DH206: Pharmacology Chapter 4: Autonomic Drugs Lisa Mayo, RDH, BSDH Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Objectives 1. 2. Review of nervous system ANS ANS Anatomy Review 4. ANS Drugs Overview 5. PANS Drugs 6. SANS Drugs 3. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Objective #1 Review of Nervous System Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Nervous System Primary function: control & coordinate the activity of all the systems in the body Elaborate system that functions in both conscious and unconscious levels 2 subdivisions 1) CNS Brain & spinal cord oReceive information from afferent nerves oInitiates appropriate responses via efferent nerves 2) PNS: Peripheral Nervous System (next slide) 12 pairs cranial nerves, 31 pairs spinal nerves 2 subdivisions: somatic & visceral based on the type of muscle to which these nerves innervate Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. PNS Subdivisions PNS 1. Somatic Division Branches of cranial & spinal motor nerves that innervate skeletal muscle CONSCIOUS CONTROL 2. Visceral Division (ANS): this chapter covers Visceral nerves are the branches of the cranial and spinal motor nerves that innervate cardiac & smooth muscle (involuntary) internal organs & glands UNCONSCIOUS CONTROL Nerves regulated by hypothalamus & medulla oblongata Visceral nerves commonly called ANS 2 subdivisions: Parasympathetic & Sympathetic Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Objective #2: ANS Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ANS Function: regulate organs (either ↑ or ↓ their activity) ALL organs have PANS & SANS receptors Practice of medicine and dentistry greatly benefitted from the understanding of the ANS Relies on neurotransmitters (NTs) & receptors to cause a response NT: synthesized in the neuron & stored in axon When an AP occurs – NT released into synapse – eventually bind to target organs in the body Results in either excitation or inhibition of the organ NT removed: degradation by enzymes, or through “reuptake” NT used in ANS: Norepi, ACH Referred to as Other NT’s: epi, dopamine, serotonin, GABA catecholamines Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ANS Receptors Receive NTs from axon terminals Located on the dendrites of POSTganglionic neurons or smooth muscle, cardiac muscle, glands Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ANS Divisions 1. PANS: parasympathetic autonomic nervous system Also known as the craniosacral division 2. SANS: sympathetic autonomic nervous system Also known as the thoracolumbar division Most organs receive a nerve from each division Exception: blood vessels do NOT receive PANS ○ Why BP is controlled by SANS drugs & not PANS drugs ○ Decrease stimulation = vasodilation ○ Increase stimulation = vasoconstriction Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ANS: PANS Active during periods of rest & restoration of body energy stores Increase body functions (ex: digestion, waste elimination) When PANS activated: only select nerves can be stimulated (unlike SANS) and confined to particular body systems Ex: urination Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. PANS Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ANS: SANS Innervates blood vessels (PANS does not) When SANS engaged, the whole body is stimulated (unlike PANS) Fight-or-Flight Adrenal medulla releases epi, some norepi into blood ↓ Catecholamines act as hormones ↓ Travel to all sympathetic receptors ↓ Produce intense stimulation ↓ Increase activity: heart rate, bronchodilation Decrease activity: GI and urinary tracts Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ANS: PANS vs SANS Majority of time: actions produced are opposites SANS stimulates radial smooth muscles → increase in pupil size (dilation) ○ Dilated pupils are termed mydriasis PANS stimulates circular smooth muscles → decrease in pupil size ○ Constricted pupils are termed myosis Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ANS Body Effects in text found p.34, Table 4-1 Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Objective #3 ANS Anatomy Review Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ANS: Anatomy Review Peripheral motor (efferent) nerves Branches of nerves that travel from brain/spinal column to organs Neurons that emerge from the spinal column are called PREGANGLIONIC NERVE FIBERS Neurons that travel from the ganglion to the organs are called POSTSYNAPTIC NERVE FIBERS SYNAPSE: space between the preganglionic and postganglionic fibers Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Synapse Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ANS: Anatomy Review Main pharmacological difference between PANS & SANS is the NT released from nerve endings PANS: ACH, ACH SANS: ACH, Norepinephrine Nerves that release ACH = cholinergic nerve Nerves that release