Exam 1 Study Guide.docx

Block 1 Physiologic actions associated with activation of the following systems on heart rate and the muscles that control pupil diameter, salivary glands, bladder and gastrointestinal tract 1. Parasympathetic nervous system → Cranio-sacral, Rest and Digest Eyes (pupil): Miosis Salivary Glands: Prom...

Block 1 Physiologic actions associated with activation of the following systems on heart rate and the muscles that control pupil diameter, salivary glands, bladder and gastrointestinal tract 1. Parasympathetic nervous system → Cranio-sacral, Rest and Digest Eyes (pupil): Miosis Salivary Glands: Promote salivary secretions Heart: Maintain steady heart rate Lungs: Maintain steady breathing and bronchial secretions Stomach: Promote digestion (including enzyme secretions) and maintain peristalsis Liver: Stimulate bile release Bladder: Promote Urination Skin: N/A Skeletal Muscle: N/A Adrenal Glands: N/A 2. Sympathetic nervous system → Thoraco-lumber, Fight or Flight Eyes (pupil): Mydriasis Salivary Glands: Halt salivary secretions Heart: Increase heart rate Lungs: Bronchodilation, reduce bronchial secretions Stomach: Halts digestion and peristalsis and reduces digestive enzyme secretions Liver: Stimulate glucose release Bladder: Urinary retention Skin: Sweating Skeletal Muscle: Vasodilation Adrenal Glands: Mobilize norepinephrine and epinephrine Identify the symptoms of: 3. Cholinergic crisis (aka Cholinergic Toxicity) → Adverse Effects potentially associated with all cholinergic (muscarinic,nicotinic) agonists and cholinesterase inhibitors Salivation - Salivary Glands Lacrimation - Other Urination - Bladder Diarrhea - Stomach GI distress - Stomach Emesis - Other. Diaphoresis - Other Diarrhea - Stomach Urination - Bladder Miosis - Eyes (pupil) Bronchospasm - Lungs Emesis - Other Lacrimation - Other Salivation - Salivary glands 4. Anticholinergic Syndrome → Adverse effects potentially associated with all muscarinic antagonists OPPOSITE of SLUDGE-DDUMBELS Eyes (pupil): Mydriasis Salivary Glands: Xerostomia Heart: Tachycardia Lungs: Bronchodilation Stomach: GI relaxation, especially Constipation Bladder: Urinary Retention Other: Anhidrosis/Hypohidrosis, Dry Eye Pharmacology of: 5. Cholinergic Agonist on pupil diameter Drug Names: Acetylcholine (ROA: ocular injection) Carbachol (ROA: ocular injection, ophthalmic) MOA: Binds both nicotinic and muscarinic receptors Pupil diameter: Miosis → pupil constriction 6. Muscarinic Agonist on pupil diameter Drug name: Pilocarpine (ROA: ophthalmic) MOA: Muscarinic Agonist Therapeutic Class: Miotic → pupil constriction Pharm Action: induce miosis and decrease intraocular pressure Adverse Effect: minimized due to local application (SLUDGE-DDUMBELS if it penetrates systemic circulation) 7. Muscarinic Antagonist on pupil diameter Drug names: Atropine Cyclopentolate Tropicamide MOA: Muscarinic Antagonist Therapeutic Class: Mydriatic, Cycloplegic Clinical use: eye procedures Pharm Action: induce mydriasis (pupil dilation) or cycloplegia (paralyze muscles that control pupil diameter) Adverse Effects: minimized due to local application (Anticholinergic syndrome-like symptoms if it penetrates systemic circulation) Pharmacology of: 8. Muscarinic agonist on respiratory function Drug name: Methacholine MOA: Muscarinic Agonist Indication: Bronchoprovocation Test (bronchial hyperreactivity diagnostic tool) Pharm Action: Bronchoconstriction Adverse Effects: SLUDGE-DDUMBELS (notably sweating and blurred vision) 9. Short-acting muscarinic antagonist