Agonistas Colinérgicos (Diretos/Muscarínicos) | Aula 10 | Farmacologia rápida e fácil | Flavonoide

Introduction to Cholinergic Agonists

Overview of the Course Structure

• The instructor announces a change in the structure of the course on cholinergic agonists, now divided into three parts instead of two for better engagement.

• Emphasizes the importance of acetylcholine (ACh) in various bodily functions and its role in cholinergic neurons within both autonomic and somatic nervous systems.

Focus on Cholinergic Agonists

• Discussion centers on cholinergic agonists acting primarily on muscarinic receptors located in parasympathetic tissues.

• Future lessons will cover nicotinic receptors found in the somatic nervous system, adding depth to understanding receptor interactions.

Types of Cholinergic Agonists

Direct vs. Indirect Agonists

• Two main types of cholinergic agonists are introduced: direct agonists that bind to receptors and indirect agonists that inhibit acetylcholinesterase, increasing endogenous ACh levels.

• Indirect agonists are also referred to as anticholinesterases due to their mechanism of action.

Clinical Relevance

• Direct cholinergic agonists target muscarinic receptors predominantly found in parasympathetic tissues, while indirect ones have more affinity for nicotinic receptors at neuromuscular junctions.

Characteristics of Direct Cholinergic Agonists

Chemical Structure and Functionality

• Direct cholinergic agonists resemble acetylcholine structurally but have slight modifications; they are classified as esters or alkaloids based on their origin.

• Esters of choline are highlighted for their quaternary amine structure, which affects their pharmacokinetics such as solubility and absorption rates.

Pharmacokinetic Properties

• Quaternary amines face challenges crossing membranes due to positive charge, leading to lower oral bioavailability compared to tertiary amines like pilocarpine which can easily cross membranes due to being lipophilic.

Conclusion on Alkaloids and Their Usage

Clinical Significance

Understanding Parasympathetic Drugs and Their Mechanisms

Overview of Parasympathetic Drugs

• Parasympathetic drugs are antagonistic to sympathetic amimetic drugs, meaning they produce effects opposite to those of the sympathetic nervous system. For example, while sympathetic activation can lead to tachycardia (increased heart rate), these medications induce bradycardia (decreased heart rate).

• An exception exists with sweat glands, which are innervated solely by the sympathetic nervous system; however, their post-ganglionic receptors are cholinergic rather than adrenergic. This means that cholinergic agonists can enhance secretion from these glands.

Acetylcholine and Its Limitations

• Acetylcholine is a classic cholinergic agonist but is not commonly used in practice due to its rapid degradation by acetylcholinesterase enzymes.

• The presence of acetylcholine throughout the body leads to unpredictable results when administered as a drug because it interacts with various muscarinic and nicotinic receptors.

Modified Cholinergic Agonists

• To overcome the instability of acetylcholine, modified versions like methacholine were developed. Methacholine has a methyl group added, making it three times more resistant to degradation by acetylcholinesterases.

• Despite its increased stability, methacholine still faces some degradation in circulation and exhibits high selectivity for M2 receptors in the heart. However, its unpredictable effects prevent its use for cardiac conditions.

Beta Agonists: A More Predictable Option

• Betacol is another modified cholinergic agent that shows greater resistance to breakdown and preferentially targets muscarinic receptors over nicotinic ones. This specificity allows for more predictable therapeutic outcomes.

• Betacol is utilized clinically for stimulating smooth muscle contractions in gastrointestinal and urinary tracts, enhancing peristalsis and aiding bladder contraction during urinary retention scenarios.

Carbacol: A Unique Cholinergic Agent

• Carbacol differs from Betacol as it also activates nicotinic receptors at autonomic ganglia; thus, it cannot be used systemically due to unpredictable responses.

• It is primarily employed topically in treating glaucoma by contracting ciliary muscles within the eye, facilitating aqueous humor drainage and reducing intraocular pressure.

Pilocarpine: A Natural Alkaloid

Jaborandi: Historical and Medical Insights

Overview of Jaborandi's Use

• Jaborandi, known for inducing sweating and salivation, has been utilized by the Tupi-Guarani indigenous people for centuries.

• The first pill containing Jaborandi was developed by Brazilian physician Sinfrônio Coutinho in 1874, leading to the creation of the Carpina eye drop.

Current Applications and Limitations

• Although initially significant for treating glaucoma, Jaborandi is less commonly used today due to the development of newer medications with fewer side effects.

• It remains relevant in ophthalmic surgeries and acute glaucoma crises due to its rapid absorption and effectiveness.

Additional Therapeutic Uses

• Jaborandi can also treat xerostomia (dry mouth), particularly in conditions like Sjögren's syndrome, as it stimulates saliva production.

Adverse Effects and Considerations

• Two main hypotheses explain adverse effects: either unintended action on other tissues or an exaggerated response where desired effects are too strong.

• Common adverse effects include hypotension (low blood pressure), which occurs due to relaxation of smooth muscle in blood vessels.

Contraindications