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119 Cards in this Set
- Front
- Back
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What hormones act on intracellular receptors to effect gene expression?
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corticosteroids
mineralcorticosteroids Sex steroids Vitamin D Thyroid Hormone P450 inducers |
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What are the modulators of protein tyrosine kinase signaling?
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Insulin
Epidermal growth factor platelet derived growth factor |
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What drugs block tyrosine kinase?
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Imatinib
Sorafenib Sunitinib |
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How do cytokine receptors work?
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Ligangs like Growth hormone, eythropoetin and interferions activate the JAK protein kinases, which dimerize, phosporilate tyrosines which activate STATs. When SATS are phosporilated the for dimers which dissociate and travel to the nucleus to regulate gene transcription
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What opens ligand gated nicotinic channels?
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Acetocholine brining Na+ into the cell
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What drugs/molecules affect the GABAa channels? What molecule is moving?
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Chloride moves in HYPERPOLARIZING
GABA opens the channel Benzodiazapine increases the frequency of the channel opening and enhances GABA Phenobarbital increases the duration of the channel opening |
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What do G-proteins stimulate?
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The binding abd hydrolysis of GTP to GDP
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What is the role of B-arrestin?
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In G-protein coupled receptors that continue to be bound by and agonist will phosporilate G-protein receptor kinases (GRKs) When these are phosporilated B-arrestin can bind and desensitize the receptor to g-proteins. Once the agonist is removed the GRK effect is terminated
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What drugs increase cAMP formation?
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Epinepherine, Norepinepherine & Isoproterenol (B1 & B2)
Dopamine (DA1) Dobutamine (b1) Histamine (H2) FSH Glucagon ACTH Also caffiene and theoophyllinr by inhibiting phospodiesterase |
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What drugs inhibit cAMP formation?
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Norepi - Hypotension (a2)
Clonadine (HyperTN) (a2) Dopamine- Hypotension (D2) acetylcholine (M2) Morphine (u, k, delta) serotonin (5-HT1) |
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Which Gq coupled receptors act through IP3/DAG?
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M1 & M3 receptors -Ach
Alpha-1 receptors - NE and Phenylephrine 5-HT1c receptors - seratonin |
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What is the role of cGMP and how is it made?
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It causes relaxation of the vascular smooth muscle.
Production enhanced by atrial naturetice peptide or Nitric Oxide (NO) NO made in endothelial cels by activation of muscarinic or histmine receptors->increases intracellula Ca2+->activates calmodulin->activates NOsynthase_> convets arginine to citrulline and NO. NO activates gyanlyly cyclase in the membrane which converts GTP->cGMP which activates protein kinase G causing vasodialation |
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How is cGMP inactivated?
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By phospodiesterase V.
Sildenafil (Viagra) inhibits this enzyme increasing the concentration of cGMP. |
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What is acetylcholine's antagonist?
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Atropine
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What is Epinepherins a1 receptor antagonist?
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phentolamine
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What is Epi's B1 & B2 antagonist?
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Popranolol
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What is the antagonist for histamine H1 receptors?
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benadryl
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What is the antagonist for histamine H2 receptors?
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Cimetidine
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What do competitive antagonists do to the Km and Vmax?
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decrease Km (can't sit)
No change Vmax (can still get maximal response |
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What do noncompetitive antagonists do to the Km and Vmax?
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Decrease the Vmax (they can't work/reach max effect)
No chage to Km - they can still sit in the receptor site |
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What is the therapeutic ratio for humans?
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TR= TD50/ED50
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What toxicities do amionglycosides have?
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Renal and ototoxic
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What toxicities does chloramphenicol have?
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aplastic anemia
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What toxicities does tetrecycline have?
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teethe discoloration
retardation of bone growth photosensitization |
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What toxicities does isotretinonin have?
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photosensitzation
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How would a Type I hypersensitivity present clinically?
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GI Allergy
Urticaria Asthma Anaphalactic Shock IG-E Mediated |
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How would a Type II hypersensitivity present clinically?
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Luekopenia
Thrombocytopenia Hemolytic Anemia Granulocytopenia IgM & IgG Mediated |
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How would a Type III hypersensitivity present clinically?
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Serum Sickness
Vasculitis Arthritis Glomular Nephritis Ag-Ab Complex mediated |
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How would a Type IV hypersensitivity present clinically?
