Drug List

Peripherally Acting Sympathetic Neuronal Blockers

Decrease availability of sympathetic transmitter, NE, to its receptors 

RESERPINE

Drug List

Centrally Acting Sympathetic Neuronal Blockers

Stimulate a2 receptor sites in brain and indirectly reduce sympathetic neuronal traffic from central sympathetic vasomotor centers to peripheral CV organs

METHYLDOPA, CLONIDINE, GUANFACINE

-Peripheral

-Dec uptake of intraneuronal DA and NE into storage vesicles, deplete stored level of NE, reduce amount released

- reduced BP by dec cardiac output and peripheral arterial resistance

-treats hypertension 

-sedation and mental depression (CNS)

-postural HYPOtension, bradycardia, fluid retention, diarrhea (excess GI motility), ulcers

Unknown

Although cleared from circulation fast, its depleting action on NE vesicles is IRREVERSIBLE and LONG LASING beyond termination of drug

Centrally Acting Adrenergic Neuronal Inhibitors

General

-a2 rec agonists, act on CNS sites

-dec sympathetic neuronal outflow from CNS to peripheral organs (heart, vessels, kidney)

- less side effects bc dont signif interfere w/normal, reflex changes in symp, so fewer orthostatic hypotensive symptoms, no help for Raynaud's 

-Methyldopa has unique autoimmune effects

Alpha-methyldopa or just plain Methyldopa

Actions/Uses

PRODRUG (must be converted to be active)

-a2 adrenergic agonist in central vasomotor centers, dampening outflow of sympathetic nerve activity to peripheral tissues (heart, kidney, arterial vessels)

-renin release dec, HR and cardiac output may dec, **arterial periph resis dec**

-converted to alphamethyldopaNOREPI

-use during pregnancy hypertension

Alpha-methyldopa or just plain Methyldopa

Side Effects

-Peripheral fluid retention, centrally-mediated DRY MOUTH and SEDATION

-Methyldopa, unique autoimmune disorders not seen with other a2 drugs

1. Positive Coombs test in patients eventho actual hemolytic anemia is rare and reversed if stop drug

2. Abnormal liver function tests appear in first few weeks of taking drug, severe hepatic necrosis in small number

Clonidine

Main Uses/Side Effect

-very small dose required, can be absorbed thru skin (patch) for hypertension

-patch: smoother bp control with less severe side effects, might have some dermatitis

- when stopped too abruptly --> rebound hypertension (not so with methyldopa)

Clonidine

Additional Effects besides Hypertension

1. treat migraine, ADHD, menopausal hot flashes, PTSD

2. nicotine, alcohol, morphine withdrawal

3. analgesic effects if direct injection into spinal cord

(Still involve central a2 agonist actions?)

Similar to Clonidine for hypertension treatment

but less sedation and less rebound syndrome

recently being used for *ADHD* (Intuniv)