Drugs Acting On ANS PDF

DRUGS ACTING ON ANS M.Y. Ajao (PhD.) Background: THE NERVOUS SYSTEM The nervous system is a complex part of the human body concerned with the regulation and coordination of body activities such as movement, digestion of food, sleep, and elimination of waste products. The nervous sy...

DRUGS ACTING ON ANS M.Y. Ajao (PhD.) Background: THE NERVOUS SYSTEM The nervous system is a complex part of the human body concerned with the regulation and coordination of body activities such as movement, digestion of food, sleep, and elimination of waste products. The nervous system has two main divisions: the central nervous system (CNS) and the peripheral nervous system (PeNS) CNS (brain and spinal cord) - receives, integrates, and interprets nerve impulses. PeNS (nerves outside of the brain and spinal cord) -connects all parts of the body with the CNS  Peripheral Nervous System = Somatic nervous system (SoNS) and the Autonomic nervous system (ANS). (SoNS)  Is concerned with sensation and voluntary movement. SoNS has sensory part which sends messages to the brain concerning the internal and external environment, such as sensations of heat, pain, cold, and pressure. SoNS also has the voluntary part which is concerned with the voluntary movement of skeletal muscles, such as walking, chewing food, or writing a letter. (ANS)  Is concerned with functions essential to the survival of the organism.  Functional activity of the autonomic nervous is not consciously controlled (ie, the activity is automatic).  This system controls blood pressure, heart rate, gastrointestinal activity, and glandular secretions.  ANS is divided into: Sympathetic (SNS)and Parasympathetic nervous system (PNS).  The SNS regulate the expenditure of energy and stressful situations, such as danger, intense emotion, or severe illness.  The PNS helps conserve body energy and is partly responsible for such activities as slowing the heart rate, digesting food, and eliminating body wastes.  Neurotransmitters:  Are chemical substances called neurohormones.  These are released at the nerve endings that facilitate the transmission of nerve impulses.  The two neurohormones of the sympathetic nervous system (SNS) are epinephrine and norepinephrine.  Epinephrine is secreted by the adrenal medulla while Norepinephrine is secreted mainly at nerve endings of sympathetic (also called adrenergic) nerve fibers.  The PNS has two neurohormones (neurotransmitters): acetylcholine (ACh) and acetylcholinesterase (AChE).  ACh is a neurotransmitter responsible for the transmission of nerve impulses to effector cells of the parasympathetic nervous system. ACh plays an important role in the transmission of nerve impulses at synapses and myoneural junctions.  ACh is quickly destroyed by the enzyme AChE, thereby allowing the nerve impulse to pass, but not remain in an excited state.  These two neurohormones (Ach & AchE) are released at nerve endings of parasympathetic nerve fibers, at some nerve endings in the sympathetic nervous system, and at nerve endings of skeletal muscles.  When a parasympathetic nerve fiber is stimulated, the nerve fiber releases ACh, and the nerve impulses pass (travel) from the nerve fiber to the effector organ.  After the impulse has crossed over to the effector organ , ACh is inactivated (destroyed) by the neurohormone AChE.  When the next nerve impulse is ready to travel along the nerve fiber, ACh is again released and then inactivated by AChE.  CHOLINERGIC DRUGS  Cholinergic drugs mimic the activity of the parasympathetic nervous system (PNS). They also are called parasympathomimetic drugs.  They have limited usefulness in medicine because of adverse reactions that may occur during administration. However, in some diseases or conditions cholinergic drugs may be of value ACTIONS:  Cholinergic drugs may act like the neurohormone ACh or they may inhibit the release of the neurohormone AChE.  Cholinergic drugs that act like ACh are called direct-acting cholinergics.  If a cholinergic drug inhibits the body’s release of AChE, it prolongs the activity of the ACh produced by the body. Cholinergic drugs that prolong the activity of ACh by inhibiting the release of AChE are called indirect-acting cholinergics.  