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86 Cards in this Set
- Front
- Back
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What do pharmacokinetics describe?
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Where the drug goes and how much needed for desired effect.
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What factors affect pharmacokinetics?
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Absorption, distribution, metabolism, and excretion.
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What affects absorption?
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Rate is affected by route of drug administration and extent is determined by metabolism and lipid solubility.
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What affects the distribution?
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Diffusion across gradient, lipid/water partitioning, charge and pH.
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Are most drugs weak acids or weak bases?
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Yes.
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Are drugs more likely to be trapped in ionized or neutral form?
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Ionized, since ions don't easily cross membranes.
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How is the metabolism of a drug defined?
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Clearance from the body compartments and eventual elimination from the body.
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What is first pass metabolism?
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The reduction in bioavailability in orally administered drugs.
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What is the volume of distribution (Vd) and what are the units?
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Vd = dose/plasma concentration (liters/kg)
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What has a higher Vd, protein-bound drugs or lipid soluble drugs?
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Lipid soluble drugs have a much higher Vd.
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What is clearance (CL)?
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(CL = ke * Vd) or the ratio of the rate of elimination by all routes to the concentration of drug in biological fluids.
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Where does most elimination (ke) occur?
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Through the liver and kidney, and is usually either 1st or 0th order.
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What is the half-life of a drug?
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half-life = 0.693 * Vd/CL
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What is the dosing rate at steady state (DRss)?
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DRss = CL * TC/F , where F=bioavailability fraction. Rule of thumb indicates that it takes 4-5 half lives to reach the steady state level.
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How do you calculate the maintenance dose (MD)?
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MD = DR/F * DI, where DI = dosing interval
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What is the loading dose (LD)?
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LD = Vd * TC, where TC = target concentration.
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What are pharmacodynamics?
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This term describes how a drug works. This is determined by 1) drug-receptor interactions; 2) duration of drug action.
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What are the 2 phases in drug metabolism?
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Phase I = conversion of drug to more polar or reactive compound; Phase II = increase water solubility to increase water solubility.
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What are the cytochrome P-450 group of enzymes?
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Enzymes located in the smooth ER which help catabolize drugs.
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What is the effect of CIMETIDINE?
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CIMETIDINE is a P-450 inhibitor and slows down drug metabolism.
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What is the rule of thumb which tells you whether a drug is a weak acid or a weak base?
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The sodium salt of a drug indicates a weak acid and the HCl salt of a drug indicates a weak base.
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What is an alkanizing agent?
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bicarbonate
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What is and acidifying agent?
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ammonium chloride
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What are some factors that affect Vd?
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disease (obesity, renal disease), size (capillary permeability), lipid solubility, and charge
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What does it mean when the rate of elimination is a first order event?
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The ke is dependent on concentration and elimination is not saturable.
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What does zero order elimination rate meatn?
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The ke is independent of concentration, elimination IS saturable, and half-life is unpredictable.
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What are examples of drugs with a zero order elimination rate?
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aspirin, alcohol, and phenytoin
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What proportion of the therapeutic level of a drug is remaining after 3 half-lives of dosing?
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87.5% (1 hl = 50%, 2 hl = 75%)
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What are the 3 basic reactions in Phase I of drug metabolism?
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oxidation, reduction, and hydrolysis
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P-450 is responsible for which Phase I reaction?
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oxidation
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What are 4 reactions in Phase II drug metabolism?
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glucoronidation, sulfation, acetylation and glutathione conjugation
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Which is the most important organ in drug metabolism?
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Liver is most important, followed by the kidney.
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What are the 2 components of the cytochrome P-450 enzyme system?
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oxidase and reductase
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What are examples of P-450 inducers?
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barbiturates, ethanol, which enhance the metabolism of warfarin (anticoagulant) and tylenol (analgesic), respectively.
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What are examples of P-450 inhibitors?
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cimetidine and allopurinol, which decrease the metabolism of valium and tolbutamide, respectively
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What is the EC50?
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Concentration of a drug required to yield 50% of maximal effect.
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What drugs act through competitive antagonism?
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propranolol and atropine
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What drug acts as a non-competitive antagonist?
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phenoxybenzamine
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Which drugs are full agonists?
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norepinephrine and acetylcholine
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Which drug is a partial agonist?
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pindolol
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What two neuronal receptors are coupled to ion channels?
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Cholinergic nicotinic receptors and GABA receptors.
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Which two neuronal receptors are coupled to adenyl cyclase?
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beta-adrenoreceptors and alpha2-adrenoreceptors
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Which two neuronal receptors are coupled to diacylglycerol and inositol triphosphate?
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alpha1-adrenoreceptors and cholinergic muscarinic receptors.
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What are the 6 steps associated with neurotransmission in a cholinergic neuron?
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synthesis, storage, release, binding, degradation, choline recycling
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What is the name of the enzyme that catalyzes combination of acetyl CoA with choline to form Ach in the cytosol?
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choline acetyltransferase (CAT).
