3.10.14 Autonomics 1&2 Flashcards
How many neurons exist between the CNS and skeletal muscle in somatic motor systems?
How many neurons exist between the CNS and smooth muscle/cardiac muscle/glands of autonomic motor systems?
ONE neuron for somatic (alpha motor neuron)
TWO neurons for autonomic (preganglionic and postganglionic)
What is the state of myelination for somatic motor neurons?
What is the state of myelination for autonomic motor neurons?
All are myelinated for somatic
The preganglionic neurons are myelinated; the postganglionic neurons are unmyelinated
What neurotransmitter is secreted by somatic motor neurons?
What neurotransmitter is secreted by autonomic motor neurons?
Somatic: acetylcholine (always)
Autonomic: preganglionic = acetylcholine; postsynaptic = acetylcholine (parasympathetic) and norepinephrine (sympathetic, except for neurons of thermoregulatory sweat glands)
What autonomic division is referred to as thoracolumbar? What region is this name associated with?
Sympathetic
T1-L2 spinal cord
What autonomic division is referred to as craniosacral? What region is this name associated with?
Parasympathetic
Brainstem
S2-S4 spinal cord
Where are second neurons of the sympathetic division located?
Body wall (prevertebral and paravertebral ganglia)
Viscera
Adrenal medulla
Where are second neurons of the parasympathetic division located?
Viscera (ganglia in the head; terminal ganglia on or near the target organ)
What are the two types of nicotinic receptors?
Nn (found in ANS ganglia; associated with neurons)
Nm (found in neuromuscular end plates)
Where are muscarinic receptors found?
What differentiates muscarinic receptors from one another? (Name the subtypes)
Muscarinics are found in all postsynaptic parasypathetics and in postsynaptic sympathetics that innervate thermoregulatory sweat glands
They are organized by different subtypes of G-coupled receptors and different target organs/tissues:
M1-M3, Q-I-Q
Gq –> increase IP3 and DAG
Gi –> inhibit/decrease cAMP, open K+ channels
What are the two types of adrenergic receptors?
Alpha (A1 = Gq, A2 = Gi –> inhibit/decrease cAMP)
Beta (B1,2 = Gs –> stimulate/increase cAMP)
Which adrenergic receptors is considered an autoreceptor? Why is this so flippin’ special?
Alpha-2 autoreceptors - regulation of NT release (negative feedback)
Important for autonomic drug effects: CNS effect may predominate over direct PNS effect
What does atropine do?
Muscarinic receptor blocker (postganglionic parasympathetics)
What does botulinum toxin do?
Blocks release of acetylcholine
What does cocaine do?
Blocks monoamine (dopamine, norepinephrine, epinephrine) re-uptake
What does curare do?
Nicotinic receptor blocker (skeletal muscle)
What does neostigmine do?
Inhibits acetylcholinesterase activity
What do organophosphates do?
Irreversibly inactivates acetylcholinesterase
What do tricyclic antidepressants do?
Blocks monoamine (dopamine, norepinephrine, epinephrine) re-uptake
What receptor contracts (mydriasis) dilator pupillae muscles (eye)? (What ANS division?)
A1 adrenergic receptors (sympathetic)
What receptor increases outflow of aqueous humor? What decreases secretion of aqueous humor? (What ANS division?)
A agonists increase outflow
B blockers decrease secretion
(sympathetic)
What receptor accelerates heart rate (SI node stimulus)? (What ANS division?)
B1 (B2) - Sympathetic
What receptor increases contractility of the heart? (What ANS division?)
B1 (B2) - Sympathetic
What receptor constricts skin/splanchnic blood vessels? (What ANS division?)
Alpha - Sympathetic
What receptor relaxes renal blood vessels? (What ANS division?)
D1 - Sympathetic
What receptor relaxes blood vessels to skeletal muscle? (What ANS division?)
B2 - Sympathetic
What receptor relaxes bronchiolar smooth muscle? (What ANS division?)
B2 - Sympathetic
What receptor relaxes smooth muscle of the GI tract walls? (What ANS division?)
B2 - Sympathetic
What receptor contracts sphincters of the GI tract? (What ANS division?)
A1 - Sympathetic
What receptor inhibits secretions of the GI tract? (What ANS division?)
A2 - Sympathetic
What receptor relaxes the bladder wall detrusor muscles? (What ANS division?)
B2 - Sympathetic
What receptor contracts the sphincter of bladder? (What ANS division?)
A1 - Sympathetic
What receptor relaxes the uterus (pregnancy)? Contracts? (What ANS division?)
