A.3

Question 1

What are adaptive mechanisms (pharmalogical tolerance)?

Answer 1

1. Receptor desensitization
2. Receptor internalization
3. Depletion of mediator
4. CYP induction

Question 2

Drug tolerance

Answer 2

A state of adaptation in which exposure to a drug induces changes that result in a reduction of the drug’s effects over time.
- Higher dose of the drug is required to achieve the same level of response
- May involve both physiological and psychological mechanisms
- Tolerance may be prevented by ´´drug holidays´´
- Tolerance may also develop to the side effects of a given drug (desirable)

Question 3

pharmacodynamic drug interactions

Answer 3

A change in a drug´s effect on the body, when the drug is taken together with a second drug

Question 4

Neutral interaction

Answer 4

Two non-related drugs with no effect on each other

Question 5

Synergestic interaction

Answer 5

1. Additive synergism (2 effects are added), interaction results in a total effect that is the exact sum of the individual effect of each drug (e.g. aspirin + ibuprofen
2. Potentiating synergism: Interaction results in a total effect that is greater than the sum of the individual effects of each drug (e.g. Aminoglycosides + beta lactam antibiotics)
3. Pharmacodynamic synergism: 2 drugs with different MOA potentiate each other action (e.g. ACE inhibitor + Thiazide diuretics → stronger anti HTN effect)

Question 6

Antagonistic interaction

Answer 6

The effect of one drug is reduced by another
e.g. morphine + naloxone

Question 7

tolerance

Answer 7

Altered responsiveness if a drug is administered repeatedly or for prolonged time → need higher drug concentrations to achieve the same effect

Question 8

causes of tolerance

Answer 8

1. upregulation
2. down regulation (desensitization)

Question 9

Upregulation

Answer 9

Sustained exposure to antagonist drug may result in enhanced receptor expression
- Clinical importance upon withdrawal of a drug (e.g. B-agonist activity is increased after withdrawal of B-blocker = rebound effect! → NEVER stop B-blockers suddenly, only gradually

Question 10

Down regulation: Desensitization

Answer 10

Sustained exposure to agonist drug may result in diminshed receptor expression
- Clinical importance: sustained adrenergic stimulation in the treatment of asthma (e.g. dobutamine decreases the number of B1-receptors → may result in dobutamine resistant cardiogenic shock

Question 11

cross tolerance

Answer 11

Occurs when tolerance to the effects of one drug produces tolerance to another drug → often occurs between two drugs with similar functions/effects (MLSB → Macrolide, lincosamide (clindamycin) and Streptogramin (Quinupristin/Dalfopristin))

Question 12

tachyphylaxis

Answer 12

Drug tolerance that develops rapidly with diminished responsiveness due to diminished endogenous mediators
- E.g nitroglycerin, short acting B-agonist (SABA)

Question 13

receptor desensitization

Answer 13

Receptor-effector uncoupling (succhinyl choline)