Although a specific cholinergic drug may act in either of these two ways, the results of drug action are basically the same USES: The major uses of the cholinergic drugs are in the treatment of glaucoma, myasthenia gravis, and urinary retention.  Glaucoma may be treated by topical application (eg, eye drops) of a cholinergic drug, such as carbachol or pilocarpine (Isopto Carpine). Treatment of glaucoma with a cholinergic drug produces miosis (constriction of the iris). This opens the blocked channels and allows the normal passage of aqueous humor, thus reducing intraocular pressure.  Myasthenia gravis is a disease that involves rapid fatigue of skeletal muscles because of the lack of ACh released at the nerve endings Drugs used to treat this disorder include ambenonium (Mytelase) and pyridostigmine (Mestinon).  Urinary retention results when micturition (voiding of urine) is impaired. Treatment of urinary retention with cholinergic drugs, such as ambenonium, bethanechol chloride (Urecholine), or pyridostigmine results in the spontaneous passage of urine A.Rs =  Oral or parenteral administration can result in nausea, diarrhea, abdominal cramping, salivation, flushing of the skin, cardiac arrhythmias, and muscle weakness.  Topical administration usually produces few adverse effects, but a temporary reduction of visual acuity (sharpness) and headache may occur. CONTRAINDICATIONS: These drugs are contraindicated in patients with known hypersensitivity to the drugs, asthma, peptic ulcer disease, coronary artery disease, and hyperthyroidism PRECAUTIONS:  These drugs are used cautiously in patients with hypertension, epilepsy, cardiac arrhythmias, bradycardia, recent coronary occlusion, and megacolon.  The safety of these drugs has not been established for use during pregnancy, lactation, or in children. Symptoms of cholinergic crisis (cholinergic drug toxicity)  Include severe abdominal cramping, diarrhea, excessive salivation, muscle weakness, rigidity and spasm, and clenching of the jaw.  Patients exhibiting these symptoms require immediate medical treatment and their condition must be immediately reported to the doctor.  In the case of overdosage, an antidote such as atropine and other treatment also may be prescribed. The usual dosage of atropine is 0.4 to 0.6 mg IV. Managing A.Rs:  Observe the patient closely for the appearance of adverse drug reactions, such as a change in vital signs or an increase in symptoms.  Document any complaints the patient may have and notifies the doctor. Cholinergic Blocking Drugs  The cholinergic blocking drugs have an effect on the autonomic nervous system. These drugs block the action of the neurotransmitter acetylcholine in the parasympathetic nervous system.  Cholinergic blocking drugs also are called anticholinergics or parasympathomimetic blocking drugs.  Because parasympathetic nerves influence many areas of the body, the effects of the cholinergic blocking drugs are numerous in the body, including the eyes, the respiratory and gastrointestinal tracts, the heart, and the bladder  Examples of cholinergic blocking drugs include atropine, scopolamine, and propantheline. ACTIONS:  Cholinergic blocking drugs inhibit the activity of acetylcholine in parasympathetic nerve fibers  When the activity of acetylcholine is inhibited, nerve impulses traveling along parasympathetic nerve fibers cannot pass from the nerve fiber to the effector organ or structure Effects: o Central nervous system—dreamless sleep, drowsiness o Eye—mydriasis (dilatation of the pupil), cycloplegia (paralysis of accommodation or inability to focus the eye) o Respiratory tract—drying of the secretions of the mouth, nose, throat, bronchi, relaxation of smooth muscles of the bronchi resulting in slight bronchodilatation o Gastrointestinal tract—decrease in secretions of the stomach, decrease in gastric and intestinal movement (motility) o Cardiovascular system—increase in pulse rate o Urinary tract—dilatation of smooth muscles of the ureters and kidney pelvis, contraction of the detrusor muscle of the bladder USES:  Some of the uses of Atropine include treatment of pylorospasm, peptic ulcer, ureteral and biliary colic, vagal-induced bradycardia, parkinsonism.  