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66 Cards in this Set
- Front
- Back
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3 primary processes of pharmicokinetics
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absorption
distribution elimination |
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what is absorption
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the process in which a drug is delivered from its site of administration to the blood stream
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what do the rate and efficacy of absorption depend on?
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route of administration
blood flow surface area solubility of drug drug-drug interaction ph |
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in what way does the ph of a drug affect its charge
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acidic drugs are uncharged when protonated
basic drugs are charged when protonated |
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how does charge affect a drugs ability to permeate a cell membrane
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- a drug will pass thru cell membranes if uncharged
- therefore, the amount of drug absorbed depends upon its ratio of charged to uncharged species, which is determined by the ambient ph at the site of administration and the pka of the drug |
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what is bioavailability
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the fraction of administered drug that gains access to its site of action or a biologic fluid that allows access to the site of action
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what is the bioavailability of an IV injected drug
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100%
all of the drug enters the systemic circulation |
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what is the bioavail.. of a drug that is not IV injected
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less than 100%
some of the drug may not be absorbed or it may become inactivated (ie: first pass metabolism) |
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what factors affect bioavail..?
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1- first pass metabolism
2- all factors that affect absorption (ph, blood flow, drug solubility, drug-drug interactions, route of administration) |
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what are the routes of drug administration
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1. enteral admin (alimentary):swallowed, sublingual, buccal, rectal
2. parenteral - any route that is not enteral (there are a bunch) |
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4 types of alimentary routes of administration and the advantage of each
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oral
sublingual buccal rectal ___________________ oral- most common. convenient, patient compliance and utilization of small intestine sublingual- nitroglycerin given this route. allows the drug to drain via the superior vena cava thus bypassing first pass metabolism buccal- same as sublingual rectal- useful when oral route is unavailable due to vomiting or loss of conciousness. 50% of drug absorbed will bypass the liver |
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4 parenteral routes of administration
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1- intravenous - most rapid & potent. 100% in circ
2- intramuscular- more rapid than oral. minimizes hazards of intravascular injection 3- subcutaneous- same as intramuscular but usually a bit slower 4- intrathecal- in cases of acute cns infections or spinal anesthesia, drugs can be more affective if injected directly into the spinal subarachnoid space |
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what category of drugs is commonly administered by inhilation
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pulmonary agents
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how are inhaled drugs administered
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by machine aerosolization or vaporization; inhalation of aerosol or fine powder
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when is topical administration used
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1- local drug actin for tx of localized disease
2- systemic drug action by admins of a drug via a mucus membrane or the skin(nicotine patch...) |
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what is distribution
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process by which a drug leaves the blood stream and enters the interstitium or the cells of tissues
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by what 3 mechanism are drugs absorbed into cells
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1- passive diffusion- governed by a concentration gradient across a membrane, which makes a drug move from an area of hi conc to low conc. this is the most important & common absorp mechanism
2- transport by specific carrier proteins..a form of passive diffusion facilitated by carrier proteins 3- active transport- transport against conc gradient. the E comes from dephosphorylation of ATP |
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what does distribution depend on
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- blood flow
- capillary permeability- structure varies depending on the organ (tight in brain, wide in liver & spleen) - binding to plasma proteins such as albumin - limits access to cellular compartments - drug structure- small lipophilic molecules will be able to distribute to more compartments than will large polar molecules |
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why does the body biotransform (metabolize) drugs
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the lipophilic properties of drugs that allow them to pass thru cell membranes hinder their elimination. therefore, drugs are modified to become more polar so that elimination can occur more quickly
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what are the 2 general sets of modifications that occur in biotransformation
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phase I & phase II reactions
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what happens in phase I reaction
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lipophilic molecules are converted to more polar molecules by introduction, or unmasking, of a polar functional group
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examples of phase I rxns
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oxidation
reduction(dehydrogenation) hydrolysis |
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what happens in phase II conjugation reactions
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conjugation= formation of a covalent linkage between functional groups on the parent drug and another substrate
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what substrates are added in phase II reactions
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glucuronate (most common)
acetate glutathione sulphate |
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in what organ do phase I and phase II rxns occur
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liver
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where in the liver do these rxns occur on a cellular level
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phase I- endoplasmic rticulum
phase II- cytosol |
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what factors affect drug biotransformation
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- genetic differences- each individual has a varying capacity to metabolize a drug through a given pathway
- induction of the cytochrome P-450 system - may increase biotransformation - inhibition of cytochrome P-450 sys - if 2 drugs are competing for the active site of the same enzyme, then one of the drugs will have a decreased rate of transformation - disease...esp of liver - age & gender |
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define first order kinetics
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process by which a constant fraction of a drug is metabolized per unit time.(for example, 10% of a certain drug is eliminated every 2 hours(starting conc = 100mg/dl). so after 2 hours, the conc will be 90mg/dl; after 4 hours it will be 80mg/dl)
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define zero order kinetics
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process by which a constant amt of drug is metabolized per unit time regardless of drug conc. ethanol is metab this way.
