Pharmacokinetics

Question 1

Actions of body on drug

Answer 1

. Absorption
. Distribution
. Metabolism
. Excretion

Question 2

Pharmacokinetics

Answer 2

. Quantitiative description of time course for absorption, distribution, metabolism., and excretion. Of drugs

Question 3

Pharmacodynamics

Answer 3

Quantitative description of biochemical and physiological effects of drugs and mechanisms underlying effects

Question 4

For most drugs, the duration of action is related to the time the blood level is above ________

Answer 4

the minimal effective concentration

Question 5

Factors that determine blood levels of drug

Answer 5

. Dose
. Route of administration
. Rate and extent of absorption
. Distribution of tissues (sites of actions/loss)
. Rate and extent of metabolism 
. Rate and extent of excretion

Question 6

Oral administration

Answer 6

,. Most common
. Not appropriate for all drugs
. Slow onset
. Not good if patient unconscious

Question 7

Parenteral drug administration

Answer 7

. IV, IA , subQ
. Rapid onset
. Drug must be water soluble and non irritating
. Invasive procedure

Question 8

Most common transport of drugs across biological membranes

Answer 8

. Passive diffusion

Question 9

Chemical properties of drug

Answer 9

Water solubility
. Lipid solubility
. Stability in stomach

Question 10

Bioavailability

Answer 10

Percentage of an orally ministered drug that reaches the systemic circulation

Question 11

How blood flow affects drug

Answer 11

Highly perfused organs like lungs, heart, liver, and kidneys receive the most drug

Question 12

Drug binding to plasma proteins characteristics

Answer 12

. Albumin most important
. Bound drug can’t distribute to tissues
. Drug interactions mean one drug can displace another from the protein binding sites

Question 13

Distribution of drugs to liver

Answer 13

. Large blood flow
. Site of drug metabolism
. Portal-hepatic circulation where drug undergoes first pass metabolism
. Major site for metabolism

Question 14

Distribution of drugs to kidney

Answer 14

. High blood flow

. Site of excretion for many drugs and metabolites

Question 15

Distribution of drugs to fat

Answer 15

. Low blood flow
. Slow accumulation of lipid soluble drugs
. Site of loss
. Redistribution of drugs from other sites

Question 16

Distribution of drugs to brain

Answer 16

. BBB

. Small lipid soluble drugs can cross

Question 17

Distribution of drugs to fetus

Answer 17

Placental barrier is not strong barrier and many drugs can cross

Question 18

Volume of distribution

Answer 18

. Measure of how drug is distributed in the body
. Volume in which a drug would have to be dissolved in order to account for all of the drug at the concentration present in the plasma
. Vd=amount of drug in body/Cpss
. Amount of drug in body is equal to the dose if drug is given via IV
. High number means more drug in tissues
. Lower number means drug is mostly in plasma

Question 19

Typical volumes of body water compartments

Answer 19

. Total water = 40-45L
. Extracellular = 12-16L
. Blood 5-6L
. Plasma = 2.5-3.0L

Question 20

Ways of terminating drug action

Answer 20

. Excrete drug from body
. Metabolize drug to inactive form
. Most effective and most common = metabolism and excretion

Question 21

Types of metabolism reactions

Answer 21

. Microsomal oxidation
. Non-microsomal oxidation
. Reductions
. Hydrolysis
. Conjugations

Question 22

Microsomal oxidation

Answer 22

. Main route for many drugs
. Micro some pinched off pieces of smooth ER formed during homogenization
. Contain a family of enzymes and cytochromes that can oxidize drugs (mixed function oxidase or cytochrome isozymes)
. Highest conc. In liver
. Induction and inhibition by drugs
, potential for drug rxns
. Effects caused by altered hepatic function
. Occasionally can form toxic metabolites

Question 23

Examples of rxns catalyzed by mixed function oxidase

Answer 23

. Side chain oxidation 
. Hydroxylation
. N-oxidation
. Sulfoxidation 
. N-dealkylation

Question 24

Conjugation rxns

Answer 24

. Phase II reactions
. Involve the coupling of drug or metabolites to small polar molecules
. Glucuronide conjugation
. Sulfate conjugation

Question 25

Kinetics of drug metabolism

Answer 25

. Most drugs first order where rate of metabolism spends on concentration of the drug in blood . Zero order means rate of metabolism doesn’t depend on conc. Of blood

Question 26

Factors affecting drug metabolism

Answer 26

``` . Age . Disease . Nutrition . Genetic factors . Other drugs . Duration of treatment ```

Question 27

Filtration of drugs

Answer 27

. Low molecular weight drugs are readily filtered . Drug bound to plasma protein is not excreted . Alterations in GFR Cana defect the rate of drug excretion

Question 28

Tubular secretion of drugs

Answer 28

. Active process . System for organic acids . System for organic bases . Competition of drugs for transport systems

Question 29

Reabsorption of drugs

Answer 29

. Passive diffusion . Lipophilic drugs reabsorbed . Hydrophilic or ionized drugs remain in tubule and be excreted . Acidic urine favors excretion of basic drugs whereas basic urine favors the excretion of acidic drugs

Question 30

Clearance

Answer 30

. Clearance = rate of elimination/Cp . Cp is conc, of drug in plasma . Describes volume of plasma that is cleared of drug in a unit time

Question 31

First order elimination

Answer 31

. Rate of elimination depends on conc. Of drug that is present . Exponential relationship . Fixed half life

Question 32

Characteristics of zero order kinetics

Answer 32

. rate of metabolism is constant and does not depend on conc. Of drug . Linear relationship . No fixed half life

Question 33

Time for onset of action in drug

Answer 33

. Time between administration and first measurable response

Question 34

Tome to peak effect for drug

Answer 34

. Time needed to reach max effect

Question 35

Duration of action

Answer 35

. Time from first measurable effect to time when effect is no longer measurable

Question 36

Alpha and beta phase of drug decline in blood

Answer 36

. Alpha : rapid decline in conc. From drug moving into tissues . Beta: metabolism and excretion of drug phase, slower decline than alpha phase

Question 37

Plateau principle

Answer 37

All drugs at any dosage will reach a steady state blood level after 4-5 half lives

Question 38

Peak/trough values will decrease if _________

Answer 38

. Drug is administered at dosage intervals that are much shorter than the T 1/2 for elimination of the drug

Question 39

Estimation of half lives

Answer 39

T1/2= (0.963)(Vd)/CLp . Vd is volume of distribution . CLp is clearance from plasma

Question 40

Loading dose calculation

Answer 40

Loading dose = target Cp x Vd/F . Cp is desired plasma conc. . Vd is volume of distribution . F fractional bioavailability

Question 41

Calculation of maintenance dose

Answer 41

. Dosing rate= target Cpss x CLp/F . Cpss is steady state conc. In plasma . CL is rare if clearance . F is fractional bioavailability ( 1 if dose if through IV)

Question 42

Estimation of drug clearance

Answer 42

``` . CLp= F x dose per unit time/Css . CLp = (0.693)(Vd)/ T1/2 patient . F is bioavailability . CSS is steady state conc. In patient . T 1/2 patient is the elimination of half life for drug in patient ```