Principles of Pharmacology

Question 1

1. What is pharmacodynamics?

2. What is pharmacokinetics?

Answer 1

1. the actions that a drug has on the body

2. the actions that the body has on a drug (ADME)

Question 2

Define the following:

1. Full Agonist
2. Partial Agonist
3. Antagonist
4. Inverse Agonist
5. Efficacy
6. Potency
7. Tolerance
8. Desensitisation

Answer 2

1. increase in response with increase in drug concentration until max response is achieved
2. increase in response with increase in drug concentration but unable to produce a maximum response
3. reduce the activity of an agonist at a receptor
4. acts to reduce the level of spontaneous receptor activity, shifting it to a more inactive state
5. the measure of action of a drug, once binding has occurred
6. determined both affinity and efficacy. Higher a drug’s potency, the lower the concentration required to elicit responses
7. a decrease in response to repeated doses of a drug. Often necessitates an increase in dosage to maintain adequate clinical response
8. long and short term changes arising from a decrease in response at a receptor

Question 3

1. What is volume of distribution?
2. What 2 measurements are needed to calculate volume of distribution?
3. How is volume of distribution?

Answer 3

1. the theoretical volume necessary to contain the total amount of an administered drug at the same concentration that is observed in the blood plasma
2. dose of drug administered
   plasma concentration of drug (obtained from blood sample)
3. Vd = amount of drug in body (i.e. dose administered) / plasma concentration of drug

Question 4

1. What is assumed of the single compartment model of drug distribution?
2. What is the 2 compartment model of drug distribution?
3. What could cause a reduction of drug plasma concentration of a drug that follows the 2 compartment model?
4. Name an example of a drug that follows the 2 compartment model

Answer 4

1. that the rates of absorption, metabolism and excretion are directly proportional to the concentration of drug in the compartment from which transfer is occuring
2. a drug is administered into the plasma (central compartment) but can distribute itself into another compartment (peripheral compartment)
3. elimination of the drug, or distribution from the central to peripheral compartment
4. lithium

Question 5

1. What is the half life of the drug?
2. In general, how many half lives does it take to achieve steady state of a drug?
3. Name 2 factors that influence a drug’s half life

Answer 5

1. time it takes for the concentration of the drug in the plasma or the total amount in the body to be reduced by 50%
2. 5
3. clearance (dependent on liver and renal function)
   volume of distribution

Question 6

How can renal failure and diarrhoea and vomiting affect drug plasma concentration?

Answer 6

1. reduced drug absorption and increased drug elimination

2. reduced volume of distribution

Question 7

1. What is the oral availability of a drug?

2. Name 2 things that affect the oral availability of a drug

Answer 7

1. the fraction of a drug that reaches the systemic circulation after oral ingestion

Drug absorption - ability of a drug to cross the gut wall into the portal vein
first pass metabolism

Question 8

1. What is transmembrane drug efflux?
2. What does it have an effect on?
3. How does pH affect oral availability?

Answer 8

1. presence of drug efflux pumps in the membrane of enterocytes, that pump drug against concentration gradient back into gut lumen
2. oral availability of drugs
3. drugs are ionised at their opposing pH/ Gut mucosa is impermeable to drugs in ionised form.
   The pH of the stomach is acidic - weak acids are absorbed at a faster rate from the stomach because they are not found in the ionised form
   The pH of the small intestine is basic - weak bases are absorbed at a faster rate from the small intestine because they can’t be ionised in the basic medium.

Drug ionisation also affects drug distribution throughout the body - ion trapping

Question 9

How does cirrhosis affect the oral availability of drugs?

Answer 9

increases oral bioavailability because first pass metabolism is reduced (thus a greater proportion of the drug can enter the systemic circulation)

Question 10

Name 6 potential impacts of liver disease on prescribing

Answer 10

1. impaired drug metabolism
2. hypoproteinaemia - thus reduced drug binding
3. reduced blood coagulation
4. hepatic encephalopathy - care must be taken when giving centrally acting drugs
5. fluid overload (increased Vd)
6. caution with hepatotoxic drugs

Question 11

Describe first order kinetics

Answer 11

the amount of drug eliminated per unit time is proportional to the drug concentration

Question 12

1. Describe zero order kinetics
2. What is zero order kinetics dependent on?
3. With zero order kinetics, what is the consequences of small dose increases and why?
4. Name the consequence of switching from first order kinetics to second order kinetics
5. give an example of a drug which displays this phenomenon

Answer 12

1. the amount of drug eliminated is constant per unit time, and is not related to the concentration
2. rate of enzyme activity. As enzymes involved in drug metabolism become saturated at higher drug doses, the drug is not metabolised proportionately to dose at these higher doses
3. small dose increases lead to larger increases in plasma concentration, as the rate of elimination can’t be increased due to saturation of metabolising enzymes
4. HAS AN IMPACT ON THERAPEUTIC INDEX
   - at low doses, first order kinetics means a drug has a broad therapeutic window
   - at higher doses, zero order kinetics means a drug has a narrow therapeutic window.

Question 13

Describe the process of Drug dose calculations when switching from one drug preparation to another (that have different bioavailabilities)

Answer 13

1. Calculate the SERUM CONCENTRATION based on oral bioavailability of the current preparation
   - bioavailability x dose = serum concentration
2. divide the serum concentration by the bioavalability of the second preparation
   serum concentration/bioavailability = dose of second preparation
3. divide the liquid dose by the volume per dose of the solution

Question 14

2 oral preparations of digoxin give different bioavailabilities

• Tablets - F = 0.63
• Liquid - F = 0.75

Patient has been taking 125microg of oral digoxin but needs to change to liquid digoxin.
Liquid digoxin is available in 50microg/L solutions
Calculate how much liquid will be required to maintain the serum concentration

Answer 14

1. calculate serum concentration
   125 x 0.63 = 78.75 micrograms
2. calculate the dose of liquid digoxin required to maintain serum concentration
3. 75 / 0.75 = 105 microg
4. Calculate the amount of liquid required to achieve this dose
   105 / 50 = 2.1ml