Ca Channel Antagonists HTN

Question 1

Ca is key is what processes?

Answer 1

Contractility of skeletal, cardiac and SM

Release of neurotransmitters from vesicles by exocytosis

Question 2

In resting conditions intracellular calcium is? Extracellular?

Answer 2

Low

High

Question 3

These calcium levels are achieved by?

Answer 3

Active efflux pumps

Active reuptake of calcium into sarcoplasmic reticulum

Question 4

Voltage-gated Ca channels

Answer 4

Open in response to depolarization of cell membrane

Question 5

Three types of Voltage-gated Ca channels

Answer 5

L type
T type (transient, tiny)
N type (neuronal)

Question 6

L type

Answer 6

Long lasting large channels
Cardiac, SM, SA and AV nodal cells
-Located on the plasma membrane

Question 7

Agonists-mediated Ca release

Answer 7

results from activation of IP3 by an agonist to release intracellular Ca from storage sites (SR)

Question 8

Receptor-operated Ca channels

Answer 8

Receptor forms a channel and the channel opens when the receptor is occupied by a ligand
- NMDA receptor

Question 9

What initiates a contraction?

Answer 9

Entry of calcium into the smooth muscle cell or myocardial cells

Question 10

So calcium enters the SM cell, now what?

Answer 10

Ca complexes with calmodulin to activate MLCK

MLCK phosphorylates myosin causing an interaction between myosin and actin

Question 11

Myosin and actin are?

Answer 11

The main cells involved in contraction of a cell

Question 12

What is different between cardiac and SM cells?

Answer 12

SA and AV do not contract, they generate impulses that spread throughout the heart
Calcium helps generate the impulses

Question 13

Calcium Channel Blockers Dihydropyridines

Answer 13

• End in dipine

Question 14

Calcium Channel Blockers Non- Dihydropyridines

Answer 14

Diltiazem

Verapamil

Question 15

CCB MOA

Answer 15

Inhibit L type calcium channels leading to decreased peripheral resistance and reduced BP

Question 16

Resting State

Answer 16

Closed by ready to open

Waiting for potential change in the membrane

Question 17

Open State

Answer 17

Open channel and calcium is entering the cell

Question 18

Inactivated (Closed) state

Answer 18

Closed and not ready to open
Even if there is a change in potential, the channel will not open
Channel is trying to recover

Question 19

Dihydropyridines MOA

Answer 19

Prefer the closed channel – they bind and stabilize it so the recovery process takes much longer

Question 20

Where are the most closed channels?

Answer 20

Vasculature- Arterial muscle cells

Question 21

Non-dihydropyridines MOA

Answer 21

Prefer the open channels – bind and force them to close with a slow recovery period

Question 22

Where are the most open channels?

Answer 22

Myocardium

Work mainly on SA and AV

Question 23

CCB Cardiovascular effect

Answer 23

Inhibit L type channels and reduce contraction of SM cells → vasodilation , contraction of cardiac myocites (inotropic effect), and pacemaker rate in SA and conduction velocity in AV node (chronotropic effect)

Question 24

What exactly occurs in the vasodilatory effect?

Answer 24

Decrease peripheral resistance and vascular resistance

Increased blood flow

Question 25

Non-dihydropyridine decrease?

Answer 25

Vessel tone Heart rate AV conduction

Question 26

Non-dihydropyridine increase?

Answer 26

Blood flow | Peripheral vasodilation

Question 27

Dihydropyridine decrease?

Answer 27

Vessel tone

Question 28

Dihydropyridine increase?

Answer 28

Blood flow Peripheral vasodilation Heart rate heart contractility

Question 29

CCB uses?

