α&β Adrenergic Receptor Agonists & Antagonists

Dr. Rose

Direct-Acting Mixed-Acting α & β Agonists

• MOA

• Clinical Use

• Adverse effects

• Norepinephrine (Levophed)

  • Equal affinity for α1 & α2 but β1>>>β2

  • ↑HR↑Na+ &fluid retention, ↑Peripheral vasoconstriction

  • Used in IV to treat SHOCK

  • Adverse effects are hypertension, reflex bradycardia, cardiac arrhythmias

• Droxidopa (Northera)

  • NE oral pro-drug converted to NE outside CNS by DOPA

  • Used for symptomatic neurogenic orthostatic hypotension in those with primary autonomic failure or dopamine β-hydroxylase deficiency

  • Adverse effects include headache and hypertension

• Epinephrine (Adrenalin)

  • Equal affinity for α1=α2 and β1=β2; more potent for β2 than NE

    • Low doses vasodilate and high doses vasoconstrict peripherally and divert blood to

  • ↑HR↑Na+&fluid retention

  • @β2 Bronchodilation, glycogenolysis and gluconeogenesis

  • Clinical use: stop bleeding, increase potency of lidocaine in dental treatments, asthma, CPR, anaphylactic shock

• Ephedrine - “mini epi”

  • Similar to Epinephrine but partial agonist, so not as strong

  • Only use is for induced hypotension during anesthesia

  • Adverse effects include insomnia, hypertension, palpitations and ventricular tachyarrhythmias

• Dopamine (D) Hydrochloride (Intropin)

  • D1>>β>>α

  • Low doses ↑RBF, vasodilates

  • Medium doses ↑CO

  • High doses ↑BP

  • Adverse effects include cardiac arrythmias, local extravasation causes necrosis

Indirect-Acting Sympathomimetics (α&β Agonists)

• Drugs

  • MOA

• Adverse effects (all the same)

• Amphetamine: increase NE release by displacing it from storage or via reverse transport NET

• Tyramine-containing foods like wine and cheese also displace NE, primarily dangerous when on MAO inhibitor drugs (antidepressants)

• Tricyclic antidepressants (TCA’s), SNRI’s and Cocaine: block NET transporter and increase NE in synapse

• Adverse effects are ↑BP and HR

• Reserpine: depletes NE and makes indirect-acting sympathomimetics lose effect

Selective α1 Agonists

• Phenylephrine (Neosynephrine) PROTOTYPE

  • ↑Ca+, Vasoconstriction, ↑BP

  • Used for hypotension and shock, mydriasis, nasal decongestant

• Midodrine (Pro-Amatine)

  • Same MOA, oral only, pro-drug

  • Used for symptomatic orthostatic hypotension and maintaining BP during hemodialysis

• Adverse effects: hypertension, rebound congestion, reflex bradycardia, urinary retention, goosebumps

Selective α2 Agonists

• Clonidine (Catapres)

  • Stimulates α2 receptor in the brain (NO BARORECEPTORS), in high doses also acts on α1

  • Used for severe hypertension, ADHD and epidural, opioid withdrawal

• Guanfacine (Tenex, Intuniv)

  • Same as clonidine

  • Hypertension and ADHD

• Tizanidine (Zanaflex)

  • Related to clonidine, central acting on SK, no CV effect

  • Used as a muscle relaxant

  • Drug interaction with ciprofloxacin

• α-Methyldopa (Aldomet)

  • Same as Clonidine but is a pro-drug

  • Antihypertensive, crosses placental barrier

• Dexmedetomidine (Precedex/Igalmi)

  • Related to clonidine as well, used as sedative for ICU patents, schizophrenic and bipolar

• Apraclonidine (Iopidine)

  • Clonidine derivative, ↓cAMP and increases production of aqueous humor; does not cross BBB

  • ↓IOP for glaucoma

• Brimonidine (Alphagan)

