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91 Cards in this Set
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- 3rd side (hint)
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Define pharmacokinetics (PK)
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Field of study that deals with time required for drug absorption, distribution in the body, metabolism, and method of excretion
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Define Volume of distribution (Vd)
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A proportionality constant that relates the amount of drug in the body to the plasma concentration; apparent fluid volume in which a drug appears to be dissolved; Vd = (dose)/ (plasma drug concentration)
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Define clearance (Cl)
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Volume of blood cleared of the drug per unit time; Cl = (rate of elimination of drug)/ (plasma drug concentration); total body Cl = Cl hepatic + Cl renal + Cl pulmonary + Cl other
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Define Half-life (t½ )
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Time required for plasma concentration of drug to decrease by one-half after absorption and distribution are complete; t ½ = (0.693 x Vd)/ (Cl)
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Define Bioavailability (F)
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The fraction of drug absorbed into the systemic circulation after extravascular administration; F= (AUC0)/(AUCiv), where AUC0 and AUCiv are the extravascular and intravenous areas under the plasma concentration vs. time curves, respectively
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None
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Define Steady state (Css)
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Steady state is reached when the rate of drug into the body = the rate of drug out of the body; Css = plasma concentration of drug at steady state
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None
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How many half-lives does it take for a drug to reach (clinical) steady state
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5 half lives
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How much drug is left after 1 half life
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50%
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How much drug is left after 2 half-lives
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25%
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How much drug is left after 3 half lives
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12.5%
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During constant infusion, what percent of steady state is reached after 1 half life
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50%
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During constant infusion, what percent of steady state is reached after 2 half lives
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75%
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During constant infusion, what percent of steady state is reached after 3 half lives
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87.5%
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What is the equation for infusion rate (k0)
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k0 = Cl x Css
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What is the equation for loading dose (LD)
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LD = (Vd x Css)/ F; for examination purposes, F is usually 1
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What is the equation for maintenance dose (MD)
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(Cl x Css x tau)/ (F); where tau is the dosing interval
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What is the equation for clearance (Cl)
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Cl = K x Vd, where K is the elimination constant
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What is the equation for volume of distribution
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Vd = (LD)/(Css)
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What is the equation for Half-life (t ½)
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(T ½) = (0.693)/(K) or (0.693 x Vd)/ (Cl)
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What happens to the steady state concentration of a drug if the infusion rate is doubled
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Steady state concentration is also doubled; remember that dose and concentration are directly proportional (linear kinetics); Css = k0/ Cl
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If there is no active secretion or reabsorption, then renal clearance (Cl renal) is equal to what
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Glomerular filtration rate (GFR)
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If a drug is protein bound, then Cl renal is equal to what?
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GFR x free fraction (of drug)
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What happens to the LD in patients with impaired renal or hepatic function
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Stays the same
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What happens to the MD in patients with impaired renal or hepatic function
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Decreased
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What type of elimination refers to a rate of elimination that is constant regardless of concentration
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Zero-order elimination
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What type of elimination refers to a plasma concentration that decreases exponentially with time
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First-order elimination
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What type of elimination refers to a rate of elimination that is proportional to the drug concentration
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First-order elimination
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What type of elimination refers to a plasma concentration that decreases linearly with time
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Zero-order elimination
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What type of elimination refers to a rate of elimination that is independent of concentration
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Zero-order elimination
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What type of elimination refers to a rate of elimination that is dependent on concentration
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First-order elimination
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What are some examples of drugs/ substances that undergo zero-order elimination
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Aspirin (ASA) at high/ toxic concentration
Phenytoin Ethanol |
None
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Describe phase I metabolism