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What is the effect of botulinum toxin?
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Blocks the release of the Ach-filled vesicles at the pre-synaptic terminal.
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What is the function of acetylcholinesterase?
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Cleaves Ach to acetylcholine and choline.
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Name 4 direct-acting cholinergic agonists.
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acetylcholine, bethanechol, carbachol, pilocarpine
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Name 4 indirect acting, reversible, cholinergic agonists.
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edrophonium, neostigmine, physostigmine, pyridostigmine.
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What are 2 indirect-acting, irreversible, cholinergic agonists.
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echothiophate, isofluorophate.
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How many different types of muscarinic receptors are there?
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5: M1-M5.
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Where are M1 receptors located?
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Gastric parietal cells.
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Where are M2 receptors located?
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Cardiac cells and smooth muscle.
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Where are M3 receptors located?
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Exocrine glands and smooth muscle.
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What is the mechanism of action of the M2 subtype muscarinic receptor?
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G protein stimulation, AC inhibition, increased K+ conductance, decreased rate and force of contraction.
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Effects of a1 stimulation.
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vasoconstriction, + peripheral resistance, + BP, mydriasis, + closure of internal sphincter of bladder
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Effects of a2 stimulation.
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inhibit NE release, inhibit insulin release
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Effects of b1 stimulation.
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tachycardia, + lipolysis, + myocardial contractility
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Effects of b2 stimulation.
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vasodilation, slight - in peripheral resistance, bronchodilation, + liver & muscle glycogenolysis, + glucagon release, relaxed uterine smooth muscle
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What are the 5 catecholamines used widely clinically?
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DINED - dopamine, isoproterenol, norepinephrine, epinephrine, dobutamine
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What are the target receptors and therapeutic uses of epinephrine?
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(a1, a2, b1, b2); acute asthma, open-angle glaucoma, anaphylactic shock, in local anesthetics to + duration of action
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What are the target receptors and therapeutic uses of norepinephrine?
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(a1, a2, b1); treatment of shock
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What are the target receptors and therapeutic uses of isoproterenol?
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(b1, b2); bronchodilator in asthma, cardiac stimulant
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What are the target receptors and therapeutic uses of dopamine?
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(dopaminergic, b1); treatment of shock, congestive heart failure
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What are the target receptors and therapeutic uses of dobutamine?
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(b1); congestive heart failure
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What are the target receptors and therapeutic uses of phenylephrine?
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(a1); nasal decongestant, treatment of supraventricular tachycardia
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What are the target receptors and therapeutic uses of methoxamine?
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(a1); treatment of supraventricular tachycardia
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What are the target receptors and therapeutic uses of clonidine?
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(a2); hypertension
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What are the target receptors and therapeutic uses of metaproterenol?
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(b2>b1); treatment of bronchospasm
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What are the target receptors and therapeutic uses of terbutaline, ritodrine, and albuterol?
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(b2); treatment of bronchospasm and premature labor
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What are the target receptors and therapeutic uses of amphetamine?
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(a, b, CNS); CNS stimulant in treatment of children with attention deficit syndrome
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What are the target receptors and therapeutic uses of ephedrine?
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(a, b, CNS); treatment of asthma, nasal decongestant
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What is the receptor selectivity and therapeutic use of propranolol?
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(b1, b2); hypertension, glaucoma, migraine, hyperthyroidism, angina pectoris, myocardial infarction
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Are black and white patients equally responsive to all hypertension treatments?
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No, black patients are not as responsive to b-blocker therapy.
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Why are b-blockers contraindicated in patients with asthma or COPD?
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b2 blockade leads to bronchoconstriction
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What is the effect of b-blockers on renal perfusion?
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Lower blood pressure leads to decreased renal perfusion, resulting in Na+ retention and + plasma volume.
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What is the receptor selectivity and therapeutic use of timolol?
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(b1, b2); glaucoma, hypertension
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What is the receptor selectivity and therapeutic use of acebutolol, atenolol, metoprolol?
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(b1); hypertension
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What is the receptor selectivity and therapeutic use of labetalol?
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(a1, b1, b2); hypertension
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What is commonly used to treat hypertension?
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propranolol, metoprolol, timolol, other b-blockers reduce cardiac output and renin secretion
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What is commonly used to treat glaucoma?
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Timolol, and other b-blockers reduce secretion of aqueous humor.
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What is commonly used to treat migraine?
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Propranolol provides prophylactic effect.
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What is commonly used to treat thyrotoWhat is commonly used to treatosis?
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Propranolol reduces cardiac rate and potential for arrhythmias.
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What b-blockers are indicated for arrhythmia prophylaWhat is commonly used to treatis after MI?
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Propranolol, Metoprolol and timolol reduce CO and renin secretion.
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What b-blockers are used for supraventricular tachycardias?
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Propranolol, esmolol, and acebutolol slow AV conduction velocity.
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What is commonly used to treat angina pectoris?
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Propranolol, nadolol, and other b-blockers reduce cardiac rate and force.
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