Pharmacokinetics and Pharmacodynamics

Question 1

Define pharamcodynamics

Answer 1

What the drug does to the body

Question 2

What are the four main types of receptors?

Answer 2

ReceptorsEnzymesCarrier/transportersIon Channels

Question 3

Define agonist

Answer 3

Bind to and stabilise receptor sites in the active state

Question 4

Define antagonist

Answer 4

Bind to and stabilise the receptor site in the inactive state

Question 5

Define partial agonist/antagonist

Answer 5

When drugs act as a mixture of both agonists and antagonists. the overall action of the rugs depends on the proportion of each receptor type activated

Question 6

Define affinity

Answer 6

The ability of a drug to bind at a receptor site

Question 7

Define Efficacy

Answer 7

The maximal effect of a drug when it is bound to a receptor

Question 8

Define Kd

Answer 8

The concentration at which half available agonist receptors are bound

Question 9

Define Ki

Answer 9

The concentration at which half available antagonist receptors are bound

Question 10

Define efficacy

Answer 10

The maximal effect of a drug when bound to a receptor

Question 11

Define potency for an agonist

Answer 11

Concentration that produces 50% of a maximal response

Question 12

Define potency for an antagonist

Answer 12

Concentration that reduces the maximum activation by 50%

Question 13

Define competitive antagonism

Answer 13

The antagonist competes for the active site with the agonist. It can be overcome by increasing the agonist concentration

Question 14

Define non-competitive antagonism

Answer 14

The antagonist binds to a site other than the actives site OR is bound to the active site but removal is very slow. You cannot overcome this antagonism by adding more of an agonist. The maximal effect is decreased in proportion to the degree of antagonist binding.

Question 15

What actions does metoclopramide have?

Answer 15

Is a dopamine antagonist- antiemetic- gastroprokineticTherefore it increases the rate of gastric emptying and therefore increase the rate of uptake via the small intestine. This can potential increase the absorption of some drugs.

Question 16

How can the distribution phase be affected by drug:drug interactions?

Answer 16

• Competition at protein/ lipid binding sitesCan have serious issues if the drug has non-linear kinetics and has a narrow therapeutic window so the concentration of the drug builds up.

Question 17

How can drug/drug interactions affect metabolism?

Answer 17

They can cause induction or inhibition of certain CYP enzymes

Question 18

What are the main mechanisms which affect drug excretion?

Answer 18

1. Protein binding- decreased binding increases amount of unbound drug, which increases its rate of removal2. Tubular secretion- inhibiting tubular secretion will increase the plasma levels of a drug3. Urinary pH- this has an effect on acidic/basic drugs being able to diffuse back into the blood

Question 19

Describe a specfic drug-drug interaction

Answer 19

Propanolo (non-selective beta antagonist) reduces the effects of salbutamol (Beta2 receptor agonist). Therefore, betablockers should not be administrated to asthmatics or should be done with caution.

Question 20

Give some anticonvulsants which commonly give rise to drug-drug interactions

Answer 20

PhenytoinCarbamezepine

Question 21

Give an anticoagulant which commonly gives rise to drug-drug interactions

Answer 21

Warfarin

Question 22

Give an antidepressant which commonly gives rise to drug-drug interactions

Answer 22

Monoamine oxidases

Question 23

Give some antibiotics which commonly give rise to drug-drug interactions

Answer 23

RifampicinMacrolidesQuinolones

Question 24

Give an antiarrhthymic which commonly gives rise to drug-drug interactions

Answer 24

Amiodarone

Question 25

What are the mechanisms by which induction takes place in CYP450 enzymes?

Answer 25

Increased transcriptionIncreased translationSlower degradation

Question 26

What does induction of CYP450 enzymes do?

Answer 26

Increases the rate of elimination

Question 27

What happens when CYP450 enzymes are inhibited?

Answer 27

Drug half-lives increaseDrug clearance decreases

Question 28

Why do drug interactions occur when hepatic disease is present?

Answer 28

• Decreased clearance of hepatic metabolised drugs- Reduced CYP450 activity- Hypoalbuminaemia due to malnutrition and nephrotic syndromeleads to less albumin for drugs to bind to so the free plasma drug levels are higher

Question 29

Why do drug interactions occur with renal disease?

Answer 29

• Falling GFR (acute or chronic)- Reduced clearance of renally excreted drugs (Digoxin, aminoglycosides)- Electrolyte disturbances may predispose to toxicity - NephrotoxinsE.g. Aminoglycosides are nephrotoxic, and can further enhance their own and other drug toxicities by reducing GFR

Question 30

Why do drug interactions occur with cardiac disease?

Answer 30

• Decreased organ perfusion- Excessive response to hypotensive agents

Question 31

What interactions can occur with certain types of food?

Answer 31

Grapefruit and cranberry juice inhibit CYP450 enzymes. They will reduced the clearance of a number of drugs including warfarin and statins.

Question 32

Define on-target adverse drug reactions

Answer 32

These are due to:- an exaggerated therapeutic effect of a drug, usually due to increased dosing. e.g. hypertension treatment leading to hypotension- The same effect, but occurring in different tissuese.g. antihistamine receptors acting on immune system receptors as well as H1 receptors in the heart, causing drowsiness.

Question 33

Define off-target adverse drug reactions

Answer 33

These are interactions with other receptor subtypes which occur secondarily to the one intended for therapeutic effect. This is very common in most drugs.

Question 34

Give some groups of people who are prone to adverse effects

Answer 34

Pregnant women- teratogenicity- thalidomideBreast feeding womenElderly - polypharmacy- reduced renal clearance- nervous system is more sensitive to drugsPatients with genetic enzyme defects- G6PD deficiency, haemolysis occurs is an oxidant drug is taken

Question 35

When are drug interaction likely to occur?

Answer 35

With polypharmacy- the more drugs you are taking, the greater the risk of a drug-drug interaction occuring