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Drugs Affecting the Autonomic Nervous System NRSG 305 – Pharmacology in Nursing by Joanna Shedd, MS, RN 1 Autonomic Nervous System • Parasympathetic>preganglionic>post ganglionic>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 2 3 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 4 Receptors in the autonomic nervous system • Diagram needed 5 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 6 7 8 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) 9 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 10 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 11 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 12 Neurotransmitter Disintegration •Ach •Destroyed by acetylcholinesterase •Norepinephrine (NE) •Reuptake of NE into nerve terminals for reuse •Inactivation by monoamine oxidase (MAO) 13 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 14 Autonomic Drug Classes •Sympathomimetics or adrenergic agonists – stimulate sympathetic system (SNS) •Parasympathomimetics or muscarinic agonists – stimulate parasympathetic system (PNS) 15 Autonomic Drug Classes •Adrenergic antagonists or adrenergic blockers – inhibit SNS •Anticholinergics or parasympatholytics or muscarinic blockers – inhibit PNS 16 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 17 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 18 Adverse effects of Bethanechol •Hypotension •Bradycardia •Increased secretions •Exacerbation of asthma 19 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 20 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 21 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 22 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 23 Myasthenia Gravis •Ptosis •Difficulty swallowing •Weakness of skeletal muscles •Anticholinesterases will increase Ach at the NMJ and increase muscle strength 24 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 25 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 26 Common Names •Neostigmine/ Prostigmin •Physostigmine/ Antilirium •Edrophonium/ Tensilon •Pyridostigmine/ Mestinon •Donepezil/ Aricept 27 Cholinergic and Myasthenic Crisis •Cholinergic •Profuse secretions •Laryngospasm •Bronchoconstriction •Convulsions •Paralysis •Caused by overdose of medications or exacerbation of Myastenia Gravis 28 Cholinergic and Myasthenic Crisis •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 29 Treatment of Cholinergic or Myasthenic crisis •Cholinergic Crisis •Atropine anticholinergic •Ventilatory support •Withhold the offending agent 30 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 31 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 32 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– preanesthetic use to decrease secretions, disorders of the eye, bradycardia, intestinal hypermotility, muscarinic agonist poisoning . 33 34 Adverse effects of Atropine •Xerostomia (dry mouth) •Blurred vision •Increase IOP (blocks ach=increased pressure) •Urinary retention •Constipation •Tachycardia •Anhidrosis – abnormal deficiency of sweat 35 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) 36 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 37 Anti-muscarinic Poisoning-Blocks ACH Too much atropine Atropine is an antimuscarinic/Anti-cholinergic Overdose of Anti-muscarinic: •Caused by some antimuscarinic drugs •Symptoms are due to blockade of muscarinic receptors 38 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 39 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. 40 Mustard Gas Poisoning 41 Indications of Adrenergic Agonists or Sympathomimetics •Stimulates alpha 1 Give for treatment of: •Hemostasis •Nasal decongestant •Decreased BP •Miosis 42 Indications of Adrenergic Agonists or Sympathomimetics •Alpha 2 •No clinical significance in the periphery •Centrally there is decrease sympathetic outflow •Smooth muscle constriction 43 Adverse effects of Alpha 1 •Hypertension due to vasoconstriction •Necrosis of tissues because of lack of blood flow due to vasoconstriction •Tachycardia 44 Indications of Adrenergic Agonists •Beta 1 •Cardiac arrest •Heart failure •Shock •Atrioventricular block 45 Indications of Adrenergic Agonists Beta 2 •Asthma (bronchodilates) •Delay of pre-term labor (relaxes uterine muscles) 46 Adrenergic Agonists Adverse Effects •Beta 1 •Tachycardia •Angina pectoris 47 Adrenergic Agonists Adverse Effects Beta 2 agonist •Hyperglycemia •Tremor 48 Indications for Epinephrine Usage •Treatment of choice for anaphylaxis •Alpha and beta adrenergic •AV block •During cardiac arrest •Decrease BP •Bronchoconstriction 49 Adverse effects of Epinephrine •Hypertensive crisis •Dysrhythmias •Angina pectoris •Hyperglycemia •Necrosis 50 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 51 Indications (reason to give) of Adrenergic Antagonists Blocks Sympathetic •Essential hypertension •Benign prostatic hyperplasia (BPH) •Pheocromocytoma •Raynaud’s disease (decreased circulation from vasoconstriction) 52 Adverse Effects of Alpha Adrenergic Antagonists Blocks sympathetic •Orthostatic hypotension •Reflex tachycardia •Nasal congestion 53 Adrenergic - Uses •Prazosin- HTN •Terazosin- HTN and BPH_ •Doxazosin- HTN and BPH •Tamsulosin- BPH •Phentolamine-vasodilation 54 Therapeutic Indications (reason to use)of Beta Adrenergic Antagonists •Angina pectoris •Hypertension •Cardiac Dysrhythmias 55 Adverse Effects of Beta Adrenergic Antagonists Beta 1 blocked Causes: •Bradycardia •Reduced cardiac output •Precipitation of heart failure •AV heart block •Rebound cardiac excitation 56 Adverse Effects of Beta Adrenergic Antagonists Beta 2 Blocked Causes: •Bronchoconstriction •Inhibition of glycogenolysis (increased blood sugar) 57 Beta Blockers •Propanolol •Non-selective beta blocker •Used for HTN, angina, cardiac dysrhythmias, and MI •Metoprolol •Selective beta 1 blocker at therapeutic doses •Used for HTN, angina, heart failure, and MI 58 59