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what is drug excretion
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the process by which a drug or its metabolite is removed from the body
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what is the difference between excretion and secretion
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excretion is the removal of a drug and/or its metabolite from the body.
secretion occurs when a drug is actively transported from one body compartment to another (ie: drugs that are secreted into the renal tubule from the medullary capillaries) |
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what are the major routes of excretion
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a- renal - urine is 1 of most common routes of elimination
b- fecal c- respiration - primarily for anesthetic gases and vapors d- renal secretion e- skin secretion (sweat) f- secretion of a drug into breastmilk |
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what is a receptor
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a macromolecule typically made of protein that interacts with either an endogenous ligand or a drug to mediate a biologic effect. (biologic effect is called pharmacologic effect when a drug interacts with a receptor)
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what are the 2 main fxns of a receptor
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1- ligand (drug, substrate) binding
2- activation of an effector system (message propagation) |
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what is an effector
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an effector transduces drug receptor interactions into cellular effects (aka signal transduction). there are 4 major mechanisms of signal transduction (aka receptor (drug) superfamilies)
1- receptor operated channels (ROCs)- ligand gated ion channels 2- G protein-coupled receptors (second messenger systems) 3- receptors that posess tyrosine kinase activity (tyrosine kinase receptors) 4- DNA coupled receptors |
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what are the 3 best known second messenger systems, and what enzyme catalyzes each of them
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1- cAMP assoc with adenylate cyclase
2- cGMP assoc with guanylate cyclase 3- inositol phosphate (IP3) assoc with phospholipase C |
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what drug is an agonist
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a drug that binds to and activates receptors
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what is a full agonst
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a drug that, when bound to a receptor, produces 100% of the maximum possible biologic response
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what are partial agonsits
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drugs that produce less than 100% of the maximum possible biologic response no matter how hi their concentration
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what are antagonists
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drugs that bind to cell receptors or enzymes that inhibit a biologic response
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what does a competitive antagonist do
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it binds reversibly to the same cell receptors as the agonist or to the same active site of enzymes
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how can a competitive antagonist be overcome
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by increasing the concentration of the agonist
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what does a non-competitive antagonist do?
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it binds irreveribly to a cell receptor or a different site on an enzyme than its agonist does. a non-competitive antagonist cannot be overcome by increasing the agonist concentration.
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what is the difference between drug efficacy and drug potency
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efficacy is the ability of a drug to produce a measurable biologic effect. potency is related to the amount of drug necessary to cause a biologic effect
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_______ is related to the amount of drug necessary to cause a biologic effect
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potency
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example of efficacy
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if 2 drugs, drug a & drug b, are both claimed to reduce a patients heart rate by 25%, then they both have the same efficacy
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example of potency
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only 1mg of drug A needs to be given to achieve a certain reduction in heart rate, whereas 10mg of drug B is needed to achieve the same reduction. therefore, it can be inferred that drug A is more potent
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drug X is able to reduce the systolic blood pressure with 20mmHg, whereas drug Y merely can lower bp w/ 5mmHg. therefore, it can be inferred that drug X has more ________ than drug Y
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efficacy
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what is EC50
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1- the EC50 of a graded dose response curve represents the drug concentraion necessary to reach 50% of its maximal effect
2- the EC50 of a quantal dose response curve represents the drug concentration at which 50% of the population exhibits a response |
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how many half-lives are required to reach a stedy state concentration
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approximately 4-5 half lives
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how many half lives are required to eliminate most of the drug from the body? (first order kinetics is assumed)
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approx 4-5 half lives
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what is clearance
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clearance is defined as the volume of blood (plasma) cleared of drug per unit time
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what is therapeutic index (TI)
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the ratio of a drug's toxic dose to its therapeutic dose. a safe drug will have a high TI
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which is the least common mechanism for absorption of drugs into cells
active transport passive diffusion |
active transport
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t/f
phase I and II biotransformation reactions occur in the kidney |
false
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this would be an example of_______:
drug X is able to reduce the systolic bp with 20mmHg, whereas drug Y is merely able to lower the systolic bp with 5 mmHg. therefore, it can be inferred that drug X has the greater efficacy... |
efficacy
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example of_______:
only 1 mg of drug A needs to be given to achieve a certain reduction in heart rate, whereas 10 mg of drug B is needed to achieve the same. therefore, it can be inferred that drug A has the greater potency |
potency
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will a charged or non-charged drug molecule be more easily distributed
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non-charged drug molecule
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will a charged/non-charged drug molecule be more easily absorbed
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non-charged drug molecule
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which drug molecule will most effectively be absorbed and distributed within the body?
- small & polar - large & polar - small & lipophilic - large & lipophilic |
small & lipophilic drug molecule
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99% of Coumadin is bound to plasma albumin, while only 25% of Amoxil is bound to plasma albumin. Which of the drugs will most easily leave the blood stream (only considering plasma protein binding)
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Amoxil
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which drug is least likely to be distributed from the blood stream to the interstitium and target cells
- drug circulating thru---> liver brain spleen |
drug circulating thru the brain
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will a basic drug or an acidic drug be more effectively absorbed from the small intestine to the blood stream
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basic drug (weak base; pka 7) passing thru jejunum/ileum (pH is 8)
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which of the following drugs will most easily be eliminated via the kidney (pH 5)
- diazepam (weak base - pKa 3.5) - penicillin (weak acid - pKa 2.5) |
penicillin
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what is volume of distribution (Vd)
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Vd equals the apparent volume into which a drug is able to distribute
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which of the following drugs will most easily be absorbed in the small intestine (pH-8)
diazepam - (pKa 3.5)- weak base panicillin - (pKa 2.5)- weak acid |
diazepam
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