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Metabolism that generally yields more polar, water-soluble metabolites (may still be active); enzyme activity decreases with age
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Describe phase II metabolism
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Metabolism that generally yields very polar, inactive metabolites (renally excreted); enzyme activity does not decrease with age
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Phase I (microsomal) metabolism involves what types of reactions
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Oxidation; reduction; hydrolysis (carried out by cytochrome P-450 enzymes)
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Phase II (nonmicrosomal) metabolism involves what types of reactions
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Acetylation
Amidation Glucuronidation Glutathione conjugation Sulfation |
None
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Give examples of drugs that undergo phase II metabolism
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Minoxidil; procainamide; hydralazine; isoniazid (INH); morphine; lorazepam; oxazepam; temazepam; 6-mercaptopurine; chloral hydrate; zaleplon; acetaminophen
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Where are cytochrome P-450 enzymes found
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Smooth endoplasmic reticulum of cells in mainly the liver, but also found in the GI tract, kidney, and lungs
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Explain what phase 1 in drug development is trying to accomplish
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Safety in healthy individuals; PK
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Explain what phase 2 in drug development is trying to accomplish
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Efficacy in diseased individuals (small scale trials, single or double blind)
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Explain what phase 3 in drug development is trying to accomplish
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Efficacy in diseased individuals (large scale trials, mainly double blind)
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Explain what phase 4 in drug development is trying to accomplish
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Postmarketing surveillance (monitored release)
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At what point during drug development is an investigational new drug application filed
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Before phase 1
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At what point during drug development is a new drug application filed
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After phase 3 (and before phase 4)
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What does the term bioequivalence mean
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When comparing two formulations of the same compound, they are said to be bioequivalent to each other if they have the same bioavailability and the same rate of absorption
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What is the first-pass effect
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After oral administration, many drugs are absorbed intact from the small intestine and transported first via the portal system to the liver, where they undergo extensive metabolism
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None
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How many liters are found in blood
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5L
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How many liters are found in plasma
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3L
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How many liters are found in total body water
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42L
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What is the most common plasma protein that drugs bind to
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Albumin
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Displacing a drug that is bound to plasma albumin will increase its what
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Free fraction (therefore may possibly increase the risk of toxicity because the concentration of active drug has been increased, yet depending on the drug, may actually increase its metabolism because more drug is available to metabolizing enzymes)
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For passive diffusion, state the direction of flow, if energy is required, if a carrier is required, and if the system is saturable
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Downhill; no energy required; no carrier; not saturable (proportional to concentration gradient)
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For facilitated diffusion, state the direction of flow, if energy is required, if a carrier is required, and if the system is saturable
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Downhill; no energy required; carrier required; saturable
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For active transport, state the direction of flow, if energy is required, if a carrier is required, and if the system is saturable
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Uphill (against concentration; electrical gradient); energy required; carrier required; saturable
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The permeation of drugs across cellular membranes is dependent on what
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Solubility; concentration gradient; ionization; surface area; vascularity
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Acidification of urine will increase renal elimination of what types of drugs
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Weak bases (ionized form of drug will be trapped in the renal tubules and thus excreted in the urine)
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Acidification of urine will decrease renal elimination of what types of drugs
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Weak acids (nonionized form of drug can cross membranes)
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Alkalinization of urine will increase renal elimination of what types of drugs
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Weak acids (ionized form of a drug will be trapped in the renal tubules and thus excreted in the urine)
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Alkalinization of urine will decrease renal elimination of what types of drugs
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Weak bases (nonionized form of drug can cross membranes)
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What agents are used to acidify urine
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NH4Cl; high dose vitamin C
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What agents are used to alkalinize urine
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NaHCO3; acetazolamide
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Give an example of two weakly acidic drugs
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ASA; barbiturates
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None
