ANS Drugs Flashcards
Transmitters released at ANS synapses
Acetylcholine
Norepinephrine
Dopamine
Which ANS synapses release acetylcholine
All preganglionic neurons
All parasympathetic postganglionic neurons
A few sympathetic postganglionic neurons
Which ANS synapses release NE
Most sympathetic neurons
Which ANS synpases release dopamine
Sympathetic fibers that innervate the renal vasculature and some other vessel beds
What is the predominant tone of the heart?
Parasympathetic
Different types of nicotinic receptor?
Neuronal – the one at the ans ganglia
Muscular – the one at the NMJ
Different types of muscarinic receptor
M2 M4 are coupled to Gi and Go
M1, 3, 5 are coupled to Gq
These activate PLC, which cleave DAG and IP3, which cause Ca release and stimulate PKC
A1 receptor cascade
Coupled to Gq. Elevate intracellular Ca 2 and stimulate protein kinase C. Contract smooth muscles. Also cause miosis.
Where do B1 receptors predominate
In the heart and in JG cells
Where do B2 receptors predominate?
In the vasculature, in bronchial smooth muscle.
Mediate vasodilation and bronchodilation
Where are Dopamine receptors
Prominent on the renal vasculature and mediate vascodilation
How is EPI/NE released from adrenals?
Behaves with a sympathetic ganglion. ACh released to adrenals, Adrenals release NE and EPI.
Baroreceptor reflex
Baroreceptors sense decrease/increase in BP, change heart rate to match .
Sympathetic activity effect on the vasculature
Net increase in total peripheral resistance, decrease in venous capacitance.
Where do beta receptors predominate in the vasculature.
Coronaries and skeletal muscles (where needed during sympathetic outflow).
Why is renal function preserved in flight/flight?
Because DA released in sympathetic outflow on renal vasculature causes vasodilation
Effects of sympathetic activity on the heart
Mediated by B1 receptors in ventricles and B2 receptors in the atria/sa node. Positive chronotropy, positive inotropy, positive lusitrophy
How does B stimulation increase chronotropy
Increases cAMP, which increases activity of funny current. Drives to threshold quicker
What is the channel that opposes the funny current?
GIRK.
How does B stimulation increase AV nodal propagation?
Because cAMP activates PKA, which phosphorylates L-type Ca channels, causing them to open and allow more Ca out. More rapid action potential and faster propagation.
How does B stimulation increase inotropy and lusitropy?
P the phospholamban. Higher ca in er. More available for release, pushed out of cell quickly.
Epinephrine acts on… and causes…
B1, B2, B3, A1, A2 agonist
At high doses causes vasoconstriction (increases mean BP) and increases HR. Direct effects predominate over reflex
At low doses, diastolic BP is decreased because it is more potent at B2 than A1.
Epinephrine at low doses
Decreases diastolic BP because epinephrine has great activity at B2 relative to A2. So will dilate.. ya know?
Uses for epi
Cardiac arrest, inotropic support.
Acute asthma, analphylaxis.
Prolong action of local anesthetic because causes vasoconstriciton at high doses
NE
A1, A2, B1
(no activity at B2)
Increases BP more than Epi.
DECREASES heart rate due to strong pressor effect.
Inotropic effect is still intact.
Uses of NE
Cardiogenic shock
Septic/hypovolemic shock
Adverse effects of NE
Severe hypertension, reduced renal flow.
Necrosis and tissue sloughing after IV injection due to extravasation of the drug (look for blanching)!
Isoproterenol
B1, B2, B3 agonist.
Potent vasodilator (B2).
Increases HR substantially reflex is in same direction as direct, inotropy. Decreases both diastolic and MAP.
Decreases or slightly increases systolic pressure.
Uses of isoproterenol
Treatment of bradycardia in heart transplant patients.
Can treat some arrhythmias (torsades)
Adverse effects of isoproterenol
Palpitations, tachycardia, cardiac ischemia, flushing
Dobutamine
Selective B1 agonist
Structurally resembles dopamine but has little activity at DA receptors.
Inotropy, chronotropy, but ino bigger because B2 dominate at SA.
Dobutamine uses
Cardiac decompensation after CHF or cardiac surgery. Can cause ventricular ectopic activity.
Dopamine
Low dose
intermediate dose
high dose
Direct agonist at D1>B2>A
Low Dose; Renal dose activates only D1 receptors. Increase renal blood flow and urine output. Can cause hypotension
Intermediate dose: activates D1 and B1 receptors
Increased renal blood flow, heart rate, cardiac contractility, and CO. Generally no change in TPR. Can cause hypotension
High dose: activates all receptors. Causes vasoconstriction and increased BP.
Dopamine uses
Treatment of cardiogenic shock especially in oliguric patients.
