An Adrenergic Drug Would Be Prescribed to Produce What Physiological Effect?

THE PHARMACOLOGY OF
ADRENERGIC RECEPTORS

This study guide will facilitate the agreement of sympathomimetics and sympatholytics and the adrenergic receptors at which these drugs collaborate. The educational goal is to sympathise the uses in dental do of drugs that interact at the adrenergic receptors too as toxicities that could occur as a result of these interactions. In addition, dental patients are likely to be taking drugs that act at these receptors. The presence of these drugs could modify the actions of drugs prescribed in dental practice also equally produce interactions that could have serious consequences.

Learning Objectives, Lecture I

one. Integrate pharmacodynamic principles to understand the actions of drugs that collaborate with the adrenergic receptors and how these interactions are relevant to dental practise.

ii. Understand the furnishings of epinephrine and norepinephrine on the cardiovascular system.

iii. Understand the rationale and potential toxicities for the use of epinephrine in dental exercise.

4. Understand the mechanisms for drug interactions involving drugs used in cardiovascular therapeutics as they relate to dental practice.

Key drugs
Epinephrine - Adrenalin
Norepinephrine- Levophed

The adrenergic receptors which subserve the response of the sympathetic nervous organisation have
been divided into two discrete subtypes: blastoff adrenergic receptors (alpha receptors) and beta adrenergic receptors (beta receptors). The classification of these receptors, and indeed receptors in general, is based on the interaction of agonists and antagonists with the receptors. The actions of epinephrine, widely used in combination with local coldhearted drugs, are produced as a upshot of interactions with these receptors.

Beta Receptor Systems

Most tissues limited multiple receptors. All the same, the dominant beta receptor in the normal heart is the beta₁ receptor while the beta₂ receptor is the ascendant regulatory receptor in vascular and non vascular smoothen musculus. Epinephrine activates both the beta_ane and beta₂-receptors. Norepinephrine activates simply the beta₁-receptor.

Outcome of Beta₁ Receptor Activation on the Eye: Activation of the beta₁ receptor leads to increases in contractile force and heart rate. Drugs that actuate the beta₁ receptor can exist used in centre failure to improve the contractile state of the failing centre. Drugs that activate the beta₁ receptor likewise increase eye charge per unit. Indeed, excess stimulation the beta₁ receptor tin induce significant increases in center rate and arrhythmias. Arrhythmias are a major concern with drugs such every bit epinephrine that tin be captivated systemically after intra-oral injection.

Effect of Beta_two Receptor Activation on Smooth Muscle: Activation of the beta₂ receptor leads to vascular and nonvascular smooth musculus relaxation. Drugs that actuate the beta_two receptor can be used to care for equally asthma (by relaxing airway smoothen muscle) and premature labor (past relaxing uterine shine muscle).

Alpha RECEPTORS SYSTEMS:

The receptor mediating the vasconstrictor actions of catecholamines is referred to equally an alpha receptor.
Alpha receptors have been further subdivided into blastoff₁ and alpha₂ receptors. Both epinephrine and norepinephrine activates both the alpha₁ and alpha_ii receptors.

Presynaptic Alpha_ii Receptors
Alpha₂ receptors also be presynaptically associated with nervus terminals. Activation of these receptors inhibits the release of norepinephrine.
Norepinephrine acts at presynaptic alpha₂ receptors to inhibit its own release.

Norepinephrine acts at presynaptic alpha₂ receptors to inhibit its ain release.

Postsynaptic Alpha₁ Receptors on Vascular Smooth Muscle:

Associated with vascular smooth muscle are a big number of blastoff₁ receptors relative to beta_two receptors. Activation of these receptors by sympathetic nervous system manual or drugs will upshot in vasoconstriction and an increment in peripheral resistance and systemic arterial claret pressure.

Applications to Therapeutics
Oral dosing of norepinephrine or epinephrine is not possible due to the rapid metabolism of catechol nucleus in gastrointestinal mucosa and liver. Therefore, these agents are given I.V., I.Thou., topically and in droplets sprays.

Epinephrine is oftentimes used in combination local coldhearted agents to prolong the duration of anesthetic action. This would include articaine, bupivacaine or lidocaine. This combination is used because epinephrine tin induce vasoconstriction thus limiting the diffusion of the local coldhearted from the site of injection. This not only prolongs the deportment of the local anesthetic only also to reduce the toxicity of the local anesthetic by limiting its systemic absorption. Lidocaine in toxic doses can produce cardiac arrthythmias and convulsions.

Epinephrine can also be topically practical in surgical procedures to induce vasoconstriction and thus reduce blood loss. Epinephrine is used in the treatment of shock and in emergency situations related to bronchial asthma.

