2013-08-26 Autonomic Pharmacology Flashcards
Draw out how NE is synthesized, stored and released.
–Where do metyrosine, reserpine, guanethidine Cocaine, and TCAs work?
see slide 16
Draw out how ACh is synthesized, stored and released.
–Where do vesamicol, botullinum, and cholinesterase inhibitors act?
see slide 15
Where do parasympathetic neurons exit the spinal cord?
craniosacral
III, VII, IX, X
S2, S3, S4
Where do sympathetic neurons exit the spinal cord?
thoracolumbar
T1-L3
Diagram effects of carotid baroreceptors on ANS
Draw out slide 5
Where are the depressor and pressor sensors located?
In the medulla
Clicker Q1: Noradrenergic sympathetic neurons run:
A. from nucleus ambiguus to the cranial segments of spinal cord
B. From RVLM to the thoracolumbar segments of the spinal cord
C. from the thoracolumbar segments of the spinal cord to the sympathetic ganglia
D. from the sympathetic ganglia to the effectors organs
E. from the vagus nerve to the heart
D
What is neurotransmitter from the thoracolumbar segments of the spinal cord to the sympathetic ganglia?
ACh
Which one of the following features do the SANS and the PANS share in common?
A. both orig in same nuc w/in medulla
B. both exit spinal cord at the same level
C. both have neurons from the central nervous system to their ganglia that are cholinergic neurons
D. Their post-gang neurons always produce ACh as their neurotransmitter
E. Their shared main purpose is to maintain BP in the face of hypotension or fright
C
Fill out table for follow SANS vs. PANS
- -CNS nucleus or origin
- -exit spinal cord
- -location of ganglia
- -length of pre-ganglionic fibers
- -length of post-ganglionic fibers
- -Ganglionic transmitter
- -Ganglionic receptor
Postganglionic fibers release
Tissues with receptors but no innervation
see slide 12
NANC (nonadrenergic/noncholinergic) system
nerve fibers assoc’d w/ autonomic nerves that release purines or peptides NOT NE or ACh
What are the different cholinoreceptors in the peripheral nervous system?
Muscarinic: M1, M2, M3
Nicotinic: N_n, (nerve) N_m (NMJ)
M1 receptor
- location
- mechanism
- 2nd messanger
- action
M1 receptor
- location: nerve endings
- mechanism: Gq-coupled
- 2nd messanger: IP3/DAG cascade via Ca2+ release from SER
- action: activates myenteric pleux
M2 receptor
- location
- mechanism
- 2nd messanger
- action
M2
- location: heart, some nerve endings
- mechanism: Gi-coupled
- 2nd messanger: decr cAMP, activate K+ channels
- action: slow SA node
M3 receptor
- location
- mechanism
- 2nd messanger
- action
M3
- location: smooth muscle, glands, endothelium
- mechanism: Gq-coupled
- 2nd messanger: IP3/DAG cascade via Ca2+ release from SER
- action: contract detrusor muscle; incr salivation
N_N receptors
- location
- mechanism
- 2nd messanger
- action
N_N
- location: ANS ganglia
- mechanism: Na-K ion channel
- 2nd messanger: Na+
- action: depolarizes postganglionic fiber/evoking AP
N_M
- location
- mechanism
- 2nd messanger
- action
N_M
- location: neuromuscular end plate
- mechanism: Na-K ion channel
- 2nd messanger: Na+
- action: depolarized muscle cell evoking AP
What are the different adrenoreceptors in the SANS?
α1 α2 β1 β2 β3 Dopamine1
Draw table listing
- -location
- -G prot
- -2nd messenger
- -major action
for the different adrenoreceptors in SANS
see slide 18
What is MOA of sarin gas?
AChE inhibitor—>too much ACh
- bronchorrhea
- SKM paralysis
GPCR anatomy and function
Anatomy of a GPRC
–GPCR has 7 membrane-spanning domains; binds ligand
–GPCR is also bound to a G-protein trimer (alpha, beta, gamma subunits) with a bound GDP in membrane
Function:
- -G-prot swaps GDP for GTPwhen triggered by ligand causing alpha subunit to break away
- -alpha subunit triggers “specific events”
- -remaining beta and gamma trigger “general events”
The specificity of the GPCR system depends on the type of alpha subunit:
G_s: stimulates adenylate cyclase—> incr cAMP
G_i: inhibits adenylate cyclas—>decr cAMP
G_q: nothing to do with cAMP; stimulates phospholipase C —> IP3/DAG cascade
G_q further mechanism:
- -ligand to GCPR
- -GDP on alpha_q subunit of G-prot swapped for GTP breaking away
- -stimulated phospholipase C
- -phospholipase creates IP3 and DAG
- —IP3 causing Ca2+ leak from SER; Ca2+ then activates Ca2+-specific protein kinase
- —DAG activated PKC (prot kinase C)
G_s/i further mechanism:
- -ligand to GCPR
- -GDP on alpha_s/i subunit of G-prot swapped for GTP breaking away
- -stimulates adenylate cyclase
- -incr cAMP production
- -cAMP activates protein kinase A
What happens when your BP drops?
