Pharmacodynamics

Question 1

Pharmacodynamics

Answer 1

Effects of drugs on the body (or on microorganisms in the body); biochemical and physiological mechanisms of drug action and the relationship between drug concentration and effect.

Question 2

Drugs act by binding receptors

Answer 2

“receptor” is a protein, which may be
- An enzyme
- Cell surface receptor (membrane protein)
- Nuclear receptor, which affects transcription of new mRNA/proteins in the nucleus of the cell.

Question 3

Drugs act by binding receptors

Answer 3

A drug may be an agonist or antagonist.
- Agonist activates the receptor.
- Antagonist blocks/inhibits the receptor.

Question 4

Enzymes

Answer 4

Proteins that catalyze (speed up) chemical reactions. End in -ase.
- Enzymes have active sites where their substrates bind.
- Inhibitors (antagonists) many bind…
- at the active site, mimicking substrates.
- away from the active site, but in a way that alters the active site.

Question 5

Drug dose responses

Answer 5

• Phase 1: low drug dose.
• Phase 2: physiological response increases in proportion to # of receptors bound by the drug.
• Phase 3: receptors all bound/saturated with drug.

Question 6

Drug dose responses: Phase 3: Plateau

Answer 6

More drug produces no/little further effect.

Question 7

Therapeutic range

Answer 7

Range of plasma drug concentration above the level needed for therapeutic effect, below level of toxic effects.
- Often measured as therapeutic index.
- Want a high therapeutic index!

Question 8

Drug efficacy

Answer 8

• Some drugs produce a larger effect than others - they are more effective.
• Mostly a factor for agonists (not antagonists).

Question 9

Drug potency

Answer 9

How much drug is needed to give a response.

Question 10

Tolerance

Answer 10

Decreased effect of a drug due to prolonged use.

Question 11

Pharmacodynamic tolerance

Answer 11

• Number of drug receptors changes with time.
• Body/cells adapt to repeated stimulation. Eg. morphine.

Question 12

Metabolic tolerance / enzyme induction

Answer 12

• Increased synthesis of cytochrome P450’s.
• Faster drug inactivation (liver cells adapt).

Question 13

Drug dependence

Answer 13

When an individual has a strong compulsion to take a drug regardless of actual clinical need.

Question 14

Physical dependence

Answer 14

Physically observable withdrawal symptoms.

Question 15

Psychological dependence

Answer 15

Physically observed symptoms are not evident, but patient still has a convulsion to obtain the drug.

Question 16

Drug interactions

Answer 16

• Taking two or more drugs at the same time may alter the effects of the drugs.
• Several ways this can happen, may result in increased or decreased drug effects.
• Additive or synergistic effects
• Competition for inactivation
• Enzyme induction
• Competition for serum albumin

Question 17

Additive or synergistic effects

Answer 17

Two drugs that have similar effects individually may work together to create a larger effect.
- Helpful sometimes, eg antihypertensives.
- Harmful sometimes.
- Primary purposes of the drugs may be different.

Question 18

Competition for inactivation

Answer 18

An isozyme may be busy/saturated inactivating one drug, so if a second one is added, t 1/2 of both increases.
- Mainly affects cytochrome P450 enzymes.

Question 19

Enzyme Induction

Answer 19

• Opposite of competition for inactivation.
• Stimulation of cytochrome P-450 synthesis.
- Regular administration (several weeks) of some drugs stimulates the liver to make more drug metabolizing enzymes.
- higher level of enzymes results in faster inactivation of any drug using that CYP.
- Net effect: active levels of both drugs decrease.
Regular use of alcohol can cause induction of cytochrome P-450 isozymes which can result in faster drug metabolism.
- However chronic alcoholism can cause cirrhosis of the liver resulting in liver tissue death and lower liver enzyme levels.
- predicting the metabolic competency of a heavy drinker can be hard to predict.

Question 20

Competition for serum albumin

Answer 20

• Non-polar drugs can compete for binding to serum albumin in blood transport.
- Net result: increased levels of available, unbound drug.
• Common drugs bound by albumin:
- warfarin (Coumadin)
- sulfonamides (antibiotics)
- digoxin (treatment of congestive heart failure)
- Dilantin (anti-seizure)
• When a second drug that binds to serum albumin is added to a patient on Coumadin, the Coumadin may be displaced from albumin and increase actual levels of active (non-protein bound) warfarin, causing greatly increased risk of bleeding and hemorrhage.