Fenoldopam and use
D1 agonist. Dilates peripheral vessles and increases natriuresis. Used to treat severe hypertension and in patients with renal compromise.
When NOT to use fenoldopam?
In patients with glaucoma.
Albuterol
Selective B2 agonist.
Used as a bronchodilator for asthma and other pulmonary disease.
Works by increasing cAMP in bronchial smooth muscles which causes relaxation and stabilization of mast cells.
Phenylephrine
Alpha agonist, only slight affinity for a1. Causes vasoconstriction.
Can be used for hypotension, but much more commonly is used as a decongestant
Clonidine
Selective A2 agonist.
Decreases sympathetic outflow from the CNS.
Used in management of HTN and hypertensive crisis.
Drowsiness, fatigue, xerostomia
Tyramine
Not clinically used, but a byproduct of tyrosine metabolism, which is degraded by MAO-A>MAO-B
Evokes release of NE from adrenergic nerves.
Can cause hypertensive crisis.
Black Box warning for Beta blockers
Abrupt withdrawal from beta blockers can cause angina/MI due to upregulation of receptors. If taken off beta blockers too quickly, heart will be hyperactive and need lots of O2.
Who should avoid B blockers
Asthmatics (due to possibility of B2 blockade -> bronchospasm)
Also, diabetes patients. Beta blockers can induce hypoglycemia and prevent diabetics from feeling the symptoms of hypoglycemia.
Propranolol
Non selective B antagonist
Used for angina/svt and vt/pvc/htn/mi/pheochromocytoma
Metoprolol
Selective B1 antagonist, but can block B2 receptors at the doses used for treating angina.
Used for stable angina/chf/hypertension
Pindolol
Partial agonist at B1, B2 receptors.
So this has ISA (intrinsic sympathomimetic activity). In the absence of normal agonist, it is an agonist. Acts as a beta antagonist when sympathetic drive is high.
Stimulation in a limited range.
Used for HTN and angina.
NO blackbox warning.
Labetalol
B1 and A1 antagonist.
Partial agonist at B2 (intrinsic sympathomimetic activity).
Used in hypertensive emergency, especially due to excessive sympathetic activity. Tyramine crisis, pheocromocytoma, methamphetamine.
Carvedilol
Antagonist at B1 and B2 receptors. But also some A1 receptor blockade, so has vasodilatory effect.
Inhibits cardiac remodeling in CHF. Less effect on glucose metablolism than others.
Phentolamine
Alpha antagonist with similar activity at A1 and A2.
Causes hypotension, but used to treat hypertensive emergency due to sympathetic overactivity.
Parasympathetic effects on the vasculature
Vagal activity does not affect vascular tone because they’re not parasympathetically innervated. However. Muscarinic receptors on endothelium causing NO induced vasodilation.
Parasympathetic effects on heart
Isolated in atria.
How does vagal tone decrease chronotropy?
Muscarinic receptors on SA node increases current through Girk channels (hyperpolarizing). Funny current intact but more time needed to drive Vm to spike threshold.
How does vagal tone decrease lusitropy
Reduces cAMP dependent phosphorylation of L-types in AV node causing reduced Ca flow out, makes it slower.
Parasympathetic effects on the body
Bronchoconstriction, increased secretions, increased GI motility, relaxation of sphincters, contraction of bladder wall, miosis, near vision, miosis, near vision.
Acetylcholine
Full agonist at MAchR and NAChR.
Degraded very quickly by plasmacholinesterases
Bethanecol
Muscarinic agonist. Negligible nicotinic activity.
Long duration of action.
Used for urinary retention, neurogenic bladder.
Contraindicated in asthma
Nicotine
Agonist at nicotinic receptors.
Activates ganglia (both parasympathetic and sympathetic outflow, so produces dominant tone).
Increases BP, Increases HR (due to epi release)
Neostigmine/Physostigmine
Anticholinesterases. Prevent degrading of ACh in synapse. Used in myesthenia gravis, and atropine poisoning.
Neostigmine can’t cross BBB.
Anticholinesterase poisoning (organophosphates)
Sludge and the killer B’s
Bronchorrhea, bronchospasm, bradycardia
Atropine and scopolamine.
Muscarinic antagonists
Hot as a hair, mad as a hatter, dry as a bone.
Used for AV block and for bradycardias.
Ipratropium
Muscarinic antagonist, inhalation only. Confined to mouth and airways due to quaternary amine. Used to combat acute asthma exacerbation. Also fights bronchospasm associated with COPD.
Ganglionic blockers
Not used clinically but antagonists of Nn receptors. Functionally denervate targets, so organ specific effects that are opposite to the predominant tone.
Hr increases, BP declines, GI stops moving.
