Chapter 32
Cholinergic agents
Basic Kinds of Cholinergic Nerves: Use acetylcholine as the neurotransmitter: list
All preganglionic nerves in the ANS, both sympathetic and parasympathetic
Postganglionic nerves of the PSNS and a few SNS nerves
Motor nerves on skeletal muscles
Cholinergic nerves within the CNS
Sequence of Events at a Cholinergic Synapse
1. Synthesis of acetylcholine (Ach) from choline (a substance in the diet) and a cofactor (the enzyme is choline acetyltransferase, CoA)
2. Uptake of neurotransmitter into storage (synaptic) vescicle
3. Release of neurotransmitters by an AP in the presyna
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Muscarinic Receptors def
Receptors that are stimulated by muscarine (plant alkaloid from mushrooms-reason wild mushrooms can have toxic effects)
Muscarinic Receptors: loc
Found in visceral effector organs
Found in sweat glands
Found in some vascular smooth muscle
Muscarinic Receptors: stimulations
Pupil constriction
accomodation of the lens
Increased GI motility
Increased GI secretions
Increased salivation
Increased urinary bladder constriction
Decreased heart rate
Male erection
sweating
Nicotinic Receptors: loc
Located in the CNS,
adrenal medulla,
autonomic ganglia,(any of the various ganglia that are part of the autonomic nervous system and are located along the sympathetic trunks, on the peripheral plexuses, and within the walls of organs)
and neuromuscular ju
Nicotinic Receptors: stimulation causes
Muscle contraction
Autonomic response (autonomic ganglia stimulation)
Release of norepinephrine and epinephrine from the adrenal medulla
Cholinergic Drugs: def
Chemicals that act at the same site as the neurotransmitter acetylcholine (ACh)
increase the activity of the ACh receptor sites throughout the body
Cholinergic Drugs: action
Often called parasympathomimetic drugs because their action mimics that of the PSNS
Since the actions of these drugs cannot be limited to a specific site, their effects can be widespread throughout the body, and are usually associated with many undesirabl
Types of Cholinergic Agonists: list
Cholinergic agonists work either:
Direct-acting cholinergic agonists
Indirect-acting cholinergic agonists
(directly or indirectly)
Direct-acting cholinergic agonists : loc
Occupy receptor sites for ACh on the membranes of the target organs (effector cells) of postganglionic cholinergic nerves
Direct-acting cholinergic agonists : causes
Causes increased stimulation of the cholinergic receptors.
Indirect-acting cholinergic agonists : how it works
React with the enzyme acetylcholinesterase, preventing it from breaking down the ACh that was released from the nerve
(produce their effects indirectly by producing an increase in the level of Ach in the synaptic cleft, leading to increased stimulation of
Indirect-acting cholinergic agonists : causes
Causes increased stimulation of the ACh receptor sites
Pharmacodynamics of Cholinergic Drugs
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Direct-Acting Cholinergic Agonists : Actions
Act at cholinergic receptors in the peripheral nervous system to mimic the effects of ACH and parasympathetic stimulation
Pharmacokinetics
well absorbed after oral administration
relatively short half life -1-6 hours
metabolism, excretion of these drugs unknown
drugs used topically are not generally absorbed systematically
Direct-Acting Cholinergic Agonists : Indications
usually stimulate muscarinic receptors w/in PNS
Increase the tone (normal degree of vigor and tension; in muscle, the resistance to passive elongation or stretch) of the detrusor muscle of the bladder and relax the bladder sphincter -
increase urinary exc
Direct-Acting Cholinergic Agonists : Contraindications
Any condition exacerbated by parasympathetic effects: bradycardia, hypotension, vasomotor instability, CAD
Peptic ulcer disease (avoid increasing secretions)
Intestinal obstruction or recent GI surgery
Asthma (protective SNS bronchodilation is overriden)
Direct-Acting Cholinergic Agonists : Adverse reactions
GI: Nausea, vomiting, cramps, diarrhea, increased salivation, and involuntary defecation, swallowing difficulties, aspiration (increase in salivary secretions), dehydration
cardiovascular: Bradycardia, hypotension, heart block, cardiac arrest
Urinary trac
Direct-Acting Cholinergic Agonists :Drug-to-drug interaction
Acetylcholinesterase inhibitorsincreased effect
Direct-Acting Cholinergic Agonists : list
Bethanechol (Duvoid, Urecholine)
Carbachol (Miostat) and pilocarpine (Pilocar)
Carbachol (Miostat) and pilocarpine (Pilocar): indications
Induce miosis or pupil constriction
Relieve intraocular pressure of glaucoma
For use in certain surgical procedures
Pilocarpine: indication
Pilocarpine is often used to treat glaucoma. Glaucoma results when the aqueous humor
(fluid) in the eye can not flow out of the internal canal and causes an increased pressure
in the eye.
Pilocarpine reduces intraocular pressure by causing the pupils to c
Pilocarpine: actions
Direct acting, constricts iris sphincter to cause pupil to dilate, increases salivation
Pilocarpine: pharmacokinetics
oral route: peak about 1 hr, topical (eye) about 10-30 minutes, decrease in intraocular pressure (IOP) in about 3 hrs
Pilocarpine: adverse reactions
blurred vision, myopia, bronchospasm is possible
prototype
Bethanechol
Bethanechol (Duvoid, Urecholine): indications
acute postoperative or postpartum nonobstructive urinary retention
neurogenis bladder atony of the bladder with retention
Diagnoses and treats reflux esophagitis (Inflammation of the lower esophagus from regurgitation of acid gastric contents, characteriz
Bethanechol (Duvoid, Urecholine): actions
acts directly on cholinergic receptors to mimic the effects of acetylcholine
increases tone of detrusor muscles
causes emptying of the bladder
Bethanechol (Duvoid, Urecholine): adverse effects
abdominal discomfort, salivation, nausea, vomiting, sweating, flushing