Hypotensive Meds

Norepinephrine receptors are G-protein linked and divided into a1, a2, b1, b2
a1 - raises intracellular calcium: vasoconstriction, mydriasis, uterine contraction, sphincter contraction
a2 - presynaptic endings, inhibits adenylate cyclase: vasodilatation, sedation, less addiction?
b1 - activates adenylate cyclase: positive chronotropy, dromotropy, inotropy
b2 - epi > norepi, activates adenylate cyclase: bronchodilation, vasodilation, tocolysis

Norepinephrine's action in the synapse is terminated by
1. Reuptake by postganglionic nerve ending (inhibited by TCA)
2. Diffussion by receptor sites
3. Metabolism by MAO and COMT (inhibited by entacapone, tolcapone, nitecapone)

Phenylephrine:
Continuous infusion (100 mcg/mL at a rate of 0.25–1 mcg/kg/min). Gradual tachyphylaxis

Epinephrine:
Used for vfib (50mcg to 1mg) and anaphylaxis (100-500mcg bolus followed by infusion). Volatile anesthetics such as halothane potentitate dysrhythmic effects of epinephrine.
Continuous infusion (4 mcg/ml at rate of 2-20mcg/min)

Norepinephrine:
Bolus (0.1 mcg/kg) followed by infusion at rate of 2–20 mcg/min

Ephedrine:
Used in obstetrics because does not decrease uterine Q. Non-catecholamine so longer-lasting. Some antiemetic properties particularly 2/2 hypotension from neuroaxial injections

Dopamine
1-20 mcg/kg/min infusion

Dobutamine
2-20 mcg/kg/min infusion

Clondine and Precedex:
A2 agonists, sedative, analagesic, sympatholytic effects. Reduces anesthetic requirements. Abrupt withdrawal leads to hypertensive crisis.
dexmedetomidine loading dose 1 mcg/kg over 10 min followed by an infusion at 0.2–0.7 mcg/kg/hr
Clonidine oral (3–5 mcg/kg), intramuscular (2 mcg/kg), intravenous (1–3 mcg/kg)

b1,b2 are G-proteins that stimulates adenyl cyclase increasing cAMP, which activates protein kinase A, which increases intracellular calcium

a1 is also a G-protein that stimulates phospholipase C which also increases calcium

NO stimulates guanyl cyclase and increases cGMP

Phosphodiesterases break down cAMP and cGMP, PDE5-I such as viagra causes increase in cGMP and PDE3-I such as milrinone causes increase in cAMP. Theophylline and Aminophylline are nonselective PDE-I