PH3110 - How human biology influences drug handling and action 2

Question 1

What is the purpose of a single dose therapy?

Answer 1

Returns out of balance systems to normal
Feedback control systems then maintain homeostasis

Question 2

Give three examples of a single dose therapy

Answer 2

Asthma (salbutamol - reliever inhaler)
Headache (paracetamol)
Fungal infections (fluconazole)

Question 3

How does methotrexate work?

Answer 3

Inhibits dihydrofolate reductase
- stops DNA synthesis

Question 4

How often is methotrexate given?

Answer 4

Weekly dosing as it stops DNA synthesis
- high doses less frequently to hit rapidly dividing cells rather than normal ones

Question 5

What is drug tolerance?

Answer 5

Decreased sensitivity to a drug that develops as a result of exposure to the drug
- reduced effectiveness
- reduced pharmacological response

Question 6

Give two examples of drugs where tolerance occurs

Answer 6

Morphine
- days of repeated dosing
Ethanol
- months, not days

Question 7

What is acute tolerance?

Answer 7

Tachyphylaxis
- rapid decrease in the response to a drug due to previous exposure to the drug

Question 8

Why isn’t a loading dose of protriptyline given?

Answer 8

Although the half life is 3 days, so it would take 2 weeks to reach steady state, the effects of the drug aren’t seen for 4 weeks anyway so better to gradually build up to avoid adverse CNS effects

Question 9

What factors affect how long it takes for drugs to distribute into tissues?

Answer 9

Delivery of drug to tissue by blood
Ability to cross tissue membranes
Binding within blood and tissues
Partitioning into fat
- acts as a reservoir

Question 10

What is the distribution profile of thiopental?

Answer 10

Fast rise in well perfused tissue
- liver
Slower rise in poorly perfused tissue
- muscle
Even slower in adipose but most drug remain in adipose after 3 hours
- very lipophilic

Question 11

Describe the perfusion-rate limitation

Answer 11

Membranes offer no resistance
Drug in equilibrium with interstitial fluid and tissue
Blood and tissue viewed as one compartment
- e.g. benzodiazepines in brain as can’t sample brain

Question 12

Describe the permeability-rate limitation at the cell membrane

Answer 12

Tissue cell membranes offer resistance
Movement into tissue slow and insensitive to perfusion
- equilibrium not achieved by the time blood leaves organ
Blood and tissue viewed as separate compartments

Question 13

Describe the permeability-rate limitation at the capillary and cell membranes

Answer 13

Blood brain barrier
- special case
Tissue cell membranes AND capillary membrane offers resistance

Question 14

What is hysteresis?

Answer 14

The time delay between the measured concentration and the effect response

Question 15

How can hysteresis be useful?

Answer 15

Pharmacokinetic technique to assess if there is discordance between concentration-time and effect-time

Question 16

Give two reasons to explain a delayed measured response

Answer 16

Response primarily dependent on active metabolite
Response controlled by events occurring subsequent to drug reaching site of action

Question 17

What is the distribution rate constant?

Answer 17

A measure of how rapidly a drug would leave tissue if arterial concentration were suddenly to drop to zero
- analogous to the elimination rate constant for the loss of drug from whole body

Question 18

Under what conditions do drugs leave slowly from tissues?

Answer 18

Tissues with high affinity for the drug (Kpb)
Tissues that are poorly perfused

Question 19

What is the effect of the tissue affinity (Kpb) the same for all tissues?

Answer 19

Same drug reaches equilibrium at different times in different tissues

Question 20

What is the effect of different tissue affinities (Kpb) in the same tissue?

Answer 20

Time taken to reach equilibrium is different
AND
equilibrium tissue concentration are different