Adrenergic drugs in CV Pharm DSA Flashcards
Agonist drug examples
Epinephrine (alpha 1,2; Beta 1,2,3) Norepinephrine (alspha 1,2; Beta 1,3) Isoproterenol (all betas) Dobutamine (beta 1) Dopamine (D1> beta 1 > alpha1) Fenoldopam (D1) Clonidine (alpha 2) Methyldopa (alpha 2)
Alpha Receptor Antagonists
Prazosin (alpha 1)
Phentolamine (alpha 1, 2)
Beta receptor antagonists
Nonselective: Propranolol Nadolol Timolol *Pindolol *Carteolol Sotalol
Cardioselective
Atenolol
*Acebutolol
Metoprolol
Third Generation Labetalol Carvedilol Betaxolol Carteolol
Epinephrine (EPI)
Pharmacodynamics:
Epi is a full agonist at all adrenergic receptors
Cardiac Effects of EPI:
Most important: beta 1 receptors in myocardium (atria, ventricles, SA node, AV node, Purkinje fibers)
- -> increased inotropy, chronotropy
- -> systole is shorter, more powerful, CO enhanced, work of heart and oxygen consumption increased
- shortens duration of acction potential and refractory period
- increases membrane potential and improves conduction
- sometimes supraventricular arrhythmias occur with combo of epi and cholinergic stimulation
Vascular effects of EPI
- activates vasoconstriction via alpha , vasodilation via beta 2 in skeletal and splanchinc beds. (at low infusion rates) Diastolic pressure drops
- chief vascular action: smaller arterioles and precap sphincters. Differential expression of slpha and beta receptors (density). Net result–> redistribution of blood flow
- blood flow to skeletal muscles increased (due to powerful beta vasodilator action; after a beta 2 antagonist mainly constriction occurs)
Therapeutic Uses of Epinephrine:
• Restoration of cardiac rhythm in patients with cardiac arrest (ACLS protocols).
o During CPR for persistent or recurrent VT/VF (Pulseless Ventricular Tachycardia/ Ventricular Fibrillation) after 1-2 cycles of defibrillation & CPR.
o During CPR for PEA (Pulseless Electrical Activity)
o Following CPR and Transcutaneous Pacing (TCP) for Asystole.
o To treat bradycardia with serious signs and symptoms (along with atropine and dopamine).
rapid response to anaphylaxis
- prolongation of anesthtics (local)
- topical hemostatic agent on bleeding surfaces
- via nebulizer for pediatric asthma
Norepinephrine pharmacodynamics
NE is a full agonist at all adrenergic receptors, but has low affinity at beta 2 receptors, and thus, has very little effect at these receptors at normal doses.
NE CV effects
- Systolic and diastolic pressures, and usually pulse pressure, are increased by NE infusion.
- Cardiac output is unchanged or decreased, and total peripheral resistance is raised.
- Compensatory vagal reflex activity slows the heart, overcoming a direct chronotropic effect, and stroke volume is increased.
- Peripheral vascular resistance increases in most vascular beds, and renal blood flow is reduced, in response to NE infusion. NE constricts mesenteric vessels and reduces splanchnic and hepatic blood flow. Coronary flow usually is increased, probably owing both to indirectly-induced coronary dilation, and to elevated blood pressure. Unlike EPI, small doses of NE do not cause vasodilation or lower blood pressure, since the blood vessels of skeletal muscle constrict (1) rather than dilate (2), in response to NE.
Therapeutic Uses of Norepinephrine
• NE may be used as a vasoconstrictor to raise or to support blood pressure under certain intensive care conditions. In shock, the level of circulating catecholamines is already usually high and NE may further decrease perfusion to tissues, especially the kidney.
Other alpha-Adrenergic Agonist Pressor Agents
Metaraminol, mitodrine, ephedrine and other drugs with direct alpha-agonist activity and/or that indirectly release NE are sometimes used to support blood pressure during spinal anesthesia or shock.
Dopamine pharmacodynamics
- precursor for NE and EPI.
- full agonist at all dopaminergic receptors (D1, D2, D3, D4, D5). At higher concentrations, dopamine can also activate beta 1 receptors on the heart and at even higher concentrations it activates vascular alpha 1 receptors, –> generalized vasoconstriction.
*** D1 receptors mediate vasodilation in the renal and mesenteric vascular beds. Dopamine and its five receptors constitute major signalling pathways in the CNS.
Dopamine CV effects
low doses of DA causes an increase in glomerular filtration rate, renal blood flow, and Na+ excretion. These effects are especially useful in the management of states of low cardiac output, i.e., shock or CHF.
*** DA has desirable effects in the management of states of low cardiac output associated with compromised renal function, such as severe congestive heart failure and cardiogenic shock.
*** high concentrations–> positive inotropic effect (beta1 receptors) –> increase CO, contributes to its beneficial effects in the treatment of cardiogenic shock.
*** TPR usually unchanged at low/ int doses; ability of DA to reduce regional arterial resistance in some vascular beds, such as mesenteric and renal
Dobutamine
beta 1 receptor agonist
complicated; different isomers at alpha receptors cancel each other out
CV effects o dobutamine
more inotropic than chronotropic
enhances automaticity of the sinus node (less than isoproterenol)
