Autonomic Pharm II Flashcards
Effects of M2 receptor stimulation?
decreased neuronal activity to SA node and decreased atrial contractility (little to no effect on ventricles)
Effects of M3 and M5 receptor stimulation?
vasodilation of vasculature by Nitric Oxide production
Mechanism of M2 receptor activation?
Gi signaling, inhibition of adenylate cyclase–> decrease cAMP–> hyper-polarization of membrane by opening on inward potassium channels
Mechanism of M3 receptor activation?
couples through Gq–> increase IP3 and DAG levels–> increase in PKC and Calcium levels–>excitatory
Where in the heart does parasympathetic activity act?
SA and AV nodes
Does vasculature receive parasympathetic innervation?
No, but it will respond to exogenous muscarinic agonists/antagonists
Effect of IV acetylcholine on the vasculature?
vasodilation via NO synthesis
Effect of IV acetylcholine on damaged vasculature?
activation of M3 receptors–> smooth muscle contraction and vasoconstriction
Main effect of Atropine on the heart?
To increase heart rate, it is a competitive antagonist of muscarinic Ach receptors (acting mainly in the SA node)
Atropine at low doses?
Inhibits presynaptic M1 receptors–> Increase in PS activity (Ach release)–> slight slowing of heart rate
Atropine at higher doses?
Blockade of PS inhibitory effects on the SA node leading to progressive tachycardia
Effect of Atropine on the vasculature?
Minimal given that most vascular beds lack significant cholinergic innervation
What is Atropine Flush?
High doses of Atropine can dilate cutaneous blood vessels in a local area causing flushing of the skin
Atropine indications?
Abolish temporary over-activity of the Vagal tone of the heart; facilitates AV node conduction (useful in patients with inferior or posterior wall MIs)
Effect of Beta-2 receptor activation?
vasodilation in skeletal muscle vasculature and dilation of bronchial smooth muscle
Effect of Beta-1 receptor activation?
Increased heart rate and cardiac contractility; Renin release from JGA in the nephrons
How direct-acting drugs work?
stimulate the postsynaptic receptors
How indirect-acting drugs work?
stimulate the presynaptic terminal to cause release of Epi or Norepi
What is Tachyphylaxis?
Reduction in effect seen with chronic therapy
What are MAOIs and how do they work?
Monoamine oxidase Inhibitors, prevent the breakdown of neurotransmitter (indirect)
How does Tyramine and Amphetamine work?
cause the release of preformed transmitter from storage in the pre-synaptic vesicles (indirect)
How does Reserpine work?
depletes Norepi from presynaptic sympathetic neurons
Would you see any effect with a direct-acting drug if pretreated with Reserpine?
Yes, response is not reduced at all. May be increased due to Norepi induced compensatory changes
Would you see any effect with an indirect-acting drug if pretreated with Reserpine?
No, there are no catecholamines left in the vesicles to release
Dobutamine receptor specificity
B-1 > B-2,
Dopamine receptor specificity
D1=D2 > B > a
Epinephrine receptor specificity
a1=a2 : B1=B2
Isoproterenol receptor specificity
B1=B2
Norepinephrine receptor specificity
a1 > a2 > B1
Phenylephrine receptor specificity
a1 > a2
Ephedrine receptor specificity
a1 > a2 > B1
What drug will produce a widening of pulse pressure?
Beta non-specific agonists (Isoproterenol); epinephrine, at low doses it drops the diastolic due to vasodilation of skeletal muscle vasculature (B2)
Primary receptor on the heart
Beta-1
Primary receptor on the lungs
Beta-2
Which drug is commonly put into SubQ lidocaine and other local anesthetics for vasoconstriction?
Epinephrine
What drug can demonstrate pro-arrhythmogenic activity and fibrillation
Epinephrine
Epinephrine effect on the kidneys?
increase renal vascular resistance–> reduction of renal blood flow by up to 40%
Also acts on beta-1 receptors in the JGA–> renin secretion–> renin-angiotensin aldosterone axis–> elevated BP
Main catecholamine made by most pheochromocytomas?
Norepinephrine
Main differences in physiologic effects of Epi/Norepi?
Epi greatly increases Cardiac output, Norepi does not. Norepi increases the blood pressure much more than Epi
Synthesis of catecholamines from precursors?
Tyrosine–> Dopa–> Dopamine–> Norepi–> Epi
Dopamine effect at low dose?
Predominately D1 action; potent renal vasodilation–> improves GFR (critical in patients with renal hypo-perfusion)
also vasodilates mesenteric, coronary, and intracerebral vasculature
Dopamine effect at moderate dose?
D1 + B1 action; increase in Cardiac output (contractility»_space; HR) and D1 induced vasodilation
Dopamine effect at high dose?
alpha-agonism; increased peripheral vascular resistance and renal vasoconstriction
Dobutamine effects/indications?
increased CO and stroke volume without much effect on HR; used for short term tx following cardiac decompensation (CHF, Acute MI)
Isoproterenol affects these receptors?
Beta-1 and Beta-2
Isoproterenol effects?
Large increase in CO, decrease in diastolic BP due to vasodilation of skeletal muscle vasculature (decreased PVR)
Isoproterenol indications?
emergencies to stimulate the HR like complete heart block or bradycardia
Dobutamine acts on which receptors?
B-1 agonist, DOES NOT act on dopamine receptors; ultra short half-life (2 minutes)
Effects/indications of Phenylephrine?
Potent vasoconstriction, used to manage emergent hypotension; may produce reflex vasovagal bradycardia
Ephedrine receptor specificity?
Direct agonist at both alpha and beta receptors
Effects of Ephedrine?
Enhances Norepi release at sympathetic neurons, increases HR, CO, and peripheral resistance
Indications for Ephedrine?
Asthma and bronchospasm, stimulates beta receptors in the bronchiolar smooth muscle
Route of administration of Ephedrine?
Oral
Adverse effects of Ephedrine?
Fatal arrhythmias, including V-fib
Regulation of Ephedrine?
Active ingredient in OTC cold and sinus products, main precursor to methamphetamine (GO VOLS) (East TN speed dragon)
