Exam 1: Lecture 7: Antihypertensive drugs III

Question 1

Gq pathway

Answer 1

Activates phospholipase B, which metabolizes PIP2 to DAG to and IP3.

DAG activates PKC
IP3 activates receptors on ER

Question 2

Gi/o pathway

Answer 2

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

Question 3

Clonidine

Answer 3

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

Question 4

Clonidine side effects

Answer 4

dry mouth, sedation, bradycardia, hypotension

Hypotension related effects: headache, fatigue, dizziness

Question 5

Clonidine FDA approved for

Answer 5

ADHD

Question 6

Prazosin

Answer 6

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

Question 7

“First dose response” agent

Answer 7

1s dose has worse side effects than following doses

Question 8

Chronotropy

Answer 8

change in heart rate

Question 9

negative chronotropes

Answer 9

metoprolol, acetylcholine, verapamil

Question 10

positive chronotropes

Answer 10

isoproterenol, atropine, dopamine

Question 11

inotropy

Answer 11

change in the force of muscle contraction

Question 12

negative cardiac inotropes

Answer 12

B-blcokers, verapamil, Class 1A and Class 1C antiarrhythmics

Question 13

positive inotropes

Answer 13

isoproterenol, phosphodiesterase inhibitors, ATII, digoxin

Question 14

Dromotropy

Answer 14

change in electrical conduction speed of the heart

Dromotropic agents are typically both inotropic and chronotropic

Question 15

Negative Dromotropes

Answer 15

metoprolol, acetylcholine, verapamil

Question 16

Positive Dromotropes

Answer 16

isoproterenol, atropine, dopamine

Question 17

Lusitropy

Answer 17

change in the rate of myocardial relaxation

Question 18

Negative cardiac Lusitropes

Answer 18

any agent or pathway that causes increased intracellular calcium conc.

Question 19

positive lusitropes

Answer 19

isoproterenol and other catecholamines

Question 20

Bathmotropy

Answer 20

change in excitability of the heart

Question 21

Negative bathmotropic agents or events….

Answer 21

decrease the sensitivity of the heart muscle to electrical stimualton

ex. propranolol, Ca Channel blockers, Na channel blockers, hyponatremia, hypokalemia, acetylcholine and chronic hypoxia

Question 22

Positive bathmotropic agents or events…

Answer 22

increase the sensitivity of the heart muscle to electrical stimulation

Ex. catecholamines, digitalis, hyperkalemia, acute hypoxia

Question 23

Types of B-blockers

Answer 23

Nonselective agents: B1 and B2 antagonism
B1-selective
B2-selective
B3-selective
B1-antagonist, B3-agonist

Question 24

Propranolol

Answer 24

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

Question 25

Metoprolol

Answer 25

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

Question 26

Labetalol

Answer 26

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

Question 27

Esmolol

Answer 27

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

Question 28

Calcium channel blockers sites of action

Answer 28

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

Question 29

Nicardipine

Answer 29

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

Question 30

Amlodipine

Answer 30

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

Question 31

Clevidipine

Answer 31

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

Question 32

Verapamil

Answer 32

** 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