibition of heme synthesis and shortened RBC lifespan |
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Term
| Lead inhibits which enzymes? |
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Definition
| 1.d-aminoleculinic acid dehydratase, decreseing conversion of ALA to phorphybilinogen, 2. ferrochelatase, decreasing heme synth, increasing protophrophyrin IX for Dx 3. Indirectly lessens inhibition of ALA synthase 4. increases ALA levels in urine for Dx |
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Term
| Lab signs of lead poisoning? |
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Definition
| high Protophorphyrin IX, high ALA in urine, high blood lead |
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Term
|
Definition
| peripheral neuropathy (wrist drop), encephalopathy, interstitial kidney damage, decreased fertility in women, GI issues |
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Term
|
Definition
| bloodwork, urinalysis, xray of long boes for lead lines |
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Term
|
Definition
| Calcium disodium EDTA to remove from bone, dimercaprol to remove from tissues |
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Term
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Definition
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Term
|
Definition
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Term
|
Definition
| Lead, mercury, copper poisoning, also Wilson's disease (copper accumulation) |
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Term
|
Definition
| Lead, arsenic, gold, mercury poisoning |
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Term
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Definition
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Term
| People susceptible to CO poisoning |
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Definition
| pts with cardiac disease, anemic pts, children, pregnant pts, pts at high altitude |
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Term
| 4 categories of Chlorinated aromatic hydrocarbons (CAHs) |
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Definition
| insecticides (methoxychlor), fungicides (benzene hexachloride), herbicides (dioxins), industrial chemicals (polyhalogenated biphenyls/PCBs and PBBs) |
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Term
|
Definition
| symptom of MeOH poisoning, swelling of optic disc |
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Term
|
Definition
| persistent in environment, lipophilic, cross BBB to affect CNS, cross placenta, secreted in milk |
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Term
| Mechanism of CAH toxicity |
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Definition
| bind to cytosolic Ah receptor-->moves to nucleus and binds to DNA at response element-->txn of genes--> new proteins. Microsomal enzymes like AhHydroxylase (AHH) are induced, correlating strongly with toxicity. |
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Term
| Acute CAH poisoning symptoms |
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Definition
| CNS issues, cardiac arrhythmias, fibrillation, liver and kidney damage, severe skin eruptions (chloracne) |
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Term
| Chronic CAH poisoning symptoms |
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Definition
| liver damage and enlargement, hepatic porphyria 2' to induction of d-aminolevulinate synthase-->overproduction, accumulation, and increased excretion of porphyrins in urine, reproductive damage, cancer |
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Term
|
Definition
| cholestyramine increases fecal elimination by removing bile salts. Also, activated charcoal and anticonvulsants can help. |
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Term
|
Definition
| dioxin is a contaminant in common herbicides |
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Term
|
Definition
| undergoes cyclic redox, generates superoxide radicals, H2O2, and OH radicals, which induce lipid peroxidation. Lipid peroxides damage membranes and enzymes--> inflammation--> widespread proliferation of fibroblasts--> pulmonary fibrosis |
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Term
| Paraquat poisoning contraindications |
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Definition
| O2: it will enhance toxicity! |
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Term
|
Definition
| presence of RBCs in blood, symptom of warfarin poisoning |
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Term
|
Definition
| subcutaneous purpura larger than 1 centimeter or a hematoma, commonly called a bruise. May indicate warfarin poisoning. |
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Term
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Definition
| Nosebleed. May indicate warfarin poisoning |
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Term
| Warfarin interactions as drug |
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Definition
| Sulfa potentiates it by inhibiting the inactivator, cyt. P-450. dose must be lowered |
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Term
|
Definition
| blood pumped thru dialysis membrane, removes low MW toxins like MeOH |
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Term
|
Definition
| Blood is pumped through filter cartridge, removes things that hemodialysis cannot e.g. paraquat, theophylline, salicylate, phenobarbital |
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Term
| serial activated charcoal |
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Definition
| multiple doses to remove toxins secreted into gut and prevent enterohepatic and enteroenteric recirculation, e.g. CAHs, paraquat, theophylline, phenobarbital |
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Term
|
Definition
| vomiting- may be induced by ipecac syrup |
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Term
|
Definition
| if pt is awake or intubated, a large bore orogastric tube may be used to wash out GI tract. |
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Term
| Activated charcoal cannot bind which poisons? |
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Definition
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Term
| Drug excreted after phase I of biotransformation |
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Definition
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Term
| phase I of drug biotransformation |
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Definition
| creation or unmasking of chemical group required for phase II |
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Term
| phase II of drug biotransformation |
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Definition
| drug undergoes conjugation rxns with endogenous substances, usually cytoplasmic (except glucuronosyltransferases) |
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Term
| first pass biotransformation |
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Definition