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Give an example of a weakly basic drug
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Amphetamines
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Give examples of drugs that the cytochrome P-450 enzyme CYP 1A2 metabolizes
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Caffeine
Acetaminophin Ciprofloxacin; theophylline; R-warfarin |
None
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Give examples of drugs that the cytochrome P-450 enzyme CYP 2C9 metabolizes
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S-warfarin
Hexobarbital Ibuprofen Phenytoin Naproxen |
None
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Give examples of drugs that the cytochrome P-450 enzyme 2C19 metabolizes
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Propranolol
Omeprazole Diazepam |
None
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Give examples of drugs that the cytochrome P-450 enzyme CYP 2D6 metabolizes
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Codeine
β-blockers TCAs Dextromethorphan |
None
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Give examples of drugs that the cytochrome P-450 enzyme CYP 2E1 metabolizes
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Ethanol
INH Acetaminophen (at high doses) |
None
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Give examples of drugs that the cytochrome P-450 enzyme CYP 3A4 metabolizes (50-60% of all therapeutically used drugs are metabolized via CYP 3A4)
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Alprazolam; carbamazepine; cyclosporine; diltiazem; erythromycin; fluconazole; itraconazole; ketoconazole; lidocaine; lovastatin; midazolam; nifedipine; quinidine; simvastatin; tacrolimus; verapamil
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None
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Give examples of drugs that generally induce cytochrome P-450 enzymes
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Rifampin (2C9, 3A4)
Nicotine (1A2) Chronic alcohol use (2E1) Phenobarbital Phenytoin Carbamazepine St. John’s wort |
None
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Give examples of drugs that generally inhibit cytochrome P-450 enzymes
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Cimetidine, Ketoconazole
Omeprazole Ritonavir Fluoxetine Erythromycin; ciprofloxacin; quinidine; chloramphenicol; acute alcohol intoxication |
None
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Which antiepileptic medication is said to be able to autoinduce its own metabolism
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Carbamazepine
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Intracellular volume (ICV) makes up what fraction of TBW
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2/3 (ICV = 2/3 TBW)
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Extracellular volume (ECV) makes up what fraction of TBW
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1/3 (ECV = 1/3 TBW)
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Interstitial volume makes up what fraction of ECV
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2/3 (interstitial volume = 2/3 ECV)
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Plasma volume makes up what fraction of ECV
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1/3 (plasma volume = 1/3 ECV)
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What type of elimination involves a constant fraction of drug eliminated per unit time
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First-order elimination
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What type of elimination involves a constant amount of drug eliminated per unit time
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Zero-order elimination
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What is the equation for half life
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T1/2= 0.693/k
This formula allows you to go back and forth between elimination half-life and the rate constant of elimination |
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What is the equation for volume of distribution
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Vd= X0/C0
The volume of distribution can be well estimated from the dose given at zero time, X0, and the drug concentration, C, is extrapolated back to time zero (C0) for all cases when absorption is "instantaneous" (e.g. i.v. administration) |
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What are the two equations for Clearance
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Cl=keVd or Cl=(0.693Vd)/(t1/2)
Clearance is given in L/hr, volume of distribution is L, and the rate constant is in fraction per hr |
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What is the equation for dosing rate
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Dosing rate = Cl x Css
Clearance x desired steady state concentration of drug |
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What is the equation for maintenance dose
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Maintenance dose = dosing rate x dosing interval
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What is the equation for loading dose
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Loading dose = Vd x TC
TC= Target concentration (usually the same as desired Css) |
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What is the equation for steady state concentration
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Css= Dosing/Clearance
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What are some compounds acetylated by NAT-2 (phase II reaction)
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Isoniazid (INH)
Procainamide Sulfonamides Histamine, Caffeine, Dapsone, Hydralazine |
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What are two Thiopurine methyl transferase substrates (TPMT)
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6-mercaptopurine (6-MP)
Azathioprine |
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Polymorphism in the glucuronyl transferase UGT1A1 may impair the metabolism of what anti-cancer drug
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Irinotecan
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Those with variant forms of Catechol O-methyltransferase (COMT) show reduced metabolism of what drug
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Levodopa, giving enhanced drug effect and possible toxicity
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The 2677 T genotype of the multidrug resistance gene 1 (MDR-1) has been associated with lower plasma levels of what drug
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Fexofenadine
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What will be the effect of isoproterenol in a patient with Arg/Arg at codon 16 of β2 receptors
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Rapid desensitization of the venodilation response, but increased bronchodilator response
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What will be the result of warfarin treatment in a patient with polymorphisms in VKORC1
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They will be insensitive to Warfarin
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