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75 Cards in this Set
- Front
- Back
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What is pharmacokinetics?
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Deals with what the body does to the drug: absorption, distribution, sites of action, tissue storage, metabolism and excretion.
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What factors are involved in drug permeation/absorption?
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Solubility, concentration gradient, surface area, vascularity, ionization.
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In what form can drugs cross cell membranes?
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Non-ionized form (lipid soluble).
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In what form are drugs excreted?
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Ionized form (water soluble) are better renally excreted
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What factors affect renal clearance of drugs?
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The drug must be in free form, ionized or nonionized. Only nonionized drug can be actively secreted or reabsorbed.
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What effect does acidification of urine have on drugs?
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Increases ionized fraction of weak bases and increases their renal elimination. NH4Cl, vitamin C, cranberry juice.
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What effect does alkalinization of urine have on drugs?
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Increases ionized fraction of weak acids and increases their renal elimination. NaHCO3, acetazolamide.
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Urine alkalinization agents
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NaHCO3, acetazolamide
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Urine acidification agents
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NH4Cl, vitamin C, cranberry juice
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What is Cmax?
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Maximal drug level obtained with the dose
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What is Tmax?
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Time at which Cmax occurs
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What is the lag time?
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Time from administration to appearance in blood
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What is onset of activity?
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Time from administration to blood level reaching minimal effective concentraion
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What is duration of action?
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Time that the plasma concentration remains above minimial effective concentration
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What is time to peak?
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Time from administration to Cmax.
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What is bioavailability?
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Is the fraction of a dose that reaches the systemic circulation
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What is the first-pass effect?
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Is the decrease in bioavailability of an oral drug after passing from the portal blood through the liver. Portal blood will always have a higher concentration of the drug before passing for the first time through the liver.
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What is bioequivalence and what factors are involved?
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Bioequivalence is the similarity between two formulations of the same drug. To be bioequivalent they must have the same bioavailability and the same rate of absorption.
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How are rate of absorption, Tmax and Cmax related?
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The faster the rate of absorption the smaller Tmax and larger Cmax. Tmax and Cmax are rate dependant.
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What is distribution?
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Is the process by which a drug reaches the target tissues from systemic circulation.
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What factors affect distribution of a drug?
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Protein-binding capacity and competition between drugs for protein-binding sites, barriers such as placenta or brain.
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What is volume of distribution?
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Correlates dose given with the plasma level at time X. Vd=Dose/C0. C0=[plasma] at zero time.
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What is the significance of the volume of distribution?
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It's needed to calculate a loading dose; when Vd is low, a high fraction of the drug is bound to proteins; when Vd is high, a big fraction of the drug is being sequestered in tissues.
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Relationship between plasma concentration and volume of distribution
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Inversely proportional. The higher the plasma concetration, the lower the volume of distribution
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Relationship between dose and plasma concentration
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Directly proportional.
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What is redistribution?
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Is when a lipid-soluble drug gets temporarily stored in fat tissue before being eliminated.
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What is the significance of the redistribution rate?
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A second dose of a CNS drug redistributes to fat in lesser amount because fat is "saturated" therefore allowing more drug to enter the CNS and increasing the duration of action.
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What is biotransformation?
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Is the conversion of a drug to a more water-soluble form to be excreted. A metabolite may or may not have pharmacologic action.
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What is phase I biotransformation?
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Modification of the drug via oxidation, reduction or hydrolysis.
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What is microsomal metabolism?
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Cytochrome P450 isoenzymes in the SER require NADPH for oxidation and reduction of drugs.
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General inducers of the P450 enzymes
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Anticonvulsants (barbiturates, phenytoin, carbamazepine), antibiotics (rifampin), chronic alcohol, glucocorticoids.
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General inhibitors of the P450 enzymes
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Proton pump inhibitors (cimetidine, omeprazole), antibiotics (chloramphenicol, macrolides, ritonavir, ketoconazole), acute alcohol, grapefruit juice.
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What is nonmicrosomal metabolism?
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Hydrolysis reactions by esterases and amidases; MAO; alcohol dehydrogenases.
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What is phase II biotransformation?
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Modification of the drug by transferases via glucoronidation, acetylation, sulfation, gluthathhione conjugation.
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What are the major modes of drug elimination?