Norepi = adrenergic nerve Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Cholinergic nerve Cholinergic nerve Cholinergic nerve Adrenergic nerve Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ANS: Anatomy Review Summary Effects of SANS produced by Norepi released from adrenergic nerve endings 2) Epi released from the adrenal medulla 1) ○ Both norepi & epi stimulate adrenergic receptors Effects of PANS produced when ACH which binds to cholinergic receptors ○ 2 main types of cholinergic receptors (both stimulated by ACH) 1. Muscarinic: Located POSTganglionic junction PANS 2. Nicotinic: Located PREganglionic junction PANS & SANS Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ANS: Anatomy Review Cholinergic Receptors 1. Muscarinic Located on cell membranes of visceral organs and glands (PANS innervated) – stimulated by ACH released from POSTGANGLIONIC nerve endings 2. Nicotinic: 2 types receptors (nerve & muscle) 1) Nn: on both PANS and SANS ganglion & stimulated from ACH released from PREGANGLIONIC nerve endings to conduct impulses across autonomic ganglion to POSTGANGLIONIC fibers of both divisions (see next slide) 2) Nm: Part of Somatic, not ANS (skeletal muscles) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ANS: Anatomy Review Adrenergic Receptors (SANS): divided into alpha(α) & beta (β) receptors α Receptor Locations Action Alpha-1 smooth muscles ( GI system, sweat glands, eye) Vasoconstriction arteries/veins Contract eye muscles Alpha-2 POSTganglionic neurons ↓ release norepi ↓ BP ↓ secretion insulin ↓ eye secretion Called autoreceptors Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ANS: Anatomy Review Adrenergic Receptors (SANS): divided into alpha(α) & beta (β) receptors β Receptor Locations Action Beta-1 Cardiac tissue Positive chronotrophic effects (↑ heart rate) Positive inotropic effects (↑ contractibility/strength) Beta-2 Smooth muscle of bronchioles, skeletal muscles, blood vessels of heart/kidney Bronchodilation Vasodilation Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ANS: General Rules for α & β 1. 2. 3. 4. 5. α-receptor activation = generally excitatory or stimulating (vasoconstriction, uterine contraction) EXCEPT intestinal relaxation β-receptor activation generally inhibitory/relaxing EXCEPT heart which stimulates Epi released by adrenal medulla – activates both α and β but more potent on β-2 (higher affinity for those receptors) Norepi acts on ALL α and only some β. Chiefly a vasoconstrictor. β-1 predominate in the heart & blood vessels Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following neurotransmitters is released from sympathetic postganglionic neurons? a. Dopamine b. Serotonin c. Acetylcholine d. Norepinephrine Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following neurotransmitters is released from sympathetic postganglionic neurons? a. Dopamine b. Serotonin c. Acetylcholine d. Norepinephrine Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following neurotransmitters is released from sympathetic and parasympathetic preganglionic neurons? a. Dopamine b. Serotonin c. Acetylcholine d. Norepinephrine Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following neurotransmitters is released from sympathetic and parasympathetic preganglionic neurons? a. Dopamine b. Serotonin c. Acetylcholine d. Norepinephrine Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Objective #4 ANS Drugs Overview Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Autonomic Drugs All drugs are either agonist or antagonist @ cholinergic & adrenergic receptors AGONIST Sympathomimetic / Parasympathomimetic ANTAGONIST Sympatholytic / Parasympatholytic Certain ANS drugs are used in dentistry Vasoconstrictors added to local anesthetic Drugs used to ↑ or ↓ salivary flow Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. AUTONOMIC DRUGS PANS Cholinergic (Parasympathomimetic) Agents P+ Anticholinergic (Parasympatholytic/Cholinergic Pblockers) Agents SANS Adrenergic (Sympathomimetic) Agents Adrenergic Blocking (Sympatholytic/ Sympathetic blockers) Agents Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. S+ S- Autonomic Drugs: p.36-38 4 drug groups of the ANS 1. A drug that stimulates the PANS is called P+ (cholinergic or parasympathomimetic) 2. A drug that blocks the PANS is called P– (anticholinergic, parasympatholytic, or cholinergic blockers) 3. A drug that stimulates the SANS is called S+ (sympathomimetic or adrenergic) 4. A drug that blocks the SANS is called S– (adrenergic blockers, sympathetic blockers, or sympatholytic) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Objective #5 PANS Drugs Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. PANS DRUGS: p.38-43 1. Cholinergic (parasympathomimetic) agents ○ Produce the effects of PANS (see handout) 2. Anticholinergic (parasympatholytic) agents ○ Produce