Also, preoperatively to reduce secretions of the upper respiratory tract before the administration of a general anesthetic  Scopolamine hydrobromide: Preanesthetic sedation, motion sickness  Clidinium bromide: Adjunctive therapy for peptic ulcer  Glycopyrrolate: peptic ulcer A.Rs =  Central nervous system—headache, flushing, nervousness, drowsiness, weakness, insomnia, nasal congestion, fever  Eyes—blurred vision, mydriasis, photophobia, cycloplegia, increased ocular tension  Gastrointestinal tract—nausea, vomiting, difficulty in swallowing, heartburn  Urinary tract—urinary hesitancy and retention, dysuria  Cardiovascular system—palpitations, bradycardia (after low doses of atropine), tachycardia (after higher doses of atropine)  Other—urticaria, anaphylactic shock, other skin manifestations CONTRAINDICATIONS & PRECAUTIONS  Contraindicated in those with glaucoma, tachyarrhythmias, myocardial infarction, and congestive heart failure  Administration of these drugs can result in urinary retention. The nurse should give these drugs with great caution to patients with an enlarged prostate and asthma  ADRENERGIC DRUGS  Adrenergic drugs mimic the activity of the sympathetic nervous system. These drugs also are called sympathomimetic drugs.  Epinephrine and norepinephrine are neurohormones produced naturally by the body.  Synthetic preparations of these two neurohormones which are identical to those naturally produced by the body, are used in medicine  Examples include: metaraminol (Aramine), isoproterenol (Isuprel), and ephedrine. Actions of Adrenergic drugs Generally, adrenergic drugs produce one or more of the following responses in varying degrees: CNS—wakefulness, quick reaction to stimuli, quickened reflexes PNS—relaxation of the smooth muscles of the bronchi; constriction of blood vessels, sphincters of the stomach; dilatation of coronary blood vessels; decrease in gastric motility Heart—increase in the heart rate Metabolism—increased use of glucose (sugar) and liberation of fatty acids from adipose tissue. Adrenergic Nerve Receptors Adrenergic nerve fibers have either alpha (α) or beta (β) receptors. Adrenergic drugs may act on α receptors only, β receptors only, or on both α and β receptors. Whether an adrenergic drug acts on (α), (β) and (α) & (β) receptors, these accounts for the variation of responses for this group of drugs. The α and β receptors can be further divided into α1- and α2- adrenergic receptors and β1- and β2-adrenergic USES OF ADRENERGIC DRUGS: Adrenergic drugs have a wide variety of uses: Hypovolemic and septic shock Moderately severe to severe episodes of hypotension Control of superficial bleeding during surgical and dental procedures of the mouth, nose, throat, and skin Bronchial asthma Cardiac decompensation and arrest Allergic reactions (anaphylactic shock, angioneurotic edema) Temporary treatment of heart block Ventricular arrhythmias (under certain conditions) Nasal congestion (applied topically); and In conjunction with local anesthetics to prolong anesthetic action in medicine and dentistry. Examples adrenergic drugs and uses:  Dobutamine; Dobutrex- Cardiac decompensation due to depressed contractility caused by organic heart disease or cardiac surgical procedures S.E = Headache, nausea, increased HR, palpitation , angina and chest pain  Dopamine; Intropin- Shock due to Myocadiac infarctioI, trauma, open-heart surgery and renal failure S.E = Nausea, vomiting, ectopic beats, tachycardia, anginal pain and Palpitations  Isoproterenol; Isuprel- shock, bronchospasm during anesthesia S.E = Insomnia, anxiety, headache, dizziness and pallor  Epinephrine; Adrenalin chloride - treatment and prophylaxisof cardiac arrest, heart block; muscosal congestion of hay fever, rhinitis etc. S.E = Anxiety, insomnia, , headache, light-headedness, dizziness, nausea, dysuria, pallor Others include : Ephedrine, Levalbuterol, midodrine and norepinephrine READ UP: Uses of others… Shock :  The adrenergic drugs are important in the care and treatment of patients in shock.  Shock is defined as a life-threatening condition of inadequate perfusion.  