Term
| Describe the pathway of autonomic neurotransmission, at the pre-post synapse? |
|
Definition
| Nerve impulse -> membrane depol -> calcium entry -> synaptic vesicle exocytosis -> Diffusion of NT across the synapse -> activation of nt receptors -> depol of postgang fiber, or response of effector cell |
|
|
Term
| What do vasoconstrictor neurons release? |
|
Definition
|
|
Term
| What to enteric excitatory motor neurons release? |
|
Definition
|
|
Term
| What do enteric inhibitory motor neurons release? |
|
Definition
| ATP and vasoactive intestinal peptide |
|
|
Term
| What is released at the interneuronal synapses in the ENS? |
|
Definition
|
|
Term
| Describe the process of cholinergic transmission? |
|
Definition
|
|
Term
| What is the rate limiting step in cholinergic transmission |
|
Definition
|
|
Term
| What is responsible for the creation of ACh? |
|
Definition
|
|
Term
| What two substances come together to form ACh? |
|
Definition
|
|
Term
| Where do hemicholinums inhibit cholinergic transmission? |
|
Definition
| Prevent the uptake of Choline by CHT |
|
|
Term
| Where does vesamicol inhibit cholinergic transmission? |
|
Definition
| Prevents the uptake of ACh into presynaptic vesicles |
|
|
Term
| Where does botulinum toxin inhibit cholinergic transmission? |
|
Definition
| Inhibits the SNAPS and VAMPS, therefore preventing ACh release |
|
|
Term
| What is another inhibitor of cholinergic transmission? |
|
Definition
| Black widow venom (alpha-latrotoxin) |
|
|
Term
| List the differences between autonomic and skeletal neuromuscular junctions? (4) |
|
Definition
- Multiple release sites per axon in ANS
- Multiple transmitters released from autnomic varicosities
- Different postjunctional receptors for ACh
- Diffusion distances |
|
|
Term
| What post-syn receptors are in the NMJ? |
|
Definition
| Nicotinic (skeletal muscle) |
|
|
Term
| What post-syn receptors are in the autonomic? |
|
Definition
| Muscarinic (smooth muscles) |
|
|
Term
| Name the 7 cholinoceptors |
|
Definition
1. Muscarinic 1-5
2. Nictinic Nn
3. Nicotinic Nm |
|
|
Term
| How does M1 work, and where is it found? |
|
Definition
- CNS neurons, some glands, autonomic post-gang neurons
- G protein receptor (q/11) activates the PIP2 pathway (PLC, PI turnover) |
|
|
Term
| How does M2 work, and where is it found? |
|
Definition
- Myocardium
- inhibits adenylyl cyclase, opens ion channels (K+ in heart); decrease in Ca2+ |
|
|
Term
| How does M3 work, and where is it found? |
|
Definition
- Endothelium, smooth muscle
- G protein receptor (q/11) activates the PIP2 pathway (PLC, PI turnover) |
|
|
Term
| How does Nn (ganglionic) work, and where is it found? |
|
Definition
- Transmission at symp and parasymp ganglia
- Opens Na+/K+ channels -> depolarization |
|
|
Term
| How does Nm work, and where is it found? |
|
Definition
- Skeletal muscle NT end plates
- Opens Na+/K+ channels -> depolarization |
|
|
Term
| What are nicotinic actions? |
|
Definition
| Actions similar to those induced by nicotine |
|
|
Term
| What mediates these actions? |
|
Definition
| Nicotinic cholinergic receptors |
|
|
Term
| What is the action of Nm? |
|
Definition
| Stimulation of voluntary muscle |
|
|
Term
| What are the two actions of Nn? |
|
Definition
1. Stimulation of all autonomic ganglia
2. Secretion of epinephrine from adrenal medulla |
|
|
Term
| (T/F) Nicotnic receptors share homology with glutamate, aspartate, GABA, P2x, Glycine, and 5-HT3 receptors |
|
Definition
|
|
Term
| What occurs when Ach binds the muscarinic receptors on endothelium? |
|
Definition
| Release of NO and vasodilation |
|
|
Term
| What is the consequence of endothelial damage? |
|
Definition
| Reduces vasodilator effect |
|
|
Term
|
Definition
|
|
Term
| Name the 3 types of drugs that affect muscarinic receptors? |