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Contact dermatitis
Tuberculosis Allergic encephalitis Sensitized T-Cell mediated |
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What drug has the idiosyncrasy of apnea?
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Succinylcholine (it is a muscle paralysis agent used for surgeries. A serum cholinesterase that is incapable of destroying the drug is responsible
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What is the consequence of being a fast or slow acetylator?
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In relation to isoniazid...
Slow acetylators can have b6 def anemia and neuropathies Fast acetylators can have hepatotoxicity |
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What drug used to treat G6P-dehydrogensase has been shown to cause hemolytic anemia?
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Primaquine
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What drug can cause prophyria in patients with abnormal heme biosynthesis?
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Barbituates
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What is pharmacodynamics?
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The effects of drugs and their mechanism of actions
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What is pharmackinetics?
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the way the body handles adsorption, distribution, biotransformation and excretion also metabolisma nd half life
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What is the ionization formula for an acid?
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ph-pKa=log (A-)/(HA)
A- is ionized HA is unionized or protinated |
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What is the ionization formula for a base?
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pH-pKA=log(B)/(BH+)
B is unionized BH+ is protinated and ionized |
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What drugs would you use to detox acids like salicyclates or barbituates?
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Bicarb ot acetazolamide - they will make the urine basic
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What drugs would you use to detos from amphetamine or clonadine (bases)?
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Ammonium Chloride
It will acidify the urine |
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How do you measure bioavailability?
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The AUCoral/AUCiv x 100
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What is the formula for Volume of Distribution?
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Vd= total amount of drug in the body (iv)/concentration in the plasma
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What is the standard value of body fluid in the Plasma? Extracellular compartment? Total Body?
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3L - Plasma
12L - Extracellular 41 L- Total body water |
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What is the relationship of Vd to plasma protein binding?
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Low Vd means drug is high in the plasma (blood)
Drugs with high plasma protein binding have a low Vd |
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What drugs tend to diffuse into breastmilk?
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Basic drugs because milk is more acidic than plasma
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What is 1st Order Elimination?
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When a drug is eliminated in a constant proportion.
The concentration of the drug is the limiting factor Shows as a straight line on a semilogarythmic plot of concetration vs time. |
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What is Zero Order elimination?
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It involves the saturation/max amount of a drug that can be removed per unit time. Example EtOH is 10g per hour regardless if how much alochol is in blood.
Zero order elimination is a straight line in the linear system |
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What are the two equations for drug Clearance?
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CL=Vd x Kcl
CL=VD x (0.7/halflife) |
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Describe the relationship between the steady state concentration and half-life, dose and clearance.
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Css is proportional to the dose and half life and INVERSLY proprtional to the clearence
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What is teh formula for loading dose?
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LD= Css x Vd
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What is the formula for the maintainance dose?
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MD= Css x CL
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What is a phase 1 reaction?
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conversion of lipod soluble parent compound into more polar coumpounds.
-Oxidations -Reductions -Hydrolysis reactions |
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What is a phase 2 reaction?
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Conjugation Reactions
Hydroxyl roups conjugated with glucuronic acid or sulfate Organic Acids conjugated with glycine |
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What is the cutoff for synthetic products to be excreted?
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less than 350 kidney
greater than 350 GI |
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What drugs are metabolized int he intestine?
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chlorpromazine
clonazepam |
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What drugs are metabolized int he Intestinal wall?
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Epinepherine
NorEpinepherine Tyramine |
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What drugs are destroyed by gastric juices
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Insulin
Polypeptides |
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What drugs are metabolized in gastric acid?
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Penicilliin-G
Erythromycin |
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What factors contribute to drug interactions?
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1)Plasma-Protein binding: if drug and another substance compete for same site on PP then the free amount rises and can have interactions
2)Induction: the P450 system can be induced to make more metabolites to clear a drug (when more of that drug is taken) A drug inducing its own metabolism is metabolic tolerance |
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What does it mean to be inducable?
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a drug that increases the activity of microsomal oxidase and conjugating systems when administered repeatedly.
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What are the features of glucuronyl transferase?
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-Most common enzyme in phase II rxn
-It is microsomal and therefore enducable, and subsequently a possible site of drug interactions |
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What are the Nonmicrosomal metabolism – non-inducible molecules/enzymes?