In shock, there is an inadequate supply of arterial blood flow and oxygen delivery to the cells and tissues.  The body initiates compensatory mechanisms to counteract the symptoms of shock (eg, the release of epinephrine and norepinephrine).  In some situations, the body is able to compensate and blood pressure is maintained.  However, if shock is untreated and compensatory mechanisms of the body fail, irreversible shock occurs and death follows. There are five types of shock: o hypovolemic shock o cardiogenic shock o septic shock o obstructive shock, and neurogenic shock. Clinical manifestations in shock  For example, in the early stages of shock the extremities may be warm because compensatory mechanisms are initiated and the blood flow to the skin and extremities is maintained  If the condition is untreated, the skin and extremities become cool and clammy because of the failure of the compensatory mechanisms and the progression of shock. Thus, more advanced shock may be referred to as cold shock  Regardless of the type, shock results in a;  decrease in cardiac output, decrease in arterial blood pressure (hypotension)  Re-absorption of water by the kidneys (causing a decrease in urinary output)  decrease in the exchange of oxygen and carbon dioxide in the lungs  increase in carbon dioxide in the blood and decrease in oxygen in the blood, hypoxia (decreased oxygen reaching the cells)  And increased concentration of intravascular fluid. This scenario compromises the functioning of vital organs such as the heart, brain, and kidneys  Adrenergic Blocking Drugs Known as sympathomimetic blocking drugs, may be divided into four groups:  Alpha (α)-adrenergic blocking drugs—drugs that block α- adrenergic receptors. These drugs produce their greatest effect on α receptors of adrenergic receptors of adrenergic nerves that control the vascular system.  Beta (β)-adrenergic blocking drugs—drugs that block β- adrenergic receptors. These drugs produce their greatest effect on β receptors of adrenergic nerves, primarily the β receptors of the heart.  Antiadrenergic drugs—drugs that block adrenergic nerve fibers. These drugs block the adrenergic nerve fibers within the central nervous system (CNS) or within the peripheral nervous system.  α/β-Adrenergic blocking drugs—drugs that block both α- and β- adrenergic receptors. These drugs act on both α and β nerve fibers. α-ADRENERGIC BLOCKING DRUGS Actions:  Stimulation of α-adrenergic fibers results in vasoconstriction.  If stimulation of these α-adrenergic fibers is interrupted or blocked, the result will be vasodilation.  This is the direct opposite of the effect of an adrenergic drug having mainly α activity.  Phentolamine (Regitine) is an example of an α- adrenergic blocking drug Uses: o Phentolamine (Regitine) is used for its vasodilating effect on peripheral blood vessels and therefore may be beneficial in the treatment of hypertension caused by pheochromocytoma, a tumor of the adrenal gland that produces excessive amounts of epinephrine and norepinephrine o The drug is used to control hypertension during preoperative preparation and surgical excision of pheochromocytoma o Drugs such as norepinephrine or dopamine are particularly damaging to the surrounding tissues if extravasation (infiltration) occurs during intravenous administration. Phentolamine is used to prevent or treat tissue damage caused by extravasation of these drugs ARs = Administration of an α-adrenergic blocking drug may result in weakness, orthostatic hypotension, cardiac arrhythmias, hypotension, and tachycardia CONTRAINDICATIONS & PRECAUTIONS Adrenergic blocking drugs are contraindicated in patients who are hypersensitive to the drugs and in patients with coronary artery disease. These drugs are used cautiously during pregnancy (Pregnancy Category C) and lactation, after a recent myocardial infarction, and in patients with renal failure β-ADRENERGIC BLOCKING DRUGS  β-Adrenergic blocking drugs, also called β blockers, decrease the activity of the sympathetic nervous system on certain tissues.  β-Adrenergic receptors are found mainly in the heart. Stimulation of β receptors of the heart results in an increase in the heart rate.  