Ans Drugs - Autonomic Nervous System PDF

U C ANS DRUGS C Autonomic Nervous System Instructor: CHERMAINE F. CORPUZ  O PARASYMPATHETIC SYMPATHETIC CH...

U C ANS DRUGS C Autonomic Nervous System Instructor: CHERMAINE F. CORPUZ  O PARASYMPATHETIC SYMPATHETIC CHOLINERGICS ADRENERGICS FUNCTIONS Enhance the action of acethycholine, They produced effects similar to those produced stimulating the Parasympathetic Nervous by the Sympathetic Nervous Sytem System. PNS - Conserve energy & regulate bodily O SNS - Triggered in times of stress, in danger or when a person is physically active functions like digestion & urination. - “fight or flight” - “rest & digest” NEUROTRANSMITTER ACETHYLCHOLINE – excitatory ADRENALINE (EPINEPHRINE) - carries messages from brain to body - blood vessels nerve O NORADRENALINE (NOREPINEPHRINE) - heart RECEPTORS Alpha & Beta Receptors Alpha Adrenergic Receptors Beta Adrenergic Receptors Dopamine Receptors EFFECT Mimics Ach: Mimics NE: 8 PARASYMPATHOMIMETICS/Cholinergic SYMPATHOMIMETICS/Adrenergic Agonist 8 Agonist Blocks NE: Blocks Ach: SYMPATHOLYTICS/Adrenergic Antagonist PARASYMPATHOLYTICS/Cholinergic Antagonist BODY TISSUE/ORGAN SYMPATHETIC RESPONSE PARASYMPATHETIC (sites) RESPONSE EYE DILATE PUPILS CONSTRICT PUPILS LUNGS DILATE BRONCHIOLES CONSTRICT BRONCHIOLES/INCREASE SECRETION/ SALIVATION HEART INCREASE HEART RATE DECREASE HEART RATE BLOOD VESSELS CONSTRICT BLOOD VESSELS DILATE BLOOD VESSELS GASTRO RELAXES SMOOTH MUSCLES OF INCREASE PERISTALSIS GI BLADDER RELAX BLADDER MUSCLES CONSTRICTS BLADDER UTERUS RELAX UTERINE MUSCLES  DRUG GROUPS THAT AFFECT THE SYMPATHETIC NERVOUS SYSTEM 1. Adrenergic Agonist/Adrenergics/ Sympathomimetics - drugs that stimulates the Sympathetic Nervous System because they or mimic the neurotransmitters norepinephrine & epinephrine EFFECT AT RECEPTORS RECEPTOR PHYSIOLOGIC RESPONSE Alpha1 increases force of heart contraction, vasoconstriction, increase BP, mydriasis (dilation of pupils), secretion in salivary glands decreases, urinary bladder relaxation and urinary sphincter contraction increases Alpha2 inhibits release of norepinephrine, dilates blood vessels, produces hypotension, decreases GI motility and tone Beta1 increases heart rate and force of contraction, increases renin secretion, which increases BP Beta2 dilates bronchioles, promotes GI & uterine relaxation, promotes increase in blood glucose through glycogenolysis in liver, increase blood flow in skeletal muscles CLASSIFICATION OF SYMPATHOMIMETICS 3 Categories: o_0 1. Direct-acting - directly stimulate the adrenergic receptor ex. epinephrine or norepinephrine 2. Indirect-acting - stimulate the release or norepnephrine from the terminal nerve endings ex. amphetamine 3. Mixed-acting - stimulate the adrenergic receptor sites and 55880 stimulate the release of norepinephrine from the terminal nerve endings ex. pseudoephedrine 2 chemical structures: a Catecholamines - produces sympathomimetic response 1. endogenous - ex. epinephrine, norepinephrine & dopamine 2. synthetic - ex. isoproterinol & dobutamine FEEL Non-catecholamines - stimulate the adrenergic receptors - most have a longer duration of action than the endogenous or synthetic catecholamines ex. phenylephrine, metaproterenol & albuterol EPINEPHRINE - cardiac stimulant  Dobutamine (dobutrex) C Sympathomimetic, increase force for cardiac contraction H Improve blood flow through adequate heart pumping E Administered as a continuous intravenous infusion in acute emergencies C Monitor urine output, ECG, BP Common side effects: nausea, vomiting, fever, headache, leg