Drugs Affecting the Autonomic Nervous System

BETA2 - name alpha adrenergic and Beta adrenergic agonists and describe the main pharmacological EFFECTS and uses of each. ***bronchodilation +Objective

(3 Beta-Adrenergic Drugs) * Effect - bronchodilation * Use - bronchospasm, asthma, bronchitis * SE - nervousness, restlessness * CI - severe cardiac disease, HTN * note: if patient has HTN give steroid instead given side effect and contra indications

BETA1 - NAME alpha adrenergic and Beta adrenergic agonists and describe the main pharmacological effects and uses of each. 2 +Objective

(3 Beta-Adrenergic Drugs) 3• DOPAMINE - alpha-1 & beta-1 stimulation * Use - Hypotension, shock, increase cardiac output, improve perfusion to vital organs * SE - N & V, headache * CI - V. Tach 2• EPINEPHRINE - stimulates alpha 1,2 & beta 1,2 * Use - allergic reaction, cardiac arrest * SE - nervousness, agitation * CI - cardiac dysrhythmias + DOBUTAMINE (on chart) b-1

*Cholinergic drugs - DIRECT ACTING DRUGS + STIMULATES SECRETION OF ACh

* Directly stimulates the nerve ending to secrete acetylcholine * Bethanechol (Urecholine) - Used to treat urinary retention

NAME direct and indirect acting cholinergic drugs and the effects they produce. P2 - INDIRECT NAMES +Objective

* Drugs:Physostigmine, Neostigmine, donepezil • NEOSTIGMINE (Prostigmine) (anticholinesterASE) • PROTOTYPE - Primarily used to treat Myasthenia Gravis (notes:muscle weakness - so muscle can work) • DONEPEZIL (Aricept) • Works in the CNS to inhibit synthesis of Acetylcholinesterase • Used to treat Alzheimer's disease

BETA1 - name alpha adrenergic and Beta adrenergic agonists and describe the main pharmacological EFFECTS and uses of each. +Objective

* Use - Hypotension, shock, increase cardiac output, improve perfusion to vital organs * Use - allergic reaction, cardiac arrest * SE - N & V, headache, nervousness, agitation * CI - V. Tach , cardiac dysrhythmias * Note: if you don't know the patient's history give an epipen, it covers both a-1,2 and b-1,2

*Cholinergic drugs

* increase Acetylcholine in the Synapse + Use for: - Glaucoma - Reduce intraocular pressure - Myasthenia gravis - Disease caused by the lack of ACh at the synapse - Relief of urinary retention - Increase GI motility

MOA - Mechanism of action

* the explanation of how a drug produces its intended therapeutic effect * how the drug works

P1-Name the three (3) different adrenergic receptors and describe the actions they mediate (ALPHA) +Objective add graph

*ALPHA-1 Alpha-adrenergic receptors are located on: - smooth muscle membranes and cause smooth muscle CONTRACTION when stimulated by NE, EPI, or drugs (that look like NE or EPI) - Causes vasoconstriction of most arteries and veins - notes: drugs given to patient with congestion - it constricts to INCREASE BP; circulation is NG; HYPOtensive patient *ALPHA-2 ALPHA 2 (located on presynaptic terminal) **RED**Controls the release of norepinephrine

*Anticholinergic Medication 3 (not in objective section)

+ Anticholinergic, or antimuscarinic, drugs have been used for the treatment of more or less specified gastrointestinal diseases or complaints for many centuries, first in herbal preparations (including belladonna), and in modern times as synthetic tertiary or quaternary compounds, with atropine being a pharmacological standard.

