Drugs Affecting the Autonomic Nervous System NRSG 305 – Pharmacology in Nursing by Joanna Shedd, MS, RN

Autonomic Nervous System Parasympathetic>preganglionic>postganglionic>release ach>binds to cholinergic nerves> Muscarinic Sympathetic>preganglionic>post ganglionic>release ach> postganglionic>release NE>binds to adrenergic>alpha and beta Refer to cheat sheet on page 481

Peripheral Nervous System Somatic nervous system – voluntary control over skeletal muscle Autonomic nervous system – involuntary control over the contraction of smooth muscle, cardiac muscle, gland secretion

Receptors in the autonomic nervous system Diagram needed

Autonomic Nervous System (ANS) Sympathetic – “flight or fight” Ready for immediate stress Increase of body systems Parasympathetic – “rest and digest” Nonstressful conditions Decrease body systems Digestion increased

Synapse Communication between neurons, muscles and glands Connection of neurons Synapse – end point of one neuron junction (presynaptic), synaptic cleft, and start of new neuron (postsynaptic)

Drug Effects Affect synthesis of neurotransmitters Prevent storage of neurotransmittters Influence the release of neurotransmitters Bind to the receptor site of postsynaptic neuron – increase autonomic function

ANS Neurotransmitters Acetylcholine (Ach) – released by cholinergic nerves Nicotinic receptors – Ach receptors in the preganglionic ganglia, effects similar to effects of nicotine (parasympathetic) Muscarinic receptors – Ach receptors in postganglionic ending in target tissues, similar to effects of amanita muscaria Fungus (northern hemisphere) Deep red mushroom, orange, yellow Cholinergic effects

ANS Transmitters Alpha receptors – alpha1 (vasoconstriction) decrease GI motility, elevate BP, mydriasis alpha 2 (smooth muscle constriction) beta 1 (Positive chronotropic) increases HR (Positive inotropic) contractility beta 2 (Bronchodilator) lungs

Neurotransmitter Disintegration Ach Destroyed by acetylcholinesterase Norepinephrine (NE) Reuptake of NE into nerve terminals for reuse Inactivation by monoamine oxidase (MAO)

Baroreceptor Reflex (negative feedback) The baroreceptor reflex regulates BP The receptors are located in the carotid sinus and aortic arch The brain sends impulses to the ANS When there is a decrease in BP there is vasoconstriction and an increase in CO When there is an increase in BP vasodilation and a decrease in BP

Autonomic Drug Classes Sympathomimetics or adrenergic agonists – stimulate sympathetic system (SNS) Parasympathomimetics or muscarinic agonists – stimulate parasympathetic system (PNS) Parasympathetic = increase cholinergic responses, need to increase secretions

Autonomic Drug Classes Adrenergic antagonists or adrenergic blockers – inhibit SNS Anticholinergics or parasympatholytics or muscarinic blockers – inhibit PNS Anticholinergics = parasympatholytics

Parasympathomimetics AKA – cholinergic agents Cholinergic = parasympathetic Classic – acetylcholine Does not stay long in body, rapidly destroyed after receptor binding Direct acting – bind to cholinergic receptors to produce rest/digest response – AKA muscarinic agonist Indirect acting – avoids destruction of Ach and allow to remain on cholinergic receptors for longer time – AKA cholinesterase inhibitors

Muscarinic Agonists or Parasympathomimetics Muscarinic agonist = cholinergic agent Causes receptor activation The prototype is Bethanechol/ Urecholine Reversibly binds to muscarinic cholingeric receptors Relief of urinary retention postoperatively and post-partum

Adverse effects of Bethanechol Hypotension Bradycardia Increased secretions Exacerbation of asthma

Other Parasympathomimetic Drugs Cevimeline/ Evoxac – tx of dry mouth Pilocarpine/ Isopto Carpine – used for tx of glaucoma (decreases presssure) Acetycholine – minimal therapeutic use – too rapid destruction

Nursing Management Parasympathetic Medications Watch for adverse effects: CI – Lithium: increase CNS depression taken together CI – Adenosine : increase chance heart block Elderly – CNS stimulation: Mistaken belief that symptoms may be effects of old age or age‐related illness

Parasympathomimetics Cholinesterase Inhibitors (indirect acting) Also known as anticholinesterases Prevents the breakdown of Ach which leads to a subsequent increase of ACh at all junctions where ACh is effective Classified as reversible and irreversible