on respiratory function → Duration of action: 6-8 hours Drug names: Ipratropium MOA: Muscarinic Antagonist Therapeutic Class: Bronchodilators Indication: Respiratory disorders SAMA - Acute use for bronchospasm Pharm Action: Induce bronchodilation and reduce bronchial secretions Adverse Effects: Xerostomia but minimized due to local application (Anticholinergic Syndrome-like symptoms if penetrates systemic circulation) 10. Long-acting muscarinic antagonist on respiratory function → Duration of action: >12 hours Drug names: Aclidinium - Dry powder Glycopyrrolate - Dry powder Umeclidinium - Dry powder Revefenacin Tiotropium - Dry powder Therapeutic Class: Bronchodilators Indication: Respiratory disorders LAMA - Prophylactic use for daily maintenance Pharm Action: Induce bronchodilation and reduce bronchial secretions Adverse Effects: Xerostomia but minimized due to local application (Anticholinergic Syndrome-like symptoms if penetrates systemic circulation) Pharmacology of: 11. Muscarinic agonist on bladder function (i.e. urination) Drug name: Bethanechol MOA: Muscarinic Agonist Indication: Urinary retention (related to surgical procedure or childbirth) Pharm Action: contract bladder detrusor (promote urination) Adverse Effects: SLUDGE-DDUMBELS 12. Non-M3 selective Muscarinic antagonist on bladder function (i.e. urination) Drug names: Fesoterodine Oxybutynin → can cross the Blood Brain Barrier (BBB) Tolterodine Trospium MOA: Muscarinic Antagonist Therapeutic Drug Class: Drug used to treat overactive bladder (OAB) Genitourinary/Urinary Antispasmodic Pharm Action: Bladder detrusor Muscle Relaxation Indication: OAB (Urinary incontinence, urgency, and frequency) Adverse Effects: Anticholinergic Syndrome-like symptoms 13. M3-selective muscarinic antagonist on bladder function (i.e. urination) Drug Names: Darifenacin → CYP2D6 Substrate Solifenacin MOA: Muscarinic Antagonist Therapeutic Drug Class: Drug used to treat overactive bladder (OAB) Genitourinary/Urinary Antispasmodic Pharm Action: Bladder detrusor Muscle Relaxation Indication: OAB (Urinary incontinence, urgency, and frequency) Adverse Effects: Anticholinergic Syndrome-like symptoms Pharmacology of: 14. Muscarinic antagonist use as ACLS agent Drug Name: Atropine MOA: muscarinic antagonist Indications: usually critical conditions ACLS (‘crash cart’) Cholinergic crisis antidote supplement GI distress disorder 15. Muscarinic antagonist used as Antivertigo agent Drug Name: Scopolamine MOA: muscarinic antagonist Indication: Usually NOT critical conditions Nausea and Vomiting Motion sickness (Vertigo) Induce amnesia Both Atropine and Scopolamine: Indications Reduce procedural secretion (salivation, bronchial secretions) Reduce terminal secretion (salivation, bronchial secretions) Induce mydriasis and/or cycloplegia (including for the purpose of treating iritis or uveitis) Adverse Effects: associated with Atropine and Scopolamine are Anticholinergic Syndrome-like symptoms Pharmacology of: 16. Reversible cholinesterase inhibitor that cross blood-brain barrier Drug Names: Donepezil → CYP3A4/2D6 substrate Galantamine → CYP3A4/2D6 substrate Rivastigmine → metabolized by cholinesterase Pharm Action: increased duration and amount of synaptic ACh MOA: Cholinesterase inhibitors ROA for Donepezil and Rivastigmine: Transdermal patches Indication: Used to treat Alzheimer's disease (AD) Alzheimer’s Disease: CNS pathology: degeneration of basal forebrain pathway neurons Symptom: memory loss Adverse Effects: SLUDGE-DDUMBELS 17. Short-acting and reversible