Muscarinic Agonists Flashcards
ACh and synthetic choline esters
Methacholine
Carbachol
Bethanechol
Methacholine (4)
treat bronchial hyperactivity;
asthma test.
(methyl group increase RESISTANCE to hydrolysis by cholinesterases)
-greater duration and selectivity than ACh
-SLIGHT Nicotinic action, mostly muscarinic action in CV system.
———————-
-treat bronchial hyperactivity
-given by inhalation
-used as TEST for patients who do not have clinically apparent asthma. (show intense bronchoconstriction and a reduction in vital capacity)
vasodilation – bronchial constriction?
Bethanechol:
-Urinary Tract: treat urinary retention and inadequate emptying of the BLADDER.
-GI Tract: stimulates peristalsis and increases motility.
Carbachol:
-Used topically in ophthalmology. reduces intraocular pressure in the treatment of GLAUCOMA. Induction of MIOSIS during surgery.
Both: (unsubstituted carbamoyl esters, COMPLETELY RESISTANCE to hydrolysis by cholinesterases, primarily muscarinic action )
Bethanechol:
-mainly has muscarinic actions.
-some selectivity on GI and urinary bladder motility.
Carbachol
-retains substantial NICOTINIC ACTIVITY particularly on autonomic ganglia.
Table 1
Susceptibility to Cholinesterases;
Nicotinic Activity
page 13
Three major Natural Alkaloids
Pilocarpine (3)
Muscarine (4)
Arecoline (3)
(Have the same principal sites of action as the choline esters. Pilocarpine is the only agent in this group with current cilinical use although muscarine is a toxin from poisoning.)
- treatment of xerostomia, associated with sjogren’s syndrome.
- enhances salivary secretion.
- sweating as most common side effects.
- ## topical treatment of GLAUCOMA and MIOTIC agent(non-charged Tertiary amine. can cross membrane?)
Dominant muscarinic action
-[Sialagogue 催涎剂 and MIOTIC agent.]
- cause CV pressor effects
- Sweat gland are sensitive to the drug
- increase blood flow, contract muscle but won’t cause a decrease in blood pressure (baroreceptor).
Quaternary amines
Muscarine, carbachol and bethanechol
a. poorly absorbed after oral administration.
b. limited ability to cross the blood-brain barrier.
c. generally resist hydrolysis
d. short-acting agents are due to rapid elimination by the kidneys.
Tertiary amines
Pilocarpine and Arecoline
a. readily absorbed
b. cross the BBB
c. excretion of the tertiary amines can be accelerated by acidification of the urine.
Four primary effects of ACh on the cardiovascular system
- *Baroreceptor and other reflexes can dampen the direct responses to ACh.
- Vasodilation
- Negative chronotropic effect (decrease heart rate)
- Negative dromotropic effect (decrease in conduction rate in the sinoatrial (SA) and atrioventricular (AV) nodes)
- Negative inotropic effect
(decrease the force of cardiac contraction, lesser significance in ventricular than in atrial muscle)
**cholinergic stimulation on cardiac direct parasympathetic effects ==> inhibits the effects of adrenergic activation, results in part from inhibition of cyclic AMP formation and inhibit adrenergic stimulation of the heart. (inhibits NE release from sympathetic nerve endings
Therapeutic uses of muscarinic receptor agonists
- treatment of urinary bladder disorders
- xerostomia
- diagnosis of bronchial hyperactivity
- in ophthalmology as miotic agents
- treatment of glaucoma.
Cevimeline
- fewer side effects than pilocarpine
- enhance lacrimal, salivary secretion
- high affinity for M3 muscarinic receptors (in lacrimal and salivary gland epithelia)
- long-lasting sialogogic action
- enhance lacrimal secretion in Sjogren’s syndrome.
Contraindications
- asthma, chronic obstructive pulmonary disease, urinary or GI obstruction.
- acid-peptic disease, CV disease accompanied by bradycardia, hypotension
- hyperthyroidism, precipitation of atrial fibrillation.
