Principles of pharmacokinetics

Question 1

Processes involved in pharmacokinetics

Answer 1

Absorption
Distribution
Metabolism
Elimination

Question 2

Effect of enteric coating on a tablet on its rate of absorption

Answer 2

Slows

Question 3

pKa of a drug

Answer 3

pH at which half of the drug is in its ionised form

Question 4

Aspect of drug metabolism where the drug when taken orally is partially metabolised by liver and gut mucosa and so the concentration is reduced before it reaches systemic circulation

Answer 4

First pass metabolism

Question 5

Mechanisms of absorption of drugs from the GI tract

Answer 5

Active transport
Passive diffusion
Pore filtration

Question 6

Drug absorption of hydrophilic vs. hydrophobic drugs

Answer 6

Hydrophobic drugs are absorbed better

Question 7

Site in the GI tract where most absorption takes place

Answer 7

Small intestine

Question 8

Reverse transporter which actively pumps the dug into the gut lumen from the gut cells and reduces its absorption

Answer 8

P-glycoprotein

Question 9

Effect of grapefruit juice on P-glycoprotein and drug concentrations

Answer 9

Inhibits P-glycoprotein and increases absorption of certain medications

Question 10

Time frame for absorption of drugs administered IM

Answer 10

Over 10-30 minutes

Question 11

Method of administration for most rapid drug absorption

Answer 11

IV

Question 12

Percentage bioavailability with IV administration of a drug

Answer 12

100%

Question 13

Two types of diffusion which can be involved in drug permeation

Answer 13

Simple diffusion

Facilitated diffusion

Question 14

Type of diffusion where permeation takes place passively along a concentration gradient

Answer 14

Simple diffusion

Question 15

Type of diffusion where permeation takes place along a concentration gradient but helped by the presence of carrier mechanisms

Answer 15

Facilitated diffusion

Question 16

Type of permeation where a drug is transported against a concentration gradient, requiring energy expenditure

Answer 16

Active transport

Question 17

Form of a drug in terms of ionisation which can cross the lipid membranes of a cell

Answer 17

Nonionised form

Question 18

Main plasma protein that binds to acidic drugs

Answer 18

Albumin

Question 19

Main plasma protein that binds to alkaline drugs

Answer 19

Alpha1-acid glycoprotein

Question 20

Drugs which have 95-99% protein binding

Answer 20

Diazepam
Chlorpromazine
Amitriptyline
Imipramine

Question 21

Drugs which have 90-95% protein binding

Answer 21

Phenytoin
Valproate
Clomipramine

Question 22

Equation for volume of distribution

Answer 22

Volume of distribution = quantity of drug / plasma concentration at the time of administration

Question 23

Characteristics of a drug the volume of distribution gives information about

Answer 23

If the volume of distribution is high the drug has a high affinity for tissues outside the body water and high lipid solubility
If the drug is highly protein bound its volume of distribution will be low

Question 24

Junctions found in the blood brain barrier

Answer 24

Tight junctions

Question 25

Definition of bioavailability

Answer 25

The percentage of a drug which is detected in the systemic circulation after its administration

Question 26

Percentage of first pass metabolism the rectal route avoids

Answer 26

66%

Question 27

Physiological changes in elderly people that can affect drug absorption - generally leading to same amount of drug absorption but at a slower rate

Answer 27

Reduced gastric acid secretion Reduced gastric motility Reduced small bowel surface area Reduced first pass metabolism

Question 28

Physiological changes in elderly people that can affect drug distribution

Answer 28

``` Increased proportion of body fat Decreased lean body mass Decreased total body water Increased alpha-1-acid glycoprotein levels Decreased albumin levels ```

Question 29

Physiological changes in elderly people that can affect drug metabolism

Answer 29

Decreased hepatic blood flow and cytochrome p450 enzyme activity - but only after age 80

Question 30

Physiological changes in elderly people that can affect drug excretion

Answer 30

Decreased renal function

Question 31

Solubility of drugs which are the most rapidly absorbed

Answer 31

Lipid soluble

Question 32

Permeation of a drug

Answer 32

Lipid membrane permeability of the drug

Question 32

Permeation of a drug

Answer 32

Lipid membrane permeability of the drug

Question 33

Form of a drug which is able to cross lipid membranes of a cell

Answer 33

Ionised form

Question 34

Part of a drug - protein bound vs. not bound - which is active

Answer 34

Not protein bound

Question 35

Reversibility of plasma protein binding of drugs

Answer 35

Reversible

Question 36

Effect of protein displacement on drugs

Answer 36

Increases the plasma concentration of free drug

Question 37

Reason why protein displacement is not usually clinically significant

Answer 37

The metabolism of the drug increases in parallel with the free drug concentration

Question 38

Factors which affect the ability of a drug to cross the blood brain barrier

Answer 38

Molecule size Lipid solubility Ionic status

Question 39

Ionisation of molecules that are easily able to cross the blood brain barrier

Answer 39

Unionised molecules

Question 40

Name for the areas of the brain which lack a blood brain barrier

Answer 40

Circumventricular organs

Question 41

Circumventricular organs of the brain

Answer 41