Relax: Beta - Sympathetic
Contract: Alpha - Sympathetic; M - Parasympathetic
What receptor promotes ejaculation? (What ANS division?)
Alpha - Sympathetic
What receptor sustains an erection? (What ANS division?)
M - Parasympathetic
What receptor stimulates renin, gluconeogenesis, glycogenolysis, and lypolysis? (What ANS division?)
B1, B2, B2, B3 (respectively) - Sympathetic
What receptor stimulates pilomotor, eccrine sweat, and apocrine sweat? (What ANS division?)
Alpha - Sympathetic
M - Sympathetic
Alpha - Sympathetic
What receptor contracts (miosis) sphincter pupillae muscles (eye)? (What ANS division?)
M - Parasympathetic
What receptor contracts ciliary muscles of the eye? (What ANS division?)
M - Parasympathetic
Do parasympathetic neurons cause dilation of blood vessels?
Nope; lack of sympathetic innervation = relaxation
What receptor is associated with every parasympathetic postganglionic neuron, eliciting the effects of parasympathetic innervation in eyes, the heart, bronchiolar smooth muscle, GI tract, and GU smooth muscle?
M receptors (muscarinic)
What tissues are solely innervated by the sympathetic nervous system (as opposed to dual innervation with parasympathetics)? (Hint: there are 3)
Blood vessels
Sweat glands (eccrine and apocrine)
Piloerector muscles
What is the predominant ANS tone at rest for arterioles?
Sympathetic
What is the predominant ANS tone at rest for the iris?
Parasympathetic
What is the predominant ANS tone at rest for the GI tract?
Parasympathetic
What is the predominant ANS tone at rest for the heart?
Parasympathetic
What is the predominant ANS tone at rest for salivary glands?
Parasympathetic
What is the predominant ANS tone at rest for the urinary bladder?
Parasympathetic (contract detrusor, relax sphincter)
What is the predominant ANS tone at rest for sweat glands?
Sympathetic
Which structures of the eye fall under sympathetic regulation? Parasympathetic regulation?
Sympathetic: dilator pupillae muscle
Parasympathetic: sphinctor pupillae muscle (pupil contraction; ciliary muscle (accomodation)
What structures are responsible for secretion and drainage of aqueous humour? How is this regulated (ANS division)?
Ciliary epithelium secretes
Canal of Schlemm and trabecular network drain
Contraction of the ciliary muscle puts tension on the trabecular network, opening pores and increasing drainage
What are the five CLASSES of autonomic drugs?
Direct-acting cholinomimetics Cholinoceptor blockers Indirect-acting cholinesterase inhibitors Sympathomimetics (direct/indirect) Adrenoceptor blockers
What are the five SITES OF ACTION for pharmacological manipulation of the ANS
Synthesis Storage Release Termination Receptor
What is the difference between direct and indirect effect?
Direct effect: act directly on autonomic receptors
Indirect effect: act indirectly through changes in endogenous transmitter levels in the terminal or synaptic cleft
What are the two subtypes of direct-acting cholinomimetics? Uses?
Nicotinic agonists (skeletal muscle paralysis; smoking cessation) Muscarinic agonists (non-selective for M1-5; glaucoma, Sjogren's, bowel and bladder disorders)
What drug is a derivative of acetylcholine, useful because of its increased resistance to inactivation and its selectivity? What class of drug is this?
Bethanecol
Direct-acting cholinomimetic
What drugs are classified as “naturally occurring alkaloids”? What class of drug is this?
Muscarine; nicotine
Direct-acting cholinomimetics
What might be prescribed to treat glaucoma?
Muscarinic agonists (direct-acting cholinomimetics) They increase the constriction of ciliary muscles, opening pores of the trabecular network, increasing outflow
What clinical uses are there for muscarinic agonists?
Glaucoma
Sjogren’s (decreased salivary gland secretion)
Bowel and bladder issues (decreased parasympathetic drive)
What toxic effects are specific to muscarinic agonists?
Increased parasympathetic drive (intuitive): Miosis Cycloplegia (spasm of accomodation) Bronchoconstriction Excessive GI/GU activity Secretions (sweat, GI, airway, lacrimal)
Some are less intuitive:
Tachycardia (compensatory sympathetic discharge, baroreceptor reflex)
Vasodilation (muscarinic receptors of endothelial cells cause release of nitric oxide; increases cGMP; relaxes vessels)
Why would sweat glands (sympathetic innervation) be affected by a drug that specifically cues parasympathetic receptors?
Postganglionic parasympathetics are muscarinic receptors; the drug would be a muscarinic agonist: sweat glands have muscarinic receptors (exception to the symp postganglionic adrenergic receptor rule)
What is the mnemonic for toxic effects of muscarinic agonists?
