Lecture 10/11

Question 1

Pharmacokinetics

Answer 1

Describes factors that come together to determine the concentration and effects of drugs

Question 2

Drug effects depends on

Answer 2

Mechanism of action
Effects on cellular proteins
Affinity, efficacy and potency
Absorption, distribution, metabolism and excretion

Question 3

Drug absorption and distribution

Answer 3

Bulk flow of drugs through CVS

Must go across PMs through simple diffusion, aqueous channel diffusion, carriers and pinocytosis

Question 4

Lipid solubility of drugs

Answer 4

-1/ square root of mR

Slower diffusivity in large mr drugs

Question 5

Intravenous

Answer 5

Directly into the plasma

Mainly emergencies

Question 6

Intramuscular

Answer 6

For drugs that have a high probability of being metabolised in the gut i.e. peptides
Have to consider variations on muscle blood supply

Question 7

Intrathecal

Answer 7

Firect into the CSF -> Brain -> plasma

When tight control over drug conc. of the drug is required

Question 8

Oral

Answer 8

Most widely used route
Affected by pH and enzymes
Absorption occurs in ileum

Question 9

Bioavailability

Answer 9

What proportion of the drug enters the plasma relative to the amount originally ingested

Question 10

Rectal

Answer 10

Mainly used in babies

Preferabe if GI tract is the target

Question 11

Percutaneous

Answer 11

Absorption through skin
Mainly used in patches and chronically
Drug must be high solubility and non-polar

Question 12

Placenta

Answer 12

Impermeable to most drugs

But lipid-soluble drugs are able to cross

Question 13

Breast milk

Answer 13

Some drugs can end up here

Question 14

Kidneys

Answer 14

Drugs can cross the epithelial border

Question 15

pH and ionisation

Answer 15

Many drugs are weak acids or weak bases

If HA=A-=log10(HA/A-)=log1=0

Question 16

pKa

Answer 16

The pH at which 50% of the acid is in its dissociated form

=pH+log10(HA/A-)

Question 17

Aspirin poisoning

Answer 17

If you increase plasma pH weakly acidic drugs will be extracted from the CNS into the plasma where they will become trapped
Used to treat neurotoxicity following aspirin poisoning

Question 18

OCT1

Answer 18

Organic cation transporter 1
Metformin: drug used in treatment of diabetes type 2 by acting on liver hepatocytes preventing hyperglycaemia
In genetic variants different effects are observed

Question 19

Extracellular fluid

Answer 19

Plasma - 4.5%
Interstitial fluid - 16%
Lymph - 1-2%

Question 20

Intracellular fluid

Answer 20

30-40%

Question 21

Transcellular fluids

Answer 21

2.5%

Question 22

Fat

Answer 22

20%

Question 23

Blood brain barrier

Answer 23

Tight junctions between endothelial cells impermeable to water-soluble molecules
Lipid-soluble molecules can cross but not antibiotics, chemotherapy drugs or most new bio-drugs

Question 24

BBB and inflammation

Answer 24

Inflammation causes tight junctions to become leaky e.g. during meningitis penicillin can be used because tight junctions let the antibiotic through

Question 25

Chemoreceptor trigger zone

Answer 25

Outside the BBB, detets chemicals to trigger a vomit reaction

Question 26

BBB and parkinsons treatments

Answer 26

Can be treated using dopamine, but chemoreceptor trigger zone has dopamine receptors so dopa drugs trigger a vomit reaction. Different dopa receptors in the brain and trigger zone, therefore use an antagonist to block trigger zone so the drug can cross the BBB

Question 27

Body fat and drug distribution

Answer 27

Non-polar drugs sequester into body fat, so free drug conc and effects will vary dramatically.

Question 28

Low body fat

Answer 28

Low doses will get to act faster and the effects last longer

Question 29

High body fat

Answer 29

Lipophilic drug distributes into the body fast and therefore there is a lower concentration where it is wanted

Question 30

Drug metabolism

Answer 30

Phase 1 - catabolic reactions to produce a more reactive compound
Phase 2 - synthetic reactions, involves conjugations to produce an inactive product

Question 31

Pro-drugs

Answer 31

Only become active after being metabolised

useful for slow inductions of drugs effects, the concentration will slowly increase

Question 32

Liver drug metabolism

Answer 32

Enter through the portal blood system or via plasma
Can escape this and join bile, therefore slowing metabolism
After liver - into kidneys - exit via the urine

Question 33

Paracetamol metabolism

Answer 33

Forms intermediate compound which is highly toxic to the liver, it is rapidly reacted on in phase 2 to combine with sugars and reduce time being toxic

Question 34

P450 enzymes

Answer 34

Coded for by 57 genes
other jobs than drug metabolism
Interference can have knock on effects
Inducers of P450 increases drug metabolism