|
Definition
| 1. Direct acting 2. Indirect actin 3. Muscarinic antagonists |
|
|
Term
| What do direct acting drugs (parasympathomimetics) do? |
|
Definition
| Act as muscarinic agonists |
|
|
Term
| What do indirect acting drugs (cholinomimetics) do? |
|
Definition
|
|
Term
| Name the 2 types of drugs affecting nicotinic receptors? |
|
Definition
1. Ganglionic stimulators
2. Ganglionic blockers |
|
|
Term
| List 4 cholinergic receptor agonists (choline esters)? |
|
Definition
1. ACh
2. Methacholine
3. Carbachol
4. Bethanechol |
|
|
Term
| Which receptors does ACh act on, and how strongly? |
|
Definition
| Both M and N, and both strongly |
|
|
Term
| Which receptors does methacholine act on, and how strongly? |
|
Definition
| Strongly on M, weakly on N |
|
|
Term
| Which receptors does carbachol act on, and how strongly? |
|
Definition
| Moderately on M, strongly on N |
|
|
Term
| Which receptors does bethanechol act on, and how strongly? |
|
Definition
| Moderately on M, NOT on N |
|
|
Term
| (T/F) All of these choline esters are quaternary, meaning they are charged |
|
Definition
|
|
Term
| What is the function of cholinesterases located in the synapse? |
|
Definition
| Recycles ACh by breaking it down into choline and acetate, so the choline can be recycled |
|
|
Term
| Which drug acts the strongest on the M receptors? |
|
Definition
|
|
Term
| Which drug acts the strongest on the N receptors? |
|
Definition
|
|
Term
| Which two choline esters are degraded by cholinesterase, and at what strength? |
|
Definition
Ach - strongly degraded
Methacholine - slightly degraded |
|
|
Term
| What is the function of edrophonium? |
|
Definition
| Fast acting inhibitor of cholinesterase - 2-10minute effects |
|
|
Term
| How does it elicit these effects? |
|
Definition
| Reversible binding to substrate binding site |
|
|
Term
| What is the function of physostigmine/neostigmine? |
|
Definition
| Moderately acting cholinesterase inhibitor - 6 hours |
|
|
Term
| How does it elicit these effects? |
|
Definition
| Hydrolyzed by the enzyme at a slow rate, therefore competeing with ACh/methacholine for hydrolysis |
|
|
Term
| What is the function of organophosphates? |
|
Definition
| Long lasting Ach inhitor - ~24 hours |
|
|
Term
| How does it elicit these effects? |
|
Definition
| Phosphorylates the substrate binding site and inactivates the enzyme |
|
|
Term
| Name the 4 conditions that cholinomimetics (cholinesterase inhibitors) are used for |
|
Definition
1. Myasthenia gravis
2. Glaucoma
3. GI/GU
4. Alzheimers disease |
|
|
Term
| What is used for the diagnosis of MG? The treatment? |
|
Definition
Diagnosis: edrophonium
Treatment: Neostigmine and others |
|
|
Term
| How do cholinomimetics help with glaucoma? |
|
Definition
| They increase the contraction of ciliary muscle, which increases the outflow of aqueous humour |
|
|
Term
| How do cholinomimetics help with GI/GU? |
|
Definition
| Increase GI motility and bladder emptying post-op or post-partum |
|
|
Term
| How do cholinomimetics help with alzheimers? |
|
Definition
| Maintain function of degenerating cholinergic input to hippocampus |
|
|
Term
| Name the symptoms of cholinergic toxidrome (SLUDGE)? |
|
Definition
Salivation
Lacrimation
Urination
Defecation, diaphoresis
GI cramps
Emesis
- Also bradycardia and miosis |
|
|
Term
| How is cholinergic toxidrome treated? |
|
Definition
|
|
Term
| What is Pralidoximine used for treatment of? |
|
Definition
| Organophosphate poisoning |
|
|
Term
|
Definition
| Regenerates acetylcholinesterases |
|
|
Term
| Name the 3 antimuscarinics that act as cholingeric antagonists? |
|
Definition
| 1. Atropine 2. Scopolamine 3. Ipratropium |
|
|
Term
| (T/F) Atropine and scopolamine are both tertiary amines |
|
Definition
|
|
Term
| What does this mean, and what does it allow? |