  • Same MOA and clinical use as Apraclonidine but may cross BBB

  • NOT USED AS GEL bc it can cause orthostatic hypotension

• Adverse effects: severe hypotension, xerostomia, sedation; for eye ones blurred vision

Selective α1 Blockers/Antagonists

The “-SINS”

• Prazosin (Minipress) & Terazosin (Hytrin): block α1a,α1b,α1c

  • ↓vasoconstriction & BP

  • Treat hypertension

• Doxazosin (Cardura): for BPH and hypertension comorbidity

• Tamsulosin (Flomax): selective α1a blocker specifically for BPH and causes less orthostatic hypotension

Non-Selective α1 & α2 Blockers/Antagonists

• Phentolamine (Oraverse)

  • Competitive antagonist

  • Used as local injection to prevent necrosis due to α agonist extravasation; used to reverse EPI when it is used with lidocaine for oral anesthesia, vasodilation

  • Contraindication for angina, worsens tachycardia

  • If combined with epi, it can decrease BP even more

• Phenoxybenzamine

  • Irreversible Non-competitive antagonist

  • Used for hypertension and localized sweating in pheochromocytoma

  • Contraindications: history of ischemic heart disease

Selective α2 Blockers/Antagonists

• Yohimbe (Yohimbine)

  • Increases NE release

  • No longer used, causes nervousness, tremors, hypertension, pancreatic insulin release

Direct Acting β1 Agonists

• Dobutamine (Dobutrex)

  • Used for cardiogenic shock and acute heart failure

  • Adverse effects include tachycardia, be careful with angina (coronary heart disease) patients

  • Selectivity lost at high doses; starts to hit the other receptors as well

Direct Acting β1&β2 Agonists

• Iosoproterenol (Isuprel)

  • ↑HR ↑vasodilation ↓Peripheral resistance

  • Used as a bronchodilator but may cause arrythmias

Effects of NE, Isoproterenol and EPI on BP, HR and PVR

• NE: ↑PVR↑BP↓Initial pulse rate due to reflex bradycardia

• EPI: ↓PVR~same BP ↑Pulse rate

• Isoproterenol: ↓PVR ↓BP↑Pulse rate due to reflex tachycardia

Selective β2 Agonists

All bronchodilators

• Albuterol & Levalbuterol: for oral inhalation; emergency rescue inhalers bc lasts 2-6hrs

• Salmeterol &Formoterol: even more selective for β2; not for emergency rescue bc they last 12-24hrs

• Terbutaline: uterine smooth muscle relaxant, not used anymore

• Side effects: tachycardia, palpitations

Selective β3 Agonists

• Mirabegron (Myrbetriq)

  • Used to relax bladder walls and calm overactive bladder, allow filling

  • Can cause hypertension, do not give to pt with urinary/bladder obstruction

Non-Selective β Blockers/Antagonists

• Propranolol (PROTOTYPE), Nadolodol, Timolol

  • Crosses BBB, anesthetic effects so cannot be used as eye drops

  • Used for hypertension, angina, arrhythmias, migraines

  • May cause bradycardia, cardiac depression, sedation, hypoglycemia (do not give to diabetics), may worsen peripheral vascular disease

  • If combined with EPI, alpha receptors are unopposed=more vasoconstriction

• Pindolol: same but is a partial agonist (ISA)

Cardioselective (and kidney) β1 Blockers/Antagonists

• Atenolol (Tenormin):Same effect as non-selective but safer for asthmatics, diabetics and PVD

  • Less sedative effects than non-selective β

  • Risk for rebound phenomenon if abruptly discontinued (becomes extremely tachycardic)

• Metoprolol (Troprol XL): same but approved for heart failure and post MI

• Acebutolol (Sectral): partial agonist (ISA), less risk for rebound phenomenon and side effects

Mixed β & α Blockers/Antagonists

• Carvediol (Coreg): Blocks RAAS in HF

• Labetalol (Normodyne): used for hypertensive crises in stroke patients, hypertension with clampsia or pre-clampsia, pheochromocytoma