Adrenergic receptors are molecules that bind catecholamines. Their activation leads to overall stimulatory and sympathomimetic responses. The adrenergic receptors or adrenoceptors are a class of metabotropic G protein -coupled receptors that are targets of the catecholamines, especially norepinephrine or noradrenaline, and epinephrine adrenaline.
Although dopamine is a catecholamine, its receptors are in a different category. Many cells possess these receptors, and the binding of an agonist will generally cause a sympathetic or sympathomimetic response e.
For instance, the heart rate will increase, pupils will dilate, energy will be mobilized, and blood flow will be diverted from non-essential organs to skeletal muscle. Adrenaline epinephrine : The 2D structure of adrenaline epinephrine is illustrated. Noradrenaline norepinephrine : The 2D structure of noradrenaline norepinephrine is illustrated here.
Agonist binding thus causes a rise in the intracellular concentration of the second messenger cAMP. Isoprenaline is a nonselective agonist. Adrenergic signal transduction : This schematic shows the mechanism of adrenergic receptors. The result is that high levels of circulating epinephrine cause vasoconstriction.
Smooth muscle behavior is variable depending on anatomical location. One important note is the differential effects of increased cAMP in smooth muscle compared to cardiac muscle. Increased cAMP will promote relaxation in smooth muscle, while promoting increased contractility and pulse rate in cardiac muscle.
Common or still unspecified effects include: vasoconstriction of cardiac arteries coronary artery , vasoconstriction of veins, and decreased motility of smooth muscle in the gastrointestinal tract. These drugs are reserved for use in the acute management of heart failure. These agents have a higher affinity lower equilibrium dissociation constant for beta 2 receptors when compared to beta 1.
Therefore, they selectively activate beta 2 receptors when compared to beta 1. Uses 1. Airways dysfunction; bronchial asthma, chronic bronchitis, emphysema In airways dysfunction, beta 2 selective agonists relax airways thus decreasing airways resistance.
Premature labor In premature labor, the beta 2 selective agonists relax uterine smooth muscle. Drugs that relax uterine smooth muscle are referred to as tocolytic agents. Side effects related to dental practice 1. Xerostomia, with inhaler usage. These structural modifications of the parent catecholamine nucleus result in drugs that are orally active and have longer plasma half-lives.
However, these same modifications result in lower affinity for the receptor than do the endogenous agonists epinephrine or norepinephrine. There are two structural classes of alpha 1 agonists phenethylamines which are closely aligned in structure to epinephrine and the imidazolines, compounds structurally unrelated to epinephrine.
Levonordeferin is a phenyethylamine that has been used in dental practice in combination with local anesthetics. Hypotension-to increase blood pressure during a surgical procedure where a general anesthetic has induced hypotension 2. Ophthalmic preparations-to induce mydrasis also in topical preparations for symptomatic release of eye irritation.
Cough and cold preparations-Induces constriction of nasal mucosa decreases resistance to air flow. Indirect Acting Sympathomimetics These agents require the presence of endogenous catecholamines to produce their effects.
They have little activity if catecholamines are depleted. Cocaine: Blocks reuptake of monoamines into nerve endings. Cocaine also has local anesthetic activity. Amphetamine: Promotes the release of NE from nerve endings. Amphetamine can also block the reuptake of norepinephrine.
Amphetamine-like compounds 1. Methylphenidate A major site action of cocaine, amphetamine and amphetamine-like agents is in the CNS. These drugs produce a feeling of well being and euphoria. As a result the drugs carry a significant abuse liability. Both cocaine and amphetamine are on the FDA schedule 2. Uses of Cocaine 1 below , Amphetamine and Amphetamine-like agents below 1. Cocaine has limited use as a local anesthesic and vasoconstrictor in surgical procedures involving oral, laryngeal or nasal cavities.
Appetite suppression 3. Hyperactivity in children 4. Recall that epinephrine can be absorbed systemically after intraoral administration. This epinephrine can be taken up by nerve terminals and this uptake contributes to the the termination of the actions of epinephrine. Thus, the risk of hypertension and other problems associated with systemic absorption of epinephrine will be greater in patients taking cocaine or amphetamine-like drugs.