effects opposite the PANS (see handout) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. PANS: General Inactivation of ACH Achieved through hydrolysis by certain enzymes (this occurs quickly so the effects of ACH last only a few seconds) 1. Enzyme located in the area of the cholinergic receptor – ACETYLCHOLINESTERASE (yields metabolites of choline & acetic acid) 2. Enzyme PSEUDOCHOLINESTERASE is located in liver & plasma that can hydrolyze ACH Ex: Botox: inhibits the release of ACH from the cholinergic nerve ending to produce paralysis of skeletal muscle – only lasts 3mo Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ACETYLCHOLINESTERASE choline & acetic acid metabolites PSEUDOCHOLINESTERASE In plasma/liver Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. PANS 1. Cholinergic Agents p.36-38 Cholinergic agents are classified 2 ways: 1. Direct acting Bind to muscarinic/cholinergic receptor to produce effects similar to those of ACH 2. Indirect acting (cholinesterase inhibitors) Inhibit enzyme acetylcholinesterase to produce effects similar to those of ACH Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. PANS 1. Cholinergic Agents 1. Direct acting Not useful drugs because of its extremely short duration of action Actions: see handout for heart, kidney, GI, eye effects Ex: Pilocarpine (stimulate saliva, decrease intraocular pressure) 2. Indirect acting When cholinesterase enzyme deactivates in the synaptic gap – then ACH can build up because the enzyme is not there to destroy it = ↑ concentrations of ACH at the receptor site Subdivisions (based on duration of action) 1) Reversible inhibitors: NOT tightly bound to receptors 2) Irreversible inhibitors: bind irreversibly to receptors Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. p.36, Table 4-3 USE THESE TABLES FOR REFERENCE, NOT BOOK CHOLINERGIC PARASYMPATHOMIMETIC DRUGS TYPE DRUG USES Direct Acting Bethanechol(Urecholine) Urinary retention Pilocarpine (Salagen) Glaucoma, Xerostomia Myasthenia gravis TYPE CLASS DRUG Indirect Acting Irreversible Chemical Warfare (sarin) Reversible Physostigmine(Antilirium) Neostigimine(Prostigmin) Pyridostigmine(Mestinon) Donepezil(Aricept) Tacrine(Cognex) USES Glaucoma MG MG Alzheimer's Alzheimer's NEED TO KNOW WHOLE GRAPH: USES, DRUG NAMES, CLASSIFICATION! Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. PANS 1. Cholinergic Agents Adverse reactions (excessive stimulation of PANS) SLUD (salivation, lacrimation, urination, defecation) Tx adverse rxns with pralidoxime or atropine Tx reactions caused by several drugs: Physostigmine Pharmacologic Effects (see handout) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. PANS 1. Cholinergic Agents Contraindications 1) Bronchial asthma: may cause asthma attack 2) Hyperthyroidism: may cause atrial fibrillation 3) Severe cardiac disease: reflex tachycardia may exacerbate a severe cardiac condition 4) Peptic ulcer: cholinergic agents stimulate gastric acid secretion and increase gastric motility Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. PANS 2. Anticholinergic Agents p.38-40 Prevent the action of ACH at POSTganglionic endings Release of ACH is not blocked, but the receptor site is competitively blocked by the anticholinergic Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. PANS 2. Anticholinergic Agents Atropine, scopolamine Lipid soluble Low doses: cause dry mouth, inhibit sweating Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. PANS 2. Anticholinergic (parasympatholytic) agents Pharmacological Effects 1. CNS effects ○ Drowsiness & sedation ○ OTC doses: limited amts scopolamine & used as sleep aids ○ Used in tx Parkinson’s disease & motion sickness 2. Exocrine Glands ↓ sweating Dentistry: ↓salivation & create a dry field 3. Eye: mydriasis (dilation of the pupil) used during eye exams 4. Respiratory Relax smooth muscle Ipratropium is an anticholinergic inhaler used to treat asthma Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. PANS 2. Anticholinergic Agents Contraindications (see handout) Glaucoma (Only ANS class drug that is not safe to use for pt’s with glaucoma) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. PANS 2. Anticholinergic Agents Drug Interactions: Avoid using in drugs that also cause same adverse effects SEE HANDOUT Adverse effects important to dentistry Xerostomia: provide education If pt using anticholinergic inhaler to tx asthma – need education on dry mouth Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following receptors is stimulated when pilocarpine is taken? Cholinergic nicotinic b. Cholinergic muscarinic c. Adrenergic alpha d. Adrenergic beta a. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following receptors is stimulated when pilocarpine is taken? Cholinergic nicotinic b. Cholinergic muscarinic c. Adrenergic alpha d. Adrenergic beta a. