Pharmacokinetics & Pharmacodynamics

Question 1

Pharmacokinetics

Answer 1

What the body does to the drug

Study of how drugs:

Enter the body

Reach their site of action

How they are eliminated from the body

Question 2

Pharmacodynamics

Answer 2

What the drug does to the body

Study of the mechanisms by which drugs act to produce biochemical or physiological changes in the body

The study of drug action at a biochemical level.

Mechanism of action of a drug.

Drugs can increase or decrease the rate at which a process works.

Drugs cannot make the body do something it couldn’t do otherwise.

2 mechanisms:

• A drug can change the environment of body cells e.g. decrease acid production in the stomach.
• A drug can bind to a receptor to alter cell physiology.

Question 3

Five Phases of Pharmacokinetics

Answer 3

Liberation
Absorption
Distribution
Metabolism
Elimination

Question 4

Five Phases of Pharmacokinetics:

Liberation

Answer 4

Liberation only applies to oral medications.

The process by which a drug is released from its delivery device during digestion. Tablet, capsule, etc.

The rate of liberation is determined by its composition. Powder versus tablet

Question 5

Five Phases of Pharmacokinetics:

Rx (drug) Absorption

Answer 5

How a drug enters the bloodstream. Remember time/concentration graph and delivery route flow diagram.

Depends on:

Design of Rx

Rx concentration

Surface area of absorption site

Delivery route

Surface area of Rx

pH of drug

Rate of blood flow - hypothermia, shock

Lipid or water soluble

Question 6

Five Phases of Pharmacokinetics:

Distribution

Answer 6

The distribution of a drug around the body’s bloodstream and cells.

Distributions is dependent on the chemical properties of the drug and its ability to:

Cross cell membranes - Simple diffusion, Aqueos channels, Facilitated diffusion and Active transport

Cross blood-brain barriers

Cross the placenta

Factors effecting Rx distribution:

Blood pH.

Competing tissues.

Protein and tissue binding.

Perfusion status.

Presence of other protein binding drugs.

Vascular supply to the target tissue.

Question 7

Five Phases of Pharmacokinetics:

Metabolism

Answer 7

How a drug is changed by the body

Complex liver enzyme system

Converts lipid soluble drugs to water soluble metabolites

Easier to eliminate

Question 8

Five Phases of Pharmacokinetics:

Elimination

Answer 8

How drugs are removed from the body after metabolism:
Sweat
Tears
Expired air
Kidneys  - urine
Bile
Faeces

Question 9

Movement across cell membranes

Answer 9

Passive diffusion

Diffusion through aqueous channel

Facilitated diffusion with a carrier protein

Active transport against concentration gradient with input of energy

Question 10

Plasma concentraion

Answer 10

look up “the area under the plasma drug concentration-time curve (AUC)” graph for this

Plasma conc. is important as drugs have a therapeutic effect range and this dictates dose intervals.

Drugs also have a toxic limit.

Plasma conc. is decreased via the half life law’s of First order and zero order elimination.

Question 11

Factors affecting Rx distribution

Answer 11

Protein & tissue binding
Perfusion status
Presence of other protein binding drugs
Placental barrier 
Vascular supply to the target tissue
Blood pH
CNS blood brain barriers
Competing tissues

Question 12

Biotransformation

Answer 12

First pass effect:

• Drugs absorbed into the bloodstream via the GI tract enter the liver before entering general circulation.
• This is via the hepatic portal vein.
• Liver can metabolize or inactivate drugs before they are distributed throughout body:
  Can be good if drugs are harmful/potent
  Prevents drugs such as GTN being given orally

Question 13

Biotransformation

Answer 13

First pass effect:

• Drugs absorbed into the bloodstream via the GI tract enter the liver before entering general circulation.
• This is via the hepatic portal vein.
• Liver can metabolize or inactivate drugs before they are distributed throughout body:
  Can be good if drugs are harmful/potent
  Prevents drugs such as GTN being given orally

Question 14

Elimination Half Life

Answer 14

The amount of time required for elimination processes to reduce drug serum concentration by half.

For example naloxone is known to have a shorter half life than heroin and is eliminated quickly.

Half life (First Order)
E.g 80mg of a drug is given, and it has a half life of four hours, what concentration will remain in the plasma after 12 hours?
0 hours = 80mg
4 hours later = 40mg
8 hours later = 20mg
12 hours later = 10mg

Question 15

First-order elimination

Answer 15

look up graph for this

Definition First order elimination kinetics : “Elimination of a constant fraction per time unit of the drug quantity present in the organism.

Question 16

Zero-order elimination

Answer 16

look up graph for this

Definition Zero-order elimination kinetics : “Elimination of a constant quantity per time unit of the drug quantity present in the organism.”

Question 17

difference between first-order and zero-order elimination

Answer 17

In brief : First order elimination kinetics: a constant proportion (eg. a percentage) of drug is eliminated per unit time. … First order kinetics is a concentration-dependent process (i.e. the higher the concentration, the faster the clearance), whereas zero order elimination rate is independent of concentration.

Question 18

Special Considerations

Answer 18

Children:
Underdeveloped ability to metabolise and excrete drugs.
This leads to greater sensitivity to drugs

Elderly:
Impaired ability to metabolise and excrete drugs.
This leads to greater sensitivity

Question 19

Pharmacodynamics - Drug Receptors

Answer 19

‘Lock and key’ receptor sites - specific drugs fit specific receptors in order to create an action

Agonist – a drug that binds to a receptor to stimulate a response

Antagonist - a drug that binds to a receptor to block stimulation