Exam 3 - Filtz Flashcards
(36 cards)
Acronym for Effects of Muscarinic Agonists
SLUDS S - Salivation L - Lacrimation U - Urination D - Defecation S - Sweating
Muscarinic agonist - eye
Miosis - contraction of iris sphincter (night blindness)
Nearsightedness - contraction of ciliary muscle (blurred vision)
Lacrimation.
Muscarinic agonist - GI
Longitudinal smooth muscles contract.
Relaxation of sphincters (indirect - M2).
Secretions increase.
Muscarinic agonist - Urinary Tract
Detrusor muscle contracts.
Relaxation of sphincters (indirect - M2).
Muscarinic agonist - Heart
Heart rate decreases at SA-node, and conductivity through AV-node (Direct - m3 AND Indirect - M2)
Muscarinic agonist - Lungs
Bronchoconstriction (Direct - m3 AND Indirect - M2)
Secretions.
Muscarinic agonist - Glands
Salivation increases.
Lacrimation increases.
Sweating increases.
Cholinergic Signaling
Choline into neuron by choline uptake transporter (CHT).
Choline converted to Ach by choline acetyl transferase (ChAT).
Ach taken into vesicles by vesicular acetylcholine transporter (VAT).
Intracellular calcium induces the vesicle’s calcium sensitive vesicle associated membrane protein (VAMP) to exocytose contents.
Post-synaptic receptors activated.
Location of Muscarinic Receptors:
On parasympathetically innervated target organs (for the most part).
M1 Receptors
m1, m3, and m5 gene products. Coupled to Gq G-proteins. - Increases intracellular calcium Primarily m3-subtype on parasmypathetically innervated organs: - Glands - GI Longitudinal smooth muscle - Bladder smooth muscle - Bronchiol smoothmuscle - Iris sphincter - Ciliary muscle OUTSIDE parasympathetic nervous system: - Brain - Blood vessels; m3 on the Vascular endothelium; causes release of endothelium-derived relaxing factor AKA NO. Only exogenous substances activate them.
M2 Receptors
m2, and m4 gene products.
Coupled to Gi G-proteins.
Hyperpolarization - inhibits neurotransmitter release.
Locations:
- Heart (predominantly M2)
- Preganglionic cholinergic nerve terminals.
- Presynaptic SNS adrenergic neurons as heteroreceptors: GI sphincters, Bladder sphincters, and Vascular smooth muscle; parasympathetic nerves only synapse the SNS nerves, not the organs.
Acetylcholine (Filtz)
Muscarinic agonist.
Poor selectivity for M > N.
Rapid hydrolysis by AChE.
Used in eye to induce short-term miosis.
Methacholine (Filtz)
Muscarinic agonist. Long duration - no AChE activity. Reduced activity at nicotinic receptors. Poor GI absorption. Used to increase GI motility and Bladder emptying.
Carbachol (Filtz)
Muscarinic agonist. Long duration - no AChE activity. Reduced activity at nicotinic receptors. Poor GI absorption. Used to increase GI motility and Bladder emptying.
Bethanechol (Filtz)
Muscarinic agonist. Long duration - no AChE activity. Reduced activity at nicotinic receptors. Poor GI absorption. Used to increase GI motility and Bladder emptying.
Muscarine-poison (Filtz)
Prototype muscarinic agonist derived from poisonous mushrooms.
Not a substrate of AChE - long duration.
High selectivity for M > N Receptors.
Problematic muscarinic side effects.
Pilocarpine (Filtz)
Muscarinic Agonist
Not a substrate of AChE - long duration.
High selectivity for M > N receptors.
Used topically to treat glaucoma.
Used as a sialogogue (increases salivation) to treat dry mouth.
Associated with excessive diaphoresis (sweating).
Cevimeline (Filtz)
Muscarinic Agonist
Not a substrate of AChE - long duration.
M1-selective agonist - no effect on the heart.
Approved for Sjogren’s syndrome.
- Autoimmunity against M1-receptors.
- Target whatever remaining receptors are left with Cevimeline.
Key Concept of Muscarinic Antagonists:
Antagonists have zero efficacy on their own. They only have an effect when blocking an agonist such as an endogenous neurotransmitter.
Atropine (Filtz)
Muscarinic Antagonist
Historically used as a cosmetic and poison (Catherine de Medici’s ring).
Hierarchal effects based on dose:
- 0.5 mg = dry mouth, dry skin.
- 1 mg = increased heart rate, thirst.
- 2 mg = pupillary dilatation, blurred vision, tachycardia.
- 5 mg = reduced peristalsis, urinary retention, hot dry skin, fatigue, flushing.
- 10 mg = rapid and weak pulse, ataxia, hallucinations, delirium, coma.
Use for: Cardiac stimulant, muschroom poisoning, w/ an opioid (diphenoxylate) in Lomotil for diarrhea, and nerve gas poisoning.
Long duration of action - pupils dilate 7-10 days.
Hyoscyamine (Filtz)
Muscarinic Antagonist
Natural product - very old drug.
Used for: irritable bowel syndrome, incontinence, hyperhidrosis, and peptic ulcers.
SE: Sedating - similar to scopolamine.
Scopolamine (Filtz)
Muscarinic Antagonist For motion sickness - CNS effects. Natural derivative of atropine. Easily crosses BBB. SE: Amnesia, sedation, stupor, and hallucinations. - Abused recreationally. - Very susceptible to suggestions...
Tiotropium (Filtz)
Muscarinic Antagonist
For chronic obstructive pulmonary disease (emphysema).
Poor systemic penetrance - few SE when inhaled.
Fewer effects on pulmonary secretions - doesn’t dry them up.
Longest duration of action along with Umeclidinium; Qd.
Ipratropium (Filtz)
Muscarinic Antagonist
For chronic obstructive pulmonary disease (emphysema).
Poor systemic penetrance - few SE when inhaled.
Fewer effects on pulmonary secretions - doesn’t dry them up.