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following drugs may cause xerostomia? Epinephrine b. Dopamine c. Cevimeline d. Atropine a. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following drugs may cause xerostomia? Epinephrine b. Dopamine c. Cevimeline d. Atropine a. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ A patient has an extensive history. All of the following drugs can cause xerostomia as an adverse effect EXCEPT which one? Scopolamine b. Pilocarpine c. Homatropine d. Atropine a. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ A patients has an extensive history. All of the following drugs can cause xerostomia as an adverse effect EXCEPT which one? Scopolamine b. Pilocarpine c. Homatropine d. Atropine a. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Objective #6 SANS Drugs Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS DRUGS: p.40-45 1. Adrenergic (sympathomimetic) agents 2. Adrenergic blocking agents 3. Neuromuscular blocking drugs Cholinergic nerve Adrenergic nerve Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: General NTs in SANS: norepi(NE) and epinephrine NE: released at terminal nerve endings of the SANS Epinephrine: released from adrenal medulla & distributed via the blood Both NTs stimulate many internal organs to ↑ sympathetic activity Epi will relax smooth muscle, NE does not ○ Ex: epi used for bronchodilation, NE is not Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: General p.40 Adrenergic nerve ending takes up the amino acid tyrosine ↓ Then forms DOPA (dihdroxyphenylalanine) & dopamine ↓ Then converted to Norepi ↓ Norepi then stored within vesicles inside nerve endings ↓ When nerves are stimulated – NE released – travel to smooth & cardiac muscle – attach to their receptors – produce sympathetic response ↓ Then NE will reuptake back into nerve ending or destroyed by MONOAMINE OXIDASE enzyme Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: General α-Receptors Alpha-1 adrenergic receptors When stimulated by NE or Epi = cause vasoconstriction ○ Remember: PANS drugs have NO direct action on arteries Alpha-2 adrenergic receptors Drugs used in this category tx hypertension Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. α-1 Vasoconstriction HBP Cholinergic nerve Adrenergic nerve α-2 Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. ↓ NE SANS: General -Receptors Beta-1 receptors (memory trick - 1 heart) When stimulated = ↑ heart rate & force of contraction Metabolic effects on glycogen formation (glycogenolysis) (NBQ) Beta-2 receptors (memory – 2 lungs) When stimulated = produce vasodilation (mainly skeletal & cardiac) and bronchodilation Drugs used in tx asthma Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: General Alpha & Beta Receptors 2 divisions of drugs 1. Sympathomimetics/Adrenergic S+ Alpha & beta-agonists 2. Sympatholytics/Adrenergic Blocking S Alpha, beta-blockers Antagonize or ↓ sympathetic activity Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympathomimetic Sympathomimetic/Agonist drugs divided by their mechanism of action (just like PANS drugs) 1) Direct acting Bind to & activate α or β receptors Ex: catecholamines (Epi, NE, Dopamine, Isoproterenol) 2) Indirect acting Not bind to receptor Cause release NE from nerve endings Ex: Amphetamines (Adderall) & Cocaine 3) Mixed-Acting Ephedrine & Pseudoephedrine(Sudafed) activate α1 & β2 receptors by direct & indirect methods Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympathomimetic Direct-Acting Agonists (next slides) 1) α-adrenergic agonists 2) β-adrenergic agonists Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympathomimetic Alpha-1 Agonist Drugs α1 receptor drugs (cause contraction of smooth muscle) Vasoconstrict blood vessels (can cause xerostomia) Stimulate submax/subling salivary glands = thick, viscous saliva produced Contract ocular muscles that cause dilation of the pupil (mydriasis) Next slide for clinical indications Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympathomimetic Alpha-1 Agonist Drugs Clinical Indications α1 receptor drugs IV in hypotensive states Dilate pupils for eye exams Ocular decongestants Open nasal passages = ↑breathing ○ Used as nose drops & nasal sprays for their decongestant effect ○ Ex: phenylephrine(Neo-Synephrine), oxymetazoline(Afrin) ○ Should not use more than 3-5 days due to re-bound swelling & congestion that will occur Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. DIRECT ACTING α1-agonists α1-agonist Clinical Use phenylephrine(Neo-Synephrine) Nasal decongestant oxymetazoline(Afrin) Nasal decongestant Tetrahydrozoline(Visine) Ocular decongestant Dipivefrin(Propine) Glaucoma Norepinephrine(Levarterenol, Levophed) Hypotension, Shock Epinephrine Prolong action local anesthetics Levonordefrin Prolong action local anesthetics (not as potent as