cholinesterase inhibitor that does not cross blood-brain barrier Drug name: Edrophonium Indication: Myasthenia gravis (MA) Peripheral pathology: Auto-antibodies to muscle-type nicotinic receptors Symptom: muscle weakness and fatigue 18. Long-acting and reversible cholinesterase inhibitor that does not cross blood-brain barrier Drug name: Neostigmine Pyridostigmine Indication: Myasthenia gravis (MA) Peripheral pathology: Auto-antibodies to muscle-type nicotinic receptors Symptom: muscle weakness and fatigue 19. Cholinesterase reactivator (Antidote for cholinergic crisis) Drug name: Pralidoxime MOA: Acetylcholinesterase Activator Pharmacology of: 20. Nicotinic agonist Drug name: Nicotine Therapeutic Class/Indication: OTC smoking cessation aid Nicotine OTC products are formulated as Nicotine Polycrilex available in several ROA: Gum Lozenges Nasal Spray Patches Inhalers MOA: Nicotinic agonist Pharm Action: decreased nicotine craving and withdrawal symptoms Adverse Effects: CNS: psychoactive stimulation CV: hypertension, tachycardia Other: physician and psychological dependence 21. Partial nicotinic agonist Drug name: Varenicline Therapeuto 22. Nicotinic antagonist (aka Ganglionic Blocker) Mecamylamine → Ganglionic Nicotinic Blocker Block 2 Pharmacologic Class: Tyrosine Hydroxylase Inhibitor and select AADC substrates 1. Drug Name: Tyrosine Hydroxylase Inhibitor Therapeutic class: Cardiovascular Agent, Drugs to treat Pheochromocytoma MOA: Tyrosine hydroxylase inhibitor Pharm action: reduce catecholamine synthesis Indication: Pheochromocytoma Adverse Effects: CNS/CV depression 2. Drug Name: Methyldopa MOA: Metabolized to ALPHA2 agonist (alpha-methyldopa) Pharm action: decrease blood pressure Indication: Hypertensive crisis Adverse Effects: CNS/CV depression Black Box Warning: None 3. Drug Name: Droxidopa MOA: Metabolized to NE Pharm action: increase blood pressure Indication: Hypotension Adverse Effects: CNS/CV stimulation Block Box Warning: Supine hypertension Pharmacologic Class: Alpha-Beta Agonists 4. Drug Name: Norepinephrine Black Box Warning (Norepinephrine only): Extravasation = increased ischemia and necrosis risk 5. Drug Name: Epinephrine Norepinephrine + Epinephrine MOA: Alpha-Beta Agonist Pharm Action: Vasoconstriction, increased inotropy Metabolism: MAO and COMT Indication: NE (usually to increase BP) → Shock EPI (usually to increase inotropy) → Bradycardia. Hypotensive shock, Cardiac arrest (OTHER – non CV use → Anaphylaxis, Asthma) Drug-Drug interactions: Any drug that targets adrenergic receptors 6. Drug Name: Dobutamine MAO: Major Beta 1 agonist (Minor Alpha 1 and Beta 2 Agonist) Therapeutic Class: Positive Inotropic Agent and Vasoconstrictor Pharm action: Increase sympathetic outflow (but its specifically used for its actions of the heart) Indication: acute treatment of low cardiac output states (ROA: acute use injectable) Metabolism: COMT substrate Contraindications: Hypovolemia and Myocardial ischemia Adverse Effect: CV and CNS Stimulation Drug Interactions: Any drug that targets any adrenergic receptor COMT inhibitors 7. Drug Name: Dipivefrin Therapeutic Class: Antiglaucoma Agents MOA: Prodrug hydrolyzed to EPI Pharm Action: Reduce intraocular pressure Indication: Ocular hypertension Metabolism: MAO, COMT Adverse Effect: Minimal unless it enters systemic circulation → then CNS/CV stimulation 8. Drug Name: Pseudoephedrine MOA: non-specific, Alpha-beta agonist → Beta affinity which is why it is a decongestant Therapeutic Class: Decongestant Pharm action: increase sympathetic