Question

Q20. How you treat asthma, COPD? Which meds do you use? Why you use? Q21. Have good mastery on those 4 tables indicating names of drugs and their receptor selectivity? Q22 . poisoning is antagonized by physostigmine?

Answer 1

Ans) 20) For patients whose asthma is not well controlled on inhaled steroid therapy alone, adding a long-acting beta2-agonist may be considered. For COPD, the approach is opposite. Bronchodilators are the first-line maintenance treatment for COPD and are fundamental in managing the disease symptoms.

- In asthma, compliance problems include perceived lack of efficacy and the intermittent nature of the condition. In COPD compliance problems may be more about physical disability.
- A distinction between the two diseases can be difficult in practice but asking patients for their diagnosis and being clear on the differences will help improve outcomes.

21) (a) Agonists
Ligand s that bind to a receptor and produce an appropriate response are called agonists. For example, the catecholamine adrenaline is an agonist at β-adrenoceptors.

(b) Antagonists
Ligands that prevent an agonist from binding to a receptor and thus prevent its effects are called antagonists. Antagonists do not themselves have any pharmacological actions mediated by receptors. For example, propranolol, a β-adrenoceptor antagonist, binds to β-adrenoceptors in the heart and prevents catecholamine-induced tachycardia (for example in response to exercise). However, in the absence of an agonist propranolol has no effect via adrenoceptors.

(c) Partial agonists

A full agonist is one that is capable of producing a maximal response, when it binds to a sufficient number of receptors. In contrast, a partial agonist cannot produce the maximal response of which the tissue is capable, even when it binds to the same number of receptors as a full agonist binds to when it produces a complete response. Since the effects of a ligand are generally produced by concentrations of the ligand that are well below those that would bind to all the receptors necessary to produce a complete response, this means that above a certain level of binding, a partial agonist may bind to receptors without producing any further increase in effect. However, in so doing, it may prevent the action of other agonists, and may thus appear to be acting as an antagonist. It is this mixture of actions that is called partial agonism. For example, oxprenolol, which is a β-adrenoceptor antagonist, is also a partial agonist. Thus, it may have less of an effect in slowing the heart rate than adrenoceptor antagonists that do not have partial agonist action (i.e. full antagonists); this partial agonism of β-blockers is sometimes called “intrinsic sympathomimetic activity” (ISA).

In the case of β-adrenoceptor antagonists, the amount of β-blockade produced by a given dose of the β-blocker will vary according to how much endogenous sympathetic nervous system activity there is: the more activity, the more β-blockade will result from the action of a partial agonist. This is clearly seen in the actions of the β-adrenoceptor agonist/antagonist xamoterol. Xamoterol acts as a β-adrenoceptor agonist in patients with mild heart failure, improving cardiac contraction. However, it acts as a β-blocker in patients with even moderate heart failure, worsening it. For this reason it has not proved useful in clinical practice.

Most receptors have subtypes, for which certain ligands have some degree of selectivity. For example, there are two main sub­types of β-adrenoceptors, called β1 and β2, both of which can respond to adrenaline. Some β-adrenoceptor antagonists act at both β1 and β2 subtypes, while some are selective for one or other subtype. For example, propranolol is an antagonist at both β1 and β2 receptors, while atenolol is relatively selective for β1 receptors. Note that selectivity of this kind is only relative; while a drug such as atenolol acts primarily on β1 receptors, at high enough concentrations it can also have effects on β2 receptors.

(d) Inverse agonists

An inverse agonist is a compound that binds to a receptor and produces a pharmacological response that is opposite to that of the corresponding agonist. An agonist increases the activity mediated by a receptor, an inverse agonist reduces it. In the presence of the agonist the inverse agonist acts as an antagonist. An ordinary antagonist can inhibit the actions of both agonists and inverse agonists.

22) Atropine

Explaination:

- Physostigmine, given as an atropine antidote by slow intravenous injection of 1 to 4 mg (0.5 to 1.0 mg in children), rapidly abolishes delirium and coma caused by large doses of atropine in most situations.