What are the direct-acting Ach agonists?
- Ach (not useful as a drug)
What are the indirect-acting Ach agonists?
- sarin (no therapeutic value)
What chemicals and enzyme synthesize Ach in cholinergic nerve terminals?
choline + acetyl-CoA
choline acetyltransferase (ChAT)
What enzyme rapidly breaks Ach down in the synaptic cleft?
What are the two major types of cholinergic receptors?
What kind of Ach receptor are all G-protein-coupled metabotropic receptors?
What are the two types of muscarinic receptors and what do they do?
- Evens (M2 and M4) - inhibition of cAMP production (stimulates smooth muscle) or activation of voltage-gated K+ channels (inhibits smooth muscle)
- M1, M3, and M5 - activate IP3, diacylglycerol cascase to increase intracellular Ca2+ (stimulates smooth muscle)
What specific muscle do the M2 and M4 cAMP inhibiting receptors act on?
contracts GI muscle
What specific muscle do the M2 and M4 K+ GTP receptors act on?
SA node cells (hyperpolarizes and slows HR)
What specific muscle does the M1, M3 and M5 receptors act on?
Ciliary muscle - increased Ca2+ contracts
Skeletal muscle postsynaptic receptors are what type?
Postsynaptic autonomic ganglia and adrenal medulla receptors are what type?
Presynaptic receptors in the CNS are what type?
Postsynaptic receptors on parasympathetic end organs and sweat glands are what type?
What type of Ach receptor is on the postsynaptic receptors of the CNS?
What is an important effect of direct acting muscarinic agents on small blood vessels?
causes release of NO which dilates vessels and decreases BP
What are the direct-acting muscarinic agonists?
what type of drug is carbachol?
direct-acting muscarnic agonist
*also a nicotinic agonist at high doses
what type of drug is bethanechol?
direct-acting muscarinic agonist
Which muscarnic agonists are not broken down by Achesterase?
carbachol and bethanechol
What are the indications for the direct-acting muscarinic agonists?
- paralytic ileus (post-operative)
- urinary retention
- carbachol eyedrops in wide (open) angle glaucoma
What are the adverse effects of the direct-acting muscarinic agonists?
- bronchial constriction
Who is contraindicated from receiving direct acting muscarinic agonists?
- heart conditions
- peptic ulcer
- GI or urinary obstruction
- hyperthyroidism (a fib)
What are the effects of the muscarinic antagonists?
- blunted reflexes
- inability to sweat
- urinary retention
- GI antispasmodic
- possible hallucinations
What kind of drug is atropine and what does it do?
- preanesthetic medication (reduce secretions, relax bronchi)
*crosses the BBB
What kind of drug is ipratropium and what does it do?
- bronchodilation in COPD
*stays in lungs, limited Vd
What kind of receptors are nicotinic?
excitatory ligand gated ion channels
permeable to Na+ and K+
*Nicotinic neuronal also permable to Ca2+
What is the role of postsynaptic nicotinic receptors?
produce depolarization and excitation of neurons and skeletal muscle
Where does Ach bind to nicotinic receptors?
The alpha subunit
What is the function of presynaptic nicotinic receptors?
enhance release of many other neurotransmitters in the CNS