Sympatholytic agents

Question 1

Drugs that interfere with NE release or deplete NE

Answer 1

** Reserpine
Guanethidine
Guanadrel
Bretylium

Question 2

Centrally acting a2-adrenergic agonists

Answer 2

** Clonidine
** Methyldopa
Guanfacine

Question 3

Guanethidine

Answer 3

Mechanism:
- Uptake I
- Displacement & release of NE
- Blocks NE release
Highly charged, does not enter CNS
Use: essential hypertension uncontrolled by other agents
Orthostatic hypotension and other side effects limit usefulness

Question 4

Guanadrel

Answer 4

like quanethidine

more rapid onset, shorter duration, less side effects

Question 5

Bretylium

Answer 5

Antiarrhythmic
mechanism - blocks NE release
prolongs ventricular action potential and refractory period
prophylaxis & treatment of V-fib, 2nd line agent

Question 6

Reserpine

Answer 6

Depletes NE by blocking vesicular transporter
- decreases C.O.- antihypertensive (last choice)

Think “reserve NE,” keeping it from being transported

Question 7

Centrally Acting Hypotensive Agents act where?

Answer 7

Brain stem a2-receptors

• Control (inhibit) sympathetic outflow to periphery
• Decrease sympathetic tone

Clonidine, methyldopa e.g.

Question 8

Clonidine

Answer 8

An a2-adrenergic receptor agonist

• IV- increase BP (peripheral a2) followed by decreased BP (central a2)
• Oral - decreased BP (decreased C.O., preload)
• Patch - same as oral

Clinical Use

• Essential hypertension (very little use now)
• adjunct for narcotic withdrawal
• other off-label uses

Side Effects

• dry mouth, sedation, impotence
• ** sudden withdrawal causes hypertensive crisis

Question 9

Methyldopa

Answer 9

False neurotransmitter concept
Converted to methyl-NE
stored in vesicles instead of NE
released & acts as a centrally acting a2-agonist
compare with clonidine

*** Considered a drug of choice for treating hypertension in pregnant females

What? Hyper pregnant women on meth and dope?
(just a memory device)

Question 10

Guanabenz and Guanfacine

Answer 10

Guanabenz and Guanfacine
Central a2-adrenergic receptor agonists

like clonidine but less used
Also used to treat tics or Tourette’s syndrome
Sometimes used for behavioral symptoms, such as impulse control disorders.