L6: Drug Combination

Question 1

What happens if two or more drugs combine together?

Answer 1

Drug combination is very common in clinical practice. When two or more drugs are combined together, one of the following may occur:

a) Summation or addition
b) Synergism and potentiation
c) Antagonis

Question 2

summation or addition (1+1=2)

Answer 2

• Summation means that the combined effect of two drugs is equal to the sum of their individual effects
• It usually occurs between drugs having the same mechanism
• Example: the use of two simple analgesics together.

Question 3

Synergism (1+1=3)

Answer 3

• It means that the combined effect of both drugs is greater than the sum of their individual effects.
• The two drugs usually have different mechanisms of action.
• Example: The use of penicillin with aminoglycosides to exert a bactericidal effect.

Question 4

Potentiation (1+0=2)

Answer 4

• is similar to synergism but, in potentiation, the effect of one drug itself is greatly increased by the intake of another drug without notable effect
• For example, Phenobarbitone has no analgesic action but it can potentiate the analgesic action of aspirin.

Question 5

What are the types of antagonists?

Answer 5

1. Pharmacological antagonism: Pharmacodynamics antagonism and Pharmacokinetic antagonism.
2. Physiological antagonism
3. Physical antagonism
4. Chemical antagonism

Question 6

What is pharmacodynamics antagonism?

Answer 6

Competitive antagonism

Question 7

What is pharmacokinetics antagonism?

Answer 7

Antagonism occurs at the level of absorption, distribution, metabolism and excretion.

Question 8

What is the definition of competitive antagonism?

Answer 8

The drug competes with the agonist for the same site on the receptor and it has two forms either reversible or irreversible. (With description)

Question 9

What is irreversible antagonism?

Answer 9

makes with the receptor so that you cannot overcome the inhibition by increasing the dose of the agonist (shifts the curve downwards)

Question 10

What is Physiological antagonism? And what is an example of it?

Answer 10

-antagonism between two drugs producing opposite effects by acting on different receptors.

• Example: adrenaline is the physiological antagonist of histamine because while:
  • histamine causes hypotension and bronchoconstriction through activation of histamine H1 receptors.
  • adrenaline causes hypertension and bronchodilatation through activation of adrenergic α & β receptors.

Question 11

What is physical antagonism and what is an example of it?

Answer 11

-Antagonism between two drugs carrying opposite charges

-Example:
✓ protamine is used for the treatment of heparin overdose because protamine carries +ve charge while heparin carries –ve charge

Question 12

What is chemical antagonism and what is an example for it?

Answer 12

• one acidic drug when added to a basic drug can cause precipitation of each other’s
• Example: the addition of gentamycin (basic drug) to carbenicillin (acidic drug) in the same syringe causes a chemical complex.

Question 13

What does a competitive antagonist do to ED50?

Answer 13

A competitive antagonist increases the ED50

Question 14

What are the factors modifying the dose-response relationship?

Answer 14

Factors related to the drug

1. Drug shape (stereoisomerism)
2. Drug size(MW)
3. Time of drug administration (Chronopharmacology)
4. Drug cumulation
5. Drug combination

Factors related to the patient
1. AGE:
2. WEIGHT:
3. SEX:
4. Pathological status:
✓ Liver diseases or kidney diseases could alter significantly the response of the patient to the therapeutic doses of drugs.
5. Hyper-reactivity to drugs. 
6. Hypo-reactivity to drugs.

Question 15

What are forms of hypo-activity to drugs?

Answer 15

Tolerance:
✓ decreased response to the same dose of the drug after repeated administration.
✓ It occurs over a long period

Tachyphylaxis :
✓ it is a type of tolerance, which occurs very rapidly

Question 16

What are the probable mechanisms of hypo-reactivity to drugs?

Answer 16

1. Receptor down-regulation:

✓ Prolonged exposure to the agonist leads to a decrease in the number of receptors due to endocytosis by the cells ✓ e.g. B2 agonists.

2. Increased metabolic degradation:
   ✓ Barbiturates can activate hepatic enzymes and accelerate their own metabolism and metabolism of other drugs.

Question 17

What are other terms for hyper-reactivity to drugs?

Answer 17

 Hyper susceptibility
 Super sensitivity
 Intolerance

Question 18

What is intolerance and it shouldn’t be confused with?

Answer 18

✓ It is an exaggerated response that occurs to a pharmacologic dose of a drug.

✓ It is not to be confused with drug allergy

Question 19

What is the definition of the rebound effect and what is an example for it?

Answer 19

• it is the re-emergence of symptoms that were controlled while taking a medication
• E.g. sudden stop of beta-blockers causes severe tachycardia due to up-regulation of beta receptors
• Drug withdrawal is the group of symptoms that occur upon the abrupt discontinuation e.g. morphine.