Morgan & Mikhail Chap 13(Anticholinergic Agents)

Question 1

Anticholinergics

Answer 1

This chapter presents the pharmacology of drugs that block muscarinic receptors. Although the classification anticholinergic usually refers to this latter group, a more precise term would be antimuscarinic.

Question 2

Pharmacological characteristics of anticholinergic drugs

Answer 2

Question 3

MECHANISMS OF ACTION

Answer 3

Anticholinergics are esters of an aromatic acid combined with an organic base
(Figure 13–1). The ester linkage is essential for effective binding of the
anticholinergics to the acetylcholine receptors. This competitively blocks binding by acetylcholine and prevents receptor activation. The cellular effects of acetylcholine, mediated through second messengers, are inhibited. Muscarinic receptors are not
homogeneous, and receptor subgroups have been identified, including central nervous system (M1,4,5), autonomic ganglia and gastric parietal cells (M1), cardiac (M2), and smooth muscle (M3) receptors. These receptors vary in their affinity for receptor antagonists.

Question 4

General Pharmacological Characteristics

Answer 4

In normal clinical doses, only muscarinic receptors are blocked by the anticholinergic
drugs discussed in this chapter. The clinical response to an anticholinergic drug
depends on the degree of baseline vagal tone.

A. Cardiovascular
Blockade of muscarinic receptors in the sinoatrial node produces tachycardia. This effect is especially useful in reversing bradycardia due to vagal reflexes (eg, baroreceptor reflex, peritoneal traction, oculocardiac reflex)

B. Respiratory
Anticholinergics inhibit respiratory tract secretions, from the nose to the bronchi, a valuable property during endoscopic or surgical procedures on the airway. Relaxation of the bronchial smooth musculature reduces airway resistance and increases anatomic dead space. These effects are more pronounced in patients with chronic obstructive pulmonary disease or asthma.

Question 5

ATROPINE

Answer 5

As a premedication, atropine is administered intravenously or intramuscularly in a
range of 0.01 to 0.02 mg/kg, up to the usual adult dose of 0.4 to 0.6 mg. Larger
intravenous doses of up to 2 mg may be required to completely block the cardiac vagal nerves in treating severe bradycardia.

Atropine has particularly potent effects on the heart and bronchial smooth
muscle and is the most efficacious anticholinergic for treating bradyarrhythmia. Patients with coronary artery disease may not tolerate the increased myocardial oxygen demand and decreased oxygen supply associated with the tachycardia caused by atropine. A derivative of atropine, ipratropium bromide, is available in a metered-dose inhaler for
the treatment of bronchospasm.

Ipratropium solution (0.5 mg in 2.5 mL) is effective in the
treatment of acute bronchospasm in patients with chronic obstructive pulmonary disease, particularly when combined with a β-agonist drug (eg, albuterol).

Question 6

SCOPOLAMINE

Answer 6

Scopolamine is a more potent antisialagogue than atropine and causes greater central nervous system effects.

Clinical dosages usually result in drowsiness and amnesia, though restlessness, dizziness, and delirium are possible. The sedative effects
may be desirable for premedication but can interfere with awakening following short procedures. Scopolamine has the added virtue of preventing motion sickness.

The lipid solubility allows transdermal absorption, and transdermal scopolamine (1 mg patch) has been used to prevent postoperative nausea and vomiting. Because of its pronounced mydriatic effects, scopolamine is best avoided in patients with closed-angle glaucoma.

Question 7

GLYCOPYRROLATE

Answer 7

The usual dose of glycopyrrolate is one-half that of atropine. For instance, the
premedication dose is 0.005 to 0.01 mg/kg up to 0.2 to 0.3 mg in adults. Glycopyrrolate
for injection is packaged as a solution of 0.2 mg/mL.

Because of its quaternary structure, glycopyrrolate cannot cross the blood–brain
barrier and is almost devoid of central nervous system and ophthalmic activity. Potent
inhibition of salivary gland and respiratory tract secretions is the primary rationale for using glycopyrrolate as a premedication. Heart rate usually increases after intravenous
—but not intramuscular—administration.

Glycopyrrolate has a longer duration of action
than atropine (2–4 h versus 30 min after intravenous administration).