11 & 12 - Adrenergic Agonists and Antagonists

Baroreflex Pathway

Decreased BP → decreases stretch

Decreasing afferent nerve activity

Medulla increases sympathetic output (to increase BP)

• Increasing symp. Nerve activity

NE is released from sympathetic post-ganglionic nerve

• B1 increased, so HR increases

• Alpha 1 increased, BP normalized

Selectivity of adrenergic agonists

Is dose dependent

• Drugs will only activate certain receptors at a low dose or others at a high does

Affinity

Equal to potency of a drug

Epinephrine reversal phenomenon

Hypertension to hypotension

• Due to alpha 1 receptors being blocked, so now B2 receptors dominate

Beta blockers with ISA

Act as partial agonists alone

Act as competitive antagonists/blockers when combined with full agonist

• Intrinsic sympathomimetic activity (ISA)

Uses of beta blockers:

• HTN

• Angina

• Arrhythmia

• Post-MI

• Chronic CHF

• Glaucoma

• Hyperthyroidism

Side effects of beta blockers:

• Bronchospasm

• Hyperlipidemia (VLDL)

• Hypoglycemia and hyperglycemia (masks symptoms of hypo-dangerous)

Contraindications of beta blockers with ISA:

• Hyperthyroidism

• Angina (MI within past 1mo)

Non-selective beta blocker contraindications:

• Asthma

• Diabetes

Beta blocker overdose treatment:

Use glucagon! Binds to Gs to activate adenylyl cyclase (increasing cAMP)

Rebound hypertension (from beta blocker withdrawal)

Made too many receptors on drug

Suddenly stopping drug causes more NE to be attached, leading to tachycardia and HTN

BPH (benign prostate hypertrophy)

Activation of alpha 1a receptors increases smooth muscle tone (bladder, prostate)

Blocking these receptors via Tamsulosin relaxes them, increasing emptying (symptomatic relief)

Side effects of alpha blockers:

Orthostatic hypertension

• Decreased venous tone → lower baroreceptor stretch → blood accumulates → less venous return → less cardiac output (CO) → lower BP→ sympathetic output increased in response

• Alpha 1 decreases BP

Favorable effect on blood glucose!

First dose effect of alpha 1 blockers Prazosin:

Postural hypotension after receiving first dose

• Give lower initial dose to avoid this

Competitive Antagonists

All M blockers and beta blockers are THIS.

With ISA, beta blockers are partial agonists acting as competitive antagonists with full agonists present.

Epinephrine

THIS reverses alpha-blockers!

Alpha Blockers

THESE have first dose effect because of vein dilation

Rebound Tachycardia and HTN

Avoid THESE by tapering off beta-blockers

MAO inhibitors

Pts on THESE should avoid red wine (cheese)

Mixed Direct & Indirect

THESE agonists deplete faster

• Example is ephedrine

Asthma

With THIS, you avoid beta blockers, the only one that is safe to use are Beta 1 blockers

Contraindications of BB+ISA

Hyperthyroidism

Angina within 1 month of MI

Beta blockers (especially B1)

THESE can mask the symptoms of hypoglycemia

The other one can prevent recovery from hypoglycemia

D1

Increases kidney perfusion and natriuresis (urine)

Dopamine and Fenoldopam

THESE increase kidney perfusion (thanks to D1 agonist activity)