Adrenergic Drugs
For a review of adrenergic receptors, see here: Adrenergics
B1 Selective Agonists
Dobutamine
Increases contractility (through renin in the kidney) more than heart rate. Short duration of action (1-2 mins) which is useful for heart failure.
Isoproterenol
Selective B1 and B2 agonist.
Stimulation of B2 in skeletal muscle results in vasodilation and a big drop in diastolic blood pressure. Stimulation of B1 in the heart increases heart rate and raises systolic blood pressure.
Baroreceptor reflex is still triggered from the big diastolic drop, increasing heart rate.
B2 Selective Agonists
Albuterol, Terbutaline, Ritodrine
Unusually inhaled, which increases bronchodilation for the treatment of asthma.
Being selective for B2 is good because only 20% of Beta receptors in the heart are B2. This prevents an increase in cardiac demand when in a low oxygen state (i.e. and asthma attack).
Isoproterenol
Selective B1 and B2 agonist.
Stimulation of B2 in skeletal muscle results in vasodilation and a big drop in diastolic blood pressure. Stimulation of B1 in the heart increases heart rate and raises systolic blood pressure.
Baroreceptor reflex is still triggered from the big diastolic drop, increasing heart rate.
A1 Selective Agonists
Phenylephrine
Creates systemic vasoconstriction, increasing blood pressure and triggering the baroreceptor reflex.
Used as a nasal spray for nasal decongestant. Overuse can lead to rebound hyperemia.
A2 Partial Agonists
Clonidine and alpha-methyldopa
Cause vasoconstriction through A2B (via IV administration). However, if it acts on A2A in the CNS (vasomotor center) or presynaptic neurons, it reduces the concentration of catecholamines and drops blood pressure.
Brimonidine
Decreases aqueous humor production, lowering intraocular pressure.
Used for treatment of glaucoma.
Alpha Antagonists
For Phentolamine, see here: Adrenergic Drugs > Phentolamine
Phenoxybenzamine
Irreversible A1 and A2 antagonist.
Used in extreme cases of vasoconstriction, like frostbite.
Prazosin
A1A, A1B, A1D antagonist.
Used to treat hypertension.
Tamsulosin (FLOMAX)
A1A antagonist. A1A receptors are only present in the prostate.
Used to treat benign prostatic hyperplasia.
Beta Antagonists
Beta blockers. lol.
Uses
- Hypertension (decreases cardiac output)
- Angina (decreases heart rate / oxygen demand)
- Arrhythmias (decreases conduction)
- Heart failure (decreases heart stimulation generally)
- Glaucoma (decreases aqueous humor production)
- Migraines
- Post-MI workup
Propranolol
Non-selective B1 and B2 antagonist.
Chronic use can lead to disuse supersensitivity.
Metoprolol/Atenolol
Selective B1 antagonist.
Has better tolerance for exercise as B2 isn't blocked which allows for vasodilation of skeletal muscle. No bronchoconstriction as well.
Timolol
B1 and B2 antagonist. Used for glaucoma.
Pindolol
Weak B1 and B2 partial agonist. Partial agonism will decrease heart rate by moderately stimulating B1.
Combined A1 and Beta Antagonists
Carvedilol
Decreases total peripheral resistance, diastolic blood pressure, and therefore reduces hypertrophy of cardiomyocytes.
Used for moderate heart failure.
Labetalol
Does not have hyperproliferative properties like carvedilol.
Treats hypertension during pregnancy and hypertensive emergencies.
Drugs Targeting Tyrosine Hydroxylase (TH)
Metyrosine
Competitive inhibitor of TH: Decreases catecholamines.
Used for pheochromocytomas (catecholamine secreting tumors)
L-DOPA
Increases substrates after TH: Increases catecholamines.
Used for Parkinson's disease and for TH deficiencies.
Drugs Inhibiting Catecholamine Storage
Reserpine
Blocks VMAT1, inhibiting uptake and resulting in degradation: Decreases catecholamines.
Previously used for schizophrenia and hypertension, but is no longer used.
