Pharmacokinetics

Question 1

What is pharmacokinetics

Answer 1

What the body does to the drug
1. Absorption
2. Distribution
3. Metabolism
4. Excretion

Question 2

Can you describe absorption?

Answer 2

○ Absorption of a drug = absorption into the blood
○ Absorption depends on the form of a drug and site of admin
○ It is influenced by the different transport mechanisms across the membrane

Question 3

Physiological factors affecting absorption?

Answer 3

1. Blood flow
2. Surface area (Greater surface area, greater absorption)
3. Gastric motility
4. Other substances (food=delayed stomach emptying) can lead to inhibited or increased absorption

Question 4

Physio-chemical factors affecting absorption?

Answer 4

1. Acid base status (the balance of water solubility and lipid solubility)
2. Ionisation (uncharger and unionised=increases absorption

Question 5

Explain passive diffusion?
(Gap in fence)

Answer 5

○ Depenent on lipid solubility of the drug
○ Drugs have to be lipid soluble to pass the membrane
○ Drugs flow from an area of high to low concentration

Question 6

Explain facilitated passive diffusion?
(Larger molecules=walk through gate)

Answer 6

○ Passive movement of molecules across the cell membrane via the aid of membrane protein
○ Require no energy
○ Not lipid soluble

Question 7

Explain active transport?
(Voltage operated gate)

Answer 7

○ Active transport uses energy to move molecules from low to high concentration.
○ needs energy
○ uses carrier proteins called protein pumps

Question 8

Define distribution?

Answer 8

○ Distribution=Distribution from the blood to the peripheral tissues
○ As soon as a drug enters the blood it will start to be distributed throughout the body

Question 9

Explain first pass metabolism?

Answer 9

○ Breaks down drug so not all of it goes to distribution
○ Drug absorbed through intestine
–> to hepatic portal vein
–> to the liver
–> Liver metabolises either partially or fully before entering systemic circulation
–> affects bioavailability

Question 10

Factors affecting distribution?

Answer 10

1. Blood circulation
2. Degree if the drugs binding to plasma proteins
3. The water and lipid solubility of the drug
4. Distribution barriers

Better blood flow=better Distribution

Question 11

Drug binding to plasma proteins

Answer 11

○ Drugs will bind proteins
○ Different proteins will have different affinity to bind different drugs
○ only free drugs are active
○ protein bounds drugs are inert
○ some drugs displace others from their binding sites

Question 12

Physiological factors affecting protein binding?

Answer 12

1. Burns
2. Malnutrition
3. Liber disease
   (All reduced levels of plasma albumin)
   –> Less proteins in the blood means less protein binding & more free drug –> leading to over dose, side effects, adverse effects

Question 13

Define metabolism?

Answer 13

○ A process whereby the chemical structure of a drug is changed
○ aim = make drug more water soluble

Question 14

What are the 2 phases of metabolism?

Answer 14

Phase 1 = where the drug is modified to a reactive metabolite
1. Oxidation
2. Reduction
3. Hydrolysis

Phase 2 = fuses together with another compound to form a water soluble conjugated complex

Question 15

Enzyme process/interactions

Answer 15

○ The metabolic activity of the liver is carried out by the enzymatic process
○ Can be affected by age, disease, drug interaction

○ Enzyme induction = drugs metabolism faster + drug concentration decreased
& ○ Enzyme inhibition = drugs metabolised slower + drug concentration increased

Question 16

Define excretion?

Answer 16

○ The kidneys = most important organ for elimination by excretion
○ water-soluble drugs will follow the flow of filtration through the rest of the nephron and be excreted in the urine

○ Lipid-soluble drugs are subject to reabsorption
–> to the blood, through the liver again to be metabolised to water-soluble metabolites

Question 17

The 5 R’s of drugs administration

Answer 17

1. Right patient
2. Right drug
3. Right dose
4. Right route
5. Right time/frequency

Question 18

Nature of the drug

Answer 18

1. Available in suitable forms
2. Administered by appropriate route
3. Absorbed
4. Distributed
5. Metabolised
6. Excreted

Question 19

Define therapeutic window/narrow therapeutic index?

Answer 19

The intention is to achieve the therapeutic effect quickly, for an appropriate duration of action and without side effects

Question 20

Define time to onset?

Answer 20

Time it takes for a drug to reach its site of action at a concentration necessary for it to work

Question 21

Define half-life?

Answer 21

The time it takes for the peak concentration of a drug in the plasma to reduce d by half

Question 22

Define duration of effect?

Answer 22

The time interval where the concentration of drug at its site of action is above its therapeutic concentration

○ may be prolonged in elderly or people with poor liver or kidney function

Question 23

Define bioavailability?

Answer 23

○ The percentage of drug administered that reaches the systematic circulation after absorption

Question 24

Define steady state ?

Answer 24

○ When the drug going into the body = the drug going out
○ usually achieved after 4-5 half lives

Question 25

Define clearance?

Answer 25

○ A measure of a person’s ability to metabolise and excreted a drug
○ How quickly a drug is cleared from the blood
○ is affected by: renal function, BP and urine PH

Question 26

Define volume of distribution?

Answer 26

○ The volume of plasma in which the total amount of drug in the body would need to be dissolved in order to reflect the drug concentration in the plasma