| drugs absorbed from gut go to liver first and may be largely inactivated before reaching bloodstream. Reduces f. |
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Term
| prodrug (def and example) |
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Definition
| a drug that is given in an inactive form that must be converted to its active form by an endogenous enzyme, like oseltamivir |
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Term
| importance of solubility in drug metabolism |
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Definition
| water soluble metabolites are essential form elimination. lipid soluble drugs and metabolites are recirculated. |
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Term
| example of drug toxic byproduct |
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Definition
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Term
| Metabolism of hydrophilic drugs |
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Definition
| These drugs, such as aminoglycosides, are excreted without subjection to metabolism. |
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Term
| Cytochrome P450 rxns require what components? |
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Definition
| requires NADPH cyt P450 reductase (a flavoprotein), cytochrome P450 (a hemoprotein), and membrane lipids. |
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Term
| Calcium Disodium EDTA is easily confused with what (and what are the consequences of a mixup?) |
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Definition
| Disodium EDTA without the calcium can cause hypocalcemia, which can cause tetany and death. |
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Term
| CYP reactions catalyze what? |
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Definition
| oxidization, using one O atom to hydroxylate drug- Monooxygenase. most commonly oxidates, hydroxylates, dealkylates, and deaminates |
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Term
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Definition
| CYP3A4, accounts for 50% of all Cyp-mediated drug oxidation rxns. Large active site, which can be occupied by 2 drugs at once! |
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Term
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Definition
| 30% of CYP-mediated drug rxns, works on antipsychotics, tricyclic antidepressants, beta blockers, opioids |
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Term
|
Definition
| 10% of CYP mediated rxns, works on drugs with narrow TR (warfarin, phenytoin), prefers weak acid drugs. Most drugs are weak bases. |
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Term
|
Definition
| arylhydrocarbon hydroxylase or P448, induced by CAHs and PAHs through AhR. |
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Term
|
Definition
| Induced by chronic EtOH abuse |
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Term
| Ketoconazole and triazolam- what happens? |
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Definition
| ketoconazole blocks CYP3A4, increasing triazolam levels in plasma 17x |
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Term
| Suicide inactivation of CYP (Example) |
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Definition
| Erythromycin binds covalently to enzyme after metabolism and permanently inactivates CYP3A4 |
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Term
| Phase I vs. Phase II: saturation dose? |
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Definition
| Phase I is saturated at a lower dose than Phase II |
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Term
| Phase I vs. Phase II: basal activity? |
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Definition
| Phase I has relatively lower basal activity than phase II. |
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Term
| function of glucuronation? |
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Definition
| makes drug water soluble, allows excretion |
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Term
| drug that skips phase I and phase II, can be directly excreted? |
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Definition
| Streptomycin and Gentamycin |
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Term
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Definition
| Grapefruit juice, ketoconazole, metronidazole, erythromycin |
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Term
| Cyp inducers effect on Cyp-processed drugs |
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Definition
| the other drug processed by the induced Cyp is less effective due to increased Cyp. |
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Term
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Definition
| Rifampin, Isoniazid, St. John's Wort |
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Term
|
Definition
| decreased water solubility, crystals in urine |
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Term
| preferred drug metabolism for neonates and infants |
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Definition
| drugs that are processed via sulfation rather than glucuronidation are preferred. |
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Term
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Definition
| Drug that alters the interaction of another drug (the object drug) |
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Term
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Definition
| Polypeptide drug metabolized mostly in the intestinal mucosa (rather than liver), narrow TI. Erythromycin inactivates CYP3A4, makes Cyc. A more potent |
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Term
| Children 2-12 YO: clearance, half life, dosing interval |
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Definition
| Clearance increases, half lives decrease, dosing may increase |
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Term
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Definition
| Conjugative metabolism is more intact than oxidative metabolism, so drugs that are conjugated are preferred (lorazepam>diazepam) |
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Term
|
Definition
| has a narrow therapeutic index, its plasma concentration is altered by precipitant drug |
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Term
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Definition
| mast cells (90%), CSF, basophils. mostly in complex w/ heparin. |
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Term
| Biosynthesis pathway of Histamine, starting with Histidine |
|
Definition
| L-histidine-decarboxylase |
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Term
|
Definition
| histamine-N-methyl transferase, followed by MAO-B or less often DAO, excretion |
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|
Term
| inhibits secretion of histamine |
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Definition
