Pharmacology

Question 1

What are the most important parameters for pharmacokinetics

Answer 1

Clearance
Volume of distribution
Fractional oral bioavailability
Half life

Question 2

What is clearance what does it determine

Answer 2

• Describes the efficiency of irreversible elimination from the body.
• It is the volume of plasma cleared of drug per unit time (ml/min)

Determines the maintenance dose rate.

Influences the half life, the lower the clearance the longer the half life

Question 3

What dose Vd determine

Answer 3

The volume into which a drug appears to distribute (with a concentration equal to that of plasma concentration)

• Loading dose
• Influences t 1/2, the bigger the vd the longer the 1/2 life.

Question 4

What is fractional oral bioavailability what does it determine and what is it affected by

Answer 4

Fraction or percentage of the administered dose that reaches the systemic circulation.

Determines
The route and modifies the clearance and vd

Affected by
Solubility/ formulation
First pass metabolism
Transporters

Question 5

What is half and what does it determine

Answer 5

• The time for the concentration of drug in plasma to halve.
• Provides an index of the time course of elimination and the time course of accumulation.

Determines
- Duration of action after a single dose
- Time to reach steady state with chronic dosing (5x t 1/2)
- The dose interval

Question 6

Define elimination

Answer 6

Removal of medication from the body (i.e by metabolism by liver or kidneys).
It is not the same as clearance and it is not linear as it is proportional to plasma concentration (first order elimination)
i.e absolute amount eliminated per time may change but the fraction will be constant.

Question 7

What is 0 order elimination

Answer 7

Saturable elimination

Same rate of elimination occurs irrespective of the drug concentration.
This means you get variability in your plasma concentration when you increase the dose
e.g phenytoin, alcohol

i.e the fraction eliminated does change

Question 8

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Answer 8

clearance

Question 9

What is bioequivalance

Answer 9

Bioequivalence is defined as the absence of a significant difference in the rate and extent of absorption into. the systemic circulation, of two pharmaceutically equivalent medicines, when administered in the same dose. under similar conditions.

Key metric that must be equivalent is AUC (generic/innovator)

Question 10

What is E max

Answer 10

Maximal effect of the drug
Measure of drug efficacy

Question 11

What is the EC50

Answer 11

Concentration required to produce 50% of the maximal effect
Measure of drug potency

Question 12

How do you calculate the therapeutic index

Answer 12

EC50 (toxic effect)/ EC50 of desired effect

Question 13

What is a drug agonist

Answer 13

Stimulates receptor to elicit maximal affect

Question 14

What is a partial agonist

Answer 14

Stimulates receptor to elicit submaximal effect (even with all the receptors occupied)

In a way acts as a competitive antagonist e.g buprenorphine

Reduces the emax and increases ec50

Question 15

What is a competitive antaogonist

Answer 15

Competes with agonist (amount and affinity)

e.g. metoprolol on beta-receptors, naloxone on opioid receptors

Increases the EC50

Question 16

What is a non competitive antagonist

Answer 16

Either binds irreversibly with its receptor e.g aspirin on COX 1

OR
it is an allosteric modulator and acts at a different site
e.g Naproxen on COX2

Reduces Emax and increases the EC50

Question 17

What receptors do drugs act on

Answer 17

• Cell surface receptors
  − Nuclear receptors
  − Enzymes
  − Channels or transporters
  − Signal transduction proteins

Question 18

Outline the difference between cell surface receptors and nuclear receptors

Answer 18

Cell surface receptors
- Alter a signal
- Extracellular drug
- Rapid

Nuclear receptors
- Alter DNA expression
- Intracellular drug
- Slower (protein synthesis)

Question 19

How does Gentamicin work, what is its F, renal clearance and half life

Answer 19

Binds to 30s ribosomal subunit to inhibit protein synthesis.
F = 0%
90% renal clearance
T half 2 hours