Week 13 / Pharmacology 3/Polypharmacy

Question 1

What is polypharmacy ?

Answer 1

The study of the use of 2 and more drugs , and studying the effects

Question 2

What is drug-drug antagonism, and what are the different types of drug antagonism?

Answer 2

It refers to the interaction between two drugs where the effect of one drug is diminished or completely abolished in the presence of the other.

1. Competitive Antagonism (Pharmacological / Receptor):
   When two drugs compete for the same receptor, reducing the effect of one.
2. Non-competitive Antagonism:
   One drug blocks the effect of another by interacting with different parts of a receptor or signaling pathway.
3. Chemical Antagonism:
   One drug directly interacts with another to neutralize its effects chemically.
4. Pharmacokinetic Antagonism:
   One drug affects the absorption, metabolism, or excretion of another, reducing its concentration or effect.
5. Physiological (Functional) Antagonism:
   Two drugs act on different systems or receptors but produce opposite physiological effects, canceling each other out.

Question 3

What is competitive antagonism, and what are its subtypes?

Answer 3

Competitive Antagonism:
It occurs when an agonist and an antagonist drug compete for the same receptor binding site. The binding of the antagonist reduces the chances of the agonist binding, thereby decreasing the agonist’s effect.

Subtypes of Competitive Antagonism:

1. Reversible (Surmountable) Antagonism:
   The antagonist can be displaced by increasing the concentration of the agonist, allowing the agonist to eventually bind to the receptor.
2. Irreversible (Insurmountable) Antagonism:
   The antagonist forms a permanent or strong bond with the receptor, preventing the agonist from binding, regardless of its concentration.

Question 4

What is reversible competitive antagonism, and how does it affect the dose-response curve of an agonist?

Answer 4

Flashcard Answer:

Reversible Competitive Antagonism:
In this type of antagonism, both the agonist and antagonist bind reversibly to the same receptor. The fraction of receptors occupied by each drug depends on their relative concentrations and receptor affinities. Antagonism can be overcome by increasing the concentration of the agonist drug.

Effects on the Agonist Log Dose-Response (D-R) Curve:
1. Parallel Shift to the Right:
The presence of the antagonist causes the dose-response curve to shift to the right, meaning a higher dose of the agonist is needed to achieve the same effect.

2. No Reduction in Maximal Response:
   The maximum possible response of the agonist remains unchanged, as the antagonist effect can be surmounted by increasing the agonist concentration.

Question 5

What is irreversible competitive antagonism, and how does it affect the dose-response curve of an agonist?

Answer 5

In this type of antagonism, the antagonist drug binds irreversibly to the receptor, often due to high affinity or covalent bonding. This permanently inactivates a fraction of receptors, making them unavailable for agonist binding. The antagonism cannot be overcome by increasing the agonist concentration.

Effects on the Agonist Log Dose-Response (D-R) Curve:
1. Reduction in the Slope of the Curve:
The slope of the dose-response curve decreases as fewer receptors are available for agonist binding.

2. Reduction in the Maximal Response:
   The maximum response that can be achieved by the agonist is reduced, as some receptors are permanently blocked by the antagonist.

Question 6

What is non-competitive antagonism, and how does it affect the dose-response curve of an agonist?

Answer 6

In non-competitive antagonism, the antagonist drug does not compete with the agonist for the same receptor binding site. Instead, the antagonist may bind to a different site on the receptor or interfere with the signaling pathway (response coupling). The antagonism cannot be overcome by increasing the concentration of the agonist.

Effects on the Agonist Log Dose-Response (D-R) Curve:
1. Reduction in the Slope of the Curve:
The slope decreases as the antagonist prevents the full activation of the receptor, even with more agonist present.

2. Reduction in Maximal Response:
   The maximal response achievable by the agonist is lowered since the antagonist limits the receptor’s ability to fully respond.

Question 7

What is chemical antagonism, and what are some examples?

Answer 7

Chemical Antagonism:
This type of antagonism occurs when the antagonist drug directly interacts with the agonist drug in solution. The antagonist binds to or combines with the active drug (agonist), rendering it inactive or unavailable to interact with its target receptors.

Examples of Chemical Antagonism:
1. Protamine vs Heparin:
Protamine binds to heparin, neutralizing its anticoagulant effects.

2. Dimercaprol vs Heavy Metals (Hg, Cu, Pb):
   Dimercaprol binds to heavy metals like mercury, copper, and lead, reducing their toxicity.

Question 8

What is pharmacokinetic antagonism, and what are some examples?

Answer 8

In this type of antagonism, the antagonist drug reduces the effective concentration of the active drug (agonist) at its site of action. This can occur through various mechanisms, such as reducing absorption, increasing metabolism, or enhancing excretion of the active drug.

Mechanisms and Examples:
1. Reduced Absorption from the GIT:
The antagonist drug interferes with the absorption of the active drug from the gastrointestinal tract.
Example: Ferrous salts vs Tetracycline antibiotics — Ferrous salts reduce the absorption of tetracycline antibiotics.

2. Increased Metabolic Degradation:
   The antagonist drug enhances the metabolism of the active drug, reducing its concentration.
   Example: Phenobarbital vs Warfarin — Phenobarbital increases the metabolic breakdown of warfarin.
3. Increased Renal Excretion:
   The antagonist drug increases the excretion of the active drug via the kidneys.
   Example: Sodium Bicarbonate (NaHCO3) vs Aspirin — NaHCO3 increases the renal excretion of aspirin, reducing its effectiveness.

Question 9

What is physiological (functional) antagonism, and what are some examples?

Answer 9

This occurs when two drugs with opposing effects act within the same biological system, effectively canceling each other’s effects. The two drugs produce these opposite responses by acting on different receptors or pathways.

Examples of Physiological Antagonism:
1. Acetylcholine vs Noradrenaline (Heart Rate):
Acetylcholine decreases heart rate by acting on muscarinic receptors, while noradrenaline increases heart rate by acting on adrenergic receptors.

2. Glucocorticoids vs Insulin (Blood Sugar Levels):
   Glucocorticoids increase blood sugar by promoting gluconeogenesis, while insulin decreases blood sugar by promoting glucose uptake into cells.

Question 10

What is the difference between summation and additivity in drug interactions?

Answer 10

Summation:
Occurs when two drugs, regardless of their mechanisms of action, elicit the same overall response, and the combined effect is equal to the algebraic sum of their individual effects.

Additivity:
Occurs when two drugs act through the same mechanism, and the combined effect is exactly what is expected by simply adding their individual effects together.

Question 11

What is synergism or potentiation in pharmacology, and how can one drug enhance the effect of another? Provide examples.

Answer 11

Answer:
Synergism or potentiation occurs when the combined effect of two drugs is greater than the sum of their individual effects. One drug can enhance the effect of the other by either:
1. Increasing the concentration of the other drug at its receptor sites (e.g., tyramine & MAO inhibitors), or
2. Increasing the responsiveness of the other drug’s receptor-effector protein (e.g., benzodiazepines & GABA at the GABAA receptor).