cramps Report signs of an allergic reaction: hives, difficulty of breathing swelling of face, lips, tongue and throat During administration report any signs of dyspnea, chest pain, headache and IV site discomfort K Do not mix with alkaline solution For adults: 2.5-10mcg is the usual IV rate For congestive heart failure management in adults: initial dose: 0.5-1mcg/kg/min Maintenance dose: 2-20mcg/kg/min IV infusion Maximum dose: 40mcg/kg/min IV infusion  Dopamine HCL C Inotropic, Dopaminergic H Adequate renal perfusion, stronger heart contractions E Administer as prescribed C Side effects: nausea, vomiting, palpitation, hypotension K When extravasation occurs, have phentolamine ready Calculate extreme caution Remember that doses of dopamine come in: 40, 80 and 160mg/dl Conversion: 1000mcg=1 mg  ADRENERGIC AGONIST Ephedrine HCL; For hypotension and bronchospasm. May cause weakness, restlessness, Ephedrine sulfate: headache dizziness, tremor, dysrhythmia, tachycardia, HPN and palpitations Norepinephrine For acute hypotension, cardiogenic shock, and septic shock. Monitor BP and bitartrate rhythm every 2-5mins during infusion. May cause anxiety, headache confusion, bradycardia, hypertension, pulmonary edema, dyspnea, tissue necrosis Phenylephrine HCL For sinus and nasal congestion, hypotension and shock, glaucoma, pupillary dilation. Have patient blow nose before drug is administered. May cause headache, blurred vision, nasal irritation, tachycardia, tissue necrosis Albuterol For bronchospasm. May cause headache, nasopharyngitis, tremor, dizziness, nausea, vomiting, muscle cramps, infection, palpitations, tachycardia and palpitations Terbutaline sulfate For acute bronchospasm. May cause nervousness, tremors, dizziness, confusion, fatigue, pruritus, abdominal pain, nausea, vomiting, hyperglycemia, hypotension and hypokalemia Clonidine HCL For hypertension. May cause dizziness, drowsiness, hypotension, depression, bradycardia, peripheral edema, angina, constipation, erectile/ejaculatory dysfunction CENTRAL-ACTING ALPHA AGONISTS Alpha2 drugs - produce vasodilation by stimulating alpha2 receptors in the CNS leading to decrease in BP Clonidine - selective alpha2 adrenergic agonist used primarily to treat hypertension - may produce bradycardia, hypotension, sedation & dry mouth at very low doses Methyldopa - alpha-adrenergic agonist that acts within the CNS - not used much as antihypertensive due to SE 2. Adrenergic Antagonist/Adrenergic Blockers/ Symphatholytics - drugs that block the effects of adrenergic neurotransmitters - act as antagonist to adrenergic agonists by blocking the alpha and beta-receptor sites EFFECT AT RECEPTORS RECEPTOR PHYSIOLOGIC RESPONSE Alpha 1 vasodilation, decreases BP, reflex tachycardia might result, miosis (constriction of pupils), suppresses ejaculation, reduces contraction of smooth muscle in bladder neck and prostate gland Beta 1 decreases heart rate, reduces force of contractions Beta 2 constricts bronchioles, contracts uterus, inhibits glycogenolysis which can decrease blood glucose  Group of Drugs: a. Alpha-Adrenergic Antagonists (Alpha Blockers) - block or inhibit a response at the alpha adrenergic receptor site - promotes vasodilation - decrease in BP (dizziness) - used to treat peripheral vascular disease (Raynaud’s disease) - also helpful in decreasing symptoms of BPH a.1 selective alpha blockers - blocks alpha 1 a.2 non-selective alpha - blocks alpha 1 & 2 NOTE: Alpha Blockers can cause orthostatic hypotension & reflex tachycardia, reasons why these drugs are not as frequently prescribed