Pharmacology - Autonomics I Flashcards
Postganglionic PS fibers release:
Aceytlcholine
“cholinergic”
Postganglionic symptathetic fibers generally release:
Norepinephrine
“adrenergic”
T/F: Not all postganglionic sympathetic fibers are adrenergic - other NTs can be used.
True
All preganglionic neurons, both sympathetic and parasympathetic, release:
ACh and stimulate nicotinic receptors on postganglionic neurons
All preganglionic neurons, both sympathetic and parasympathetic, release ACh and stimulate ______ receptors on postganglionic neurons.
Nicotinic
All postganglionic PS neurons release ACh and stimulate _____ ACh receptors on target tissues.
Muscarinic
Postganglionic symptathetic fibers to sweat glands release:
ACh
Postganglionic sympathetic fibers to renal vessels release:
Dopamine
____ blocks ACh and, when, injected, can locally inhibit muscle contraction.
Botulinim Toxin A
Drugs that block NE synthesis, storage or release, for example, guanethidine, are useful in several diseases like hyptertension, because they block _____ function
sympathetic, but NOT parasympathetic
What is the physiologic effect of cocaine?
To block NE uptake –> increase adrenergic transmission
Cholinoceptors include:
Muscarinic
Nicotinic
Where are M1 receptors found?
Location:
CNS
sympathetic PG neurons
Effects:
formation of IP3 and DAG
increased intracellular Ca
**same as M3 receptors (exocrine glands, CNS, vessels)
**same as M5 receptors (vascular endothelium esp cerebral vessels, CNS)
Where are M2 receptors found?
Location:
Myocardium
Smooth muscle
CNS
Effects:
open K channels
inhibit Adenyl cyclase
**same as M4 receptors (CNS)
Nicotinic receptors, both Nn (N2) and Nm (N1) have what effect?
Opening of Na and K channels, depolarization
Where are Nm (N1) receptors found?
Skeletal muscle neuromuscular end plates
What is the effect of Alpha 1 adrenergic receptors?
Effects:
Formation os IP3 and DAG
increased intracellular Ca
Location:
Postsynaptic effector cells esp smooth muscle
What is the effect of Alpha 2 (adrenoreceptors) receptors?
Effects:
Inhibition of adenyl cyclase
decreased cAMP
Location: Presynaptic adrenergic nerve terminals, platelets lipocytes smooth muscle
All beta (adrenoreceptors) receptors have what function?
stimulate AC
increase cAMP
all found in heart, beta-1 found most widespread in the body
All muscarinic receptors (M1-M5) are
GPCRs
M2, M4 –> Gi (decrease cAMP, hyperpolarize) –> inhibition of neurotransmitter release
M1, M3, M5 –> Gq (increase IP3 and DAG)
**enables ACh to have specific effects, depending on the receptor
Class: Bethanechol
Direct acting carbamic acid ester
cholinomimetic
MOA: Bethanechol
Direct-acting muscarinic cholinomimetic
Uses: Bethanechol
Post-operative and neurogenic ileus; urinary retention (bowel and bladder smooth muscle ACh-innervated)
Side Effects: Bethanechol
SLUDGE
Salivation: stimulation of the salivary glands
Lacrimation: stimulation of the lacrimal glands
Urination: relaxation of the internal sphincter muscle of urethra, and contraction of the detrusor muscles
Diaphoresis
Gastrointestinal upset: Smooth muscle tone changes causing gastrointestinal problems, including diarrhea
Emesis: Vomiting
Class: Pilocarpine
Direct acting non-ester alkaloid
cholinomimetic
MOA: Pilocarpine
Direct-acting muscarinic cholinomimetic
Uses: Pilocarpine
Glaucoma (ACh activates sphincter and ciliary muscles of eye)
Side Effects: Pilocarpine
SLUDGE
Salivation: stimulation of the salivary glands
Lacrimation: stimulation of the lacrimal glands
Urination: relaxation of the internal sphincter muscle of urethra, and contraction of the detrusor muscles
Diaphoresis
Gastrointestinal upset: Smooth muscle tone changes causing gastrointestinal problems, including diarrhea
Emesis: Vomiting
Class: Cevimeline
Direct acting non-ester alkaloid
cholinomimetic
MOA: Cevimeline
Direct-acting muscarinic cholinomimetic
Uses: Cevimeline
Dry mouth/xerostomia (in, e.g., Sjogren’s, post-radiation therapy; via increased salivation)
Side Effects: Cevimeline
SLUDGE
Salivation: stimulation of the salivary glands
Lacrimation: stimulation of the lacrimal glands
