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MSU Pharm Woo Ch. 2

Principles of Pharmacology

QuestionAnswer
Individual patient's ability to absorb, distribute, metabolize and elminate a drug. Pharmacokinetics
What is the objective of drug therapy? to delivery and maintain therapeutic levles of a drug in the target tissues.
How are drus most commonly eliminated? kidneys
The study of the effects of drugs on the body. Pharmacodynamics
This occurs when receptors are continually stimulated by drugs and their responsiveness decreases down-regulation
Severe dwon-regulation may result in lack of response to a drug. This is know as refractioriness
Chronic reduction in receptor's activity due to an antagonist up-regulation or hypersensitzation.
Rapid withdrawal of antihypertensives resulting in hypertnsive episodes is an example of what type of drug receptor activity? up-regulation
Type of drug-receptor relationship, in which interaction between a drug and a receptor is temporary, with the drug action ending when the drug leaves the receptor site. reversible agonist
Type of drug-receptor activity in which a drug occupies a receptor permanently. irreversible
Type of antagonist drug receptor activity in which the binding of drug and antagonist is reversible. competitive antagonist
Competitive anatagonist referst to the fact that the effect of the antagonist can or cannot be overcome by higher does of the agonist competing for the receptor site? can
Type of drug receptor activity- receptor is irreversibly blocked by the antagonisth noncompetitive inhibitor
Type of drug-receptor activityin which a drug agonist acts to compete with a full agonists for drug recepotrs partial agonist
What is the result of a partial agonist decrease of efrfect on the recepor over what is seen with the agonist alone.
Which drug receptor principle provides relationship between drug concentration and drug effect Reversible agonist
Drugs that bind to receptors may be _______, _______________, or antagonistic. agonists, partial agonists
Is drug-receptor binding usually reversible? Yes
Whow is drug receptor binding graded? The more receptors filled, the greater the pharmacological response will be.
A drug's desired therapeutic effects and its adverse effects is called therapeutic index
The ratio of the does required to produce death or serious toxicity in 50 percent of subjects compared witht he does recired for effective treatment Therapeutic index
Which therapeutic index would require the closer monitoring? wide or narrow index? narrow
The time needd for the drug concentration to reach a minimum level at which effective concentrations are reached Onset of action
Measures that can decrease the time it takes to for onset of action. IV and IM administration`
Time required for the maximum effect to occur after administration time to peak
Time during which the blood levels are above the minimum effective concentration of a drug duration of action
Is duration of action affected by the rout e of administration of a drug? no
Point at which a drug level drops below the minimum effective concentration termination of action
Why does a prescriber need to be aware of the dose-response curve of a drug? to determine how soon the med will take effect, how long the drug will be effective, and when the drug will terminate.
Two important properties of dose response efficacy and potency
How is efficacy measured by the maximum effect that the drug can achieve.
The relative measure that compares the doses of two different drugs that are required to achieve the same effect. Potency
When is a drug said to be potent? when it possess a high intrensic activity and a low unit dose.
Clinical effectiveness of a drug deponds on what 2 things? maximum efficacy and blility to reach relevant receptors?
Does clinial effectiveness depend on a drugs potency? no
The study and analysis of the time course of the drug in the body Pharmacokinetics
Where are drugs generally metabolized? liver
What is the first stage of pharmacokinetics? absorption
The simple diffusion of drug from areas of high concentration to ares of lower concentrationl Passive difusion
Occurs where the drug molecule combines with another molecule to facilitate absorption facilitated diffusion
occurs where the molecule is actively transpored across the cell membrane, often via the ATP pum. Active transport
Drugs injected directly into venous circulation begin distribution throughout the body when immediately
To prolong absorbtion or of an IM injection, what can be done? formulated in oil or as a suspension.
Can drugs formulated in oil be given IV NO
How are most drugs absorbed by passive diffusion
Where are most drugs absorbed GI tract
What type of drugs diffuse well Nonionized, lipid-soluble
Active transport is used in absorbtion of _____, which is usually against a concentration gradient. Going into a higher concentration. electroytes
Levadopa is absobed using what type of transport active transport
A form of active transort in which the cel engulfs the drug particle in a lipid vacuole and transports it across the cell membrane. Pinocytosis
What is pinocytosis most commonly used to transport? fat soluble vitamins
Drug molecules can pass throught the cell membrane if they are unionized
What determines how much of a total drug concentraion is un-ionized? the local pH of the GI tract and chemical nature of the drug.