Methamphetamine can be produced from over the counter cough and cold medications such as pseudoephedrine. Lithium, muriatic acid, sulfuric acid, red phosphorus and lye are used in this preparation. When smoked these highly corrosive agents are vaporized resulting in significant damage to teeth and gums. Sympatholytics: synthetic analogs which bind to beta or alpha receptors or act through other mechanisms to block the actions of endogenous neurotransmitters or other sympathomimetics.
Review the pharmacodynamic properties and characteristics of antagonists. Understand the pharmacologic properties and therapeutic uses of clonidine, prazosin analogs, the beta blockers and MAO-inhibitors. Understand the special precautions that exist for sympatholytic drugs in dental practice. This drug stimulates alpha 2 receptors in the nucleus tractus solitarius NTS to decrease sympathetic outflow to the heart and blood vessels.
The decrease in sympathetic tone results in a decrease in peripheral vascular resistance. Clonidine is used in dental practice in the management of chronic pain. It can be given orally or in patch form. Clonidine is a second-line antihypertensive that has many other uses including opiate withdrawal, nicotine withdrawal, vascular headaches, diabetic diarrhea, glaucoma, ulcerative colitis and Tourette's syndrome.
Side Effects The use of clonidine may result in clinical symptoms related to dry mouth, such as difficulty in swallowing and speech. Chronic use of xerostomia-producing drugs is associated with a higher incidence of oral candidiasis and dental caries. E ffects on the Cardiovascular System: 1. Relaxes arterial and venous smooth muscle as well as nonvascular smooth muscle.
Thus an alpha-blocker medication causes vasodilation and can be used to treat hypertension. Next are the beta receptors. Beta-1 receptors are located in the heart. When beta-1 receptors are stimulated they increase the heart rate and increase the heart's strength of contraction or contractility.
The beta-2 receptors are located in the bronchioles of the lungs and the arteries of the skeletal muscles. When these receptors are stimulated, they increase the diameter of the bronchioles to let more air in and out during breathing and they dilate the vessels of the skeletal muscles so they can receive the increased blood flow produced by stimulating the alpha and beta 1 receptors. So reflect for a moment: If norepinephrine or epinephrine is the neurotransmitter of the sympathetic nervous system and it interacts with all the receptors we just described, then we know that norepinephrine or epinephrine stimulates the alpha, beta-1 and beta-2 receptors and thus it is an alpha agonist, a beta-1 agonist and a beta-2 agonist.
When we administer epinephrine or adrenaline to a patient, we expect alpha, beta-1 and beta-2 agonist effects; we expect an:. We can also stimulate a single receptor site such as a beta-2 agonist medication like an albuterol inhaler that stimulates beta-2 receptors in the lungs then we can dilate the bronchioles in the patient with bronchospasm without causing excessive stimulation of the heart.
The sympathetic receptors can be over-stimulated by the non-therapeutic use of substances like cocaine and methamphetamines. Or the excessive use or overdose of sympathomimetic medication like pseudoephedrine or those used to treat attention deficit disorders.
Severe alcohol withdrawal may also induce sympathetic overdrive. Excessive stimulation of the sympathetic receptors can result in dangerously high blood pressure, tachycardia, dysrhythmias and hyperthermia, any one of which may cause organ damage with the real potential for organism death. Now let's switch to the parasympathetic or cholinergic receptors. These are easier since there are only two types, muscarinic receptors and nicotinic receptors.
And I will make it even easier by getting rid of the nicotinic receptors after I tell you they are involved in muscle contraction and are affected by substances such as curare used on those poison-tipped arrows that cause muscle paralysis by blocking these nicotinic receptors. Medications such as succinlycholine are available to block the nicotinic receptors and induce paralysis necessary for certain medical procedures. We are left with the one parasympathetic receptor you must learn, the muscarinic receptor.
When this receptor is stimulated, it causes a decrease in the heart rate, a decrease in heart contractility and a decrease in the size of the bronchioles. When we are at rest, we can slow down and conserve energy. The parasympathetic nervous system helps us do this. What would happen if we block the muscarinic receptors? That would cause the heart rate and contractility to increase, dilation of the bronchioles and less production of secretions in the body.
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