Week 13 / Pharmacology 4

Question 1

What are the type of scopes are there in drug responsiveness?

Answer 1

inter-patient variation
intra-patient variation

Question 2

Q: What is meant by inter-patient variation in drug responsiveness?

Answer 2

A: Inter-patient variation refers to differences in how different patients respond to the same drug, which can be influenced by factors like age, gender, genetics, and other individual characteristics.

Question 3

Q: What is intra-patient variation in drug responsiveness?

Answer 3

A: Intra-patient variation refers to changes in drug responsiveness within the same patient over time, which may be influenced by factors like disease progression, drug interactions, or changes in physiology.

Question 4

Q: What are some possible consequences of variation in drug responsiveness?

Answer 4

A: Possible consequences include:
Lack of efficacy
Unexpected side effects

Question 5

Q: What are the possible mechanisms for variation in drug responsiveness?

Answer 5

A: Possible mechanisms include:

Pharmacokinetic factors (e.g., absorption, distribution, metabolism, excretion)

Pharmacodynamic factors (e.g., receptor sensitivity, signal transduction)

Question 6

Q: What are the two types of variation in drug responsiveness?

Answer 6

A: The two types of variation are:

Qualitative variations (differences in the type of response to the drug)
Quantitative variations (differences in the magnitude or intensity of the drug response)

Question 7

Q: What is hyper-responsiveness in drug variation?

Answer 7

A: Hyper-responsiveness refers to an exaggerated or stronger-than-expected response to a drug, often due to heightened receptor sensitivity or other factors.

Question 8

What are the types Quantitative variations in drug responsiveness ?

Answer 8

Hyper-responsiveness
Hypo-responsiveness or tolerance

Question 9

Q: What is hypo-responsiveness or tolerance in drug variation?

Answer 9

A: Hypo-responsiveness, or tolerance, refers to a decreased response to a drug after repeated use, requiring higher doses to achieve the same effect.

Question 10

What are the types of tolerance in drug responsiveness ?

Answer 10

Innate vs acquired tolerance

Tolerance vs Tachyphylaxis

Question 11

Q: What is acquired tolerance?

Answer 11

A: Acquired tolerance is a state of progressively decreasing responsiveness to a drug as a result of prior or repeated exposure to the drug or another drug with a similar action.

Question 12

Q: What are the mechanisms of acquired tolerance?

Answer 12

A: The mechanisms of acquired tolerance include:

Pharmacodynamic
Metabolic
Exhaustion / Depletion of mediators
Physiological adaptation

Question 13

Q: What is receptor down-regulation in the context of pharmacodynamic tolerance?

Answer 13

A: Receptor down-regulation refers to the reduction in receptor density, leading to decreased responsiveness to the drug. An example is the reduction in β-adrenergic receptor density after prolonged exposure to β-agonists.

Question 14

Q: What is receptor uncoupling in pharmacodynamic tolerance?

Answer 14

A: Receptor uncoupling occurs when receptors become detached or disconnected from their effector systems, meaning the receptor can’t trigger the intended biological response. An example is β-adrenergic receptors losing their ability to activate downstream signaling.

Question 15

Q: What is the metabolic mechanism of acquired tolerance?

Answer 15

A: The metabolic mechanism of acquired tolerance involves enhanced drug metabolism due to the induction of metabolizing enzymes, which leads to reduced drug concentration at the target site. An example is the induction of liver enzymes in response to alcohol or barbiturates.

Question 16

Q: What is the exhaustion/depletion of mediators mechanism in acquired tolerance?

Answer 16

A: Exhaustion or depletion of mediators occurs when indirectly-acting drugs deplete the endogenous stores of the mediators necessary for the drug’s action. This is common with drugs like amphetamine and nitrates.

Question 17

Q: What is physiological adaptation in acquired tolerance?

Answer 17

A: Physiological adaptation involves compensatory or homeostatic mechanisms in the body that blunt or cancel out the drug’s effects over time. This mechanism is seen with drugs like diuretics and nitrates.

Question 18

Q: What is the difference between absolute selectivity and relative selectivity in drug action?

Answer 18

A: Absolute selectivity implies a drug has only one specific effect, but no drug is entirely absolutely selective. Relative selectivity refers to the degree to which a drug acts on a given site relative to all possible sites of interaction.

Question 19

Q: Why is drug selectivity considered relative and not absolute?

Answer 19

A: Drug selectivity is relative because no drug has only one single effect; it produces a spectrum of effects. This means the action of a drug on a specific site is relative to other potential sites of interaction.

Question 20

Q: How are drug effects categorized in clinical selectivity?

Answer 20

A: Drug effects are divided into therapeutic effects and undesirable/side effects. Undesirable effects can range from minor to serious.

Question 21

Q: How do undesirable effects of a drug occur?

Answer 21

A: Undesirable effects can occur in several ways:

Both therapeutic and undesirable effects may be mediated via the same receptor-effector mechanism (e.g., nitrates, insulin, warfarin).
Both effects may be mediated by identical receptors located in different tissues (e.g., haloperidol, verapamil).
Both effects may be mediated via different types of receptors (e.g., salbutamol, propranolol).

Question 22

Q: What is the Therapeutic Index?

Answer 22

A: The Therapeutic Index (TI) is determined by the ratio of the median toxic dose (TD50) to the median effective dose (ED50):

Therapeutic Index = TD50 / ED50
It provides a useful measure of the drug’s margin of safety and the benefit-to-risk ratio.
Example: Penicillin has a higher TI compared to warfarin.