as beta antagonist. b. Beta-Adrenergic Antagonists (Beta Blockers) - useful in treating mild to moderate hypertension, angina, heart failure & myocardial infarction (MI) - decrease heart rate - decrease in BP b.1 nonselective - blocking both beta 1 & 2 - contraindicated in asthma; use with extreme caution in patients with COPD - bronchoconstriction may occur Propranolol Hydrochloride - first beta blocker prescribed to treat angina, cardiac dysrhytmia, hypertension & heart failure - may also be given for migrain prophylaxis  b.2 selective - greater affinity for certain receptors Atenolol - selective beta 1 blocker, decreases sympathetic outflow to the periphery & suppresses the RAAS (Renin-Angiotension-Aldosterone Response) contraindications: bradycardia, heart block, cardiogenic shock, acute heart failure, asthma & sick sinus syndrome  Intrinsic Sympathomimetic Activity (ISA) - ability of certain beta blockers to bind with a beta receptor to prevent strong agonists from binding to that receptor, producing complete activation ex. non-selective - carvedilol,penbutolol & pindolol selective - acebutolol Adrenergic Neuron Antagonists/Blockers - drugs that block the release of norepinephrine from the sympathetic terminal neurons - clinical use is to decrease BP  ATENOLOL INDICATIONS: Hypertension, situational Drug-lab-food interaction: increased absorption with anxiety, migraines, prophylaxis and treatment atropine and other anticholinergics; decreased of acute MI, angina, glaucoma effects with NSAIDs; increased risk of hypoglycemia with insulin and sulfonylureas; increased hypotension with prazosin and terazosin; increased lidocaine and verapamil levels with toxicity CONTRAINDICATIONS: Bradycardia, heart Pharmacokinetics: blockers, shock, asthma, and COPD, Absorption- 50% absorbed in the GI pregnancy and lactation Metabolism: t1/2: 6-7 hours Caution: Renal dysfunction, DM, Excretion: Urine and Feces Bronchospasm, Myasthenia Gravis Pharmacodynamics: Oral- 1h Peak:2-4h Duration: 24h Side effects: dizziness, headache, depression, Adverse Reaction: Bradycardia, tachycardia, fatigue, nausea, diarrhea, edema, cool hypotension, chest pain, heart failure, dyspnea extremities, erectile dysfunction Life threatening: Bronchospasm, renal failure, dysrhythmia, thrombocytopenia  PROPRANOLOL HYDROCHLORIDE C Antianginal; antiarrhythmic; antihypertensive; reduces portal pressure and decrease risk of bleeding from esophageal varices H Normal BP E Best taken with meals C Avoid drinking; do not discontinue abruptly Side effects: bradycardia, hypotension, bronchospasm Take with full glass of water at the same time each day Check the following: K BP: May cause hypotension Respiration: May cause bronchospasm Radial Pulse: if less than 50 beats per minute, hold the drug and notify the physician Avoid: opening, chewing, crushing, extended release capsule; avoid stopping intake abruptly: avoid using aluminum-containing antacid; may decrease absorption  METHYLDOPA C Anti Hypertensive H Lowered BP E Take the drug regularly exactly as prescribed C Impotence can be expected; elevated hepatic enzyme K Check BP; may cause hypotension  ADRENERGIC ANTAGONIST Drug Uses and considerations Nadolol For HPN and angina. May cause dizziness, drowsiness, fatigue, bradycardia, hypotension, palpitations, erectile dysfunction, dysrhythmias Pindolol For HPN. May cause bradycardia, hypotension, edema, fatigue, weakness, dizziness, visual impairment and dyspnea Metoprolol tartrate For HPN, angina, HF and acute MI. May cause bradycardia, dizziness, drowsiness, fatigue, sleep