*Cholinergic drugs - ADVERSE REACTIONS

- Bradycardia (low HR) - Hypotension - Headache, dizziness - Increased secretions - Abdominal cramping - Increased respiratory secretions and possibly bronchospasms

BETA2 - NAME alpha adrenergic and Beta adrenergic agonists and describe the main pharmacological effects and uses of each. 2 +Objective

1• ALBUTEROL - Beta-2 agonist (bronchodilation) * Use - bronchospasm, asthma, bronchitis + TERABUTALINE (on chart) b-2 + ISOPROTERENOL (on chart) b-1,2 + EPINEPHRINE (on chart) a-1,2, b-1,2

+DRUG PROTOTYPE

A representative drug from a drug class, it is usually the most studied member of each class and other drugs in that class are noted merely for their differences when compared to it. It eases the learning of pharmacology Most prescribed drug

*Adrenergic (Beta-1) BLOCKING drugs ADVERSE REACTIONS

ADRENERGIC BETA-1 BLOCKING DRUGS • Adverse reactions - Drowsiness, fatigue - Bradycardia (HR < 60) - Hypotension - Orthostatic hypotension (dizzy when getting up) - Diarrhea

+RECEPTORS / RECEPTOR SITES

ALPHA 1 - vasoconstriction/sm contraction ALPHA 2 - decreases NE and therefore BP BETA 1 - mostly dominant on heart BETA 2 - mostly dominant on lungs there are more, but prof. notes these are enough...

+RECEPTOR Responses to Stimulation

ALPHA 2 (located on presynaptic terminal) - **RED** Control the release of norepinephrine * notes: works in CNS Axon * neurotransmitter stored in vesicles * neurotransmitter released into synapse Enzymes in cleft destroy neurotransmitter *** or *** Dendrite (on) Neurotransmitter attaches to receptor

ALPHA2 - name alpha adrenergic and Beta adrenergic agonists and describe the main pharmacological EFFECTS and uses of each. ***centrally-acting vasoDILATORS +Objective

ALPHA-2 adrenergic agonists • α2- agonists (centrally-acting vasoDILATORS) • Decrease blood pressure

Describe the two divisions of ANS and explain how they differ +Objective

ANS is divided into 2 divisions: - Parasympathetic (peace/rest/relax) - Sympathetic (stress/fight/flight) • Parasympathetic nerves originate from: - Cranial and sacral spinal nerves also called the craniosacral division • Sympathetic nerves originate from: - Thoracic and lumbar spinal nerves - also called the thoracolumbar division • Almost all visceral organs and glands receive:a nerve branch from each division * each organ has both receptors so we can rest when we need to - one calms/one stresses Difference: One division INCREASES the activity of the gland or organ while the other division DECREASES activity

+Adrenergic drugs

Adrenergic drugs are also called adrenergic amines or sympathomimetic drugs. They are medicines that work by stimulating the sympathetic nervous system (SNS). The SNS is part of the automatic nervous system (ANS). It helps to regulate your body's reaction to stress or an emergency. During these times, the SNS releases chemicals called neurotransmitters from the adrenal gland. These chemicals act on your body to increase heart rate, sweating, and breathing rate, and decrease digestion. The response by your body is sometimes called the "fight or flight" response.

+How Do Adrenergic Drugs Work?

Adrenergic drugs stimulate the adrenergic nerves. The structures of the drugs closely resemble the neurotransmitters that your body produces during times of stress, such as norepinephrine. Norepinephrine acts directly on the adrenergic receptors. Therefore, adrenergic drugs are able to interact with the same receptor sites as the neurotransmitter.

Explain how the adrenergic nerve endings function both to release and inactivate norepinephrine. +Objective

Adrenergic/Sympathetic NEUROTRANSMITTERS (neurohormones) CATECHOLAMINES - when nerve is agitated, they are secreted - Epinephrine (prototype) - secreted by Adrenal gland (medulla) at top of kidney, direct response at nerve ending - Norepinephrine - secreted by Adrenal gland. Stored @ cleft in the axon, direct response at the nerve ending as well - NE and EPI are inactivated by neuronal reuptake back into the nerve ending for reuse or metabolism by Monoamine oxidase (MAO) **RED**

ALPHA1 - name alpha adrenergic and Beta adrenergic agonists and describe the main pharmacological EFFECTS and uses of each. ***systemic vasoCONSTRICTORS +Objective