| B-adrenoreceptor agonists (epinephrine), cromolyn sodium inhibits release of mediators in lung mast cells |
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Term
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Definition
| inhibits release of allergy mediators in lung mast cells |
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Term
| effect of organic bases on histamine levels |
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Definition
| quaternary amines, antibiotic bases, etc. can trigger release of histamine |
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Term
| Organic bases that can trigger histamine response |
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Definition
| Tubocurarine, succinylcholine, morphine, contrast media, vancomycin |
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Term
| Difference between 1st and 2nd gen. antihistamines |
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Definition
| 1st gen is lipid soluble, crosses the BBB, causes drowsiness, antimuscarinic action |
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Term
| important 1st gen H1 antagonists |
|
Definition
| Diphenhydramine, pyrilamine |
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Term
|
Definition
| 2nd gen H1 antagonists, e.g. cetirizine |
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Term
|
Definition
| 2nd gen H1 antagonists, e.g. chlorpheniramine |
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Term
|
Definition
| 2nd gen H1 antagonists, e.g. promethazine |
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Term
|
Definition
| Cyproheptadine, Loratadine, Fexofenadine |
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Term
|
Definition
| Prostaglandins (PGs), prostacyclins(PGI2), thromboxane (TXA2) |
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Term
| Products of lipoxygenases |
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Definition
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Term
| Storage/release of eicosanoids |
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Definition
| Not stored at all, short-lived, released as needed |
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Term
|
Definition
| cleaves phospholipids to release arachadonic acid for processing into eicosanoids. Dexamethasone inhibits it. |
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Term
|
Definition
| glucocorticoid, inhibits PLA2, also directly suppresses COX-2 expression |
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Term
| Drug that irreversibly inactivates COX 1 |
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Definition
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|
Term
| Reversible inactivators of COX 1 |
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Definition
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|
Term
| COX-2 selective antagonist |
|
Definition
| celecoxib (also vioxx, but it was too selective) avoids some kidney/GI irritation |
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Term
|
Definition
| local inflammation (not GI or Kidney) |
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Term
|
Definition
| COX-1 variant, targeted by acetominophen in CNS |
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Term
|
Definition
Increase cAMP (Good)
- vasodilator
- decrease platelet aggregation
- decrease gastric acid
- relax bronchial muscle
Decrease cAMP (Bad)
- increase uterine muscle tone
- increase pain & temperature |
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Term
|
Definition
Increase cAMP (good)
vasodilator
decrease platelet aggregation
increases Renin
Decrease gastric acid
Relax bronchial muscle & uterine tone
(side effect = pain) |
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Term
|
Definition
Increases Ca++ (bad)
Vasoconstrictor
GI smooth muscle contraction
Bronchial muscle contraction
Uterine muscle tone increase |
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Term
|
Definition
Increases Ca++ (bad)
vasoconstrictor
increase platelet aggregation
contract bronchial muscle
increase uterine muscle tone |
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Term
|
Definition
Increases Ca++ (bad)
decrease blood volume
Increase leukocyte aggregatoin
GI muscle contraction
bronchial muscle contraction --> edema
pain |
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Term
|
Definition
• Stimulates G-protein coupled receptors → phospholipase C, D, A2
• Vasodilator, increases vascular permeability (edema), platelet aggregation, generates superoxide (reactive oxygen species)
• Stimulates smooth muscle contraction
• MOST POTENT ULCEROGENIC SUBSTANCE
• Inhibitor = prostacyclins |
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Term
| Serotonin is synthesized from |
|
Definition
|
|
Term
|
Definition
| metabolized by MAO & aldehyde dehydrogenase, and is sequestered by platelets |
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|
Term
| Serotonin synthesis & storage |
|
Definition
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|
Term
| Kinin effects on cardiovascular system |
|
Definition
Vasodilate arteries
Vasoconstrict veins
Contraction of endothelial cells |
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Term
|
Definition
1. Angiotensinogen is increased by corticosteroids, estrogen, thyroid hormones
2. Renin (rate limiting) cleaves angiotensin I (from angiotensinogen)
3. ACE converts AT I --> AT II
4. AT2 = vasocontriction, increases NE release, stimulates aldosterone & glucocorticoid biosynth, vasopressin release --> Increases BP |
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Term
|
Definition
| activates guanylyl cyclase -> produces cGMP -> activates protein kinase G -> relaxes smooth muscle & increases vascular tone; facilitates neurotransmitter release |
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Term
|
Definition
Cell wall synthesis inhibitor
B-lactam binds to PBPs
-inhibited by B lactamase |
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Term
|
Definition
cell wall inhibitor, bind to PBPs but more resistant to B-lactamase
1st gen = G+ --> later gen = G- |
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Term
|
Definition
cell wall synth inhibitor
irriversibly binds peptidoglycan precursor
not susceptible to B-lactamase |
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Term
|
Definition
binds to 30S subunit to inhibit protein synth
high renal & ototoxicity (cochlear = irriversible, vestibular = reversible) |
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Term
|
Definition
Block tRNA binding to 30S subunit
Adverse effects
-discoloration of teeth
-hepatotoxicity
-nephrotoxicity, phototoxicity |
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Term
|
Definition
-bind 50S subunit
-ex: erythromycin
-G+ |
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Term
|
Definition
Binds to 50S
Adverse effects = may cause superinfection by C difficile |
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Term
|
Definition
Inhibit DNA gyrase (topoisomerase)
CNS problems w/ coffee
Phototoxicity |
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