Pharmokinetics

Question 1

Pharmokinetics

Answer 1

The study of the rate and extent to which drugs are absorbed into the body and distributed to the body tissues

The rate and pathways by which drugs are eliminated from the body by metabolism and excretion

The relationship between time and plasma drug concentration

‘What the body does to the drug’

Question 2

Four main stages of pharmokinetics

Answer 2

Absorption, distribution, metabolism, excretion

Question 3

Enteral routes for drug absorption

Answer 3

Oral, buccal(mucosal orally), sublingual (under the tongue), rectal

Question 4

Parenteral routes of drug absorption

Answer 4

Intravenous, intramuscular, subcutaneous, inhaled

Question 5

Topical application

Answer 5

Method of drug absorption

Question 6

For a drug to be successful after oral administration it must

Answer 6

Be swallowed -> survive gastric acid -> avoid unacceptable food binding -> be lipid soluble so can be absorbed across the gastro-intestinal mucosa -> survive hepatic (liver enzymes) first-pass metabolism and the enterohepatic circulation

Question 7

Benefits of oral routes

Answer 7

Convenient, simple, can be easily self administered, Better for long term treatments for less acute illnesses

Question 8

Intravenous route

Answer 8

No concerns about absorption, rapidly achieves high drug concentrations, no ‘first pass’ effect -> better for very ill patients where rapid, certain effect is critical to outcome

Question 9

Intramuscular route

Answer 9

Simple to administer, unpredictable rate of absorption, painful, drug only gets into bloodstream if there is good circulation

Question 10

Subcutaneous route

Answer 10

Good for drugs that have to be administered parenterally, are absorbed well from subcutaneous fat (lipid soluble), that ideally can be injected by patients themselves

Question 11

Inhaled route

Answer 11

For a drug to be successful after inhalation in must be inhaled into the target airways in the lung -> i.e. if drugs are too small they will only go to the alveoli not the small airway

Question 12

Speed and efficiency of distribution into the body by passive diffusion depends on

Answer 12

Molecular size, lipid solubility and protein binding

Question 13

Volume o fdistribution

Answer 13

The apparent volume of distribution is the volume that the dose appears to have distributed into shortly after intravenous injection based on the plasma drug concentration

Question 14

Drugs with high volume distribution

Answer 14

Take long time for body to get rid of the drugs after it is stop being administered

Question 15

Liver is a major site of drug metabolism it

Answer 15

Reduces biological activity (so its not a threat) and increases water-solubility (so they can get out of the body)

Question 16

Phase 1 metabolism

Answer 16

Enzymes which cause oxidation in microsomal mixed function oxidase system -> Make molecules more polar so that they can be excreted through the urinary system

Question 17

Phase 2 metabolism

Answer 17

No always needed -> conjugation by either acetylation or glucoronidation

Question 18

Factors effecting drug metabolism

Answer 18

Genetics, age, gender, nutrition, disease, dose, drugs, route

Question 19

Increased metabolism

Answer 19

Faster elimination,shorter half life, reduced activity, potential for increased exposure to toxic metabolites

Question 20

Decreased metabolism

Answer 20

Slower elimination, longer half life, increased activity, potential drug accumulation and toxic effects

Question 21

Hepatic drug interactions

Answer 21

Presence of one drug may influence the metabolism of another

The first drug may induce metabolism of the second by stimulating the liver to produce more metabolising enzymes - takes days/weeks

The first may inhibit metabolism of the second by competing for the metabolising enzyme - immediate

Question 22

First pass metabolism

Answer 22

Occurs in the gut wall and liver -> is a major determinant of the peak plasma drug concentration and thus of drug response after an oral dose

Question 23

Drug molecules undergoing first pass metabolism

Answer 23

QAre vulnerable to metabolism by enzymes in the intestinal wall and liver prior to entry into the systemic circulation

Question 24

Portal vein and liver sinusoids

Answer 24

Drugs absorbed through the stomach or any part of the small intestine must pass through these before entering the systemic circulation

Question 25

Bio transformation of unchanged drug to inactive metabolite

Answer 25

Reduces drug response

Question 26

Bio transformation of active drug to active metabolite

Answer 26

Results in no change in drug response

Question 27

Bio transformation of inactive drug(pro-drug) to active metabolite

Answer 27

Results in increased drug response

Question 28

Potential routes of drug excretion

Answer 28

Renal excretion, biliary excretion, faeces, breast milk, sweat

Question 29

Excretion

Answer 29

Process by which drugs and their metabolites are removed from the body and may involve fluid, solids or gases

