Session 2 - Basic Pharmo Concepts

Question 1

Equation of Oral Bioavailability

Answer 1

ral Bioavailability (F)=(AUC oral)/(AUC IV) × 100

Question 2

Equation for Volume of distribution

Answer 2

Volume of Distribution (Vd)= (Total Amount of Drug in Body)/(Plasma Concentration of Drug at Time=Zero)

Question 3

What is total clearance

Answer 3

Total Clearance = Hepatic Clearance + Renal Clearance

Question 4

How is clearance calculated?

Answer 4

Clearance=(Amount in urine × Urine flow rate)/(Arterial Plasma Concentration)

Question 5

HOw is half life calculated/

Answer 5

(0.693 × Volume of Distribution)/Clearance

Question 6

How is first order kinetics calculated?

Answer 6

Rate of Metabolism=(Vmax [C])/Km

Question 7

How are 0 order kinetics calculated?

Answer 7

Rate of Metabolism=(Vmax [C])/([C])

Question 8

HOw is steady state conc in plasma calculated?

Answer 8

Steady State Concentration in Plasma (CpSS)= (Dose Rate)/Clearance

Question 9

How is loading dose calculated?

Answer 9

Loading Dose (Dose L)= Vd ×CpSS

Question 10

Define agonist, antagonist and partial ag/antag

Answer 10

Agonist – Bind to and stabilise receptor sites in the Active conformation

Antagonist – Bind to and stabilise receptor sites in the Inactive conformation

Partial Agonist/Antagonist – When drugs act as a mixture of both of the above, they are said to act as Partial Agonists or Partial Antagonists. The overall action of the drugs is dependent on the proportion of receptor sites it stabilises in the Active or Inactive confirmation.

Question 11

What is affinity?

Answer 11

Affinity – The tendency of a drug to bind to a specific receptor site.

Question 12

What are kd and ki?

Answer 12

o Kd – Concentration at which half available agonist receptors are bound
o Ki – Concentration at which half available antagonist receptors are bound

Question 13

WHat is efficacy?

Answer 13

Efficacy – The maximal effect of a drug when bound to a receptor.

Question 14

What is agonist potency?

Answer 14

Potency (Agonist) – Concentration that produces 50% of maximal response

Question 15

What overcomes competitive antagonism?

Answer 15

In competitive antagonism agonist efficacy can be restored, by increasing agonist concentration. This increases the competition for receptor sites.

Question 16

What is non competitive antagonism?

Answer 16

In non-competitive antagonism the antagonist can bind in two ways:
1. At the same site for the agonist binding irreversibly or unbinding very slowly
2. At a separate site to the agonist either reversibly or irreversibly
In this case, no matter how much agonist is added, the maximal effect will be depressed proportional to the degree of antagonist binding. However, because the agonist does not have to compete to occupy its binding site, the EC50 remains the same.

Question 17

What is a therapeutic window?

Answer 17

The therapeutic window is the concentration of drug that is high enough to have a therapeutic effect, but not so high that is has a toxic effect.

Some drugs have extremely narrow therapeutic windows, e.g. Phenytoin meaning they have to be closely monitored.

Question 18

What is the calculation for therapeutic index?

Answer 18

Therapeutic Index= (Toxic Dose in 50% of People (TD50))/(Effective Dose in 50% of People (ED50))

Question 19

What two factors can effect absorption of drugs?

Answer 19

Gut motility

Passive or active absorption

Question 20

What effects metabolism?

Answer 20

Induction and inhibition of the CYP450 enzymes

Question 21

What effects elimination? (3)

Answer 21

Level of protein binding
- Decreased binding increases the amount of free, unbound rug, accelerating its removal
Tubular secretion
Urinary pH

Question 22

Give 5 clsaees of drugs which commonly interact with other drugs

Answer 22

o	Anticonvulsants
	Phenytoin
	Carbamezepine
o	Anticoagulants
	Warfarin
o	Antidepressants
	Monoaimine Oxidases
o	Antibiotics
	Rifampicin
	Macrolides
	Quinolones
o	Antiarrhythmics
	Amiodarone

Question 23

Give three ways in which CYP450 can induced?

Answer 23

Increased transcription
Increased translation
Slower degradation

Question 24

What two bad things can happen if CYP enzymes are induced?

Answer 24

o Withdrawal of the inducing agent without a change in the therapeutic agent can lead to toxicity if dosing is not re-adjusted.
o Induction may lead to increased production of a toxic metabolite

Question 25

What two bad things can happen if CYP enzymes are inhibited?

Answer 25

o Introduction of an inhibiting agent without a change in the therapeutic agent can lead to toxicity if dosing is not re-adjusted
o Withdrawal of an inhibiting agent without a change in the therapeutic agent can lead to concentrations falling to a sub-therapeutic level

Question 26

How does hepatic disease cause drug metabolism to go awry? 3

Answer 26

o Reduced clearance of hepatic metabolised drugs
o Reduced CYP450 activity
 This leads to drugs having much longer half-lives, which in turn leads to toxicity.
 E.g. Opiates in Cirrhosis – Small doses accumulate, leading to coma.
o Hypoalbuminaemia (malnutrition, nephrotic syndrome)
 Less albumin for drugs to bind to, free drug plasma levels higher

Question 27

How does renal disease mess up drugs?

Answer 27

o Reduced clearance of hepatic metabolised drugs
o Reduced CYP450 activity
 This leads to drugs having much longer half-lives, which in turn leads to toxicity.
 E.g. Opiates in Cirrhosis – Small doses accumulate, leading to coma.
o Hypoalbuminaemia (malnutrition, nephrotic syndrome)
 Less albumin for drugs to bind to, free drug plasma levels higher

Question 28

How does cardiac disease effect drugs?

Answer 28

Reduce organ perfusion

Question 29

What is an on target ADR?

Answer 29

On Target ADRs are due to an exaggerated therapeutic effect of the drug, most likely due to increased dosing or another factor affecting the drugs pharmacokinetics or pharmacodynamics.
o Hypertension treatment leading to hypotension
 Dizziness, unsteadiness, syncope
On Target ADRs often consist of effects on the same effector, but in different tissues.
o Antihistamine H1 receptor antagonists acting on Immune System H1 Receptors
 Also act on CNS H1 Receptors causing drowsiness

Question 30

What is an off target ADR?

Answer 30

Off Target ADRs are interactions with other receptor types secondarily to the one intended for therapeutic effect. Virtually all drugs do this.
Off Target ADRs can also occur with metabolites that subsequently act as a toxin.
o Paracetamol in overdose
 NAPQI

Question 31

Give four groups prone to drug ADRs

Answer 31

o Pregnant Women
 Teratogenicity
 Thalidomide
o Breast Feeding Women
 Man drugs can be passed on in the breast milk
o Elderly
 Polypharmacy
 Reduced renal clearance
 Nervous system is more sensitive to drugs
o Patients with genetic enzyme defects
 Glucose-6-Phosphate Dehydrogenase deficiency, resulting in haemolysis if an oxidant drug (e.g. aspirin) is taken

Question 32

What is polypharmacy?

Answer 32

The risk of adverse drug reactions increases with every drug a patient takes. Hospital patients are often on a cocktail of 8 or more drugs, which takes the overall chance of an ADR to 80%.