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Autonomic Nervous System (ANS) Drugs by Mind Map: Autonomic Nervous System (ANS) Drugs
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Autonomic Nervous System (ANS) Drugs

Adrenergic Pharmacology

Sympathetic Agonists

Non specific, Epinephrine is a direct stimulator at all adrenergic receptors. In addition to local vasoconstriction, it is indicated for hypotension and shock, allergy, and bronchoconstriction., Epinephrine Indications: Local Vasoconstriction Hypotension and Shock Bronchoconstriction Allergy Mechanism: Direct stimulation of α and β adrenergic receptors, The Epi-Pen is used in cases of severe brochoconstriction either from allergy (anaphylaxis) or from an asthma exacerbation., Image of an EpiPen, Disease Related Concerns Cardiac: β1 stimulation increases the work of the heart and decreases cardiac efficiency • Cerebrovascular disease: Use with caution in patients with cerebrovascular disease • Diabetes: Increases in circulating blood glucose from stimulation of liver glycogenolysis and glucagon secretion Inhibition of insulin secretion • Parkinson's disease: may cause temporary worsening of symptoms. • Thyroid disease: Use with caution in patients with thyroid disease, Antidepressants: Include include the tricyclics and the serotonin-norepinephrine reuptake inhibitors (the SNRIs). These block reuptake and degradation of epi, leading to more cardiac adverse effects β-Blockers: Non-Selective: Block β receptors in the peripheral blood vessels, epi acts as a pure α agonist and blood pressure rises Selective Block β1 receptors in heart, at high doses block β 2 receptors in peripheral blood vessels

Alpha α, α Sympathetic Agonists Methylphenidate (Ritalin), (Concerta) Amphetamine (Adderall) Mechanism: Release of Norepi from synaptic vesicle Use: ADHD and Narcolepsy, The FDA asked the Drug Safety and Risk Management advisory committee to look into studying the cardiac risk in both adult and children taking ADHD drugs: * sudden death in patients who have heart problems or heart defects * stroke and heart attack in adults * increased blood pressure and heart rate Abuse and addiction: Schedule 2 (Ritalin and Adderall) Dyskinesia, muscle tightness, bruxism, Provigil (Modafinil) MOA: α 1 agonist, inhibitor of dopamine reuptake Indication: narcolepsy, shift work disorder Adverse Effects: mania, delusions, hallucinations, suicidal ideation and aggression, persistent sleepiness Provigil is a drug that is similar to Ritalin. It is also indicated for narcolepsy. Its other indication is shift work disorder. Shift work disorder is a circadian rhythm sleep disorder characterized by insomnia and excessive sleepiness affecting people whose work hours overlap with the typical sleep period. Provigil is an alpha 1 agonist and an inhibitor of dopamine reuptake. It has many adverse effects mainly in the CNS including mania, delusions and hallucinations., Catapres is an inverse agonist. This means that is binds to receptors as an agonist but has the opposite effects that you would expect from an agonist. Catapres binds to alpha 2 receptors on the pre-synaptic neuron. This causes a negative feedback signal that inhibits the release of norepinephrine into the synapse. Less norepinephrine means that blood pressure will decrease. Catapres is indicated for hypertension and can cause dry mouth and orthostatic hypertension., Alpha Adrenergic Synapse Image

Beta β, β2 Sympathetic Agonist There is only 1 drug in the beta sympathetic agonist drug class that is widely used. It is Proventil. It binds specifically to beta 2 receptors. It is indicated for asthma and COPD. It is available in an inhaler. The beta 2 receptors in the lungs will receive most of the drug. This decreases the chance for adverse effects in the rest of the body.

Sympathetic Antagonists

Alpha α, When drugs are antagonists in the sympathetic arm of the ANS, their effects are like that of acetylcholine., Effects of Acetylcholine: Bradycardia Vasodilation Bronchoconstriction Relaxation of urinary sphincter Increase GI secretions Sweating Contraction of iris SLUD Response: Salivation Lacrimation Urination Defecation, Drugs that are antagonists of adrenergic receptors are used most commonly in heart disease and benign prostatic hyperplasia (BPH)., Therapeutic Uses of Drugs at Adrenegeric Receptors (Antagonists) HTN, Post myocardial infarction, CHF, Treatment of arrhythmias, Ischemic heart disease α blocker: Hytrin β blockers: Toprol, Propranolol, Coreg Benign prostatic hyperplasia: α blocker: Hytrin, Flomax, Hytrin and Flomax are alpha sympathetic antagonists that are used treat BPH. Hytrin is also used to treat HTN. Hytrin is the drug of choice when a patient has both BPH and HTN. Both of these agents block alpha receptors which leads to smooth muscle relaxation. Flomax targets receptors alpha receptor subtypes that are found only in the prostate gland. As a consequence, patients on Flomax may experience fewer adverse effects than patients on Hytrin.