Tetrabenazine
Blocks VMAT2, inhibiting uptake and resulting in degradation: Decreases catecholamines.
Used in CNS disorders like Huntington's disease, tardive dyskinesia, and Tourette's.
Drugs Inhibiting Catecholamine Release
Clonidine
A2A and A2C agonist, decreasing cAMP resulting in hyperpolarization: Decreases catecholamines.
Used as an antihypertensive.
Botulinum toxin
Blocks VAMP/SNAP-25, which prevents vesicular docking: Decreases catecholamines.
Used (in small doses) for cerebral palsy, spasticity, and excess sweating.
Drugs Increasing Catecholamine Release
Tyramine
Displaces norepinephrine from cytoplasm: Increases catecholamines.
Not prescribed, but is consumed (red wine, cheese, yogurts) which is why patients on MAO inhibitors must avoid these foods to prevent potentially lethal hypertension.
Amphetamines
Inhibit reuptake pumps, VMAT, and MAO: Increases catecholamines.
Note: VMAT is blocked by reserpine to decrease catecholamines. Amphetamines have the opposite effect as the amphetamine buildup in the cytosol is so great, the pumps reverse and, independent of Ca2+ signaling, start moving the drug out of the cell.
Used for ADHD and narcolepsy. Tolerance develops quickly, strong abuse potential.
Ephedrine/Pseudoephedrine
Drug enters via the reuptake pump, displacing norepinephrine from the cytoplasm: Increases catecholamines.
Also a weak B receptor agonist. Precursor to amphetamines. Chronic usage may cause downregulation of alpha receptors and result in nasal blood vessel dilation.
Used as OTC cold medication and weight loss.
Drugs Inhibiting Catecholamine Reuptake
Cocaine
Inhibits norepinephrine/dopamine/serotonin transporters: Increases catecholamines.
Used as a party lubricant and for taking long looks in the mirror.
Desipramine
Inhibits norepinephrine/serotonin transporters: Increases catecholamines.
This drug is not abused like cocaine because it does not act on dopamine.
Used as antidepressants (tricyclic class). Will pharmacologically inhibit Ephedrine/Pseudoephedrine.
Drugs Inhibiting MAOs
MAOIs
Phenelzine
Inhibits MAO-A and MAO-B, reducing catecholamine degradation: Increases catecholamines.
Used as a 3rd line antidepressant.
Selegiline
Inhibits MAO-B, reducing catecholamine degradation: Increases catecholamines.
Used as an adjunctive treatment for Parkinson's (MAO-B degrades dopamine).
Drugs Inhibiting Phosphodiesterases (PDEs)
PDEs break down cAMP/cGMP. By inhibiting these, the cAMP/cGMP signals remain high.
Aminophylline/Theophylline
Increases catecholamine SIGNAL via PDE-4.
Used for asthma and COPD. Can result in tachycardia.
Sildenafil/Vardenafil/Tadalafil
Increases catecholamine SIGNAL via PDE-5.
Used for erectile dysfunction and pulmonary hypertension.
Vasodilators
Phentolamine
Blocks A1 and A2. Reduces total peripheral resistance (systolic) and venus return (diastolic).
The drop in blood pressure triggers the baroreceptor reflex, increasing heart rate.
Epinephrine (High Dose)
Stimulates A1 and A2b, constricting blood vessels. This increases total peripheral resistance (systolic) and venus return (diastolic).
Note: Because B2 has a higher affinity for epinephrine than Alpha receptors, for low dose epinephrine vasodilation will occur in the periphery and total peripheral resistance will drop. However, there is no net change in blood pressure (systolic increases from increased cardiac output), and won't result in baroreceptor reflex correction.
Epinephrine + Phentolamine
Phentolamine inhibits Alpha receptors, resulting in a reduction in total peripheral resistance (systolic) and venus return (diastolic).
Because epinephrine can no longer bind to Alpha receptors, it only affects the heart through Beta receptors, increasing heart rate.
Additionally, B2 stimulation will lead to vasodilation, reducing total peripheral resistance (systolic) and venus return (diastolic), dropping blood pressure and further increasing heart rate.