Alpha-1 adrenergic agonists Alpha-1 Adrenergic drugs α1- agonists (systemic vasoCONSTRICTORS) • Alpha 1 Therapeutic Uses - Control topical superficial bleeding - Treat nasal congestion - Elevate blood pressure-INCREASE BP - Delay absorption of local anesthesia-constriction increases & increases 100x & stays in area longer; longer numbing time - Decrease intraocular pressure (pressure in eye) * if patient has an hypertension, can cause issues - don't give if there is high BP, diabetic, BPH - benign prostrate hypertension (would constrict more) • ADVERSE EFFECTS VS. THERAPEUTIC EFFECTS - Increased HR (tachycardia) - Increased Blood pressure - Decreased Gastric motility - Restlessness, irritability, anxiety, pallor - Increased Alertness

+Alpha 1 adrenergic blocking agents

Alpha-blockers, α-blockers, or α-adrenergic-antagonists are pharmacological agents that act as receptor antagonists of α-adrenergic receptors (α-adrenoceptors) • May activate reflexes that oppose fall in BP such as SIDE EFFECT: fluid retention and increased heart rate • Can prevent alpha medicated contraction of smooth muscle in nonvascular tissues • Useful in treating BPH (benign prostrate hypertension-on surface of prostrate alpha-1 receptors are dominant) inhibits contraction of muscles in prostate and bladder (if you block the receptors it has to dilate)

+WHAT ARE ADRENERGIC NERVE FIBERS?

An adrenergic nerve fibre is a neuron for which the neurotransmitter is either adrenaline (epinephrine), noradrenaline or dopamine. Adrenergic nerve terminals are found in the secondary neurons of the sympathetic nervous system (SNS), controlling amongst other things heart rate and force of contraction. ADRENERGIC RECEPTORS

*Anticholinergic Medication Adverse reactions / Side effects (not in objective section)

Anticholinergic drugs • OXYBUTYNIN (DITROPAN) • Synthetic antimuscarinic + INCREASES BLADDER CAPACITY - DECREASES FREQUENCY OF VOIDING • TOLTERODINE (DETROL, DETROL LA) • Synthetic antimuscarinic - DELAYS THE URGE TO VOID - INHIBITS BLADDER CONTRACTIONS - Dry mouth - Blurred vision - Photophobia - intolerance to visual perception of light - Urinary retention - Constipation - Tachycardia (high HR > 100) - Drowsiness

P2-Name the three different adrenergic receptors and describe the actions they mediate (BETA) +Objective

BETA-1 - HEART Beta-1 receptors are located primarily: Heart Activation of the BETA-1 receptor 1* INCREASE the force of myocardial contraction 2* INCREASE the rate of contraction 3* EXCESS stimulation leads to arrhythmias BETA-2 - LUNGS - relaxing Beta-2 receptors are mostly located on: * smooth muscle and cause relaxation of smooth muscle, especially bronchiolar and uterine smooth muscle Activation of the BETA-2 receptor 1* bronchoDILATION and a DECREASE in airway resistance 2* RELAXATION of non vascular and vascular smooth muscle

+Cholinergic Drugs

Cholinergic agonists mimic the actions of acetylcholine. Cholinergic transmission involves the neurotransmitter acetylcholine being released from nerve fibers, binding to designated receptors on other cholinergic nerve fibers and passing on the message to bring about a response. Stimulation of the cholinergic system (also known as the parasympathetic nervous system) causes vasodilatation, constriction of pupils in the eyes, secretion of sweat, saliva and tears, slow heart rate, mucus secretion in the respiratory tract and constriction of bronchioles.