Where in the GI tract does most absorption of orally administered drugs occur? small intestine
Why does absorbption of most orally administered drugs take place in the small intestine? the mucosal villi provide the largest surface area in the GI tract.
What type of foods can prolong gastric emptying? solid, high-fat foods
What effect do anticholinergics have on drug absorption prolong intestinal transit and increase total drug absorption
What effect do laxitives have on drug absorption decrease absorption
What stimulates gastric blood flow and absorption? food
What decreases GI blood flow and lowers absorption? Physical activity
The metabolism of a part of the administered dose of a drug before it reaches the systemic circulation is First-Pass metabolism
What do ine drugs, nitro, isoproterenol, propranolol and warfin have in commom significant first pass metabolism effect
Drugs with a significant first pass effect require what 2 things? alternate administration site or dosing
When drugs leave the liver circulation and enter the biliary tract to be excreted in the bile, eventually returning to the intestine and becoming available for reabsorption throught the intestinal wall back into the bloodstream enterohepatic recycling
The amount of the drug dose that reaches the systemic circulation determines bioavailability
What determines the disintegration, dissolution, and drug availability in the body combination of inert ingredients
Does bioavailability take into account the rate of absorbtion no
When a drug is initially distributed where does it go? high-flow areas such as the heart, liver, kidney, and brain
Second phase of distribution goes where? fat, bone, and skin
Drugs that are bound to a protein are called drug-protein complex
Can bound drugs cross over the plasma membrane no
What is an unbound drug called free drug
Can a free drug cross the plasma membrane yes
Can a bound drug free itself from binding? yes
The percentage of drug that remains free and available for binding depends on the amount of plasma protein
A mathematically determined measure of size of a compartment that would be filled by the amount of a drug in the same concentration as that found in the blood or plasma Volume of distribution
When measuring Vd the measure of the serum concentration immediately after IV administration of a drug is known as Co
When measuring Vd the measure of the amount of drug given is known as Xo, Vd
When is Vd useful expressing affinity of a drug to tissue and storage sites & calculating a drug's clearance from the body.
If a drug has a high volume of distribution, would the dose ordered need to be high or low to achieve a target concentration high
a proportionality factor that relates the amount of drug in the body to the concentration of drug measured in a biological fluid. Volume of distribution
Drugs that have a volume of distribution 7 L or less are thought to be confined to the plasma, or liquid part of the blood.
If the volume is between 7 and 15 L, the drug is thought to be distributed throughout the blood (plasma and red blood cells).
If the volume of distribution is larger than 42, the drug is thought to be distributed to all tissues including and espically fatty tissues
The larger the volume of distribution, the more likely that the drug is found where in the body tissues
The smaller the volume of distribution, the more likely that the drug is confined to the circulatory system.
Why is the blood-brain barrier impermeable to water-soluable drugs? Because it is surrounded bya sheath of glial connective tissue
What type of drugs generally cross the blood-brain barrier lipd soluable
Identify medications that are lipid soluble that can generally cross the blood brain barrier atropine, general anesthetic and psychotropics
The placental barrier is a _____ membrane that allows passage of drugs by simple diffusion. lipid
The process of chemically changing a drug to a different compound called a metabolite. Drug metabolism
When drugs are metabolized, the change is usually and _______ in water solubility accompanied by a ______ in lipid solubility. increase, decrease
What is an example of a drug that is administered as an inactive prodrug that must be metabolized to an active metabolite to have any effect ACE inhibitors
What are phase one chemical reactions that occur in drug metabolism? oxidation, reduction, and hydrolysis
Chemical reaction in drug metabolism that typically insert an oxygen atom into the drug molecule. Oxidation
The most clinically significant oxidation enzymes include cytochrome P450
Phase two actions in drug metabolism are called synthetic or conjugation reactions
What happens in phase two(conjugation) reactions during drug metabolism? attachment of another chemical group to the drug.