|
Definition
| It means they are uncharged, and can enter the CNS well |
|
|
Term
| (T/F) Ipratropium is a synthetic atropine analog |
|
Definition
|
|
Term
| (T/F) It is a quaternary amine |
|
Definition
|
|
Term
| What does this mean, and what is a consequence of the quaternary structure? |
|
Definition
| It is charged (+) therefore poor CNS penetration |
|
|
Term
| List some examples of the clinical uses of antimuscarinics |
|
Definition
1. Parkinsons
2. Motion sickness
3. Opthalmoscopic examination
4. Asthma
5. Anesthetic premedication
6. Urinary incontinence
7. Cholinergic poisoning |
|
|
Term
| What condition is benzotropine used in? |
|
Definition
|
|
Term
| What is Scopolamine used to treat? |
|
Definition
|
|
Term
| What is Tropicamide used to treat? |
|
Definition
| Opthalmoscopic examination |
|
|
Term
| (T/F) Dry secretions of anti-muscarinics are used for pre-surgery treatment |
|
Definition
|
|
Term
| What condition is Tolteradine/Oroxybutynin used in? |
|
Definition
|
|
Term
| What type of drug is used in cholinergic poisoning? |
|
Definition
| Usually use a tertiary compound so you can have CNS penetration |
|
|
Term
| When else are tertiary antimuscarinics used? |
|
Definition
| During insecticide and nerve gas poisoning |
|
|
Term
| List 7 symptoms of anticholinergic toxidrome |
|
Definition
1. Dry mouth/skin
2. Urine retention
3. Decreased bowel sounds
4. Tachycardia
5. Hyperthermia
6. Mydriasis
7. Delirium |
|
|
Term
| Where do drugs acting on nicotinic receptors act? (3) |
|
Definition
1. At the pre-post gang synapse in the PNS and SNS
2. At the pre-gang-adrenal medualla synapse
3. At the neuromuscular junction |
|
|
Term
| (T/F) Nicotinic receptors are gated |
|
Definition
|
|
Term
| Name the 3 phases a gated channel goes through (ie Na+) |
|
Definition
1. Resting
2. Active
3. Desensitization |
|
|
Term
| Name two nicotinic agonists |
|
Definition
|
|
Term
| List 3 properties of these drugs |
|
Definition
1. Tertiary amines
2. Lipid soluble
3. Nicotine is much more potent than lobeline |
|
|
Term
| (T/F) These two agonists are used clinically |
|
Definition
|
|
Term
|
Definition
| Because it acts on all the cholinergic receptors therefore elicits a multitude of effects |
|
|
Term
| Where is it usually found? |
|
Definition
|
|
Term
| (T/F) Dependence has been known to occur with nicotine |
|
Definition
|
|
Term
| (T/F) Nicotine is a liquid alkaloid |
|
Definition
|
|
Term
| (T/F) The pharmacological actions of nicotine are simple and predictable |
|
Definition
| False, they are complex and unpredictable; Nicotine affects a variety of neuroeffector and ganglionic sites |
|
|
Term
| Does nicotine stimulate or desensitize receptors (or both)? |
|
Definition
|
|
Term
| How can nicotine increase HR? (2) |
|
Definition
1. Excitation of sympathetic ganglia
2. Paralysis of parasympathetic cardiac ganglia |
|
|
Term
| How does nicotine paralyze the PNS cardiac ganglia? |
|
Definition
| Eliciting the release of epinephrine from medulla |
|
|
Term
| How can nicotine decrease HR? (2) |
|
Definition
1. Paralysis of sympathetic ganglia
2. Stimulation of parasympathetic cardiac ganglia |
|
|
Term
| What is the result of nicotine stimulating the release of epinephrine from the medulla? |
|
Definition
|
|
Term
| What are the effects of nicotine on the peripheral NS? |
|
Definition
| Transient stimulation, followed by long lasting depression of autonomic ganglia |
|
|
Term
| What are the effects of nicotine on the cardiovascular system? |
|
Definition
| Increased HR and BP, triggered through the sympathetic ganglia and adrenal medulla |
|
|
Term
| What are the effects of nicotine on the GIT? (2) |
|
Definition
- Increases motility and tone
- Nausea, vomiting and diarrhea |
|
|
Term
| (T/F) Ganglionic blocking drugs are commonly used clinically |