Beta β, Remember that sympathetic antagonists have the effects of acetylcholine. This lists the therapeutic effects of beta blockers. The most important one is that cardiac output decreases. The exact signal transduction steps between the binding of the beta receptor by a beta blocker and the pharmacological effects are unknown. PCOL Effects of Beta Blockers ↓ the force and rate of myocardial contraction ↓ O2 consumption of the heart ↓ of blood pressure in hypertensive patients CO decreases HR decreases Reduction in plasma renin activity Decrease CNS sympathetic outflow Alteration in baroreceptor responsiveness, There are two classes of beta blockers: selective and nonselective., Selective for β1 Selective beta blockers bind at the beta 1 receptor in the heart. The mechanism of action is competitive inhibition of epinephrine and norepinephrine at the beta 1 receptor. Selective beta blockers like Toprol are almost always used to treat heart disease or hypertension., Nonselective The non-selective beta blockers like Inderal block both beta 1 and beta 2 receptors. Non-selective beta blockers can be used to treat heart disease and also a number of other conditions, for instance migraines, stage fright or tremor., Beta blockers are well tolerated, but do have a few adverse effects. Adverse effects: Altered taste Orthostatic hypotension Non-Selective: hypertension and bradycardia, β Antagonists Carvedilol (Coreg) is a unique beta blocker in that it also blocks alpha receptors. It decreases heart rate and contractility and also decreases blood pressure through alpha blockade. It is most commonly used in heart failure.

Cholinergic Pharmacology

Drugs that act at cholinergic receptors have a mechanism of action that drugs that act at adrenergic receptors do not have. Cholinergic drugs are able to inhibit the breakdown of acetylcholine by inhibiting the action of cholinesterase.

Diagram of cholinergic synapse

Parasympathetic Agonists

Review of pharmacological effects that cholinergic agonists might produce in the body: Effects of Acetylcholine: Bradycardia Vasodilation Bronchoconstriction Relaxation of urinary sphincter Increase GI secretions Sweating Contraction of iris SLUD Response: Salivation Lacrimation Urination Defecation

Cognex, used for Alzheimer's, is the most predominant drug in this class.

Cholinergic drugs have 2 possible mechanisms by which they ace. They can inhibit cholinesterase to increase the half life of acetylcholine at the receptor site or they can be direct acting by binding to and stimulating the cholinergic receptors. Cholinergic drugs are not well tolerated. They are contraindicated in asthma, cardiovascular disease and ulcer. The adverse effects include the parasympathetic reactions of the SLUD response as well as many more, including nausea, diarrhea, vomiting, rhinitis, urinary frequency, bronchospasm, hypotension, arrhythmias

Tacrine (Cognex) is a cholinesterase inhibitor. It is used in dementia associated with Alzheimer’s disease or Parkinson’s disease. Idea: Prolong acetylcholine half life in the brain

Parasympathetic Antagonists

Expect these drugs to have the same pharmacological effects of the sympathetic agonists.

Review of the pharmacological effects of norepinephrine. These are the therapeutic effects of the parasympathetic antagonists: Tachycardia Vasoconstriction Bronchodilation Contraction of urinary sphincter Decreased GI secretions Glycogenolysis Gluconeogenesis Lipolysis

General therapeutic uses of antimuscarinic drugs: Bronchodilation: Asthma and COPD * Ipratropium (Atrovent) * Tiotropium (Spiriva) Urinary: antispasmodics * Tolterodine (Detrol) * Darifenacin (Enablex), Atrovent is a drug that blocks the cholinergic receptors in the lungs. The causes bronchodilation. It is available on its own in an inhaler or as a combination product with albuterol in the Combivent inhaler. Spiriva is also a drug that blocks the cholinergic receptors in the lungs, but it has a much longer half-life then Atrovent. It is used as once daily dosing in patients that have COPD., M3 is the cholinergic receptor found in the urinary sphincter muscle. Enablex has less adverse effects than Detrol, less dry mouth and constipation.

Anticholinergic drugs can interact with antihistamines. This interaction can lead to severe dry mouth. Enablex is a CYP2D6 inhibitor. This is the P450 enzyme in the liver that is responsible for the metabolism of codeine. If a patient is taking Enablex, codeine may not be effective to control dental pain.