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• Esterases and amidases
• pseudocholinesterases – genetic polymorphism • local anesthetics, succinylcholine • Monoamine oxidases • endogenous amines, tyramine • Alcohol and aldehyde dehydrogenases • genetic polymorphism • ethanol metabolism |
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How is ethanol metabolized?
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alcohol dehydrogenase and CYP2E1
-Consitiative and not inducible |
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What does xanthine oxidase inactivate?
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6-mercaptopurine
-Consitiative and not inducible |
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What does monoamine oxidase inactivate?
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Amines:
-Tyrosine, NE, 5-Hydroxytryptamine -Consitiative and not inducible |
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How is warfarin inactivaded?
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conversion of a ketone to hodroxyl by CYP2A6
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What bonds are subject to hydrolysis making them constituative and non-indcable/non-microsomal?
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Ester and Amide bonds
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What is the target of a phase II reaction? What is the result?
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A hydroxyl, thiol or amino group
conjugation results in a pharmacologically inactive and less lipid soluble (compared to precursor) compound |
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What groups most often involved in conjugate formation?
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glycoronyls-
sulfates methyls- acetyls- glycyls- glutathiones- |
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Why do some drugs that go throguht the enterohepatic circulation have longer half lives?
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Glucoronides that are secreted into the bile are cleaved by glucornidases in the small intestine and able to be reabsorbed
Ex. Conjugated estrogens |
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What is the clinical implication of the fact that certain drugs metabolize differently in some people due to pure biological variation?
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Figure out if fast or slow metabloizers
slow metabolizers get less fast metabolozers get a larger dose |
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What is the effect of glomular filtration on drug metabolism?
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Drugs less than 45,000 are filtered
Plasma is 68K and isn't filtered nor are the drugs that are strongly bound to it |
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How do drugs that are plasma bound or that miss filtration in the glomerulous get dealt with?
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There are 2 non-selective carrier systems for acids and bases in the tubular lumen that transport drugs against the electrical concentration gradient. Penicillin for example though 80% bound to PP is cleared very quickly this way.
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What is Probenecid?
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A molecule that competes for the same transporter in the kidney as penicillin.
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What is the effect of the renal tubule on drug clearance?
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It is permable to most drugs which therefore alows them to be reabsorbed. Ionized drugs get trapped and peed out. Lipid soluble drugs cross back very easily and take longer to eliminate.
Ex. Digoxin and aminoglycosides |
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What are the enzyme educing drugs for CYP-3A4
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Rifampin/Rifabutin
barbituates phenytoin carbamazepine glucocorticoids St. jons wort |
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What is the effect of glomular filtration on drug metabolism?
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Drugs less than 45,000 are filtered
Plasma is 68K and isn't filtered nor are the drugs that are strongly bound to it |
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How do drugs that are plasma bound or that miss filtration in the glomerulous get dealt with?
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There are 2 non-selective carrier systems for acids and bases in the tubular lumen that transport drugs against the electrical concentration gradient. Penicillin for example though 80% bound to PP is cleared very quickly this way.
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What is Probenecid?
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A molecule that competes for the same transporter in the kidney as penicillin.
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What is the effect of the renal tubule on drug clearance?
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It is permable to most drugs which therefore alows them to be reabsorbed. Ionized drugs get trapped and peed out. Lipid soluble drugs cross back very easily and take longer to eliminate.
Ex. Digoxin and aminoglycosides |
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What are the enzyme educing drugs for CYP-3A4
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Rifampin/Rifabutin
barbituates phenytoin carbamazepine glucocorticoids St. jons wort |
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What are the CYP-1A2 Inducers?
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smoking (benzapyrene)
Charcoal broiled foods cruciferous vegetables dioxin |
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What are the inducers for CYP-2D6?
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None
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What are the inhibitors of the P450 system?
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cimetidine
amiodarone paroxetine fluoxetine |
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What are the CYP3A4 Inhibitors?
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ketoconazole
itraconazole HIV protease inhibitors (ritonavir) Erythromycin Clarithromycin diltiazem nicardipine verapamil grapefrut juice |
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What are the CYP2D6 inhibitors?
