Autonomic Pharm I Flashcards
primary result of alpha-1 activation?
vasoconstriction by activation of smooth muscle
alpha-1 specific antagonists?
Doxazosin, Terazosin, Prazosin
balanced alpha-1/alpha-2 antagonists?
Phenoxybenzamine, Phentolamine
subtypes of alpha-1 receptors?
alpha-1a, alpha-1b, alpha-1d
location of alpha-1a receptors?
bladder neck and prostate, blockade can improve symptoms of BPH and improve urine flow
Stimulation of alpha-1 receptors induces vasoconstriction in these in vessels
vasculature of the skeletal muscle and skin, and the splachnic vessels
synaptic location of alpha-1 receptors?
post-synaptic membrane, mediates downstream events
synaptic location of alpha-2 receptors?
pre-synaptic terminal, functions as auto-receptor to terminate further NE release
activation of alpha-2 receptors produces?
agonists produce bradycardia and hypotension, they terminate further NE release
blockade of alpha-1 receptors causes?
lower blood pressure, prevents NE-stimulated smooth muscle contraction in the vasculature
Which alpha antagonist requires more than one daily dosing?
Prazosin
Alpha antagonist most correlated with first dose orthostatic hypotension?
Prazosin
Alpha antagonists that are more likely to cause sinus tachycarida?
Non-specific blockers, by virtue of augmenting action of endogenous NE release by inhibiting alpha-2
Phenoxybenzamine mechanism?
Binds covalently (me last you long time) to both alpha-1 and alpha-2
Phenoxybenzamine effect on blood pressure?
reduction via vasodilation, but less substantially than alpha-1 specific antagonists due to increased cardiac output seen with alpha-2 inhibition
Indications of Phenoxybenzamine?
Pheochromocytoma and “off label” use for Raynaud’s Syndrome
Mechanism of Phentolamine?
Non-specific, competitive alpha antagonist (short-acting)
Cardio-stimulation with Phentolamine?
Yes, due to antagonism of alpha-2
Phentolamine at low doses?
Blood pressure RISES due to cardio-stimulatory effect predominating
Phentolamine at high doses?
Blood pressure falls due to alpha-1 mediated vasodilation
Indications for Phentolamine?
Pheochromocytoma and hypertensive emergency (only hospital use)
Precipitous fall in blood pressure causes what response?
Baroreceptors initiate sympathetic stimulation of the heart and subsequent tachycardia
Are alpha antagonists very common in the treatment of HTN?
No, they are no longer used much due to better drugs
Main locations of beta receptors?
the heart (B1), skeletal muscle vasculature (B2), bronchial smooth muscle (B2), and juxtaglomerular apparatus in the kidney (B1)
Stimulation of beta-2 in vasculature of muscles causes?
inhibitory action, prevents calcium entry into vascular smooth muscle–> relaxation/increased perfusion of skeletal muscle (vasodilation)
Stimulation of beta-1 causes?
acceleration of heart rate and increase in contractile force
subtype of beta receptors in juxtaglomerular cells?
Beta-1
stimulation of beta-1 receptors in the kidney causes?
release of renin, which eventually makes angiotensin II and induce potent vasoconstriction
What is sympathomimetic activity?
the drug agent functions as a weak partial agonist that will provide some cardio-stimulation (but prevent excessive stimulation via endogenous NE/E)
What types of patients would sympathomimetic drugs be useful?
the elderly, stroke patients, and others very susceptible to bradycardia caused by beta-blockers
Most common CNS adverse effect seen in highly lipophilic beta antagonists?
Bad dreams
Beta antagonists with names “A-M”
beta-1 selective
Beta antagonists with names “N-T”
non-selective
Beta antagonists ending in “ILOL” and “ALOL”
possess extended actions in preventing alpha-mediated reflex vasoconstriction (act as alpha 1 antagonists)
Beta antagonist that also blocks calcium channels?
Carvedilol, Betaxolol
Mechanism of beta-blocker antihypertensive effect?
Inhibit stimulation of renin production by catecholamines. Inhibition of presynaptic B-adrenoceptors that reduces sympathetic vasoconstrictor activity
How must beta blockers be discontinued? Why?
They must be tapered off the medication. Chronic therapy causes up-regulation of the beta receptors that can cause rebound HTN if the medication is abruptly d/c
Effects of Propranolol overdose?
Seizures and coma (highly lipophilic)
Effects of Sotalol overdose?
prolongs the QT interval and can cause ventricular fibrillation and Torsade de Pointes
Rescue drug therapy used in beta antagonist overdose?
Glucagon or high-dose Insulin/Glucose (cannot use Beta agonists, receptors are blocked)
Non-specific beta blockers are contraindicated in?
patients with asthma (advised against in those with COPD)
Beta receptor with important role in tx of bronchospasm?
Beta-2
Beta blockers used cautiously in these patients?
Diabetics, B-1 antagonism masks hypoglycemic induced tachycardia–> patients unaware of low Blood sugar
Also patients on the borderline of decompensating CHF
Effects of Beta-2 antagonism on glucose metabolism?
inhibits hepatic glycogenolysis and pancreatic glucagon release
Beta blocker effect on Lipid profile?
can increase TAGs and decrease HDL; little/no effect on total cholesterol or LDL