SLUDGE Salivation Lacrimation Urination Defecation GI upset (diarrhea) Emesis
What class of drug are anti-nicotinic drugs? What are they used for?
Cholinoceptor blocker
Historically used to treat hypertension; too many side effects (all ANS ganglia), so limited use today (acute use)
What class of drugs are anti-muscarinic drugs? Example? What are they used for?
Cholinoceptor blocker
Atropine is the prototype; also scopolamine
Block exogenous cholinomimetics more easily than endogenous parasympathetics
Clinical uses: Anti-motion sickness (note: remember the dry mouth story) Ophthalmological exam Bronchodilation Surgical adjunct Temporal control of diarrhea Anti-parkinsonism
What effects are predictable of anti-muscarinic drugs?
Mydriasis (dilation)
Cycloplegia (same as muscarinic agonists)
Tachycardia
Bronchodilation, reduced secretions of lungs
Dry mouth
Reduced peristalsis
Reduced sweating
What are contraindications of anti-muscarinic drugs?
Glaucoma
Prostatic hyperplasia (urinary retention)
Children (danger of hyperthermia, reduced sweating)
Atropine toxicity? Mnemonic?
Anti-muscarinic cholinoceptor blocker
Constipation, blurred vision, dry mouth
“Dry as a bone” (sweat, salivation, lacrimation)
“Red as a beet” (dilation of blood vessels)
“Mad as a hatter” (CNS effects, delirium and hallucinations)
What major non-cholinergic drugs have prominent anti-muscarinic effects due to similar chemical structure? What symptoms would you expect?
Tricyclic antidepressants
Dry as a bone, red as a beet, mad as a hatter; constipation, blurred vision, dry mouth
Name a couple examples of cholinesterase inhibitors. How do they work?
Neostigmine and organophosphates
Potentiate the effects of ACh by blocking the inactivating enzyme
What are the clinical uses of neostigmine and organophosphates?
Cholinesterase inhibitors: Postoperative and neurogenic ileus (disruption of bowel flow) Urinary retention Myasthenia gravis (diagnostic) Alzheimer's disease
What is the toxicity of cholinesterase inhibitors?
Similar to cholinomimetic toxicity: DUMBBELSS Diarrhea Urination Miosis Bronchoconstriction Bradycardia Exitation of CNS/NMJ Lacrimation Salivation Sweating
Name some direct acting sympathomimetics
Epinephrine, norepinephrine, phenylephrine, albuterol, dopamine
What are the effects of direct acting sympathomimetics on the eye?
Alpha-agonists (phenylephrine) –> mydriasis; accomodation unaffected; facilitates aqueous humour outflow
What are the effects of direct acting sympathomimetics on the heart?
Beta agonists (B1) –> increase rate and force of contraction
What are the effects of direct acting sympathomimetics on the bronchi?
B2 agonists (albuterol) –> relax smooth muscle; bronchodilation
What are the effects of direct acting sympathomimetics on the blood vessels?
Alpha agonists constrict cutaneous blood vessels
B2 agonists dilate skeletal vessels
What are the effects of direct acting sympathomimetics on the GI tract?
Alpha agonists contract sphincters
Beta agonists relax walls (decreased peristalsis)
What are the effects of direct acting sympathomimetics on the GU tract and uterus?
Alpha agonists mediate trigone and sphincter contraction
A1 contracts prostatic smooth muscle
B2 relaxes uterine muscle (premature contractions
What are the effects of direct acting sympathomimetics on metabolism?
Beta agonists increase gluconeogenesis, glycogenolysis, and lipolysis
What are the clinical uses of direct acting sympathomimetics?
Anaphylaxis (epi-pens)
Local vasoconstriction (for administration of local anesthetics
Asthma therapy (albuterol)
Allergies (alpha agonists like phenylephrine)
Cold medicine
Name some indirect acting sympathomimetics
Tyramine and amphetamine (induces release)
Cocaine and tricyclic antidepressants (block reuptake)
What suffix is associated with alpha blockers (adrenoceptor blockers)
“-zosin” (prazosin)
What suffix is associated with beta blockers (adrenoceptor blockers)
“-olol” (propranolol)
What are the clinical uses of adrenoceptor blockers?
Glaucoma (blocker decreases secretion of aqueous humour) Pheochromocytoma (neuroendocrine tumor, increased circulating levels of catecholamines) Cardioselective blockers (B1 advantageous to asthma patients) Benign prostatic hyperplasia (alpha blockers)