``` Subfornical organ Area postrema Vascular organ of lamina terminalis Median eminence Pineal gland Part of the pituitary gland ```

Question 42

Administration method of a drug which theoretically allows it to cross the blood brain barrier

Answer 42

Nasal

Question 43

Measure of comparability of plasma levels of two different formulations of a drug given at the same dose and by the same route

Answer 43

Bioequivalence

Question 44

Mechanism by which a foreign agent is metabolised and eliminated

Answer 44

Xenobiotics

Question 45

Principle site of drug metabolism

Answer 45

Liver

Question 46

Four major routes of drug metabolism

Answer 46

Oxidation Reduction Hydrolysis Conjugation

Question 47

Number of phases of drug metabolism

Answer 47

2

Question 48

Metabolic routes involved in phase 1 metabolism

Answer 48

Oxidation Reduction Hydrolysis

Question 49

Necessity of going through phase 1 metabolism to reach phase 2

Answer 49

Not necessary in all drugs

Question 50

Metabolic route involved in phase 2 metabolism

Answer 50

Conjugation

Question 51

Most common biochemical process in phase 1 metabolism

Answer 51

Oxidation

Question 52

Attachment of a hydrophilic ionised group to a drug

Answer 52

Conjugation

Question 53

Most common substance involved in conjugation

Answer 53

Glucuronic acid

Question 54

Groups added in conjugation

Answer 54

``` Glucuronic acid Sulphate Amino acids Acetate Methyl ```

Question 55

Relative molecular mass under which a metabolised drug can be excreted in the urine

Answer 55

<300

Question 56

Relative molecular mass above which a metabolised drug must be excreted in the bile

Answer 56

>300

Question 57

Outcomes of metabolism

Answer 57

Active drug is metabolised into an inactive metabolite ready to be excreted Inactive prodrug is metabolised into its active drug

Question 58

Elimination occurs at a constant rate despite the concentration of the drug

Answer 58

Zero order kinetics | Has no constant half life as half life decreases with decreasing concentrations of the drug

Question 59

Elimination occurs at a proportional rate to the concentration of the drug - a constant fraction of the drug is eliminated per unit of time

Answer 59

First order kinetics

Question 60

Most drugs follow ___ order kinetics

Answer 60

First

Question 61

Substances which follow zero order kinetics

Answer 61

Phenytoin Ethanol Slow release preparations of drugs Depot medication

Question 62

Patient factors affecting drug excretion

Answer 62

Increased age decreases excretion Reduction in renal blood flow e.g. due to dehydration decreases excretion Renal impairment decreases excretion

Question 63

Volume of plasma cleared of a drug over a specified time period - includes metabolism to an inactive metabolite and excretion

Answer 63

Clearance

Question 64

Drugs which show renal elimination without significant hepatic metabolism

Answer 64

``` Lithium Amisulpride Sulpride Gabapentin Acamprosate Amantadine ```

Question 65

Time taken for the plasma concentration of a drug to half

Answer 65

Half life

Question 66

Dose of a drug at which 50% of people experience a specific adverse effect

Answer 66

Median toxic dose

Question 67

Dose of a drug at which 50% of patients experience a specific therapeutic effect

Answer 67

Median effective dose

Question 68

Ratio of the median toxic dose to the median therapeutic dose

Answer 68

Therapeutic index

Question 69

Plasma levels within which the efficacy of a drug is optimum without toxicity

Answer 69

Therapeutic index range

Question 70

Plasma levels within which a drug appears to have therapeutic efficacy - does not take into account toxicity

Answer 70

Therapeutic window

Question 71

Pharmacokinetic changes in pregnancy

Answer 71

``` Delayed gastric emptying Decreased gastrointestinal motility Increased volume of distribution Decreased albumin level Induction of liver metabolism Increased GFR and renal clearance ```

Question 72

Trimester in which physiological changes in pregnancy are most pronounced

Answer 72

Third

Question 73

Change to plasma volume during pregnancy

Answer 73

Increases

Question 74

Cause of delayed gastric emptying in pregnancy

Answer 74

Increased progesterone levels

Question 75

Condition under which protein binding interactions of drugs become significant

Answer 75

Renal disease - can cause proteinuria

Question 76

Part of the GI tract with poor oral absorption for most psychotropics

Answer 76

Stomach

Question 77

Parts of the body where drug metabolism occurs

Answer 77

Liver Kidneys Intestine Lungs