Clinical studies take shown that epinephrine blood levels increase post-obit its intraoral administration. The risk of this increase is dependent on characteristics of the patient. For example, hypertensive patients or those with other cardiovascular disease or patients taking other drugs that touch on sympathetic nervous system function are at higher risk than patients without these conditions. Systemically captivated epinephrine could besides increase heart rate and exacerbate cardiac rhythm disturbances or myocardial ischemia.

Learning Objectives Lecture Ii

ane. Understand the potential sites of activity for sympathomimetics and the difference between a direct and indirect acting      agonist.

2. Sympathize the pharmacologic deportment and therapeutic actions of drugs that act at the beta_i and beta₂ -adrenergic receptors likewise as the alpha_one -adrenergic receptor.

3. Know the mechanism of action and effects of amphetamine and cocaine.

iv. Empathise how the pressure of sympathomimetics alters the dental management of patients.

Key Drugs*
Amphetamine-Adderall
Albuterol - Ventolin - 13th leading prescription drug in the US in 2003- source- rxlist.com
Cocaine
Dopamine - Intropin
Methylphenidate - Ritalin - 102nd leading prescription drug in the The states in 2003- source- rxlist.com
Phenylephrine - Neosynephrine

* A more consummate list of sympathomimetics and their trade names can be found on p. 110-111 of the Yagiela text.

Sympathomimetics: synthetic analogs of naturally occurring catecholamines that mimic the actions of the endogenous neurotransmitters. These agents can be divided into direct and indirect acting sympathomimetics.

1. Direct interim agonists or antagonists can deed at postsynaptic receptors.

ii. Indirect acting agonists release neurotransmitters from presynaptic nerve terminals to produce a sympathomimetic effect.

iii. Inhibition of the membrane uptake of catecholamines by drugs such as cocaine and tricyclic antidepressants produce a sympathomimetic consequence.

4. Inhibition of monoamine oxidase by drugs such every bit Tranylcypromine.

SYMPATHOMIMETICS ACTING AT BETA RECEPTOR SYSTEMS

EXAMPLES:

Dopamine
Dobutamine
Beta₂ agonists

Uses of Dopamine and Dobutamine

Congestive eye failure and cardiogenic shock.

In congestive center failure, the failing heart is not able to eject blood as efficiently equally the normal heart. Every bit a event there is a decrease in cardiac output which triggers a host of compensatory actions. These include fluid retention, vasoconstriction, an increase in peripheral vascular resistance, an increase in the levels of circulating catecholamines and tissue hypoxia. Dopamine and dobutamine activate the myocardial beta_ane receptor and thus increase the strength of contraction of the failing middle. This will consequence in an increment in cardiac output. These drugs are reserved for use in the acute management of heart failure.

SELECTIVE BETA₂ AGONISTS

These agents accept a higher affinity (lower equilibrium dissociation constant) for beta₂ receptors when compared to beta₁. Therefore, they selectively activate beta₂ receptors when compared to beta₁.

Uses
ane. Airways dysfunction; bronchial asthma, chronic bronchitis, emphysema
In airways dysfunction, beta₂ selective agonists relax airways thus decreasing airways resistance.

2. Premature labor
In premature labor, the beta₂ selective agonists relax uterine polish muscle. Drugs that relax uterine smooth muscle are referred to as tocolytic agents.

Side effects related to dental practice

1. Xerostomia, with inhaler usage.

ALPHA₁ AGONISTS

Straight Acting Agents

These are synthetic agents that directly activate the alpha₁ -adrenergic receptor. These structural modifications of the parent catecholamine nucleus issue in drugs that are orally active and have longer plasma one-half-lives. Still, these same modifications result in lower affinity for the receptor than do the endogenous agonists (epinephrine or norepinephrine). In that location are two structural classes of alpha₁ 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 exercise in combination with local anesthetics.

Uses
1. Hypotension-to increment blood pressure during a surgical process where a general anesthetic has induced hypotension

2. Ophthalmic preparations-to induce mydrasis also in topical preparations for symptomatic release of centre irritation.

3. Coughing 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 furnishings. They take petty 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 besides block the reuptake of norepinephrine.

Amphetamine-like compounds

one. Methylphenidate

A major site action of cocaine, amphetamine and amphetamine-similar agents is in the CNS. These drugs produce a feeling of well being and euphoria. Every bit a result the drugs carry a significant abuse liability. Both cocaine and amphetamine are on the FDA schedule 2.