What is the result of phase two drug metabolism a chemical with a greater water solubility needed for renal elimination
When alcoloh, a variety of drugs and cigarette smoke stimulate the synthesis of drug-metabloizing enzyme, what is it called? enzyme induction
When drugs inhibit the metabolism of another drug, what is the process called? enzyme inhibitors
Inhibit or induce enzymes- Erythromycin inhibit
Inhibit or induce enzymes- Cimetidine inhibit
Inhibit or induce enzymes- Sodium Valproate inhibit
Inhibit or induce enzymes- oral contraceptives inhibit
Inhibit or induce enzymes- propranolol inhibit
Inhibit or induce enzymes- sulfonamides inhibit
Inhibit or induce enzymes- rifampin induce
Inhibit or induce enzymes- phenytoin induce
Inhibit or induce enzymes- Carbamazepine induce
Inhibit or induce enzymes- Primidone induce
Inhibit or induce enzymes- Griseofulvin induce
Inhibit or induce enzymes- cigarette smoke induce
Inhibit or accelerate drug metabolism- amphetamines inhibit
Inhibit or accelerate drug metabolism - ephedrine inhibit
Inhibit or accelerate drug metabolism- Phenylephrine inhibit
Inhibit or accelerate drug metabolism Digoxin inhibit
Inhibit or accelerate drug metabolism - warfarin inhibit
Inhibit or accelerate drug metabolism- theophylline inhibit
Inhibit or accelerate drug metabolism- carbamazepine inhibit
Inhibit or accelerate drug metabolism- propranolol inhibit
Inhibit or accelerate drug metabolism theophylline accelerate
Inhibit or accelerate drug metabolism imipramine accelerate
Inhibit or accelerate drug metabolism pentazocine accelerate
Inhibit or accelerate drug metabolism chlorpromazine accelerate
Inhibit or accelerate drug metabolism diazepam accelerate
Inhibit or accelerate drug metabolism dexamethasone, prednisone, methadone accelerate
What drug metabolism reactions can have some genetic influences related to ethnic and familial patterns acetylation and oxidative reactions
A patient with liver disease may have a ______rate of high clearance drugs. decreased
Does alcohol ingestion cause an induction or reduction of drug metabolism? induction
Biliary route of excretion is important for what two specific drugs? ampicillin and rifampin
Enterohepatic recirculation is important for what two specific drugs? digoxin and estrogens
The kidney usually removes a drug the is bound or unbound found where? unbound in plasma
Renal excretion is the net effect of what three mechanisms with in the kidney glomerular filtration, tubular secretion and tubular re absorption
In the healthy adult, how many mL of fluid cross the glomerular membrane, (passivly) per min 130mL
What three factors determine if a drug will be filtered via passive glomerular filtration? molecular size, protein binding, and glomerular integrity
Can drugs that are protein bound be excreted in kidney via glomerular filtration? no, must be free/unbound
Tubular secretion occurs when drugs are ______ secreted from the proximal tubule into the urine. actively
What type of drugs are generally secreted via tubular secretion? weak acids that may be subject to competition from other drugs in the body that are actively secreted.
When probenecid and pennicillin are both excreted via tubular secretion, what occurs They compete against each other and the penicillin effects are prolonged because the probenecid stays in the system longer.
Tubular re absorption passively occurs in the distal tubules for what type of drugs? lipid soluble or not highly ionized
What two specific things is tubular re absorption dependent on? properties of drug and pH of urine
An overdose of a weak base such as amphetamine can be eliminated from the body more quickly by doing what to the urine with ammonium chloride? acidifying
If a drug is actively transported by the liver cells from blood to bile, where is it excreted? feces
Enterohepatic re absorption may be interfered with by oral antibiotic because they do what to the GI tract? remove gut bacteria
Why do patients experience a metallic taste with some medications? excretion via saliva
What is the term for the time it takes to eliminate one-half of the drug from the body? half-life
What does the half-life of a drug determine? how often a drug is administered
Does double dosage of a drug, double the half life? no
How many half lives generally does it take for a drug to reach a steady state when given continuously and to totally eliminate from the body when discontinued? 4-5
A drug that is a "perfect fit" on the receptor site receptor agonist
A drug that blocks or competes for the receptor site receptor antagonist
when a drug produces decreased physiological response after repeated does of a drug tolerance
when a patient has quickly developing tolerance, initial response cannot be repeated, higher does needed tachyphylaxis
when there is a buildup of a drug cumulative effect
when a patient has abnormal or peculiar response to a drug idiosyncrasy
when a patient has a physiological withdrawal syndrome if a drug is stopped drug dependance
When the effects of drug are modified by another drug drug interaction
When combined effect of two drugs is less than sum of two drugs given separately drug antagonism
This is AKA additive effect-combining two drugs produces effect that is the sum of the individual drugs summation
AKA synergistic effect-combining two drugs produces an effect that is greater than the sum of the two drugs. synergism
Concurrent administration of drugs increases effect of another drug potentiation
The movement of a drug from the site of administration into the blood. absorption
movement of absorbed drug in bodily fluids throughout body to target tissues distribution
the enzymatic alteration of drug structure metabolism
removal of drug from body by organs of elimination excretion