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quinidine
SSRIs |
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What are the contraindications for gastric lavage or induced emesis?
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Not After 4 Hours
-no more than 30 minutes after infestion of a corrosive substance -if hydrocarbon solvents have been ingested -if coma, stupor delirium or convulsions are present or eminent |
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Would hemodyalysis be appropriate in a patient whose toxin had a high Vd
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No. The higher the Vd, the less drug is in the plasma. This is a better detox method for drugs with low Vds
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What cathartic is suggested to increase elimination in some toxicology?
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Magnesium Sulfate
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What is mannitol's role in toxicology?
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it can be used as an osmotic diuretic
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What drug is used for iron poisoning?
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deferoxamine mesylate
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What drug can be used for arsenic, gold, mercury and acute lead poisonin?
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Dimercaprol
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What drugs (3) can be used for lead poisioning?
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dimercaprol
Edetate, Calcium disodium Penicillamine |
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What diseases does Penicillamine help with?
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cheleating in Wilsons. cystinuria, RA, copper and lead
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What drug is used for Tylenol overdose?
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Acetylcysteine
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What is used for cardiac glycoside toxicity?
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Digoxin specific FAB antibodies
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What does Atropine detox?
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cholinesterase inhibitor poisions
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What does Pralidoxime chloride detox?
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it is a cholinesterase reactivator given only for organo phosphates
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What does Flumazenil detox?
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Benzo overdose
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What is Naloxone?
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An opiod antagonist
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What would you find in a cyanide antidote package?
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Sodium Nitrite, sodium thiosulfate and amyl nitrite
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What is glucagon used to detox
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poisioning with beta blockers
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What does ethanol detox?
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methanol or ethylene glycol
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What does Fomepizole detos
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ethelyine glycol poisioning: it is an alcohol dehydrogenase inhibitor
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What 3 things will Bicarb detox?
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poisioing with cardiac depressants (tricyclics, quinidine
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What does diazapam detox?
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chemical-induced convulsions
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What would you use for and isoniazid overdose?
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Pyridoxine
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What are the signs of botulism poisoning? How do you treat?
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Sx 8hrs-8days
vomiting, double vision, paralasis Tx emesis, lavage or cathartic give type ABE botulinus antitoxin |
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What are the 2 main causes, sx, and tx for acute gastroenteritis?
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Samonella and B. cereus
Sx 2-4 hr after eating, GI inflammed, mild fever, dehydration, shock Tx: anti emetic, maintain fluids supportive care |
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What are the sx of bleach ingestion? Treatment?
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Severe irritation, hypo tension, delirium, coma
Tx Rinse skin if topical MILK<>ICECREAM<>EGGS no lavage/emesis Support vitals |
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What are the hallmark sx of organophospahre (parathion, malathion) and tx?
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-They are irreversable cholineesterASE inhibitors
sx: cholimemetic SLUD, salivation,lacrimation, urination, and defiucation Tx: Atropine to block cholinergic effectgs 2-PAM to reactivae acetylcholinesterASE enzyme -Lavage/emesis if ingestion was recent |
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When are 2-PAMs strongly contraindicated?
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in carbamate poisoning. They are reversible cholinesterase inhibitors and 2-PAM will exacerbate the problem
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What is another name for 2_PAM
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Pralidoxime
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What is strychnine? What is mechanism? Sx? Tx?
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Rodentiside that competitively inhibits glycine
Sx: convulsions and sensitivty to sensory stimuli TX: IV diazepam or succinylcholine |
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How is every toxicological convulsion treated?
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Diazapam
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Detox for methanol
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Ethanol and fomepizole an synth alcohol dehydorogenase inhibitor
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What is the Dose/Effect ie Blood ETOHfor ehtanol poisioning?
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Acute poisoning, mild 50-150mg%
Moderate poisioning, 150-300% Severe poisioning, 300-500mg Coma 500mg% - acn do dyalysis |
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What drug is given to discourage alcohol use?
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Disulfiram: it inhibits acetaldehyde dehydrogenase and and accumulation of acetaldehyde causes N/V
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Tx for rubbing alcohol
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gastric lavage
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What do you do if someone drinks gasoline *(hydrocarbons/petrolium distilaltes?)
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Treat symptoms
Don't do emesis or lavage without a tracheal intubation! |