outflow, but it is specifically used for its actions as Nasal mucosa relaxation and vasoconstriction to sinus vasculature. Indication: Nasal congestion Adverse Effects: CNS/CV stimulation Drug Interactions: Any drug that targets any adrenergic receptor Agents that alter urinary pH (urinary alkalinization promotes renal reabsorption) Pharmacologic Class: Alpha Agonists 9. Non-selective Alpha1/2 Agonists → IS ALSO MOA FOR ALL 3 DRUGS Naphazoline Oxymetazoline Tetrahydrozoline Pharm action for all 3 Drugs: Vasoconstriction, Decongestant Indication for all 3 Drugs: Ocular hyperemia + Nasal congestion Adverse Effect for all 3 Drugs: Ocular hypertension and localized irritation (Benzalkonium - contact lenses out!!) ROA: Topical (ophthalmic, nasal spray) 10. Alpha1-selective Agonists → MOA · Phenylephrine Therapeutic Class: Vasoconstrictor, Decongestant Black Box Warning (BBW): Avoid extravasation, must be administered by experienced clinician. Metabolism: MAO Drug-Drug Interaction: MAO inhibitor Any drug that target alpha1 adrenergic receptors 11. Topical (ophthalmic, dermal) Alpha2 Agonists → MOA (Drug Name: Brimonidine only) Alpha2 Agonists Pharm action: reduce IOP (intraocular pressure) Indication: Ocular hypertension, Glaucoma Brimonidine Class: Dermatological Agent Pharm Action: Promote localized vasoconstriction of subcutaneous blood vessels ROA and Indication: Topical - Dermal, Facial erythema (Rosacea) Adverse Effects: Minimal 12. Systemic Alpha 2 Agonists (Drug Name: Clonidine & Guanfacine only) Pharm action: Reduce sympathetic outflow (alpha2 adrenergic receptors are presynaptic inhibitory G-protein coupled receptors) Reduce blood presssure Hypertension Adverse Effect: CV (and CNS) Depression Drug Interactions: Any drug that binds any adrenergic receptors Contraindications: Pre-existing CV disease BEERS LIST! Significant CV and CNS depression in elderly Avoid abrupt discontinuation Pharmacologic Class: Alpha1-selective Blockers 13. Non Selective Alpha1 Blockers (bind Alpha1A/1B/1D), aka ‘Zosins’ MOA: competitive Alpha1-Adrenergic Antagonist Pharm: Block actions of NE to promote smooth muscle relaxation. If it binds: Alpha1A in prostate, it will relieve bladder outlet obstruction Alpha1B in vascular smooth it will lead to vasodilation Alpha1D in bladder neck, it will relieve bladder outlet resistance Drug names: Doxazosin → CYP2D6 and CYP3A4 Substrate Terazosin Both drugs bind all 3 Alpha blockers: Alpha1A in prostate Alpha1B in vascular smooth muscle Alpha1D in bladder neck Indications for both drugs: Hypertension and BPH Contraindications Avoid with pre-existing: Angina Hepatic impariment Cataract Surgery (b/c Floppy Iris Syndrome) Advanced Age (see Beers List!) Titrate dosing to treat hypertension Beers Criteria Avoid in women with incontinence Avoid to treat hypertension Adverse Effects: Nonselective Alpha1-Blockers: CV depression symptoms, if left untreated, then CV stimulation symptoms may develop Drug Interactions Any drug that treats hypertension Any drug that treats BPH Any drug that targets alpha-adrenergic receptors Any drug that is a substrate, inhibitor or activator of CYP2D6 or CYP3A4 14. Alpha 1A-selective blocker MOA: competitive Alpha1-Adrenergic Antagonist Pharm: Block actions of NE to promote smooth muscle relaxation. If it binds: Alpha1A in prostate, it will relieve bladder outlet obstruction Alpha1B in vascular smooth it will lead to vasodilation Alpha1D in bladder neck, it will relieve bladder outlet resistance Tamsulosin → CYP2D6 and CYP3A4 Only binds Alpha1A