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27 Cards in this Set
- Front
- Back
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What is an adrenoreceptor?
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An adrenoreceptor agonist is a drug which binds to and activates adrenoreceptors. These drugs have direct actions on the cells which express these receptors. These drugs to some extent mimic the effect of norepinephrine and epinephrine. As agonists, these drugs are often called direct sympathomimetics.
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What are Non-agonist sympathomimetics?
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drugs which do not bind the adrenoreceptors but cause adrenoreceptor activation by inducing release of norepinephrine or by inhibiting reuptake or by inhibiting metabolism of norepinephrine.
These drugs are sometimes called indirect sympathomimetics. |
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What are Mixed sympathomimetics?
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Mixed sympathomimetics may have a combined effect: binding and activation of adrenoreceptors and influencing NE concentration in the synaptic gap of noradrenergic synapses (by reducing reuptake from the synaptic gap or inducing release into the synaptic gap).
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How are adrenergic receptor types different?
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Adrenergic receptor subtypes are delineated by pharmacology, dependent on differential affinity of an agonist (or antagonist) for each receptor type, by location of the receptors on different types of cell, and by the effector mechanism(s) to which receptors of each type are coupled.
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Direct Sympathomimetics: Differential Affinity for Adrenergic Receptors
Adrenoreceptor agonists or direct sympathomimetics have been divided into two types based on their chemical structure. What are they? |
Catecholamine adrenoreceptor agonists -epinephrine, norepinephrine, dopamine, isoproterenol and dobutamine - have a similar structure and some are natural products.
Non-catecholamine adrenoreceptor agonists - phenylephrine, methoxamine, terbutaline, albuterol, clonidine- are all synthetic compounds and have a variety of chemical structures. Catecholamines are not effective if administered orally; non catecholamines are effective systemically if administered orally(or by any other route). |
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Epinephrine Affinity
α1 α2 β1 β2 |
α1 high affinity
α2 high affinity β1 high affinity β2 high affinity |
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Noepinephrine Affinity
α1 α2 β1 β2 |
α1 high affinity
α2 high affinity β1 high affinity β2 slow affinity |
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Dopamine Affinity
α1 α2 β1 β2 |
α1 medium affinity;
α2 very low affinity β1 medium affinity; β2 very low affinity |
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Isoproterenol Affinity
α1 α2 β1 β2 |
α1 very low affinity
α2 very low affinity β1 high affinity β2 high affinity |
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Dobutamine Affinity
α1 α2 β1 β2 |
α1 very low affinity
α2 very low affinity β1 high affinity β2 very low affinity |
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Phenylephrine Affinity
α1 α2 β1 β2 |
α1 high affinity
α2 very low affinity β1 very low affinity β2 very low affinity |
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Methoxamine Affinity
α1 α2 β1 β2 |
α1 high affinity
α2 medium affinity; β1 very low affinity β2 very low affinity |
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Terbutaline Affinity
α1 α2 β1 β2 |
α1 very low affinity
α2 very low affinity β1 very low affinity β2 high affinity |
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Albuterol Affinity
α1 α2 β1 β2 |
α1 very low affinity
α2 very low affinity β1 very low affinity β2 high affinity |
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Clonidine Affinity
α1 α2 β1 β2 |
α1 very low affinity
α2 high affinity β1 very low affinity β2 very low affinity |
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The effect of indirect agonists is essentially similar to norepinephrine because they induce release of NE, or prevent reuptake of NE from the synaptic gap or inhibit metabolism of NE in the synaptic gap. These include?
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amphetamines, cocaine, monoamine oxidase inhibitors and tricyclic antidepressants.
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What are the effects of epinephrine (ADRENALIN)?
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Through postsynaptic α1, β1, and β2 receptors.