If stimulation of these β-adrenergic fibers is interrupted or blocked, the heart rate decreases and the vessels dilate.  These drugs decrease the excitability of the heart,decrease cardiac workload and oxygen consumption  Examples of β-adrenergic blocking drugs are esmolol (Brevibloc), metoprolol (Lopressor), nadolol (Corgard), and propranolol (Inderal).  β-Adrenergic blocking drugs, such as betaxolol (Betoptic) and timolol (Timoptic), when used topically as ophthalmic drops, appear to reduce the production of aqueous humor in the anterior chamber of the eye USES :  Used in the treatment of hypertension and certain cardiac arrhythmias (abnormal rhythm of the heart), such as ventricular arrhythmias or supraventricular tachycardia.  They are used to prevent reinfarction in patients with a recent myocardial infarction (1–4 weeks after MI). Some of these drugs have additional uses, such as the use of propranolol for migraine headaches and nadolol for angina pectoris.  Can be used topically as ophthalmic eye drops. For example, betaxolol (Betoptic) and timolol (Timoptic) are used in the treatment of glaucoma. Glaucoma is a narrowing or blockage of the drainage channels (canals of Schlemm) between the anterior and posterior chambers of the eye  A.Rs = include orthostatic hypotension, bradycardia, dizziness, vertigo, bronchospasm (especially in those with a history of asthma), hyperglycemia, nausea, vomiting, and diarrhea. Many of these reactions are mild and may disappear with therapy. More serious adverse reactions include symptoms of congestive heart failure (dyspnea, weight gain, peripheral edema). Examples of adverse reactions associated with the use of -adrenergic ophthalmic preparations include headache, depression, cardiac arrhythmias, and bronchospasm CONTRAINDICATIONS & PRECAUTIONS o The centrally acting antiadrenergic drugs are contraindicated in active hepatic disease such as acute hepatitis or active cirrhosis and in patients with a history of hypersensitivity to o These drugs and are used cautiously in patients with a history of liver disease, renal function impairment, and during pregnancy and lactation α/β-ADRENERGIC BLOCKING DRUGS ACTIONS:  They block the stimulation of α- and β-adrenergic receptors, resulting in peripheral vasodilation.  The two drugs in this category are carvedilol (Coreg) and labetalol (Normodyne) USES:  Labetalol is used in the treatment of hypertension, either alone or in combination with another drug such as a diuretic.  Carvedilol is used to treat essential hypertension and in congestive heart failure to reduce progression of the disease. A.Rs = mild and do not require discontinuation of therapy. Examples of the adverse reactions include fatigue, drowsiness, insomnia, weakness, hypotension, diarrhea, dyspnea, and skin rash. Adverse reactions of carvedilol include fatigue, hypotension, cardiac insufficiency, chest pain, bradycardia, dizziness, diarrhea, hypotension, and fatigue. CONTRAINDICATIONS & PRECAUTIONS Both carvedilol and labetalol are contraindicated in patients with hypersensitivity to the drug, bronchial asthma ANTIADRENERGIC DRUGS Actions:  One group of antiadrenergic drugs inhibits the release of norepinephrine from certain adrenergic nerve endings in the peripheral nervous system. This group is composed of peripherally acting antiadrenergic drugs. An example is guanethidine (Ismelin).  Others antiadrenergic drugs are called centrally acting antiadrenergic drugs because they act on the CNS, rather than on the peripheral nervous system.  This group affects specific CNS centers, thereby decreasing some of the activity of the sympathetic nervous system.  Although the action of both types of antiadrenergic drugs is somewhat different, the results are basically the same.  An example of a centrally acting antiadrenergic drug is clonidine USES: Antiadrenergic drugs are used mainly for the treatment of certain cardiac arrhythmias and hypertension ARs = With CNS administration Include dry mouth, drowsiness, sedation, anorexia, rash, malaise, and weakness. Adverse reactions associated with the administration of the peripherally acting antiadrenergic drugs include hypotension, weakness, light- headedness, and bradycardia