Lecture 2: Drugs acting on the ANS Flashcards
If a tissue is innervated by only one branch of the ANS, which one will it be?
Sympathetic
Four transmitters of the ANS
ACh, NE, DA, Epi
Where is DA released?
By sympathetic fibers that innervate the renal vasculature and some other vessels beds
What nAChR receptor subtype is located at the ANS ganglia?
Nn
Besides nAChR what other cholinergic receptor class is found in the ANS?
Muscarinic
Do current drugs distinguish between muscarinic subtypes?
No
What NE receptor is postsynaptic? Excitatory or inhibitory?
Alpha-1; excitatory
Describe alpha-2 receptors
Presynaptic inhibitory autoreceptors (decrease Ca2+ currents)
All beta-adrenergic receptors…
Couple to Gs and increase cyclic AMP
More beta-1 > beta-2 in…
Heart, juxtaglomerular cells
More beta-2 > beta-1 in…
Bronchial smooth muscle, arterioles
D1 receptors couple to…and mediate…
Gs; vasodilation (prominent in renal vasculature)
D2 receptors couple to…and mediate…
Gi/Go; autoreceptors on terminals of dopaminergic neurons –> inhibit release
Alpha-1 vaso…; beta-2 vaso…Alpha-1 are widely/not widely expressed. How about beta-2?
Constrict; dilate; widely; beta-2 expression varies, but is greater in coronary and skeletal muscle arterioles
Describe sympathetic effects on vasculature (3). What happens renaly?
Increased TPR, decreased venous capacitance, redistribution of blood flow (away from alpha-1 beds and toward beta-2 beds); renal blood flow maintained due to D1 receptors
Describe receptor distribution and sympathetic effects on heart (ventricles vs atria)
Ventricles: beta-1 –> positive inotropy, lusitropy; Atria: beta-1 plus beta-2 (particularly at nodes) –> positive chronotropy, dromotropy
Lusitropy is…dromotropy is…
Relaxation rate; Conduction rate
Sympathomimetic drugs
Mimic effects of sympathetic transmitters
Sympatholytic drugs
Block normal sympathetic transmission
Epinephrine activates…duration of action?
All alpha and beta receptors; 1-2 minutes
At usual doses, Epi does what to mean BP?
Increase due to alpha-1 mediated vasoconstriction over beta-2 mediated vasodilation
How does Epi affect coronoary and skeletal perfusion? How about cerebral aterioles?
Increased; cerebral arterioles show little change in tone but increased resistance elsewhere –> increased blood flow
Describe low doses of Epi
Epi is more potent at β2 receptors than at α1 receptors, so will show decreased BP
How does Epi affect the heart? (4 and final effect)
Positive chronotropy, dromotropy, inotropy, lusitropy –> increased CO
Uses of Epi (5)
Cardiac arrest to restore rhythym, inotropic support (weakening ventricles), acute severe asthma, to restrict local anesthetic to site of injection, to relieve hypersensitivity reactions (anaphylaxis)
What is the MAIN way NE is different? What is the effect?
Alpha-1, beta-1 agonist but NOT beta-2 agonist; increase in BP more than Epi
Direct effects on the heart of NE…what happens next? How does this impact the inotropic effect?
Similar to Epi via beta-1 activation; powerful vagal reflex which DECREASES HR; inotropic effect intact because LITTLE VAGAL INPUT TO VENTRICLES
T/F: NE causes positive inotropic effect?
True
Uses of NE? (1)
Shock (cardiogeic, septic, hypovolemic)
Adverse effects of NE? (3)
Severe hypertension, risk of reduced renal flow, necrosis of tissue at site of injection
Isoproterenol is the prototypical…
Beta-receptor agonist
What are the heart effects of isoproterenol? What are the primary uses and AEs?
Positive chronotropic and inotropic activity (large increase in HR, since the direct effect and reflex [↓ vagal tone] are in the same direction); treat bradycardia and some arrhythmias; palpitations, tachycardia, cardiac ischemia, flushing
Isoproterenol does what to CO, MAP?
Increases; decreases
Describe dobutamine
Selective beta-1 agonist; positive inotropic and chronotropic effects
Which effect of dobutamine is more significant?
Inotropic because beta-2 receptors play a significant role at the SA node
Uses/AEs of dobutamine
ST tx of cardiac decompensation after cardiac surgery/CHF; May increase ventricular rate in pts w/ Afib, also can cause ectopic ventricular activity
Dopamine is an agonist at…Important why?
D1 > beta-1 > alpha; varying doses affects various receptors
DA effect on BP
Hypotensive
Low DA dose
Increased renal blood flow and urine output
Intermediate DA dose. What happens to TPR?
Increased renal blood flow + cardiac effects (beta-1); no change in TPR
High DA dose
Vasoconstriction (due to alpha involvement now); increased BP, but kidney perfusion spared
Uses/AEs of DA
Treatment of cardiogenic shock (high dose); especially in oliguric patients with low or normal peripheral resistance, heart block that doesn’t respond to atropine or pacing, symptomatic bradycardia; tachycardia, anginal pain, hypotension, nausea, vomiting
Fenoldopam is a…
Selective agonist at D1 receptors (peripheral and renal vessels)
Uses/AEs of Fendolopam…Contraindication?