α1 Receptors Constriction of arterioles (especially in skin, mesentery, mucosa). This effect causes an increased total peripheral resistance (TPR),that is resistance to blood flow through blood vessels of the systemic circulation. This increased TPR is rapid (within minutes) and causes a rapid increase of blood pressure (with the potential for a subsequent reflex reduction of heart rate and reversal of the blood pressure change) Constriction of small veins (especially in skin, mesentery,mucosa) This effect causes increased return of blood to the heart and consequently increased output of blood from the heart. This effect leads to an immediate increase of blood pressure (with potential for subsequent reflex decreased heart rate or vasodilation and reversal of the blood pressure change) Mydriasis Constriction of sphincters of bladder and gastrointestinal tract: urine and feces retention Secretion of viscous saliva Decreased renin secretion from kidney leading to vasodilation and increased renal excretion of Na and H2O and decreased blood pressure Renin enhances conversion of angiotensin I in the plasma to angiotensin II or AII. AII causes rapid constriction of some arterioles (thus causing an increased TPR and blood pressure). AII also induces secretion of aldosterone from the cortex of the adrenal gland. Aldosterone acts in the kidney to enhance Na and H2O reabsorption which leads to increased blood volume and increased blood pressure; the increase of blood pressure through this mechanism is slow (taking minutes to hours) β1 Receptors Increased heart rate (+vechronotropic effect) with accompanying increased A-V node conduction(+ve dromotropic effect) and increased stroke volume (+ve inotropic effect) producing increased cardiac output. This effect is rapid and causes a rapid increase of blood pressure blood pressure (with potential subsequent reflex vasodilation to reverse the blood pressure change). That the chronotropic , inotropic and dromotropic effects all occur at the same time is logical: if these effects did not occur together, cardiac arrhythmias would develop. Increased renin secretion from kidney with subsequent increased Na and H2O reabsorption in the kidney, increased blood volume and increased blood pressure. β2 Receptors Dilation of vessels of heart and skeletal muscle rapidly causing a reduced total peripheral resistance(TPR) and decreased blood pressure (with potential subsequent reflex increased heart rate) Bronchiole dilation Glycogenolysis (especially in liver) Lipolysis Relaxation of uterus (pregnant female) Urine and feces retention (relaxation of bladder wall and GI wall muscle) Total cardiovascular effect of epinephrine Rapid increased systolic blood pressure (as a result of increased cardiac output) and decreased diastolic blood pressure as a result of sum of increased TPR due to constriction of many vessels (especially of skin, mesentery and mucosa) and simultaneous decreased TPR due to vasodilation of skeletal muscle and coronary vessels; no change mean blood pressure resulting from sum of effects on heart and blood vessels. Slow increase of blood pressure resulting from effect on renin secretion. |
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What are the effects of norepinephrine (LEVARTERENOL)?
Through postsynaptic α1 and β2 receptors. |
α1 Receptors
Constriction of arterioles (especially in skin, mesentery, mucosa). Causes rapid increase of TPR and blood pressure (with potential subsequent reflex reduction of heart rate) Constriction of small veins (especially in skin, mesentery, mucosa) leading to increased blood return to the heart, with subsequent increased cardiac output and blood pressure(with potential for subsequent reflex decreased heart rate) Mydriasis Constriction of sphincters of bladder and gastrointestinal tract: urine and feces retention Decreased renin secretion with subsequent (slowly) decreased Na and H2O reabsorption in kidney, decreased blood volume, and decreased blood pressure decrease Secretion of viscous saliva β1 Receptors Increased heart rate (+ve chronotropic effect) with accompanying increased A-V node conduction (+ve dromotropic effect) and increased stroke volume(+ve inotropic effect) producing increased cardiac output. This effect is rapid and causes a rapid increase of blood pressure blood pressure(with potential subsequent reflex vasodilation to reverse the blood pressure change). That the chronotropic , inotropic and dromotropic effects all occur at the same time is logical: if these effects did not occur together, cardiac arrhythmias would develop. Increased renin secretion from kidney with subsequent increased Na and H2O reabsorption in the kidney, increased blood volume and increased blood pressure. Total cardiovascular effect of norepinephrine Rapid increased systolic blood pressure and increased mean bp (as a result of increased cardiac output and increased TPR) but no effect on diastolic blood pressure. (Potential activation of cardiovascular reflex to decrease heart rate and decrease cardiac output.) Slow increase of blood pressure resulting from effect on renin secretion |
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What are the effects of isoproterenol (ISUPREL)?
Through postsynaptic β1, and β2 receptors. |
β1 Receptors
Increased heart rate (+ve chronotropic effect) with accompanying increased A-V node conduction (+ve dromotropic effect) and increased stroke volume(+ve inotropic effect) producing increased cardiac output. This effect is rapid and causes a rapid increase of blood pressure blood pressure(with potential subsequent reflex vasodilation to reverse the blood pressure change). That the chronotropic , inotropic and dromotropic effects all occur at the same time is logical: if these effects did not occur together, cardiac arrhythmias would develop. Increased renin secretion from kidney with subsequent increased Na and H2O reabsorption in the kidney, increased blood volume and increased blood pressure. β2 Receptors Dilation of vessels of heart and skeletal muscle producing rapidly reduced total peripheral resistance (TPR),and rapidly decreased blood pressure (with potential subsequent reflex increased heart rate) Bronchiole dilation Glycogenolysis Lipolysis Relaxation of uterus (pregnant female) Urine and feces retention (constriction of GI tract and bladder sphincters and relaxation of bladder and GI wall) Total cardiovascular effect of isoproterenol Rapid increased systolic blood pressure (as a result of increased cardiac output) and rapid and substantial decrease of diastolic blood pressure as a result of vasodilation of skeletal muscle and coronary vessels; mean bp is decreased resulting from sum of effects on heart and blood vessels. Slow increased of blood pressure resulting from effect on renin secretion |
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It’s often written that NE has no effects mediated by beta 2 adrenoreceptors. This is correct given that?
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NE can be injected to provide concentrations of NE sufficient to activate alpha-1 and Beta 1 receptors but insufficient to activate Beta 2receptors (for which norepinephrine has lower affinity). However, with larger doses, to produce higher plasma concentrations of NE, NE would also activate Beta 2 effects (as induced by epinephrine).
