Tolerance and drug resistance can be a consequence of :

RRB Staff Nurse Ahmedabad-2015

Pharmacology

Easy

Appeared in: RRB Staff Nurse Ahmedabad-2015

Explanation

Tolerance is a state where a higher dose of a drug is needed to produce the same level of response.
One primary mechanism for tolerance is increased metabolic degradation, also known as pharmacokinetic tolerance.
Repeated administration of some drugs causes enzyme induction in the liver, which accelerates the drug's breakdown.
This faster metabolism lowers the drug's concentration at its site of action, diminishing its effect and necessitating a higher dose.
Examples of drugs that induce their own metabolism include carbamazepine and rifampin.

Option A: Drug dependence is a physiological or psychological need for a drug to avoid withdrawal, not a mechanism that reduces the drug's effectiveness. While often co-occurring with tolerance, it is a separate phenomenon.
Option C: Depressed (decreased) renal excretion would lead to drug accumulation and an increased risk of toxicity, which is the opposite of tolerance. The drug's effect would be enhanced or prolonged, not diminished.
Option D: This describes the bioactivation of a prodrug. It is a necessary step for the drug to become effective, not a mechanism that causes resistance or tolerance to its effects.

Visual 1: Flowchart: Repeated Drug Administration → Liver Enzyme Induction → Increased Rate of Metabolism → Decreased Plasma Drug Concentration → Reduced Therapeutic Effect (Tolerance) → Need for Higher Dose.

Clinical Relevance

Nursing practice connection: Knowing Mechanisms of Drug Tolerance and Resistance helps nurses interpret findings accurately and avoid errors in routine assessment, medication administration, and patient teaching.
Nurses must monitor patients for signs of tolerance, such as a patient reporting that their pain medication is no longer effective. This requires careful assessment to differentiate from addiction or pseudoaddiction.
Understanding tolerance is crucial for safe medication administration, as it may necessitate upward dose adjustments by the prescriber to maintain therapeutic efficacy.
What if? If a patient on a drug known to cause tolerance (like carbamazepine) develops severe liver disease? Their ability to metabolize the drug would decrease, reversing the tolerance and dramatically increasing the risk of toxicity at the previously tolerated dose. The dose would need to be significantly reduced.

How to Approach the Question

First, define the key term in the question: 'Tolerance' means requiring a higher dose of a drug to achieve the same effect.
Next, analyze each option to see which one describes a mechanism that would lead to a reduced drug effect at a constant dose.
Evaluate Option A: Drug dependence is about withdrawal, not reduced effect.
Evaluate Option B: Increased metabolism means the drug is cleared faster, so less is available to have an effect. This matches the definition of tolerance.
Evaluate Option C: Depressed excretion means the drug stays longer, increasing its effect. This is the opposite of tolerance.
Evaluate Option D: Activation of a drug is what makes it work in the first place, not what causes tolerance.

Concept Tested & Keywords

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