Cardiovascular Stimulants (Sweatman)

Question 1

Contrast downstream receptor signaling for alpha-1/2 agonists vs. beta-1/2 agonists.

Answer 1

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Question 2

Comparatively describe drug effects on the heart and vasculature, and categorize the agonist actions as direct, indirect, or mixed function.

Answer 2

-Indirect action involves stimulated release of NE or EPI from the pre-synaptic terminal.
-Directly acting drugs mimic the action of NE or EPI on pre or post synaptic membrane.
-Mixed function is a mix of stimulated release and mimicking.
Direct actors: Selective- a1 phenylephrine, a2 clonidine, B1 dobutamine, B2 terbutaline
Non-selective- a1/2 oxymetazoline, B1/2 isoproterenol, a1/2 B1/2 EPI, a1/2 B1 NE
Mixed actors: Ephedrine (NE releasing agent & direct B2 agonist [esp. in lung])
Indirect actors: Cocaine, MOAI, COMTI, & releasing agents such as Tyramine and amphetamine

Increase heart rate and vasodilate arteries of heart.
Increase peripheral vascular SM tone (vasoconstriction)

Question 3

Explain the respective clinical utilities of the drugs.

Answer 3

Dobutamine (B1>B2,a): Stress tests, positive inotropy to counter heart failure (HF)
Dopamine (D1=D2 >B>a): unstable bradycardia, HF, shock, inotropic and chronotropic effects predominate at high doses
EPI (a1=a2=B1=B2): Anaphylaxis, cardiac arrest, Hypotension. ^ CO, HR, peripheral resis. –> ^DBP
Isoproterenol (B1=B2): Electrophysiologic evaluation of tachyarrhythmia. Can worsen ischemia.
Norepinephrine (a1>a2>B1): Hypotension, but decreased renal perfusion
Phenylephrine (a1>a2): Hypotension (vasoConstrictor)
Ephedrine (a1>a2>B1): Hypotension of anesthesia, narcolepsy, nasal congestion, asthma, bronchospasm (B2 agonist)

Question 4

What is Reserpine?

Answer 4

Pretreatment with Reserpine depletes NE from sympathetic neurons. Can be used to abort the effects of indirect actors and mitigate the effects of mixed actors but have NO INFLUENCE on direct actors because DAs do not require NE or EPI.

Question 5

Describe the ADEs of EPI.

Answer 5

Premature ventricular contractions, ventricular extrasystoles, tachycardia, or even fibrillation may be precipitated in (drug) sensitized heart

Question 6

Describe EPIs effects on the vasculature.

Answer 6

Decreased cutaneous BF
Increased B2 mediated skeletal muscle BF
Increased renal vascular resistance, decr. renal BF –> incr. renin secretion bc kidney thinks BP is low
Incr. pulm pressures. Edema when [EPI] high
Incr. coronary BF, ^ diastole duration, ^ aortic pressure

Question 7

Describe the indications, effects and ADEs of NE.

Answer 7

Indications: vasoconstrictor to raise or support BP under intensive care conditions
Effects: Decreased CO compared to EPI’s incr. CO.
Incr. peripheral resis.
Incr stroke volume.
Incr. coronary BF
ADEs: similar to EPI but increased BP more prominent, monitor BP carefully!
Necrosis at IV site

Question 8

Describe the dose-dependent effects of dopamine.

Answer 8

Low dose: predominantly D1 action (renal vasodilation)
Moderate dose: D1 + Beta-1. ^ CO and D1-induced vasodilation. Also causes release of NE from nerve terminals, causing effects on heart.
High dose: a-agonism predominates. ^ peripheral vascular resistance & renal vasoconstriction