*Anticholinergic Medication 1 (not in objective section)

Competitive antagonists - Compete with ACh - Inhibit nerve transmission • Sites of action - All systems except musculo-skeletal USES - Increase heart rate - Treat ureteral colic (paroxysm of pain due to abrupt obstruction of ureter from a calculus or blood clot in most instances) - Decrease GI motility - Parkinson's disease (degenerative disorder of CNS) - Decrease upper respiratory secretions

NAME direct and indirect acting cholinergic drugs and the effects they produce. P1 - DIRECT EFFECTS & NAME +Objective

DIRECT acting Cholinergic drugs o Directly stimulates the nerve ending to secrete acetylcholine * BETHANECHOL (Urecholine) - Used to treat urinary retention - simulates bladder to empty

*Anticholinergic Medication 2 (not in objective section)

EXAMPLES - used for GI issues - BENTYL (dicyclomine HCL) • Antispasmotic used to decrease intestinal cramping in IBS - ATROPINEA (Prototype/standard) • Acetylcholine antagonist • Antidysrhythmic • Antispasmodic • Antisecretory

Body Tissue/Organ Parasympathetic Response 'Peace-Rest-Relax'

Eye - constricts pupil Lungs - constricts bronchioles and increases secretions Heart - decreases heart rate Blood vessels - dilates blood vessels GI - increases peristalsis of GI tract Bladder - constricts bladder muscle Salivary gland - increases salivation

+Body Tissue/Organ Sympathetic Response 'Stress-Fight-Flight'

Eye - dilates pupil Lungs - dilates bronchioles - b-2 Heart - increase heart rate - b-1 Blood vessels - constricts blood vessels - a-1 GI - relaxes smooth muscles of GI tract Bladder - relaxes bladder muscle Uterus - relaxes uterine muscle

NAME direct and indirect acting cholinergic drugs and the effects they produce. P2 - INDIRECT EFFECTS +Objective

INDIRECT acting Cholinergic drugs (notes: inhibits production of AcetylcholinesterASE / anti-cholinesterase) * allows accumulation of ACh at all 3 cholinergic receptor sites • used to treat Myasthenia Gravis (notes:muscle weakness - so muscle can work) * Works in the CNS to inhibit synthesis of Acetylcholinesterase

+P3 Name the three different adrenergic receptors and describe the actions they mediate (DOPAMINE RECEPTORS) alpha-1 - vascular beta-1 - heart +Objective

Located in various tissues and organs • DOPAMINE - alpha-1 & beta-1 stimulation and causes dilation of renal, mesenteric, coronary and cerebral arteries - Use - Hypotension, shock, increase cardiac output, improve perfusion to vital organs • SE (side effects) - N (nausea) & V (vomiting), headache • CI-(contra indicated) Ventricular tachycardia (V-tach or VT - HR > 100)

+Beta-1 (EPI and NE) INCREASE

Locations: heart, myocardium, conduction system Actions: Stim INCREASES, FOC INCREASES, HR INCREASES

+Beta-2 (EPI and NE) INCREASE

Locations: lungs, blood vessels Actions: Stim INCREASES, Smooth Muscle Contraction DECREASES, Bronchodilation INCREASES

+Alpha-2 (EPI and NE) PRESYNAPTIC - DECREASE

Locations: organs, smooth muscle, glands, arteries, veins Actions: Stim INCREASES, EPI and NE Release DECREASES, HR DECREASES, BP DECREASES

+Alpha-1 (EPI and NE) VASCULAR - INCREASE

Locations: organs, smooth muscle, glands, arteries, veins Actions: Stim INCREASES, Vasoconstriction INCREASES, HR INCREASES, BP INCREASES

Explain the EFFECTS of acetylcholine on the major internal organs and glands of the body +Objective

Mechanism of Action MOA Direct acting cholinergic drugs are synthetic derivative of choline. • Effects of drug - Decrease heart rate, vasodilation, and changes in BP - Increase tone and contractibility of smooth muscle - Increase tone and contractibility of bronchial smooth muscles - Increased respiratory secretions

List the most frequently observed adverse effects of both cholinergic and anticholinergic drug therapy. ANTICHOLINERGIC +Objective

