Exam 1: Lecture 7: Antihypertensive drugs III Flashcards
Gq pathway
Activates phospholipase B, which metabolizes PIP2 to DAG to and IP3.
DAG activates PKC
IP3 activates receptors on ER
Gi/o pathway
Gai inhibits Adenylate cyclase, decreasing cAMP
GBg activates GIRK channels, increasing K+ and decreases excitability
Gbg inhibits the activity of specific Nav channels, decreasing Ca2+ flux and decreasing excitability
Clonidine
sympatholytic drugs
agonist at presynaptic a2-adrenoceptors in the vasomotor cortex
a2 receptors coupled to Gai, so activation is sympatholytic and suppresses the release of NE = suppress renin release and decrease PVR, some CO
Clonidine side effects
dry mouth, sedation, bradycardia, hypotension
Hypotension related effects: headache, fatigue, dizziness
Clonidine FDA approved for
ADHD
Prazosin
Inverse agonist at a1-adrenoceptors in vascular smooth muscle
decreases Gaq mediated signaling (opposes vasoconstrictive effect of NE)
*a1-receptors also found on immune cells, investigated for COVID-19 treatment
“First dose response” agent
1s dose has worse side effects than following doses
Chronotropy
change in heart rate
negative chronotropes
metoprolol, acetylcholine, verapamil
positive chronotropes
isoproterenol, atropine, dopamine
inotropy
change in the force of muscle contraction
negative cardiac inotropes
B-blcokers, verapamil, Class 1A and Class 1C antiarrhythmics
positive inotropes
isoproterenol, phosphodiesterase inhibitors, ATII, digoxin
Dromotropy
change in electrical conduction speed of the heart
Dromotropic agents are typically both inotropic and chronotropic
Negative Dromotropes
metoprolol, acetylcholine, verapamil
Positive Dromotropes
isoproterenol, atropine, dopamine
Lusitropy
change in the rate of myocardial relaxation
Negative cardiac Lusitropes
any agent or pathway that causes increased intracellular calcium conc.
positive lusitropes
isoproterenol and other catecholamines
Bathmotropy
change in excitability of the heart
Negative bathmotropic agents or events….
decrease the sensitivity of the heart muscle to electrical stimualton
ex. propranolol, Ca Channel blockers, Na channel blockers, hyponatremia, hypokalemia, acetylcholine and chronic hypoxia
Positive bathmotropic agents or events…
increase the sensitivity of the heart muscle to electrical stimulation
Ex. catecholamines, digitalis, hyperkalemia, acute hypoxia
Types of B-blockers
Nonselective agents: B1 and B2 antagonism B1-selective B2-selective B3-selective B1-antagonist, B3-agonist
Propranolol
Antagonist at B1 and B2, B-blocker
Lipophilic, actions in CNS at adrenoceptors, 5-HT1A,2B receptors
Indications: hypertension, arythmie, anxiety disorder, PTSD, migraine
Side effects: Class C in perg, dizziness, Headache, Dyspepsia, Hypotension
Metoprolol
B1-selective agent, B blocker
Indicated for hypertension, angina, tachycardias, heart failure and migraine
one of top 10 most prescribed drugs
Side effects: Dizziness, Fatigue, Sleep disruption, depression, bradycardia
Labetalol
Antagonist at B1 + a1 adrenoceptors, partial agonist at B2 in vascular smooth muscle
Indicated: hypertension, hypertensive crisis, pre-eclampsia (high bp pregnancy)
Atypical B-blocker, decreases PVR w/ little effect on HR or SV……increase SV, decrease HR during exercise
Side effects: dizziness, Headache, Dyspepsia, Orthostatic hypotension
Esmolol
Breviblock infusion = short acting
Selective antagonist at B1 adrenoceptors
indicated for rapid treatment of arrhythmia, used for management of surgical arrhythmia
** Rapidly metabolized by esterase’s **
Class II anti arrhythmic agent
Calcium channel blockers sites of action
Actions depends on location…
Decrease HR: Cav channels in SA node, AV node, purkinje conduction fibers, cardiomyocytes
Decrease PVR: decrease Ca influx into vascular smooth muscle = vasodilation
Nicardipine
Dihydropyridine, caredne
Indications: Hypertension, angina, and Raynaud’s disease
More selective for coronary blood vessels
Long half-life
Side effects: Dizziness, Headache, Hypotension, Fatigue, Edema
Amlodipine
dihydropyridine, norvasc
5th most common RX in US
Indications: hypertension, angina, and coronary heart disease
acts at cardiac and vascular calcium channels
very long half life
Side effects: dizziness, headache, hypotension, fatigue,edema
Clevidipine
Dihydropyridine, Clevirex
IV infusion, titrated very well..for titratable control of BP
Specific for vascular calcium channels, no direct effect on HR or conduction
** rapidly metabolized by esterase’s **
Side effects: Hypotension, Reflex change HR, headache, Nausea
Verapamil
** Non-dihydropyridine ** Isoptin
Tablet or IV
Broad spectrum Ca channel blocker, off target block of Kv channels…but not that good at off target effects
Indications: ventricular arrhythmia, hypertension w/ afibl cluster headache
Side effects: hypotension, Reflex chain HR, Headache, Nausea
