Direct Acting Sympathomimetics (Synthetic Compounds)

Question 1

ISOPROTERENOL-non-selective beta-adrenergic agonist

Answer 1

-potent beta-receptor agonist, NO appreciable affinity for alpha receptors
CV:
-B2R activation promotes peripheral vasoDILATION (decreased diastolic bp)
-B1R=positive inotropy and chronotropy (increased systolic bp)

Bronchioles:
-B2R bronchoDILATION

Toxicity: Tachyarrythmias

Therapeutic uses: Cardiac stimulation during bradycardia or heart block when peripheral resistance in high

Contraindications: angina, particularly with arrhythmias

Question 2

DOBUTAMINE-selective beta ONE-adrenergic receptor agonist

Answer 2

-catecholamine rapidly degraded by COMT
CV effects:
-increased CO
-positive inotropic effect>positive chronotropic effect due to lack of beta TWO mediated vasoDILATION and reflex tachycardia
-HIGH DOSES: beta TWO agonist activity may cause hypOtension with reflex tachycardia

Toxicity: arrythmias, hypOtension (B2R), hypErtension (inotropic and chronotropic effects)

Therapeutic Use: short-term tx of cardiac insufficiency in CHF, cardiogenic shock or excess beta-blockade

Question 3

Selective beta TWO adrenergic agonists: TERBUTALINE & ALBUTEROL

Answer 3

CV effects:
-negligible in most pt b/c lack of B1 activity, but can cause SOME B1 agonist-like response

Bronchioles: Bronchodilation

(Pregnant Uterus: relaxation)

Toxicity: Tachycardia, tolerance, skeletal muscle tremor, activation of B2R expressed on pre-synaptic nerve terminals of cholinergic somatomotor neurons (increase NT release). (can lead to muscle tremor)

Therapeutic Use: bronchospasm, chronic treatment of obstructive airway disease

Question 4

Selective alpha ONE-adrenergic agonist: PHENYLEPHRINE

Answer 4

CV effects: peripheral vasoCONSTRICTION and INCREASED bp, ACTIVATES baroreceptor reflex, thereby DECREASES HR

Ophthalmic Effects: Dilate pupil

Bronchioles: DECREASE bronchial (and upper airway) secretions

Toxicity: HypErtension

Therapeutic Use: hypOtension during anesthesia or shock, paroxysmal supraventricular tachycardia, mydriatic agent, nasal decongestant

NOTE: Phenylephrine is not a catecholamine, so IS NOT SUBJECT TO RAID DEGRADATION by COMT. Therefore, has MUCH LONGER DURATION of ACTION than endogenous catecholamines

(Contraindications: Hypertension)

Question 5

Selective alpha TWO-adrenergic agonists: CLONIDINE

Answer 5

CV effects:
-peripherally, causes mild vasoCONSTRICTION (and slight bp increase)
-crosses BBB to cause reduced sympathetic outflow–>reduces vasoCONSTRICTION and bp
{-LOSS of sympathetic activity PREDOMINATES over the direct vasoCONSTRICTOR effects of the drug=overall REDUCTION in blood pressure}
-reduction of tonic excitatory input to the sympathetic cells reduces sympathetic output to vascular smooth muscle

Toxicity: dry mouth, (sedation, bradycardia), withdrawal after chronic use can result in life-threatening hypertensive crisis (increases sympathetic activity)

Therapeutic Use: HypErtension (when cause is due to excess sympathetic drive)