Note: Dizziness & GI are common side effects for all drugs Anticholinergic - ADVERSE REACTIONS/SIDE EFFECTS - Dry mouth - Blurred vision - Photophobia - Urinary retention - Constipation - Tachycardia (high HR > 100) - Drowsiness

List the most frequently observed adverse effects of both cholinergic and anticholinergic drug therapy. CHOLINERGIC +Objective

Note: Dizziness & GI are common side effects for all drugs Cholinergic drugs - ADVERSE REACTIONS - Bradycardia (low HR < 60) - Hypotension (low BP) - Headache (congestion comes with), dizziness - Increased secretions - Abdominal cramping - Increased respiratory secretions and possibly bronchospasms

Describe the neuronal release and activation of acetylcholine +Objective

Parasympathetic (Cholinergic) Nervous System (PNS) • NEUROTRANSMITTER (neurohormone) • Acetylcholine - Produced and stored in nerve endings • Acetylcholine (ACh) binds to Cholinergic receptor (NOT a beta or an alpha receptor) sites and causes a response ***RED***• Stimulation results in "rest and digest' Notes: need ACh for action potential

Describe the fight or flight reaction and explain how it affects the activities of the different organs. +Objective

SNS • Sympathetic nervous system - Fight or Flight - Useful in highly stressful or emergency situations • SYMPATHETIC - Adrenergic (sympathomimetic) • MIMICS THE SYMPATHETIC SYSTEM in contrast with • Adrenergic blocking (sympatholytic)

+WHAT IS THE AUTONOMIC NERVOUS SYSTEM?

The Autonomic Nervous System (ANS) is the involuntary division of the nervous system. It consists of autonomic neurons that conduct impulses from the central nervous system (brain and/or spinal cord) to glands, smooth muscle and cardiac muscle. ANS neurons are responsible for regulating the secretions of certain glands (i.e., salivary glands) and the regulation of heart rate and peristalsis (contraction of smooth muscle in the digestive tract), among other functions

+What are adrenergic receptors? TARGETS OF CATECHOLAMINES - EPI & NE

The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines, "especially norepinephrine (noradrenaline) and epinephrine (adrenaline)." Many cells possess these receptors, and the binding of a catecholamine to the receptor will generally stimulate the sympathetic nervous system. The sympathetic nervous system is responsible for the fight-or-flight response, which includes widening the pupils of the eye, mobilizing energy, and diverting blood flow from non-essential organs to skeletal muscle.

+autonomic receptors

The general class of adrenoceptors can be further sub- divided into alpha-adrenoceptor, beta-adrenoceptor, and dopamine- receptor types on the basis of both agonist and antagonist selectivity and on genomic grounds. adreno-ceptor is widely used to describe receptors that respond to catecholamines such as norepinephrine. By analogy, the term cholinoceptor denotes receptors (both muscarinic and nicotinic) that respond to acetylcholine. receptors were colloquially named after the nerves that usually innervate them; thus, adrenergic (or noradrenergic) receptors and cholinergic receptors.

+WHAT IS THE ROLE OF AUTONOMIC NERVOUS SYSTEM?

The role of the ANS is to constantly fine-tune the functioning of organs and organ systems according to both internal and external stimuli. The ANS helps to maintain homeostasis (internal stability and balance) through the coordination of various activities such as hormone secretion, circulation, respiration, digestion and excretion. The ANS is always "on" and functioning unconsciously, so we are unaware of the important tasks it is performing every waking (and sleeping) minute of every day.