disturbance, nightmares, diarrheas, depression, hypotension, peripheral insufficiency/edema. HF and dysrhythmias Carvedilol For HPN and HF. May cause drowsiness, dizziness, orthostatic hypotension, bradycardia, wt. gain, dyspnea, fatigue, headache, diarrhea, peripheral edema, hyperglycemia, Labetalol For acute/chronic HPN. May cause orthostatic hypotension, nasal congestion, dizziness, fatigue, nausea, paresthesia, erectile dysfunction, hyperhidrosis and depression DRUG GROUPS THAT AFFECT THE PARASYMPATHETIC NERVOUS SYSTEM 1. CHOLINERGIC AGONISTS/ PARASYMPATHOMIMETICS - drugs that stimulates the PNS - they mimic the parasympathetic neurotransmitter acetylcholine (ACh) 2 Types of Cholinergic Receptors a. muscarinic - stimulate smooth muscle & slow heart rate b. nicotinic (neuromuscular) - affect the skeletal muscles  EFFECTS OF CHOLINERGIC AGONISTS Cardiovascular Decrease heart rate, lowered BP bec. of vasodilation and slowed conduction of AV node Gastrointestinal Increased tone and motility of smooth muscle of stomach and intestine, increase peristalsis, relaxed sphincter muscles Genitourinary Contraction of muscle of the urinary bladder, increased tome of ureters, relaxed bladder sphincter muscles and stimulated urine Ocular Increased pupillary constriction or miosis, and increased accommodation (flattening or thickening of eye lens for distant or near vision Glandular Increased salivation, perspiration and tears Bronchi Stimulation of bronchial smooth muscles contraction and increased bronchial secretions Striated Muscle Increased neuromuscular transmission and maintenance of muscle strength and tone a. DIRECT-ACTING CHOLINERGIC AGONISTS - act on receptors to activate a tissue response - primarily selective to the muscarinic receptors but are nonspecific because the muscarinic receptors are located in the smooth muscles of the GI & genitourinary tracts, glands & heart ex. Bethanecol Chloride - use to increase urination Metoclopramide HCl - use for cases of Gatsroesophageal Reflux Disease (GERD) Pilocarpine - constricts the pupils of the eyes - used to treat glaucoma  BETHANECOL CHLORIDE Drug Class: Cholinergic Parasympathomimetic Dosage: Urinary retention PO- Initially 5-10mg q1h For urinary retention and neurogenic bladder subQ: 5MG tid/qid max: 40mg/dl Contraindications: Intestinal or urinary tract Drug-Lab-Food interaction: Decrease bethanechol effect obstruction, bradycardia, hypotension, COPD, with antidysrhythmic(procainamide); ganglion blocking asthma, peptic ulcer, hyperthyroidism, seizure, agents(mecamylamine) cause significant hypotension after parkinsonism severe abdominal symptoms. False test results (amylase, lipase) may result. Atropine, flavoxate and opiates counteract bethanechol action Lab: increases AST, bilirubin, amylase, lipase Pharmacokinetics: Pharmacodynamics: PO onset: 0.5-1.5h Absorption PO; poorly absorbed Peak: 1-2h Distribution: unknown Duration: 1-6h Metabolism: t ½ Unknown SubQ Onset: 5-15mins Excretion: Urine Peak: 15-30mins Duration: 2 h Side Effects: Nausea, vomiting, diarrhea, Adverse Reaction: Tachycardia, hypotension abdominal cramps, hypersalivation, diaphoresis, Life threatening: Bronchospasm, wheezing, seizures urinary urgency and frequency, weakness, miosis, lacrimation b. INDIRECT-ACTING CHOLINERGIC AGONISTS - inhibit the action of enzyme cholinesterase (ChE) or also called as acethycholinesterase (AChE) - permit ACh to accumulate at the receptor sites cholinesterase inhibitors, acethylcholinesterase inhibitors or anticholinesterase 2 types: 1. reversible inhibitors - bind the ChE for several minutes to hours - used to treat pupillary constriction (glaucoma) - increase muscle strength (Myasthenia Gravis)  Example of drugs for Myasthenia Gravis - neostigmine (short acting) - pyridostigmine bromide (mod. acting) - ambenonium chloride (long acting) - edrophonium chloride (for dx purposes) SE: hypotension, bradycardia, sweating,hypersalivation & GI distress Contraindicated: asthma, diabetes, cardiovascular dse, intestinal & urinary obstruction  NEOSTIGMINE (PROSTIGMIN) c Cholinesterase inhibitors; use for treatment for Myasthenia Gravis h Increased muscle strength e Take tablets at suitable intervals so that the muscles are strongest during activity ( for example, early in the morning and before meals) c Report nausea, diarrhea, abdominal pain and muscle weakness. Avoid hot and excessively humid environment k Keep the antidote, pralidoxime chloride or atropine SO4 at the bedside Store away from direct heat and light. Keep in a cool dry place  Pyridostigmine (mestinon) C Cholinesterase inhibitor; use for treatment for Myasthenia Gravis H Increased muscle strength E Usually administered 30-60 minutes before meal C Side effects: abdominal cramps, diarrhea, excessive tearing, excessive sweating, skin rash, twitching, exacerbation of asthma K Monitor for muscle weakness; Keep antidote, Atropine at the bedside table  2. irreversible inhibitors - potent agents because of its long-lasting effects - used to produce pupillary constriction ex. isoflurophate, echothiophate & tabun Pralidoxime Chloride - antidote for reversible & irreversible cholinesterase inhibitors SE: may cause dizziness, blurred vision, headache, drowsiness, tachycardia, hypertonia, weakness & seizures  CHOLINERGIC AGONISTS Metoclopramide For GERD, gastroparesis, nausea and vomiting. May cause HCL drowsiness, dizziness, fatigue, restlessness, headache, nausea. Edrophonium To diagnose Myasthenia Gravis and for neuromuscular blockage chloride/ Reversal reversal. Monitor pulse, RR,BP, neurologic status and ECG frequently during administration. May cause diplopia, hypersalivation, dysphonia, dysphagia, diaphoresis, depression and seizure Pyridostigmine For Myasthenia Gravis and neuromuscular blockage reversal bromide/Mestinon and for nerve gas exposure prophylaxis. May cause nausea vomiting, abdominal cramps, diarrhea, bradycardia, blurred vision, bronchospasm, hypersalivation and increased urinary frequency Physostigmine For anticholinergic toxicity/ syndrome and glaucoma. May cause salicylate diaphoresis, hypersalivation, bradycardia, hypotension, seizures, confusion, muscle weakness and respiratory distress 2. CHOLINERGIC ANTAGONISTS/ ANTICHOLINERGICS/ PARASYMPATHOLYTICS - drugs that inhibit the actions of acetylcholine by occupying the acetylcholine receptors - blocking agents,muscarinic antagonists, cholinergic blocking agents & antispasmodics - can act as an antidote to the toxicity caused by ChE inhibitors & organophosphate ingestion - used as antispasmodics (synthetic anticholinergics) to treat peptic ulcers & intestinal spasticity  EFFECTS OF CHOLINERGIC ANTAGONISTS Cardiovascular Heart rate increase with large doses, small doses can cause decrease heart rate GI Relaxed smooth muscle tone, decreased GI motility and peristalsis, intestinal and gastric secretions are decreased Urinary Relaxed bladder detrusor muscle and increased constriction of internal sphincter; urinary retention can result Ocular Dilated pupils (mydriasis) and paralyzed ciliary muscles (cycloplegia) cause a decrease in accommodation Glandular