Urination: relaxation of the internal sphincter muscle of urethra, and contraction of the detrusor muscles
Diaphoresis
Gastrointestinal upset: Smooth muscle tone changes causing gastrointestinal problems, including diarrhea
Emesis: Vomiting
Class: Nicotine
Direct acting non-ester alkaloid
cholinomimetic
MOA: Nicotine
Direct-acting muscarinic cholinomimetic
Uses: Nicotine
Smoking cessation/reduces craving
Class: Physiostigmine
Indirect acting carbamate
cholinomimetic
MOA:
Physostigmine
Echothiophate
AChE inhibitor (short acting)
Uses:
Physostigmine
Echothiophate
Glaucoma (ACh activates papillary sphincter and ciliary muscles of eye)
Side Effects: Physostigmine
SLUDGE
general increase in cholinergic neurotransmission;
paralysis
Class: Muscarine Pilocarpine Cevimeline Nicotine
Direct acting non-ester alkaloid
cholinomimetic
Uses:
Pilocarpine
Physostigmine
Echothiophate
Glaucoma
Class: Edrophonium
Indirect acting non-ester
cholinomimetic
MOA: Edrophonium
AChE inhibitor (v. short acting)
Uses:
Edrophonium
Pyridostigmine
Neostigmine
Myasthenia Gravis
Side Effects: Edrophonium
SLUDGE
general increase in cholinergic neurotransmission;
paralysis
Class: Neostignmine
Indirect acting carbamate
cholinomimetic
Class:
Neostigmine
Physostigmine
Indirect acting carbamate
MOA: Neostigmine
AChE inhibitor (short acting)
Uses: Neostigmine
Post-operative and neurogenic ileus; urinary retention; myasthenia gravis; reversal of neuromuscular blockade
Side Effects: Neostigmine
SLUDGE
general increase in cholinergic neurotransmission;
paralysis
Class: Muscarine
Direct acting non-ester alkaloid
cholinomimetic
MOA: Muscarine
Direct-acting muscarinic cholinomimetic
Side Effects: Muscarine
SLUDGE
Class: Donepezil
Indirect acting non-ester
cholinomimetic
MOA: Donepezil
AChE inhibitor
Uses: Donepezil
Alzheimer’s (amplifies endogenous ACh in brain)
Side Effects: Donepezil
SLUDGE
general increase in cholinergic neurotransmission;
paralysis
Class:
Donepezil
Edrophonium
Indirect acting non-ester
cholinomimetic
Side Effects: Neostigmine Physostigmine Donepezil Sarin Edrophonium Echothiophate Pralidoxime
SLUDGE
general increase in cholinergic neurotransmission;
paralysis
Side Effects: Bethanechol Muscarine Pilocarpine Cevimeline
SLUDGE
Class: Echothiophate
Indirect acting organophosphate
cholinomimetic
MOA: Echothiophate
AChE inhibitor (long acting)
Uses: Echothiophate
Glaucoma (ACh activates papillary sphincter and ciliary muscles of eye)
Side Effects: Echothiophate
SLUDGE
general increase in cholinergic neurotransmission;
paralysis
Class: Sarin
Very potent indirect acting organophosphate
cholinomimetic
MOA: Sarin
AChE inhibitor
Uses: Sarin
volatile nerve gas
Side Effects: Sarin
SLUDGE
general increase in cholinergic neurotransmission;
paralysis
DEATH
Class: Pralidoxime
Strong nucleophile
cholinomimetic
MOA: Pralidoxime
AChE inhibitor
Uses: Pralidoxime
Poisoning by nerve gas, insecticide
Class: Atropine
Tertiary amine antimuscarinic
cholinergic receptor inhibitor
Class: Atropine Scopolamine Dicyclomine Tropicamide Tolterodine Benztropine
Tertiary amine antimuscarinic
cholinergic receptor inhibitor
MOA: Atropine
Blocks muscarinic receptors
MOA: Atropine Scopolamine Dicyclomine Tropicamide Tolterodine Benztropine Ipratroprium Tiotropium
Blocks muscarinic receptors
Side Effects: Atropine Scopolamine Dicyclomine Tropicamide Tolterodine Benztropine Ipratroprium Tiotropium
General block of muscarinic functions
Uses:
Atropine
Tropicamide
To cause:
Mydriasis
Cycloplegia is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation
*Tropicamide has a short half life
Uses: Scopolamine
Motion sickness
Uses: Dicyclomine
Reduce transient hypermotility of GI tract
Uses: Tolterodine
Treat transient cystitis;
postoperative bladder spasms;
incontinence
Uses: Benztropine
To prevent manifestations of Parkinson’s disease
Class:
Ipatroprium
Tiotropium
Quarternary amine antimuscarinic
cholinergic receptor inhibitor
Uses:
Ipatroprium
Tiotropium
Bronchodilation in asthma or COPD
Class: Succinylcholine
Depolarizing blocker
cholinergic receptor inhibitor
MOA: Succinylcholine
Overstimulation of nicotinic receptor, leading to desensitization of muscle unit to further ACh stimulation