Uses of Cholinesterase Inhibitors Treatment of Myasthenia gravis (increase strength by increasing neuromuscular transmission) Reverse the effects of neuromuscular blockade Occurs naturally in venoms/poisons Can be used as nerve gas

Myasthenia Gravis Ptosis Difficulty swallowing Weakness of skeletal muscles Anticholinesterases will increase Ach at the NMJ and increase muscle strength

Cholinesterase Inhibitors also called acetylcholinesterase Inhibitor Increases acetylcholine Increases glandular secretions Bradycardia Bronchial constriction Increased motility of GI smooth muscle Mild CNS stimulation with regular doses; depression of CNS with toxic levels Take this medication at the same time every day

Precautions and Contraindications with Acetylcholinesterase inhibitors Increases acetylcholine levels (sludge) Not that it will cause, just be cautious with these patient: Obstruction of GI tract Obstruction of the urinary tract Peptic ulcer disease Asthma-bronchial constriction Coronary insufficiency

Common Names Neostigmine/ Prostigmin Physostigmine/ Antilirium Edrophonium/ Tensilon Pyridostigmine/ Mestinon Donepezil/ Aricept

Cholinergic and Myasthenic Crisis Profuse secretions Laryngospasm Bronchoconstriction Convulsions Paralysis Caused by overdose of medications or exacerbation of Myastenia Gravis

Cholinergic and Myasthenic Crisis Extreme muscle weakness Caused by worsening of disease Edrophonium/ Tensilon challenge; if the symptoms are alleviated this is a Myasthenic crisis; if symptoms intensified cholinergic crisis If increasing the meds decreases the s/s=Dz. was the problem. No change=meds are the problem

Treatment of Cholinergic or Myasthenic crisis Cholinergic Crisis Atropine - anticholinergic Ventilatory support Withhold the offending agent

Nursing Management of Cholinergic or Myasthenic crisis CI – mechanical obstruction of GI and urinary Build-up of Ach at junction sites Profuse salivation Increased muscle tone Urinary frequency Bronchoconstriction Bradycardia SLUDGE=salivation, lacrimation, urination, diaphoresis, GI, emesis

Uses of Neuromuscular Blocking Agents Muscle relaxation/paralysis via inhibition of acetylcholine: ACH cause constriction so blocking it=relaxation Facilitation of mechanical ventilation Facilitation of endotracheal intubation Diagnosis of myasthenia gravis

Muscarinic Antagonists/ Parasympatholytic Drugs/ Antimuscarinic Drugs/ Muscarinic Blockers Blocks ACH, opposite of sludge AKA Anticholinergic/ cholinergic blockers Competitively blocks the actions of Ach The prototype is Atropine (blocks muscarinic) Given for the treatment of– pre-anesthetic use to decrease secretions, disorders of the eye, bradycardia, intestinal hypermotility, muscarinic agonist poisoning .

Adverse effects of Atropine Xerostomia (dry mouth) Blurred vision Increase IOP (blocks ach=increased pressure) Urinary retention Constipation Tachycardia Anhidrosis – abnormal deficiency of sweat Anhidrosis, an abnormal deficiency of sweat, can be classified as generalized (complete) or localized (partial). Generalized anhidrosis can lead to life-threatening impairment of thermoregulation. Localized anhidrosis rarely interferes with thermoregulation because it affects only a small percentage of the body’s eccrine (sweat) glands.

Other Anticholinergics Oxybutynin/ Ditropan and Detrol – tx urinary incontinence=blocks ach to decrease urination *Glycopyrrolate/ Robinul – “dry” field pre-anesthesia (respiratory secretions diminished) Scopolamine – motion sickness Ipratroprium bromide – tx of asthma (blocks ach= bronchodilation)

Atropine (Anti-Cholinergic) uses Atropine given to treat:(blocks parasympathetic) Muscarinic poisoning Caused by direct-acting muscarinic agonists and anticholinesterases (SLUDGE) Symptoms are produced by excessive activation of muscarinic receptors Supportive therapy Atropine is the drug of choice for bradycardia and cholinergic crisi

Anti-muscarinic Poisoning-Blocks ACH Too much atropine Atropine is an anti-muscarinic/Anti-cholinergic Overdose of Anti-muscarinic: Caused by some anti-muscarinic drugs Symptoms are due to blockade of muscarinic receptors