draw whole slide of 35 w/ attention to autonomic transmission
In order to dilate a pt's pupils as wide as possible, which drug combo? A. phenylephrine and ACh B. phenylephrine and atropine C. phentolamine and ACh D. phentolamine and atropine E. isoproterenol and ACh F. isoproterenol and atropine
B
adrengeric agonist: phenylephrine stimulates alpha_1
muscarinic ANTagonist: ACh causes constriction, so atropine blocks muscarinic effects of ACh
Norepinephrine (noradrenaline, Levophed™, leave-em-dead during my residency)
Drug Class PD PK Toxicity Interactions Special considerations Indications and dose/route Monitor
Drug class: pharmacologic class—direct-acting, non-specific adrenergic agonist; therapeutic class—vasopressor, vasoconstrictor
Pharmacodynamics: major action is to stimulate peripheral alpha-1 adrenoceptors, thereby leading to vasoconstriction (resistance arterioles, increase SVR) and venoconstriction (in capacitance vessels, increase preload). This increases CO, SVR, and MAP, but decreases blood flow to vulnerable tissues like skin, muscle, and kidney. Also, stimulates beta-1 receptors in the heart, increasing HR and contractility. Main effects are vasoconstriction and cardiac stimulation.
Pharmacokinetics: F ~100%. Given IV only. Metabolized by COMT and MAO, mostly in liver. Metabolites are excreted in urine. Half-life 1-2 minutes (e.g. can be titrated quickly IV). Can cross the placenta, but not the blood/brain barrier.
Toxicity: excessive vasoconstriction in mesenteric vessels, peripheral arterioles causing ischemia, infarction, gangrene; reflex bradycardia
Interactions: use cautiously in patients taking an MAO inhibitor such as phenelzine (use lower doses); risk of excessive hypertension in patients taking propranolol
Special considerations: correct volume depletion with IV fluids BEFORE giving NE infusion; select infusion site carefully—extravasation is a major problem; monitor patient and BP continuously in ICU setting; use cautiously in pediatric and geriatric patients
Indications and dose/route: for adults with acute hypotension and shock (related to low SVR) infuse 2-12 mcg/min
Monitor: BP, HR, infusion site, evidence of extravasation
Epinephrine (adrenaline,EpiPen™)
[see RANG 2.03]
Drug Class PD PK Toxicity Interactions Special considerations Indications and dose/route Monitor
Drug class: pharmacologic class—direct-acting, non-selective adrenergic agonist; therapeutic class—vasopressor, cardiac stimulant, bronchodilator, adjunct to local anesthetics, treatment for anaphylaxis
Pharmacodynamics: major action is to stimulate peripheral alpha-1 adrenoceptors, thereby leading to vasoconstriction (resistance arterioles, increase SVR) and venoconstriction (in capacitance vessels, increase preload); beta-1 receptors leading to tachycardia and increased contractility; and beta-2 receptors leading to bronchodilation; these actions are also helpful in severe allergic reactions (e.g. anaphylaxis) by stabilizing mast cells
Pharmacokinetics: can be given iv (immediate), IM (variable), SC 5-15 min), and via inhalation (1-5 min onset), ophthalmic topical; metabolized by COMT and then renally excreted;
Toxicity: excessive vasoconstriction, HTN, hemorrhagic stroke, angina, arrhythmias,
Interactions: risk of excessive hypertension in patients taking propranolol
Special considerations: utility with local anesthetics; drug of choice in severe anaphylactic reactions (along with others)
Indications and dose/route: for anaphylaxis, 0.1-0.5 mg SC or IM; for cardiac arrest, 1-5 mg IV push; for infusion, 1-4 mcg/min; also for allergy-induced asthma
Monitor: BP, HR, rhythm, infusion site, evidence of extravasation
