Pharmacokinetics

Question 1

Pharmacokinetics

Answer 1

Time course of drugs in body

Question 2

Drug targets

Answer 2

1. receptors
2. ion channels
3. enzymes - inhibit, false substitution, pro-drug
4. transporters - inhibit, false substitution

Question 3

When you take a drug, steps are:

Answer 3

1. liberation
2. absorbed
3. enters plasma
   - excreted
   - bound to plasma
   - tissue resevoir if hydrophobic
   - non-related receptors may bond
   - > wanted = therapeutic site of action

Question 4

A polin

Answer 4

A pore which allows bigger molecules but is normally gated

Question 5

Pinocytosis

Answer 5

Vesicle fuses with others -> might not need to cross memvrane

Question 6

Main way a drug crosses lipid membrane

Answer 6

Conc. different -> has to be liphophilic enough to go through but not so much to stay in membrane

Question 7

Partition coefficient =

Answer 7

[drug] chlorophorm / [drug] water

Question 8

What does partition coefficient tell us

Answer 8

Solubility -> charged/ uncharged (acid/base)

Question 9

At 50% ionisation [HA] / [A] =

Answer 9

1

Question 10

Urine can change ____

Answer 10

pH

Question 11

Dosage needs to be controlled in pregnant women because

Answer 11

drugs can accumulate in foetus -> ion-trapping from kidney to placenta

Question 12

Why is enteral G.I. a good method of drug intake?

Answer 12

Doesn’t need to be sterile, convenient

Question 13

Enteral G.I. intake includes:

Answer 13

• oral
• under tongue (pareteral) - can be thought of as transdermal
• rectum

Question 14

Every time the drug circulates it goes through which organ?

Answer 14

Liver

Question 15

Why is buccal/ sublingual/ rectal preferred?

Answer 15

Directly to general circulation so avoids first pass

• > useful with younger children
• useful for some irritants
• when patient unable to take drug -> vomiting/ unconscious
• supposetery

Question 16

Outline oral intake

Answer 16

Lipid soluble + ion -> weak acids may be bsorbed

- surface area -> stomach is small so mainly in intestines where peristalsis helps dissolve tablet

Question 17

What can affect oral intake of drugs?

Answer 17

Gut contents - decrease drug. conc. + impaired access to mucosa
Diarrhoea - babies
e.g. tetracycline + milk - chemical interaction

Question 18

Bioavailability =

Answer 18

How much drug reaches systemic circulation

F = area under the curve/ dose

Question 19

What are the steps from dose to systemic circ.

Answer 19

stomach - gut - first pass

Question 20

Bioequivalence

Answer 20

Same 500g gives same amount of drug into plasma from 1 drug brand to the next

Question 21

What is a 100% bioavailable way of introducing a drug?

Answer 21

Intravascular -> venous/arterial

Question 22

Drug distribution

Answer 22

Reversible transfer of a drug from 1 location to another in the body depending on physiochemical nature of drug

Question 23

4 types of distribution pattern:

Answer 23

1. Drug remains in vascular system
2. Low molecular weight - soluble compounds are uniformly distributed throughout the body of water
3. Specific concentration in 1 or more tissues
4. Non-uniform distribution based on lipid/water solubility

Question 24

Apparent volume fo distribution

Answer 24

VD = The volume of fluid the drug would occupy if it were evenly distributed through the volume at concentration in plasma

= Dose/ Cp 0

Question 25

VD = 3-5

Answer 25

Distribution in vascular system

Question 26

VD = 30-50

Answer 26

Total body of water

Question 27

Drug binding

Answer 27

The less a drug is bound the more effective it is

Question 28

Binding is:

Answer 28

non-specific and reversible

Question 29

Albumin

Answer 29

Plasma protein that binds to acidic drugs

Question 30

Glycoproteins bind to

Answer 30

basic drugs

Question 31

Consequences of protein binding:

Answer 31

1. Activity decreases 2. Absorption - free conc. low so constant conc. gradient -> sink effect 3. Distribution - restricted to binding protein areas 4. Storage - dissociates when free drug conc. low 5. Elimination - depends on rate limiting step of elimination -> half-life can be longer if less filtered through renal glomerulus or shorter if more brought to liver 6. Interactions - low specificity -> competition for binding sites -> more free drug so higher conc. can be toxic e.g. warfarin by acidic drugs

Question 32

Tissue perfusion limits

Answer 32

transport

Question 33

Biotransformation phases

Answer 33

1. Oxidations, reductions, hydrolyses | 2. Conjugations - liver - major site of drug metabolism

Question 34

Mechanism of elimination in nephron:

Answer 34

1. Glomerular filtraion - molecules > 60kg/mol - passively filtrates blood (20%) 2. Tubulor secretion (80%) - enzymes transporting drugs from plasma to urine - > competition reduces renal clearance - > clearance rate increases by 650 mill 3. Tubular reabsorption - acidic/basic increases reabsorption of weak acid/base

Question 35

Hepatic excretion

Answer 35

Bile is produced at a rate of 0.5-1 l/day and is a major route of excretion for a few drugs (e.g. cromoglycate) and rather more metabolites (e.g. morphine glucuronide). Drug excreted in the bile may be reabsorbed in the intestine and so enter an enterohepatic circulation. A significant proportion of drug in the body may be within this enteric pool.

Question 36

First order elimination

Answer 36

Rate of elimination is proportional to the plasma concentration of the drug, Cp. Cp will decline exponentially when drug administration is stopped. Under these conditions it is possible to define a plasma halflife - the time taken for the plasma concentration to fall by 50%. The plasma half-life is thus an important measure of the speed of drug elimination.

Question 37

Zero order elimination

Answer 37

Rate of elimination is independent of the plasma concentration, a situation which arises when the process of elimination (e.g. active secretion) has become saturated. (Michaelis-Menten kinetics apply in this situation.)

Question 38

ClT =

Answer 38

Kel x VD = [t0.5 =0.693/ClT x VD ]

Question 39

Metabolism in liver:

Answer 39

1. More reactive groups | 2. large compounds accumulate + conjugate