However, that "NE has no effects mediated by beta 2 adrenoreceptors" is incorrect: remember that NE mediates physiological effects through beta 2 receptors at synapses. In the synaptic gap, the NE concentration is sufficiently high to "overcome" the "relatively low" affinity of NE for these receptors so that sufficient receptors are bound and activated to induce responses in the effector cells. |
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What are the effects of dopamine (INOTROPIN)?
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Through postsynaptic α1 and β1 receptors.
β1 Receptors Increased heart rate(+ve chronotropic effect) with accompanying increased A-V node conduction (+ve dromotropic effect) and increased stroke volume (+ve inotropic effect) producing increased cardiac output. This effect is rapid and causes a rapid increase of blood pressure blood pressure(with potential subsequent reflex vasodilation to reverse the blood pressure change). That the chronotropic , inotropic and dromotropic effects all occur at the same time is logical: if these effects did not occur together, cardiac arrhythmias would develop. Increased renin secretion from kidney with subsequent increased Na and H2O reabsorption in the kidney, increased blood volume and increased blood pressure. α1 Receptors Minor effect (low affinity), same as epinephrine and norepinephrine at these receptors Total cardiovascular effect of dopamine Rapid increase of systolic blood pressure (as a result of increased cardiac output and increased TPR resulting from vasoconstriction of skin, mesentery and mucosa); increased mean blood pressure resulting from sum effect on heart and blood vessels. Slow increase of blood pressure resulting from effect on renin secretion It should be noted that the effects of dopamine to increase blood pressure is tempered by the effect of dopamine to cause decreased TPR due to vasodilation mediated by dopamine receptors on the smooth muscle fibers of the wall of arterioles (at lower concentrations than required to activate adrenoreceptors). |
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What are the effects of dobutamine (DOBUTREX)?
Through postsynaptic β1 receptors. |
β1 Receptors
Increased heart rate(+ve chronotropic effect) with accompanying increased A-V node conduction (+ve dromotropic effect) and increased stroke volume (+ve inotropic effect) producing increased cardiac output. This effect is rapid and causes a rapid increase of blood pressure blood pressure(with potential subsequent reflex vasodilation to reverse the blood pressure change). That the chronotropic , inotropic and dromotropic effects all occur at the same time is logical: if these effects did not occur together, cardiac arrhythmias would develop. Increased renin secretion from kidney with subsequent increased Na and H2O reabsorption in the kidney, increased blood volume and increased blood pressure. Total cardiovascular effect of dobutamine Rapid increase of systolic and mean blood pressure (as a result of increased cardiac output). Slow increase of blood pressure resulting from effect on renin secretion Effects of dobutamine are vigorous but short lived (due to short half life; 2minutes) unless continuously infused |
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What are the effects of phenylephrine (NEO-SYNEPHRINE)?
Through postsynaptic α1 receptors. |
α1 Receptors
Constriction of arterioles (especially in skin, mesentery, mucosa) producing increased TPR and increased blood pressure (with potential subsequent reflex decreased heart rate) Mydriasis Constriction of sphincters of bladder and gastrointestinal tract: urine and feces retention Decreased renin secretion with subsequent decreased Na and H2O reabsorption, decreased blood volume, and decreased blood pressure Secretion of viscous saliva Effective administered orally or injected intravenously to produce all the above effects. Clinical use mostly limited to topical application to the corneal surface of the eye (to produce mydriasis) and to mucosal surfaces of nasal passages (to produce decongestion).) |
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What are the effects of methoxamine (VASOXYL)?
Through postsynaptic α1 receptors. |
α1 Receptors
Constriction of arterioles (especially in skin, mesentery, mucosa) producing increased TPR and increased blood pressure (with potential subsequent reflex decreased heart rate) Mydriasis Constriction of sphincters of bladder and gastrointestinal tract: urine and feces retention Decreased renin secretion with subsequent decreased Na and H2O reabsorption, decreased blood volume, and decreased blood pressure Secretion of viscous saliva |
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What are the effects of terbutaline (BRETHINE), albuterol (VENTOLIN)?
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Through postsynaptic β2 receptors.
β2 Receptors Potent bronchodilator effect Potent relaxant of uterine muscle in pregnant female Used to stop premature labor Vasodilator effect (coronary and skeletal muscle arteries) causes significant decrease of blood pressure; produces reflex tachycardia (increased heart rate) as a side effect Orally effective but for effects on uterus, drug is injected and for effects on bronchiole system, drugs are formulated in aerosol inhalant. |
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What are the effects of clonidine (CATAPRESS)?
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Through presynaptic α2 receptors.
α2 Receptors Particularly high affinity for CNS 2 receptors. Effect in CNS is to reduce sympathetic "drive" or "output" to peripheral components of SNS Orally effective, antihypertensive use |
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What are the effects of Ephedrine and Pseudoephedrine (SUDAFED)?
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Mixed action: induces NE release and mimics NE.
Most marked effects when injected intravenously: stimulates heart, dilates bronchioles Orally effective drugs; penetrate CNS: used to elevate mood, prevent sleep |
