L14

Question 1

What is the sympatholytic drug class?

Answer 1

Inhibits post-gang sympa nerve

Sympa - lytic (cut)

Question 2

Which sympatholytic drug works be depleteing NE in storage vesicles?

Answer 2

Reserpine = adrenergic neuron blocker/depleter

Question 3

What are the 2 central A2 agonist drugs?

Answer 3

Methyldopa
Clonidine
= X sympa outflow from CNS

Question 4

Which drug inhibits NE synthesis to stop sympathetic activity?

Answer 4

Metyrosine

Question 5

Reserpine mechanism

Answer 5

x VMAT2

Blocks dopamine into the vesicle - no NE synthesis

Question 6

Is reserpine hydrophilic or phobic?

Answer 6

Philic = lipid soluble

Crosses BBB, placenta

Question 7

What is the recovery time when you withdraw reserpine?

Answer 7

Slow - weeks

B/c depletion of NE was gradual, the recovery and re-synthesis will be slow

Question 8

What are drug interactions with reserpine?

Answer 8

X NE releasers
- Duh, nothing there to release
↑sen to pharm NE or norad receptor agonists
- Receptors have been hypersensitized while NE has been low

Question 9

What is the difference between low and high dose reserpine?

Answer 9

Low = PNS sympatholytic 
High = CNS action = sedative

Question 10

What is the clinical use of reserpine?

Answer 10

Anti-HTN

Question 11

Reserpine adverse effects

Answer 11

Associated with high dose (CNS)

• ↑depression
• ↓ seizure threshold
• Potential CNS depressors (alcohol)

Question 12

Mechanism of clonidine

Answer 12

Directly acts to increase A2 receptors in brainstem

Question 13

Mechanism of methyldopa

Answer 13

Methyldopa –> MeDopamine –> MeNE

Conversion @ brainstem where MeNE will work

Question 14

Net effect of A2

Answer 14

↓sympa outflow to CV

Won’t get the ability to increase HR, CO, contractility etc

Question 15

Do baroreceptor reflexces change with central A2 agonists?

Answer 15

NO

Question 16

Use of methyldopa

Answer 16

HTN during preg

Question 17

Dosing methyldopa

Answer 17

In general need higher doses because competes with other AAs for transport into the brain

Question 18

Clonidine dosing, excretion & clinical use

Answer 18

Short t1/2 - given long acting formulations 
Renal excretion 
NOT for anti-HTN
Use
- Opiate withdraw
- Anesthetic to induce drowsiness
- GH release

Question 19

Central A2 agonist shared adverse SE

Answer 19

Drowsiness
Dry mouth
Withdraw excess sympa outflow

Question 20

Metyrosine mechanism

Answer 20

Block tyrosine hydroxylase (tyrosine –> DOPA)

Rate lim step

Question 21

Use metyrosine

Answer 21

CA secreting tumor management

Question 22

2 types of Ca channel blockers - include specific drugs for each

Answer 22

Dihydropyridines
Non-dihydro
- Verapamil
- Diltiazem

Question 23

Ca2+ blocker effects

Answer 23

ALL = ARTERIAL vasodilation - ↓afterload
- Includes coronary artery dilation
No changes to Na/H2O
Cardiodepressant = non-dihydros

Question 24

What tissues do Ca2+ channel blockers work in? What is the specific receptor

Answer 24

Voltage sens L type Ca channel
Tissues effects are isotype dependent 
1.2 = cardiac, smooth muscle
1.3 = SA node, cochlea
Both neuronal

Question 25

3 non-cardiac uses of CCBs

Answer 25

1. Relax uterus pre-term 2. Manage vertigo 3. Neuroprotective @ CNS to limit stroke damage

Question 26

Regulate L type Ca channels

Answer 26

1. Membrane potential - Feedback via Ca sensitive K channels to repolarize the membrane and limit Ca entry 2. Neurohormones - NE activates B receptors in heart for slow inward Ca current

Question 27

Where do DHP vs non-DHP bind the receptor to effect action

Answer 27

non-DHP - open, cardiac actions - freq dep | DHP - inactivated, vascular actions - voltage dep

Question 28

Explain the cardiac effects of non-DHP CCBs - be specific

Answer 28

SA node: ↓HR via ↓automaticity AV node: ↓conduction velocity ↓muscle contractility

Question 29

Adverse SE DHPs

Answer 29

Hypotension, flushing, headache Reflex sympa activation - give long acting forms or w/ BBs Swollen ankles due to changes in cap perm to H2O

Question 30

Adverse SE for non-DHPs

Answer 30

LV dysfxn AV block This why never use w/ BB - same adverse events GI constipation

Question 31

How are CCBs inactivated

Answer 31

``` P450 enzymes in liver If give with other drugs metabolized this way and overwhelm the enzymes, see ↑↑ plasma CCB levels Symptoms: - DHPs = hypotension - nonDHPs = bradycardia ```