Uses: Succinylcholine
Brief procedures (e.g., tracheal intubation, reset dislocated joints)
Side Effects:
Succinylcholine
Tubocurarine
Mivacurium
Respiratory paralysis;
disturbance of autonomic function
MOA:
Tubocurarine
Mivacarium
Blocks nicotinic (Nm) receptor
Class:
Tubocurarine
Mivacarium
Nondepolarizing blocker
cholinergic receptor inhibitor
Uses:
Tubocurarine
Mivacarium
Muscle relaxant for surgery w/o deep anesthesia
Class: Botulinum Toxin A
local paralytic
MOA: Botulinum Toxin A
Blocks vesicle fusion and ACh release on presynaptic terminal by degrading SNAP-25
Uses: Boltulinum Toxin A
Reduce frown lines and wrinkles;
achalasia;
strabismus;
oromandibular dystonia
Class:
Hexamethonium
Mecamylamine
Ganglionic blocker
cholinergic receptor inhibitor
MOA:
Hexamethonium
Mecamylamine
Blocks ganglionic (Nn) receptor and sympathetic tone
Uses:
Hexamethonium
Mecamylamine
Hypertensive crisis; “Bloodless” field surgery
Clinical Uses:
Ipratroprium
Tiotroprium
to cause bronchodilation in asthma and COPD
What kind of amine is atropine?
Tertiary - can interact with CNS AND peripheral muscarinic receptors well - good for nerve gas exposure
Mnemonic for atropine overdose
Dry as a bone - no glandular secretions
Blind as a bat - blockade of accomodation and excessive dilation
Red as a beet - atropine flush - dilation of cutaneous blood vessels AND inhibition of sweat glands (inhibition alpha-1 mediated vasoconstriction)
–also atropine fever from lack of sweating
Mad as a hatter - delirium - CNS
Atropine fever can be lethal in:
infants and small children
Sweat glands are sympathetic but utilize cholinergic post-ganglionic fibers
symptom managament to treat, do not use a cholinesterase inhibitor ie physostigmine
Prazosin
alpha-blocker
alpha-1 selective antagonist
Phenoxybenzamine
alpha-blocker
Antagonist: α1, α2; non-competitive blocker (covalent bond to receptor)
Therapeutic Use: Prazosin
Raynaud’s
BPH
Primary HTN
Therapeutic Use: Phenoxybenzamine
Pheochromocytoma, Raynaud’s, frostbite
MOA Tyramine
Increases NE release
gets uptaken into cleft like NE
Best way to adrenergically increase HR:
Epinephrine
Beta-1 effects greater than NE
MOA Terbutaline
beta-2 selective agonist
Uses: Prevent or reverse exercise-induced bronchospasm; mild asthma; COPD; early labor
Glaucoma is treated with muscarinic agonists or antagonists?
muscarinic agonists, which facilitate the outflow of aqueous humor
An alpha agonist vasodilates or vasocontricts?
Vasoconstricts
Parasympathetic control of salivation is mediated by:
M3 receptors found in salivary glands; these receptors elevate calcium concentration and activate the secretory process.
T/F: Although MAO may contribute to the ultimate metabolism of NE, it does not assist in the termination of NE neurotransmission.
True
Termination of NE neurotransmission:
Uptake by non-neuronal cells.
Diffusion out of the synaptic cleft.
Uptake by neuron plasma membrane.
Phenylephrine MOA
alpha-1 agonist
decongestant
vasoconstriction → increase in total peripheral resistance → increase in blood pressure → activation of a baroreceptor response to decrease sympathetic outflow and increase parasympathetic outflow, resulting in a decrease in heart rate.
For prevention of migraines, consider:
Propranolol, methysergide, and calcium channel blockers have all been shown to be prophylactic in migraine therapy.
For treatment of an acute migraine, consider:
Ergotamine and the several “triptans” (e.g. sumatriptan [Imitrex]) are effective in the acute treatment of a migraine headache.
T/F: Activation of α2 receptors which are presynaptic can reduce subsequent release of norepinephrine from post-ganglionic fibers.
True
MOA Succinylcholine
Succinylcholine (diacetylcholine) activates Nm persistently because it is poorly hydrolyzed at the NMJ. This hyperactivation causes persistent depolarization at the endplate, blocking Nm function and leading to flaccid paralysis.
Side effects: Prazosin
Orthostatic HTN;
Tachycardia
How would metoprolol decrease renin release?
blocking beta receptors on juxtaglomerular apparatus cells