Explain how sympathetic and parasympathetic nerves interact with each other to regulate organ function (maintain Homeostasis). +Objective

The sympathetic and parasympathetic nervous systems have opposite responses on body tissues and organs. different neurotransmitters released by post synaptic neurons and different receptors in plasma membrane receptors PNS • Parasympathetic nervous system - Maintains homeostasis - Works in "opposition" of the SNS - "Rest and Digest" • PARASYMPATHETIC - Cholinergic (parasympathomimetic) - MIMICS THE PARASYMPATHETIC NERVOUS SYSTEM in contrast with - Cholinergic blocking (parasympatholytic)

Several types of adrenergic receptors in the body

There are several types of adrenergic receptors in the body. The specific action of the drug depends on which type of the adrenergic receptor is affected. It also depends on whether or not the drug acts directly on the receptor or indirectly by stimulating the release of neurotransmitters. The receptors include: alpha-1 alpha-2 beta-1 beta-2

+adrenergic

adrenergic /ad·ren·er·gic/ (ad″ren-er´jik) 1. activated by, characteristic of, or secreting epinephrine or related substances, particularly the sympathetic nerve fibers that liberate norepinephrine at a synapse when a nerve impulse passes. 2. any agent that produces such an effect. See also under receptor.

+acetylcholinesterase inhibitor (often abbreviated AChEI) or anti-cholinesterase

chemical that inhibits the acetylcholinesterase enzyme from breaking down acetylcholine, thereby increasing both the level and duration of action of the neurotransmitter acetylcholine. Reversible, quasi-irreversible (or pseudirreversible in some sources) and irreversible inhibitors exist.[1]

P0-Name the three (3) different adrenergic receptors and describe the actions they mediate +Objective

dopomine, NE, EPI alpha 1,2 , beta 1,2 , dopomine a1 - dilates eyes, vessels, bladder a2 - decreases insulin, neurotransmitter in neuromuscular junctions b1 - increase HR and H conduction b2 - dilates vessels & bronchioles (for asthma), relaxes uterus dopomine - in various tissues/organs - dilates renal, mesenteric, coronary and cerebral arteries

+PRODRUG

has to be activated e.g. alpha-methyl-NE

+Examples of the affects adrenergic drugs can have on the body include:

increasing blood pressure constricting blood vessels opening the airways leading to the lungs increasing heart rate stopping bleeding

++muscarinic

relating to, resembling, producing, or mediating the effects (as a slowed heart rate, increased secretion by exocrine glands, and increased activity of smooth muscle) that are produced on organs and tissues by acetylcholine liberated by postganglionic nerve fibers of the parasympathetic nervous system and that are mimicked by muscarine <muscarinic receptors> <atropine is a muscarinic antagonist>—compare nicotinic

++nicotinic

relating to, resembling, producing, or mediating the effects that are produced by acetylcholine liberated by nerve fibers at autonomic ganglia and at the neuromuscular junctions of voluntary muscle and that are mimicked by nicotine which increases activity in small doses and inhibits it in larger doses <nicotinic receptors>—compare muscarinic

+adrenergic receptors

the adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline). Many cells possess these receptors, and the binding of a catecholamine to the receptor will generally stimulate the sympathetic nervous system. The sympathetic nervous system is responsible for the fight-or-flight response, which includes widening the pupils of the eye, mobilizing energy, and diverting blood flow from non-essential organs to skeletal muscle.

+* Monoamine oxidase (MAO)

very important - NE and EPI are inactivated by neuronal reuptake back into the nerve ending for reuse or metabolism by Monoamine oxidase (MAO) **RED**

*Adrenergic (Beta-1) BLOCKING drugs NAMING CONVENTION

xxxOLOL - DRUG NAMING CONVENTION • Beta-adrenergic blocking drugs - BETA 1 • Cardiovascular: Predominately works on vascular smooth muscle of the heart. - Cardiac muscle: increased contractility - Atrioventricular node: increased heart rate - Sinoatrial node: increase in heart rate • Beta-adrenergic blocking drugs (20+ exist) - XXXOLOL - Propranolol (Inderal) on chart - b-1,2 - Nadolol (Corgard) on chart - b-1,2 - Atenolol (Tenormin) on chart - b-1 (selective) - Timolol (Timoptic) on chart - b-1,2 + Metoprolol not on chart - b-1 * note: it's not telling if selective vs. non-selective