epi) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympathomimetic Alpha-2 Agonist Drugs α2 receptor drugs Used to tx hypertension by decreasing heart rate Protype drug = Catapres Adverse effects ○ Xerostomia ○ Orthostatic hypotension Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. DIRECT ACTING α2-agonists α2-agonist Clinical Use Clonidine(Catapres) Hypertension Withdrawal from alcohol Methydopa(Aldomet) Hypertension Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympathomimetic Direct-Acting Agonists (next slides) 1) α-adrenergic agonists 2) β-adrenergic agonists Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympathomimetic Beta Drugs Most beta drugs have VERY FEW alpha effects (EXCEPT EPI) Isoproterenol: Protype drug Non-selective drug Produce effects on heart (↑BP) & lungs (bronchodilation) @ same time New drugs are selective – now can cause an effect on the lungs & not the heart Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. DIRECT ACTING Non-Selective β-agonists Non-Selective β-agonist Clinical Use Isoproterenol(Isuprel) Asthma Isoetharine(Bronkosol) Asthma Epinephrine(Adrenaline) Anaphylactic shock Bronchodilator Vasoconstrictor Increase BP Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympathomimetic Beta Drugs β1 selective drugs Dobutamine (Dobutrex): ↑ myocardial contractility, main use is in heart failure (IV) β2 selective drugs Tx asthma through bronchodilation Vasodilation of skeletal muscle Can inhibit uterine contractions (how preterm labor is stopped) Terbutaline Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. DIRECT ACTING Selective β1-agonists β1-agonist Clinical Use Dobutamine (Dobutrex) Stimulates heart Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. DIRECT ACTING Selective β2-agonists β2-agonist Clinical Use Albuterol(Ventolin, Proventil) Asthma Terbutaline(Brethine) Asthma, Pre-term labor Metaproterenol(Alupent, Metaprel) Asthma Salmeterol(Serevent) Asthma Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympathomimetic Epinephrine Possess alpha & beta effects (β effects greater than α) Cannot give orally: enzymes would destroy it too quickly Alpha effects: vasoconstriction Mydriasis, ↑BP, ↑heart rate, palpitations Beta effects β1 stimulation: Tachycardia, cardiac arrhythmias β2 stimulation: Bronchodilator ○ Why is the drug of choice for anaphylaxis (bronchoconstriction) Increases glycogenolysis (β-receptor) ○ ↑ glucose production, release insulin = hyperglycemia Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympathomimetic Epinephrine Epi in dental local anesthetic typically causes β2 responses If use over 3-4 carpules = α1 responses will begin to occur Ex: increase systolic BP (not diastolic, just systolic) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following receptors does epi in low dose primarily stimulate? a. Alpha-1 b. Alpha-2 c. Beta-1 d. Beta-2 Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following receptors does epi in low dose primarily stimulate? a. Alpha-1 b. Alpha-2 c. Beta-1 d. Beta-2 Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Epinephrine goes through biphasic response concerning BP. After the initial increase in BP, there is a decrease. This decrease in blood pressure is due to stimulation of which of the following receptors? a. α1 b. α2 c. β1 d. β2 Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Epinephrine goes through biphasic response concerning BP. After the initial increase in BP, there is a decrease. This decrease in blood pressure is due to stimulation of which of the following receptors? a. α1 b. α2 c. β1 d. β2 Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ In high doses that are used in anaphylactic shock, which of the following receptors does epi primarily stimulate? a. α1 b. α2 c. β1 d. β2 Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ In high doses that are used in anaphylactic shock, which of the following receptors does epi primarily stimulate? a. α1 b. α2 c. β1 d. β2 Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: General Alpha & Beta Receptors 2 divisions of drugs 1. Sympathomimetics/Adrenergic S+ Alpha & beta-agonists 2. Sympatholytics/Adrenergic Blocking S Alpha, beta-blockers Antagonize or ↓ sympathetic activity Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympatholytics Used in tx of: HBP Urinary retention Migraine headaches Glaucoma Therapeutic effects & adverse effects due to the blocking of alpha or beta receptors Most all drugs are SELECTIVE – eliminate potential adverse effects Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympatholytics Alpha-Blockers Bind to alpha receptors to block actions of NE and Epi Pharmacological effects 1) Relaxation of smooth muscle bladder & prostate 2) Vasodilation 3) Decrease BP: can ↑ risk orthostatic hypotension Clinical Indications 1) Hypertension 2) Raynaud’s disease (poor blood flow to skin & extremities) 3) Prostate hyperplasia (enlarged prostate which interferes w/urinary flow through ureter) 4) Penile erectile dysfunction (α2) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. DIRECT ACTING Selective α1-antagonists α1-antagonist Clinical Use prazosin (Minipress) Hypertension doxazosin (Cardura) Hypertension terazosin (Hytrin) Hypertension, prostate hypertrophy, urinary retention Tamsulosin(Flomax) Prostate hypertrophy phenoxybenzamine, phentolamine Raynaud's DIRECT ACTING Selective α2-antagonists α2-antaonist Clinical Use Yohimbine(Aphrodyne) Penile erectile dysfunction Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympatholytics Alpha-Blockers Adverse Effects: complete opposite of alpha effects Instead of pupil dilation, will see constriction (miosis) Nasal congestion instead of decongestion Increase GI activity Reflex tachycardia will occur if the BP is lowered too much Orthostatic hypotension Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympatholytics Beta-Blockers There are no therapeutic uses for blocking beta-2 receptors General names end in olol so it is easy to recognize them β1 blockers = most widely prescribed autonomic drugs! Clinical Indications 1) Hypertension 2) Angina 3) Heart arrhythmias 4) Panic attacks 5) Migraine headaches 6) Glaucoma Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympatholytics Beta-Blockers Antagonize the beta actions of NE and Epi Patients with HBP, angina, arrhythmias have increased sympathetic activity ↓ If you can block the beta receptors with these drugs ↓ Then you reduce the effects Epi & NE ↓ Thus improve the patient’s heart issues by decreasing heart activity Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympatholytics Beta-Blockers 1. Selective β-1 (best choice for asthmatic patients who have heart conditions) (NBQ) Protype drug: Atenolol (Tenormin) Fewer side effects, only affect heart, not lungs = lower chance of drug interactions 2. Non-Selective (will block beta-1&2) NEXT SLIDE Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympatholytics Beta-Blockers 1. Selective Beta-1 2. Non-Selective (will block beta-1&2) Protype drug: Propranolol (Inderal) Block β1 & β2 (NBQ-never give to asthmatic!) Block β1 Effect on heart: Reduce cardiac output & BP Effect on eye: Reduce secretions & intraocular pressure Block β2 Effect on lungs: Bronchoconstriction in asthmatics Effect on liver: inhibit glycogenolysis, may cause hypoglycemia in diabetics Contraindicated: asthma, diabetes Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. DIRECT ACTING Selective β1-antagonists β1-antagonist/blocker Clinical Use Metoprolol(Lopressor) Hypertension Atenolol(Tenormin) Hypertension Esmolol(Brevibloc) Hypertension Bisoprolol fumerate(Zebeta) Hypertension All end in ~olol Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. DIRECT ACTING Non-Selective β-antagonists Non-selective β-antagonist/blocker Clinical Use Naldolol(Corgard) Hypertension Propranolol(Inderal) Hypertension Timolol(Blocadren) Hypertension, migraines, MVP, tremors All end in ~olol Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. SANS: Sympatholytics Beta-Blockers Metabolism Atenolol is NOT lipid-soluble ○ Does NOT pass blood-brain barrier ○ Excreted unmetabolized by kidney Propranolol is the most lipid-soluble β -blocker ○ Passes into the brain easily where it can exert pharmacological effects ○ CNS sedation, mental depression, decreased central sympathetic activity which may contribute to the lowering of BP in tx of hypertension ○ Can tx secondary tachycardia associated w/ hyperthyroidism Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ What is the best choice medication to use for a patient with angina pectoris and asthma? a. Proanolol b. Timolol c. Labectalol d. Atenolol Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ What is the best choice medication to use for a patient with angina pectoris and asthma? a. Proanolol b. Timolol c. Labectalol d. Atenolol Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following types of drugs is used in the treatment of nasal congestion? a. B1-agonist b. Selective B2-antagonist c. Alpha-1-agonist d. Alpha-2-agonist Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following types of drugs is used in the treatment of nasal congestion? a. B1-agonist b. Selective B2-antagonist c. Alpha-1-agonist d. Alpha-2-agonist Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following pathways is activated in a “fight-or-flight” situation? a. Adrenergic b. Cholinergic c. Adrenergic antagonist d. Somatic nervous system Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following pathways is activated in a “fight-or-flight” situation? a. Adrenergic b. Cholinergic c. Adrenergic antagonist d. Somatic nervous system Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.