|
Definition
|
|
Term
| What two classes of compounds comprise ganglionic blocking drugs? |
|
Definition
| 1. Linear bisquaternary compounds 2. Synthetic amines |
|
|
Term
| What drug class is Trimethaphan a part of? |
|
Definition
|
|
Term
| What drug class does hexamethonium, and decamethonium, belong to? |
|
Definition
| Linear bisquaternary compounds |
|
|
Term
| What are the effects, and consequences of each effect, of a ganglionic blockade on the arteries? What usually controls the resting state affected by the ganglionic blockade? |
|
Definition
| Vasodilation, which leads to decreased blood pressure; usually mediated by the SNS |
|
|
Term
| What are the effects, and consequences of each effect, of a ganglionic blockade on the veins? What usually controls the resting state affected by the ganglionic blockade? |
|
Definition
| Vasodilation, which leads to decreased venous return; usually mediated by the SNS |
|
|
Term
| What are the effects, and consequences of each effect, of a ganglionic blockade on the heart? What usually controls the resting state affected by the ganglionic blockade? |
|
Definition
| Tachycardia; resting heart rate usually controlled by the PNS |
|
|
Term
| What are the effects, and consequences of each effect, of a ganglionic blockade on the iris? What usually controls the resting state affected by the ganglionic blockade? |
|
Definition
| Pupillary dilation (mydriasis); usually controlled by the PNS |
|
|
Term
| What are the effects, and consequences of each effect, of a ganglionic blockade on the ciliary muscles? What usually controls the resting state affected by the ganglionic blockade? |
|
Definition
| Cycloplegia (decreased focal accomodation); usually controlled by the PNS |
|
|
Term
| What are the effects, and consequences of each effect, of a ganglionic blockade on the GIT? What usually controls the resting state affected by the ganglionic blockade? |
|
Definition
| Decreased tone and motility; usually controlled by the PNS |
|
|
Term
| What are the effects, and consequences of each effect, of a ganglionic blockade on the bladder? What usually controls the resting state affected by the ganglionic blockade? |
|
Definition
| Urinary retention; usually controlled by the PNS |
|
|
Term
| What are the effects, and consequences of each effect, of a ganglionic blockade on the salivary glands? What usually controls the resting state affected by the ganglionic blockade? |
|
Definition
| Xerostomia; usually controlled by the PNS |
|
|
Term
| What are the effects, and consequences of each effect, of a ganglionic blockade on the sweat glands? What usually controls the resting state affected by the ganglionic blockade? |
|
Definition
| Anhidrosis; controlled by both the CNS and PNS |
|
|
Term
| Where do neuromuscular blocking agents block neurotransmission? |
|
Definition
1. Presynaptically
2. Postsynaptically |
|
|
Term
| How do NBAs block presynaptically? |
|
Definition
| Inhibit ACh synthesis or release |
|
|
Term
| How do NBAs block postsynaptically? |
|
Definition
| Inhibit binding of ACh to Nm receptor |
|
|
Term
| Name the two types of blocking agents |
|
Definition
1. Non-depolarizing blocking agents
2. Depolarizing blocking agents |
|
|
Term
| What type of blocker is tubocurarine, and what does it do? |
|
Definition
| Non-depol - blocks Ach binding |
|
|
Term
| What type of blocker is succinylcholine, and what does it do? |
|
Definition
| Depolarizing - Activate and desensitize nicotinic receptor |
|
|
Term
| (T/F) Alpha-7 nicotinic receptors have been shown to be immunosuppressive |
|
Definition
|
|
Term
| What is the source of the cholinergic ligand? |
|
Definition
| A population of cholinergic lymhocytes |
|
|
Term
| What are these cholinergic lymphocytes innervated by? |
|
Definition
|
|