Treatment of severe hypertension; reflex tachycardia, headache, flushing; contraindicated in glaucoma
Albuterol is a…
Selective agonist at beta-2 receptors
Uses/AEs of Albuterol (including midl and moderate)
Bronchodilator for asthma, etc via relaxation of bronchial smooth muscle; mild to moderate: tachycardia, agitation, nausea, vomiting, hypokalemia, hyperglycemia; severe: Hypotension, dysrhythmias, seizures & acidosis
Phenylephrine is a…What are it’s effects?
Alpha-agonist, slight selectivity for alpha-1; increases BP (especially diastolic), decreases HR
Uses/AEs of Phenylephrine
Most common: decongestant, induce mydriasis and treat wide-angle gluacoma; Exacerbation of Raynaud’s, ↑BP, bronchoconstriction
Clonidine is a…What does this mean?
Selective alpha-2 agonist (only sympatholytic adrenergic agonist because it DECREASES sympathetic outflow)
Uses (3)/AEs (3) of Clonidine…
Management of hypertension/hypertensive crisis, pain management, opiate withdrawal; drowsiness, fatigue, xerostomia
Tyramine is…
Not a drug! Normal metabolite of tyrosine metabolism –> indirect sympathomimetic
Beta-adrenergic antagonists are called. Uses?
Beta blockers; hypertension, angina, arrhythmias, heart failure
“Black box” warning of beta-blockers and two other important contraindication
Abrupt withdrawal can exacerbate angina; diabetes because it can induce hypoglycemia and asthma because it can lead to bronchoconstriction
AEs of beta blockers (5)
Bradycardia, fatigue, CNS effects (insomnia, nightmares), worsening of Raynaud’s, erectile dysfunction
What is a prototype non-selective beta-antagonist? Uses.
Propranolol; angina, arrhythmias, premature ventricular contraction, hypertension, MIs, pheochromocytoma (tumor that secretes NE)
Metoprolol is a…
Beta-1 selective antagonist
Uses (4)/Contraindications (3) of Metoprolol
Stable angina, congestive HF, HT, acute MI; sinus bradycardia, heart block, cardiogenic shock
Pindolol is a…What does this mean?
Partial agonist of beta-1/beta-2 receptors; in absence of sympa stimulation, it is an agonist but an antagonist when sympa drive is high –> maintains beta receptor tone
Uses (2) of Pindolol. What’s special about Pindolol?
Hypertension, angina; no black box warning
Carvedilol is a…
Beta blocker (beta-1 and beta-2) plus alpha-1 receptor blocker
Uses of Carvedilol (3). What’s special about Carvedilol (2)?
Heart failure, angina, HT; improves outcome in HF, preferred in diabetes (less effect on glucose metabolism than most beta blockers)
Labetalol is a…
Mixed: antagonist at beta-1 and alpha-1 receptors = vasodilatory;
Partial agonist at beta-2 receptors
Use of Labetalol
Hypertensive emergency, especially if excessive sympathetic activity
Terazosin is a…Effect on BP?
Alpha blocker with similar alpha-1 and alpha-2 affinities; hypotensive
Use of Terazosin. What population is this medication preferred for?
HT, preferred over beta-blockers in diabetes
Does vagal activity affect vascular tone?
NO! Few vessels are parasympathetically innervated
Parasympathetic effects on the heart (SA node, AV node, atrial muscle)
Major effects are on the atria; SA node: negative chronotropy (reduced automaticity); AV node: negative dromotropy (slowed conduction); atrial muscle: reduced contractility
Two classes of drugs acting on parasympathetic branch
Parasympathomimetic (mimic ACh) and parasympatholytic (anticholinergic)
Acetylcholine is a…What does IV adminstration lead to? Uses?
Full agonist at all muscarnic and nicotinic receptors; small dose causes transient drop in BP and reflex tachycardia, large dose affects heart (slows HR); used in eye surgery to induce miosis
Bethanechol is a…
Muscarinic agonist
Uses (2)/AEs of Bethanechol
Urinary retention, gastroesophageal reflux; hyptension/tachycardia (peripheral) and effects of excessive parasympa activity (ab cramping, bronchial constriction, salivation…)
Neostigmine and Physostigmine are…
Cholinesterase inhibitors (carbamates)
Uses/AEs of Neostigmine (3)
Myasthenia gravis, NM block, urinary retention
Atropine and scopolamine are…
Muscarinic receptor antagonists
Uses of Atropine…(3)
Sinus bradycardia, A-V block, to reduce parasympathetic function (inhibit salivation, GI spasms, etc)
Ipratropium is a…why is it special?
Muscarinic antagonist that is inhaled only
Uses of Ipratropium…(3)
Acute asthma, bronchospasm w/ COPD, short-term relief of rhinorrhea