+Alpha 1 antagonists/blockers

xxxOSIN • Minipress (PRAZOSIN)—prototype (on chart) • Hytrin (terazOSIN) & Cardura (doxazOSIN)—both are longer acting than Minipress. • Flomax (tamsulosin). Used in BPH. Produces smooth muscle relaxation of prostate gland and bladder neck. Minimal orthostatic hypotension. Note: w/ air travel works on blood vessels and feet - could cause fluid retention in ankles and can cause thrombosis which circulates while sleeping and you die

ALPHA1 - NAME alpha adrenergic and Beta adrenergic agonists and describe the main pharmacological effects and uses of each. XXXINE / VASCULAR +Objective

• Adrenalin (epinephrINE) MOA(mechanism of action-how drug works): affects BOTH the beta 1 (cardiac/heart) and beta 2 (pulmonary/lung) receptors - produces bronchodilation - inhibits hypersensitivity reaction of mast cells. - Cardiac arrest - Anaphylactic shock-EpiPen • Nasal decongestants (OTC) * phenylephrINE - (Neo-Synephrine) a-1 * PseudoephedrINE (Sudafed) (not on chart) * OxymetazolINE (on chart) a-1,2 * tetrahydralazINE (not on chart) * xylometazolINE (not on chart) + DopamINE (on chart) a-1, b-1 + methoxamINE (on chart) a-1 + norepinephrine (on chart) a-1,2; b-1 + epinephrINE (on chart) a-1,2; b-1,2

*Functions of sympathetic nervous system receptors Review ?

• Alpha 1: receptors are in blood vessels, kidney, liver, pregnant uterus, male sexual organs, intestinal smooth muscle. Causes vasoconstriction, decreased renin secretion, uterine —smooth muscle contraction • Alpha 2: negative feedback causes less norepinephrine to be released so BP is reduced • Beta 1: increased heart rate • Beta 2: affects lungs, liver, blood vessel vasodilation, decreased motility and tone • Dopamine—blood vessels of kidneys, heart, brain.

ALPHA2 - NAME alpha adrenergic and Beta adrenergic agonists and describe the main pharmacological effects and uses of each. XXXINE / PRESYNAPTIC +Objective

• CLONIDINE (Catepres) , Guanabenz and guanfacine - are structurally related compounds and have similar antihypertensive profiles • sometimes used for management of Opioid withdrawal • α-METHYLDOPA: is a structural analog of dopa(mine) and functions as a PRODRUG. After administration, α-methyldopa is converted to α-METHYNOREPINEPHRINE, which then serves as the α2-agonist in the medulla to decrease sympathetic outflow. * OxymetazolINE (on chart) a-1,2 + norepinephrINE (on chart) a-1,2; b-1 + epinephrINE (on chart) a-1,2; b-1,2

*CHOLINERGIC Mechanism of Action -MOA

• Direct acting cholinergic drugs are synthetic derivative of CHOLINE. • Effects of drug - Decrease heart rate, vasodilation, and changes in BP - Increase tone and contractibility of smooth muscle - Increase tone and contractibility of bronchial smooth muscles - Increased respiratory secretions

*Acetylcholinesterase (aka:cholinesterase)

• Enzyme - Breaks down Acetylcholine or limits response • Maintains the balance between acetylcholine and dopamine

*Parasympathetic (Cholinergic) Nervous System +PEACE

• NEUROTRANSMITTER (neurohormone) • Acetylcholine - Produced and stored in nerve endings • Acetylcholine (ACh) binds to Cholinergic receptor sites and causes a response ***RED***• Stimulation results in "rest and digest'; peace

*Cholinergic drugs - INDIRECT ACTING DRUGS + INHIBITS BREAKDOWN OF ACh + INCREASES LEVEL & DURATION OF ACTION OF ACh

• Neostigmine (Prostigmine) (anticholinesterase) prototype * Primarily used to treat Myasthenia Gravis • Donepezil (Aricept) *Works in the CNS to inhibit synthesis of Acetylcholinesterase * Used to treat Alzheimer's disease