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Biotransformation to inactive metabolites, excretion via the kidney, bile ducts, lungs and sweat.
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What is the elimination half-life (t1/2)?
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t1/2 is the time to eliminate 50% of a given amount of drug.
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What is zero-order elimination rate kinetics?
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A constant amount is eliminated per unit time. Independent of plasma concentration, variable t1/2.
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What is first-order elimination rate kinetics?
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A constant percentage of the drug is eliminated per unit time. t1/2 is constant, directly porportional to plasma levels.
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Rate of elimination
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Equals to GFR + active secretion - reabsorption
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Clearance
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Equals to free fraction x GFR or k x Vd
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What is steady state and when is it achieved?
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Its when the rate in = rate out. 50% of SS is achieved at 1 t1/2; 90% at 3.3 t1/2; 95% at 4-5 t1/2.
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How does rate of infusion affect steady state and plasma levels at steady state?
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It takes the same amout of time to reach steady state but if rate of infusion increases the plasma levels at steady state will increase.
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Relationship between half-life and elimination
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Inversely proportional
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Relationship between half-life and clearance
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Inversely proportional
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Relationship between half-life and volume of distribution
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Directly proportional.
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Relationship between clearance and volume of distribution
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Inversely proportional
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Relationship between infusion rate and clearance
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Directly proportional.
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Relationship between infusion rate and steady state concentration
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Directly proportional.
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Relationship between steady state concentration and clearance
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Inversely proportional.
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What is pharmacodynamics?
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The effects of drugs in the body and drug receptor binding.
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Affinity
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Ability of the drug to bind its receptor. The closer to the y axis, the more affinity.
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Potency
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The quanity of drug required to produce a desired effect. The closer to the y axis, the more potent.
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Efficacy
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The maximal effect an agonist can achieve at the highest practical concentration. The taller the curve, the more efficacy.
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What is meant by the "duality" of partial agonists?
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Partial agonists can compete with full agonists for its receptor, lowering the maximal response, therefore it acts as an antagonist in the presence of a full agonist.
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Effect of a competitive antagonist
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Parallel shift of the curve to the right; appears to decrease potency; reversed by increasing agonist dose
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Effect of a noncompetitive antagonist
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Non-parallel shift to the right; appears to decrease efficacy of agonist; partially reversed by increasing agonist dose.
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Physiologic antagonism
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Two agonists with opposing actions antagonize each other: vasoconstrictor Vs. vasodilator
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Chemical antagonism
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Agonist-chemical complex lowers effect of agonist
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Potentiation
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Parallel shift of the curve to the left; appears to increase potency of agonist.
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TD50
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Dose that causes toxicity in 50% of the population
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ED50
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Effective dose in 50% of the population
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Therapeutic index
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TD50/ED50; gives a measure of the relative safety of a drug
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ANS receptors and their second messenger systems
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"qiss qiq siq sqs". α1, α2, β1, β2, M1, M2, M3, D1, D2, H1, H2, V1, V2
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Substances with intracellular receptors
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Glucocorticoids, vitamin D, thyroid hormones, gonadal steroids
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Substances with ion channel receptors
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Nicotine, choline esters (ACh), ganglion blockers, skeletal muscle relaxants.
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Substances that interact with Gs receptors
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Catecholamines, dopamine, glucagon, histamine, prostacyclin. "qiss qiq siq sqs"
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Substances that interact with Gi receptors
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Epinephrine, norepinephrine, Ach, dopamine. "qiss qiq siq sqs"
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Substances that interact with Gq receptors
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Ach, norepinephrine, angiotensin II
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Phase 1 clinical testing
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Dose-response studies on small group of volunteers without disease. Includes pharmacokinetics characterization.
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Phase 2 clinical testing
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Dose-response studies on 100 patients incomparison with placebo and a positive control. Single or double blind.
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Phase 3 clinical testing
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Dose-response studies on 1000 patients in comparison to placebo and positive control. Usually double blind
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Phase 4 clinical testing
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New drug application, marketing approval and post-marketing surveillance.
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Zero-order kinetics curve
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Linear kinetics or exponential kinetics on log graph
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First-order kinetics curve
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Exponential kinetics or linear kinetics on log graph
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Dose-response curve
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Bell curve. Shows absoption phase, distribution, metabolism and elimination phases.
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