Treatment of Anti-muscarinic Poisoning Minimize absorption of antimuscarinic agent- ipecac and activated charcoal Give antidote- Physostigmine acts by interfering with the metabolism of acetylcholine. Given to treat atropine over dose or any other anti-cholinergic crisis

Some Important Terms Muscarinic crisis-Abdominal pain, diarrhea, nausea, vomiting, lacrimation, blurred vision, bronchial hypersecretion due to parasympathetic hyperresponse Cholinergic Crisis-An over-stimulation at a neuromuscular junction due to an excess of acetylcholine (ACh), as of a result of the inactivity (perhaps even inhibition) of acetylcholinesterase, caused by nerve gas, in patients with myasthenia gravis who have overdosed on cholinergic agents, or in surgical candidates, due to an excess of cholinesterase inhibitor given to reverse surgical muscle paralysis Myastenia gravis- is treated with cholinergic drugs in attempt to decrease muscle weakness. Cholinergic drugs increase aceytcholine which stimulates muscles and decreases muscle weakness. Overdose of this drug, or adverse effects of this drug would result in a cholinergic crisis Myasthenic crisis-An acute ↑ in requirement for anticholinesterase therapy or refractoriness to same, diagnosed by a Tensilon test, with transient ↓ of symptoms Nicotinic crisis-Muscle weakness, fasciculations, cramping and dysphagia, due to over depolarization at the neuromuscular junction.

Mustard Gas Poisoning

Indications of Adrenergic Agonists or Sympathomimetics Stimulates alpha 1 Give for treatment of: Hemostasis Nasal decongestant Decreased BP Miosis

Indications of Adrenergic Agonists or Sympathomimetics Alpha 2 No clinical significance in the periphery Centrally there is decrease sympathetic outflow Smooth muscle constriction

Adverse effects of Alpha 1 Hypertension due to vasoconstriction Necrosis of tissues because of lack of blood flow due to vasoconstriction Tachycardia

Indications of Adrenergic Agonists Beta 1 Cardiac arrest Heart failure Shock Atrioventricular block

Indications of Adrenergic Agonists Beta 2 Asthma (bronchodilates) Delay of pre-term labor (relaxes uterine muscles)

Adrenergic Agonists Adverse Effects Beta 1 Tachycardia Angina pectoris

Adrenergic Agonists Adverse Effects Beta 2 agonist Hyperglycemia Tremor

Indications for Epinephrine Usage Treatment of choice for anaphylaxis Alpha and beta adrenergic AV block During cardiac arrest Decrease BP Bronchoconstriction

Adverse effects of Epinephrine Hypertensive crisis Dysrhythmias Angina pectoris Hyperglycemia Necrosis

Adrenergic Agonists/ Receptors Stimulated Isoproterenol: Beta 1 and 2 Dopamine: Dopamine, Beta 1, and Alpha 1 at high doses Dobutamine: Beta 1 Phenylephrine: Alpha 1 Terbutaline: Beta 2 Ephedrine: Alpha 1nd 2, Beta 1 and 2

Indications (reason to give) of Adrenergic Antagonists Blocks Sympathetic Essential hypertension Benign prostatic hyperplasia (BPH) Pheocromocytoma Raynaud’s disease (decreased circulation from vasoconstriction)

Adverse Effects of Alpha Adrenergic Antagonists Blocks sympathetic Orthostatic hypotension Reflex tachycardia Nasal congestion

Adrenergic - Uses Prazosin- HTN Terazosin- HTN and BPH_ Doxazosin- HTN and BPH Tamsulosin- BPH Phentolamine-vasodilation

Therapeutic Indications (reason to use)of Beta Adrenergic Antagonists Angina pectoris Hypertension Cardiac Dysrhythmias

Adverse Effects of Beta Adrenergic Antagonists Beta 1 blocked Causes: Bradycardia Reduced cardiac output Precipitation of heart failure AV heart block Rebound cardiac excitation

Adverse Effects of Beta Adrenergic Antagonists Beta 2 Blocked Causes: Bronchoconstriction Inhibition of glycogenolysis (increased blood sugar)

Beta Blockers Metoprolol Propanolol Selective beta 1 blocker at therapeutic doses Used for HTN, angina, heart failure, and MI Propanolol Non-selective beta blocker Used for HTN, angina, cardiac dysrhythmias, and MI