Uses of Cocaine (# i beneath), Amphetamine and Amphetamine-like agents (2-iv below)

one. Cocaine has express use as a local anesthesic and vasoconstrictor in surgical procedures involving oral, laryngeal or nasal cavities.

2. Ambition suppression

3. Hyperactivity in children

4. Narcolepsy

Cautions Relevant to Dentistry

1) Cocaine and amphetamine-like agents (tricyclic antidepressants besides) could potentiate the furnishings of directly acting agonists such as epinephrine. Recall that epinephrine tin can exist captivated systemically after intraoral administration. This epinephrine tin can exist taken up past nerve terminals and this uptake contributes to the the termination of the deportment of epinephrine. Thus, the chance of hypertension and other bug associated with systemic assimilation of epinephrine volition be greater in patients taking cocaine or amphetamine-like drugs.

2) An analog of amphetamine, methamphetamine, is produced illegally and is a widely abused substance. Methamphetamine can be produced from over the counter cough and cold medications such as pseudoephedrine. Lithium, muriatic acid, sulfuric acid, ruddy phosphorus and lye are used in this grooming. When smoked these highly corrosive agents are vaporized resulting in pregnant damage to teeth and gums.

Sympatholytics: synthetic analogs which demark to beta or alpha receptors or act through other mechanisms to block the actions of endogenous neurotransmitters or other sympathomimetics.

Learning Objectives Lecture 3

ane. Review the pharmacodynamic properties and characteristics of antagonists.

2. Understand the pharmacologic properties and therapeutic uses of clonidine, prazosin analogs, the beta blockers and MAO-inhibitors.

3. Sympathize the special precautions that exist for sympatholytic drugs in dental exercise.

Key Drugs*

Atenolol - Tenormin and various trade names - 4th leading prescription drug in the The states in 2003- source- rxlist.com
Clonidine - Minipres, various trade names
Propranolol - Inderal - diverse trade names
Terazosin - Hytrin

* A more consummate list of sympatholytics and their trade names can exist constitute on p. 123 of the Yagiela text.

Alpha₂ AGONISTS Equally SYMPATHOLYTICS
Clonidine

Actions and Therapeutic Uses
1. This drug stimulates alpha₂ receptors in the nucleus tractus solitarius (NTS) to decrease sympathetic outflow to the centre and blood vessels.

2. The subtract in sympathetic tone results in a subtract in peripheral vascular resistance.

3. Clonidine is used in dental practise in the management of chronic hurting. Information technology tin exist given orally or in patch form. Clonidine is a 2d-line antihypertensive that has many other uses including opiate withdrawal, nicotine withdrawal, vascular headaches, diabetic diarrhea, glaucoma, ulcerative colitis and Tourette'south syndrome.

Side Furnishings
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.

SELECTIVE ALPHA_one-ANTAGONISTS
Prazosin and analogs, terazosin, doxazosin, trimazosin.

Effects on the Cardiovascular System:
1. Relaxes arterial and venous smooth musculus equally well equally nonvascular smooth muscle.

2. Decreases peripheral vascular resistance and venous return with a resultant subtract in systemic arterial blood force per unit area.

Uses
1. Hypertension

2. Benign prostatic hypertrophy

Tamsulosin specifically blocks the alpha₁-receptor associated with the prostate and is used to treat benign prostatic hypertropy.

The Relevance of Orthostatic Hypotension to Dental Exercise
Orthostatic hypotension is a problem with prazosin analogs and to a lesser extent tamsulosin. Significantly, orthostatsis is a problem that can be seen with whatsoever vasodilator that affects the tone on venous smooth muscle. This would include, organic nitrates, hydralazine, clonidine, minixodil and the many drugs used to care for impotence. Orthostatic hypotension or postural hypotension occurs when systemic arterial blood pressure falls past more than twenty mmHg upon standing. In this situation, cerebral perfusion falls and an individual may become light headed, dizzy or laissez passer out. In changing from the supine to the standing position, gravity tends to cause blood to pool in the lower extremities. However, several reflexes, including sympathetically mediated venoconstriction minimize this pooling and maintain cerebral perfusion. If these reflex actions do not occur, then orthostatic hypotension could outcome. By blocking the alpha₁-receptors associated with venous smooth musculus, prazosin-like drugs, inhibit the sympathetically mediated vasoconstriction associated with postural changes. Hence, orthostatic hypotension can occur. Drugs like clonidine cause orthostasis due to its CNS deportment that cake the sympathetic reflexes. Vasodilators such every bit nitrates, minoxidil, hydralazine or impotence medications cause orthostasis because of their actions directly on the vasculature. A consideration for patients beingness treated with some sympatholytics is the patient'southward position during and after dental procedures. Suddenly standing upright after being in a supine position in the dental chair is very apt to crusade syncope.