Salivation, perspiration and bronchial secretions are decreased Bronchial Bronchi are dilated and bronchial secretions are decreased CNS Tremors and rigidity of muscles are decreased; drowsiness, disorientation and hallucinations can result on large doses  ATROPINE SULFATE - first derived from belladonna plant (Atropa belladonna) - used as a preop medication to decrease salivary secretions & to increase HR when bradycardia is present - antidote for muscarinic agonists poisoning such as bethanecol SE: xerostomia (dry mouth), nasal dryness, nausea, headache, blurred vision, tachycardia, constipation & urinary retention AR: dehydration, seizures, hypotension/hypertension, photophobia & coma  ATROPINE Drug class: Anticholinergic Dosage: Bradycardia Preoperative medication to reduce salivation, increased IV: 0.5-1mg, repeat q3-5mins up to 3mg heart rate for bradycardia, neuromuscular blockage reversal Contraindications: Hypersensitivity Drug-Lab-Food Interaction: Drug: Increases Caution: Renal, hepatic or respiratory impairment, anticholinergic effect with phenothiazines, COPD, cardiovascular disease, MI, GI obstruction, ileus, antihistamines, amantadine, quinidine; high dose may ulcerative colitis, glaucoma, Hyperthyroidism, urinary decrease effect or carbidopa/levodopa by delaying retention, dysrhythmias, myasthenia gravis gastric absorption Pharmacokinetics: PO/IM: well-absorbed Pharmacodynamics: Metabolism: t1/2: 2-4h IM/onset: 10-30mins IV: immediately Excretion: 75%-95% in urine Peak: 0.5-1h Peak: 5 mins Duration 4h Duration: unknown Side effects: drowsiness, dizziness, nausea, dry mouth, Adverse reaction: paradoxical bradycardia, headache, confusion, insomnia, amnesia, constipation, hypotension, angina, dyspnea, pulmonary edema flushing, hydronephrosis, blurred vision, photophobia, Life threatening: dysrhythmias, laryngospasm, coma palpitations, hyperreflexia, ataxia, weakness, dehydration  ATROPINE C Anticholinergic, Vagolytic, Drying agent H It increases heart rate in a patient with heart block; used preoperatively to decrease secretions E Administer as prescribed C Can cause facial flushing, blurred vision, dry eyes, dry mouth, and constipation, decreased sweating, delay in starting to urinate K Check BP, may cause hypotension Atropine sulfate eye drops are used to dilate the pupils before eye exams It is usually instilled into both eyes once, the night before the eye examinations, and again in the early morning of the appointment Oral atropine is no longer available in the US  ANTICHOLINERGIC AGENTS Methscopolamine For peptic ulcer. May cause confusion, anhidrosis, dysphagia, dry mouth, constipation, bromide palpitations, tachycardia, urinary retention. And erectile dysfunction Propantheline For peptic ulcer. May cause confusion, anhidrosis, dysphagia, dry mouth, constipation, bromide palpitations, hypotension, weakness, blurred vision, erectile dysfunction Scopolamine Transdermal patch. For motion sickness, may cause drowsiness, confusion, blurred vision, tachycardia, bradycardia, dry mouth, anhidrosis, orthostatic hypotension, dysphagia, constipation, photophobia, urinary retention. Benztropine Anti parkinsonism. Increase anticholinergic effect with phenothiazines and tricyclic antidepressant. May cause nausea, vomiting, dry mouth, anhidrosis, dizziness, depression, hallucinations, hyperthermia, paresthesia, mydriasis, ocular hypertension(life threatening)and ileus Ipratropium Inhalation. For bronchospasm associated with COPD and asthma. May cause headache, bromide dyspnea, back pain, epistaxis, nasopharyngitis, bronchitis