Answer 29

HTN Angina pectoris Superventricular arrhthmia Migraine

Question 30

Verapamil and Diltiazem Adverse Effects

Answer 30

Major: Cardiodepression Mod: HYPOtension, AV node blockade, peripheral edema, liver enzyme elevation Minor: headaches, facial flushing dizziness, constipation

Question 31

DHP Amlodipine Adverse Effects

Answer 31

Edema, dizziness, flushing, gingivial hyperplasia, CV, CNS, GI CYP3A4 inhibitors: HYPOtension, kidney failure - Long term = increased risk of breast cancer

Question 32

Alpha 1 Adrenergic Receptor Blocker

Answer 32

End in -zosin Doxazosin (Cardura) Terazosin (Hytrin) Prazosin (Minipress)

Question 33

Alpha 1 Adrenergic Receptor Blocker MOA

Answer 33

Blocks in arteries and veins | Probable blockage of adrenoreceptors

Question 34

Alpha 1 Adrenergic Receptor Blocker Effects

Answer 34

Decreased peripheral resistance Decrease cardiac preload (venous return) Supress sympathetic outflow in CNS Decrease LDL, TG and increased HDL

Question 35

Alpha 1 Adrenergic Receptor Blocker Adverse Effects

Answer 35

First dose effect -- postural/orthostatic HYPOtension

Question 36

Define First dose effect -- postural/orthostatic HYPOtension

Answer 36

When you change positions, you experience a drop in BP which makes you feel dizzy, unconscious, and not get enough blood to the brain so you might faint

Question 37

How does the body prevent all the blood going to your legs when you stand up?

Answer 37

Vasoconstriction

Question 38

Central Alpha 2 Adrenergic Receptors Agonists

Answer 38

Clinidine (Catapres) Guanfacine (Tenex) Guanebenz (Wytensin) Methyldopa (Aldomet)

Question 39

Central Alpha 2 Adrenergic Receptors Agonists MOA

Answer 39

Activation of central alpha2 receptors (CV control centers) --> suppression of sympathetic outflow from the brain Possible stimulation of presynaptic alpha 2 receptors and decrease NE release

Question 40

Clonidine/Guanfacine Caution

Answer 40

50% excreted unchange in the urine so watch in renal insuf.

Question 41

Clonidine Effects

Answer 41

Decrease BP Decrease HR Decrease intraocular pressure

Question 42

Clonidine Adverse Effects

Answer 42

Sedation and dry mounth Sexual dysfunction (hyperprolactinemia) Bradycardia Withdrawal rxns

Question 43

Methyldopa

Answer 43

PRO-DRUG | Delayed peak effects for 6-8 hours --> duration = 24 hours

Question 44

Methyldopa adverse effects

Answer 44

``` Sedation and dry mounth Sexual dysfunction (hyperprolactinemia) Bradycardia Withdrawal rxns Hepatoxicity Hemolytic anemia ```

Question 45

Methyldopa is beneficial in?

Answer 45

Pre-eclampsia

Question 46

Reserpine Sympatholytic Drug

Answer 46

Interferes with function of SNS Normally there is recycling of NE and Epi VMAT2 picks up NE/Epi and takes it back to be reused Reserpine BLOCKS VMAT2 via irreversible binding

Question 47

Reserpine Adverse Effects

Answer 47

Increase sodium and water retention Sedation and inability to concentrate Depression and suicidal thoughts (depletion of Epi)

Question 48

Reserpine Effects

Answer 48

Lowers BP via cardiac output and peripheral resistance

Question 49

Direct vasodilator

Answer 49

Hydralazine (Apresoline) | Minoxidil (Loniten)

Question 50

Hydralazine Effects

Answer 50

Decrease in peripheral resistance | Minimal effect on veins (no postural hypotension)

Question 51

Hydralazine Adverse Effects

Answer 51

Drug-induced lupus syndrome Increased sodium and water rentention Headache, HYPOtension, tachycardia, angina pectoris

Question 52

Hydralazine Caution

Answer 52

Aggravation of myocardial ischemia --> steals blood from dying regions

Question 53

Minoxidil MOA

Answer 53

PRO-DRUG | Activates ATP dependent potassium channels in SM and causes an efflux of K from cells leading to relaxation of the SM

Question 54

Minoxidil Effects

Answer 54

Dilation of arterioles and decreased peripheral resistance

Question 55

Minoxidil Adverse Effects

Answer 55

Increased retention of sodium and water Tachycardia, angina pectoris, myocardial ischemia Hypertrichosis (stim hair growth)