Question 30

Urinary excretion

Answer 30

Usual route for low-molecular weight drugs that are sufficiently water-soluble to absorb reabsorption from the tubule

Question 31

lipid soluble molecules

Answer 31

Can cross the renal tubular membranes so are not lost renally so must be converted into water soluble

Question 32

Drugs bound to plasma proteins

Answer 32

Are not filtered renally

Question 33

Sodium bicarbonate

Answer 33

USed to make renal tubule more alkaline in the result of an overdose of lipid soluble molecules e.g. aspirin

Question 34

Faecal excretion

Answer 34

The preferred route of elimination for large-molecular-weight drugs, including those that are conjugated with glucoronide in the liver Molecules enter bile after liver metabolism are then carried into intestinal lumen and are excreted in the faeces

Question 35

If molecules are still sufficiently lipid soluble in the faecal excretion route

Answer 35

They may be reabsorbed and re-enter the portal vein

Question 36

Entero-hepatic circulation

Answer 36

The recycling between the liver, bile, gut and portal vein

Question 37

Enterohepatic circulation

Answer 37

Prolongs the residence time of drugs in the body sustaining their effects

Question 38

Bacterial flora

Answer 38

Have enzymes capable of hydrolysing conjugates which release the drug or active metabolite for reabsorption - allowing the recycling of glucoronide conjugates

Question 39

Drugs that inactivate or kill micro-organisms e.g. broad spectrum antibiotics

Answer 39

Can reduce reabsorption and drug availability

Question 40

Clearance

Answer 40

Volume of plasma which is completely cleared of drug per unit time

Question 41

Clearance is caused predominantly by

Answer 41

either metabolism of the drug in the liver or excretion at the kidneys

Question 42

Bioavailability (oral)

Answer 42

Area under the curve of drug given orally/ area under curve of drug give intravenously - for the plasma concentration-time graph expressed as a percentage

Question 43

Ora bioavailability depends on

Answer 43

Gastric acid destruction, formulation, first-pass metabolism, solubility, ionisation, food, diarrhoea

Question 44

Drugs must be ... in order to be absorbed into the body

Answer 44

Lipid-soluble

Question 45

Drugs must be more ... in order to be eliminated in the urine or faeces

Answer 45

Water soluble

Question 46

The conversion of lipid soluble to water soluble through

Answer 46

Metabolism

Question 47

First order (exponential) kinetics

Answer 47

A constant fraction of drug is cleared in unit time

Question 48

Zero-order (saturation) kinetics

Answer 48

A constant amount of drug is cleared in unit time

Question 49

In first order kinetics rate of metabolism/elimination of a drug depends on

Answer 49

It’s concentration i.e. as conc increases, rate increases -> as conc decreases rate decreases

Question 50

Increasing drug dose in first order kinetics has a

Answer 50

predictable effect

Question 51

In zero order kinetics

Answer 51

Elimination rate reaches a maximum0> so if a drug is administered at a rate faster than its clearance then it will progressively accumulate

Question 52

Examples of zero order kinetics

Answer 52

Ethanol, phenytoin

Question 53

Half life

Answer 53

The time taken for the plasma concentration of the drug to halve

Question 54

Increasing drug dose in zero order kinetics has a

Answer 54

very unpredictable effect

Question 55

Progressive accumulation

Answer 55

Repeated doses of a drug are given at a time when the previous doses have not been completely eliminates

Question 56

Accumulation continues until

Answer 56

Steady rate is reached where the rate of elimination = the rate of administration

Question 57

Steady state actually involves

Answer 57

Fluctuations in drug concentrations - with peaks just after administration and troughs just prior to the next administration

Question 58

Long half life

Answer 58

Slow to reach steady state, loading dose may be needed, slow to be eliminated, requires less regular dosing E.g. atenolol 8hrs

Question 59

Short half life

Answer 59

Rapid steady state, not suitable orally, more regular dosing required E.g dobutamine 2mins

Question 60

Loading doses

Answer 60

Used for drugs with long half lives which will not reach a steady state concentration for Na long time -> an initial dose is given which is much larger than the maintenance dose in order to achieve a peak plasma concentration close to the plateau concentration which can then be maintained

Question 61

Maintenance dose

Answer 61

Regular dose given to ensure a steady state of drug above therapeutic effects is maintained

Question 62

Dose interval

Answer 62

A compromise between convenience for/adherence of patient and benefit of reduced fluctuation in plasma concentration

Question 63

Therapeutic drug monitoring

Answer 63

Done too look for beneficial effects and avoid adverse effects Can also be used to check for adherence