BETA ADRENERGIC RECEPTOR BLOCKERS

Cardiovascular Uses
Hypertension, ischemic heart disease, supraventricular tachyarrhythmias.

i. These drugs are competitive antagonists of the beta adrenergic receptors

2. Beta blockers are either selective for the beta₁ receptor or nonselective beta_ane and beta₂
antagonists.

iii. Propranolol is the prototype Beta Blocker as well as the prototype of a nonselective beta blocker.

4. By blocking the myocardial beta₁ receptor beta blockers, a) decrease the strength and charge per unit of myocardial contraction, b) Decreases renal renin secretion with the net consequence of c) decreasing systemic arterial blood force per unit area

5. A major disadvantage of nonselective beta blockers is the fact that they will block beta₂
receptors associated with airway or vascular smooth musculus. This is a problem in treating patients with airway dysfunction or peripheral vascular disease such as alpha₁ adrengeric
receptor-mediated vasoconstrictor tone will be unoppsed by the beta₂ receptors. To overcome this disadvantage, antagonists that selectively block the beta_ane receptor have been developed.

six. Atenolol is the prototype selective beta₁ receptor beta blocker.

Applications to Dentistry
Because nonselective β-blockers block β2-receptor mediated vasodilation, in that location is a risk of a hypertensive episode following administration of local anesthetic agents that comprise epinephrine. In this situation, the vasoconstrictor actions of epinephrine at α1 -receptors are not opposed by the vasodilatory actions of β2-receptors resulting in an exaggerated claret pressure response that could be deleterious in patients with hypertension or ischemic heart disease.

Side Furnishings
i. Sedation, fatigue

2. Exacerbation of peripheral vascular illness, airway dysfunction

Monoamine Oxidase Inhibitors
1. These drugs inhibit monoamine oxidase and are used as antidepressants in psychiatric do.

2. A side consequence that is not clearly understood is that these drugs tin can as well produce hypotension.

3. Tin can precipitate a hypertensive crisis. Patients taking MAO inhibitors must not exist given
drugs that accept indirect sympathomimetic activity or are inactivated by MAO. Occasionally,
the dentist may find reason to use the vasoconstrictor phenylephrine. Because it causes even
a pocket-size release of norepinephrine from adrenergic nerves and is discipline to metabolism past MAO,
phenylephrine must be avoided in patients taking MAO inhibitors. Epinephrine and levonordefrin, which are virtually commonly found in local coldhearted solutions, are non contraindicated, since they are direct agonists and are largely inactivated by catechol-O-methyltransferase. Notwithstanding, the avoidance of hemostatic preparations containing high concentrations of epinephrine is
recommended.

4. Opioids and other CNS depressants should be used cautiously and usually at lower doses in
patients who are taking MAO inhibitors. Meperidine is absolutely contraindicated. The dentist
should reinforce the doc'due south instructions to the patient near dietary restrictions and
contraindications of several drugs for patients taking MAO inhibitors.

Uses
ane. Hypertension

2. Depression

The following is a listing of trade names for the drugs mentioned in this handout. It is provided for your information.

Epinephrine	Adrenalin Chloride
Phenylephrine	Neo-synephrine
Isoproterenol	Isuprel
Norepinephrine	Levophed
Methoxamine	Vasoxyl
Metaraminol	Aramine
Clonidine	Catapres
Methyldopa	Aldomet
Guanabenz	Wytensin
Oxymetazoline	Afrin
Naphazoline	Naphcon Forte Ophthalmic
Tetrahydrozoline	Tyzine
Prazosin	Minipress
Terazosin	Hytrin
Doxazosin	Cardura
Acebutolol	Sectral
Atenolol	Tenormin
Betaxolol	Betopic, Kerlone
Bisoprolol	Zebeta
Esmolol	Brevibloc
Metoprolol	Lopressor, Toprol Twoscore
Carteolol	Cartrol
Nadolol	Corgard
Penbutolol	Levatol
Pindolol	Visken
Propanolol	Inderal
Sotalol	Betapace
Timolol	Blocadren
Labetalol	Trandate, Normodyne
Salmeterol	Serevent
Albuterol	Proventil, Ventolin
Bitolterol	Tornalate
Isoetharine	Bronkosol
Metaproterenol	Alupent, Metaprel
Pirbuterol	Maxair
Terbutaline	Serevent
Guanethidine	Ismelin
Reserpine	-----

jonesdiguest.blogspot.com

Source: https://www.uky.edu/~mtp/OBI836AR.html

Share this post