Adrenergics Flashcards
Neurotransmitters of the ANS
Acetylcholine, norepinephrine, epinephrine
Receptors of the ANS
Nicotinic AChR, muscarinic AChR, alpha1 adrenergic, alpha2 adrenergic, beta1 adrenergic, beta2 adrenergic
Alpha1 adrenergic receptors
Gq/Gi/Go mediators, present in vascular (contraction), genitourinary (contraction), intestinal (relaxation) smooth muscle, heart (increased excitability), and liver (glycogenolysis/gluconeogenesis)
Alpha2 adrenergic receptors
Gi/Go mediators, present in pancreatic beta cells (decreases insulin secretion), platelets (aggregation), nerves (decrease NE release), vascular smooth muscle (contraction)
Beta1 adrenergic receptors
Gs mediators, present in heart (increased AV conduction velocity, increased rate and force of contraction), renal juxtaglomerular cells (increased renin secretion)
Beta2 adrenergic receptors
Gs mediators, present in smooth muscle (relaxation), liver (glycogenolysis/gluconeogenesis), skeletal muscle (glycogenolysis and potassium uptake)
Major adrenergic receptors in the heart
Beta1, alpha1
Major adrenergic receptors in the blood vessels
Alpha1, alpha2
Major adrenergic receptors in the lungs
Beta2
Effect of beta1 receptor stimulation on heart
Results in increased cardiac contracility and heart rate
Effect of beta2 receptor stimulation in bronchial smooth muscle
Results in dilation of the airways, beta2 agonists alleviate asthma symptoms
Nonselective beta antagonists
Propranolol, pindolol, nadolol, timolol, carteolol, all beta1 = beta2 selectivity, available in sustained release preparations for long-term disease management
Propanolol
Prototype beta-blocking drug, low, dose-dependent bioavailability
Timolol
Used for glaucoma
Beta1 selective antagonists
Metaprolol, atenolol, acebutalol, nebivolol, selective for beta1 receptors, preferred in patients with diabetes mellitus and asthma
Nebivolol
Highly selective for beta1 and exhibits additional effects of vasodilation
Action of alpha1 antagonists
NE stimulates alpha1 receptors on vascular smooth muscle to contract, antagonists result in vasodilation, lower blood pressure, alpha1 antagonism also reduces urethral tone and alleviates bladder outlet obstruction in benign prostatic hyperplasia
Prazosin
Highly selective alpha1 antagonist, effective for management of hypertension, dilates arteries and veins, relative absence of tachycardia
Phenoxybenzamine
Irreversible blockage of alpha receptors, slightly selective for alpha1 over alpha2, may increase cardiac output (reflex tachycardia due to baroreceptors), side effects: nasal stuffiness, orthostatic hypotension, tachycardia, inhibition of ejaculation
Alpha2 agonists
Stimulation of alpha2 autoreceptors centrally inhibits NE release and sympathetic output
Clonidine and guanabenz
Alpha2 adrenergic agonists used for hypertension, inhibit sympathetic outflow from CNS, decreases heart rate, contracility, vasomotor tone
Carvedilol
Mixed alpha-beta antagonist, more potent at beta receptors than alpha1, effective for treatment of chronic heart failure with decreased systolic function
Epinephrine
Hormone, higher affinity for beta receptors (beta2) compared to alpha receptors, increases muscular contraction and heart rate, decreases total peripheral vascular resistance, increases blood flow to muscles, dilates airways
Norepinephrine
Higher affinity for alpha receptors than beta receptors, increases total peripheral vascular resistance, increases muscular contraction of the heart
Beta-adrenergic receptors
Coupled to G2, increase cAMP, cellular response depends on type of tissue and isoform of receptor
D1 and D5 dopaminergic receptors
Coupled to Gs with increase in cAMP, D1 are expressed in kidneys, mesentery, coronary arteries, cause relaxation in vascular smooth muscles (vasodilation)
D2, D3, D4 dopaminergic receptors
Coupled to Gi, decrease cAMP, increase potassium conductance, decrease calcium influx
Acebutolol
Partial beta1 agonist, no effect on B2, used for management of hypertension, may produce less bradycardia
Action of alpha1 adrenergic receptor
Gq, stimulates phospholipase C, leads to increased IP3 and DAG, IP3 causes release of calcium for muscle contraction, DAG activates PKC, phosphorylates proteins
Action of alpha2 adrenergic receptor
Gi, inhibits adenylyl cyclase, decreases cAMP
Terazosin
Alpha1 selective antagonist, used for treatment of hypertension, urinary complications associated with benign prostatic hyperplasia (BPH)
Doxazosin
Treatment of hypertension and BPH, long plasma half life
Tamsulosin
More selective for alpha1a and alpha1d receptors, effective for BPH, less orthostatic hypertension
Labetalol
Alpha and beta antagonist effects (slightly selective for alpha1), treatment of hypertensive emergencies, pregnancy inducing high blood pressure