in Prostate Indications: BPH Contraindications: Avoid with pre-existing: Angina Hepatic impariment Cataract Surgery (b/c Floppy Iris Syndrome) Advanced Age (see Beers List!) Titrate dosing to treat hypertension Beers Criteria Avoid in women with incontinence Avoid to treat hypertension Adverse Effects: Alpha1A Selective Blockers: Genitourinary effects Drug Interactions: Any drug that treats hypertension Any drug that treats BPH Any drug that targets alpha-adrenergic receptors Any drug that is a substrate, inhibitor or activator of CYP2D6 or CYP3A4 Pharmacologic Class: Beta Agonists 15. Beta1/Beta2 Agonist (Drug Name: Isoproterenol) Class/MOA: Beta1/2 Agonist Therapeutic Class: Positive Inotropic Agent Pharm Action: increased sympathetic outflow (specifically used for its effect on Beta1 - but Dobutamine is better) Beta1 activation: increase heart rate and contractility Indication: Critically low cardiac output due to bradycardia and AV block Metabolism: COMT substrate Contraindications Acute high alert status Avoid using with pre-existing CV disease History of Pediatric bronchospasm Sulfite hypersensitivity Drug interactions: Any drug that also targets beta-adrenergic receptors COMT inhibitors General anesthetics (increase CV stimulation) 16. Short-acting Beta2 Agonist (SABA) → Pharmacologic Class/MOA Albuterol Levalbuterol SABA Drugs Therapeutic Class: Bronchodilators ROA: usually inhaled Pharm Action: Bronchodilation Indication (Has a rapid onset of action): Acute Bronchospams (aka acute ‘exacerbations’, acute care management) NOTE: SABA/LABA are 1st line agents and preferred compared to SAMA/LAMA Adverse Effects (limited to localized administration): Related to ROA - Laryngeal spasm and irritation If enters systemic circulation - CNS and CV stimulation Contraindications: Milk Hypersensitivity Seizure disorder Glaucoma Precautions: Excessive use of sympathomimetics (like beta2 agonist) are associated with fatalities 17. Long-acting Beta2 Agonist (LABA) → Pharmacologic Class/MOA Aformoterol Formoterol Indacaterol Olodaterol Salmeterol LABA Drugs Therapeutic Class: Bronchodilators ROA: usually inhaled Pharm Action: Bronchodilation Indication (Has a slow onset of action): Bronchospasm prophylaxis (aka ‘Daily maintenance’ of a respiratory disorder like asthma or COPD) NOTE: SABA/LABA are 1st line agents and preferred compared to SAMA/LAMA Adverse Effects (limited to localized administration): Related to ROA - Laryngeal spasm and irritation If enters systemic circulation - CNS and CV stimulation Contraindications: Milk Hypersensitivty Seizure disorder Glaucoma Precautions: Use of LABA as monotherapy without inhaled corticosteroids (ICS) Excessive use of sympathomimetics (like beta2 agonist) are associated with fatalities Black Box Warnings: Salmeterol Monotherapy = increased risk of asthma-related death and hospitalization of pediatric and adolescent patients. 18. Beta3 Agonist → Pharmacological Class/MOA Mirabegron Therapeutic Class: Genitourinary Antispasmodic Pharm Action: Relaxes Bladder (to promote urinary retention) Indication: Overactive Bladder Metabolism: Moderate CYP2D6 inhibitor Minor CYP2D6 and CYP3A4 substrate Adverse Effects: CV stimulation Urinary tract infections (related to urinary retention) Drug Interactions: Any drug that is a substrate of or inhibitor/activator of CYP2D6 and CYP3A4 NOTE: Unlike muscarinic antagonist of OAB Mirabegron is not included on Beers List of inappropriate medication for use in the elderly Pharmacologic Class: Beta Blockers 19. Ophthalmic Beta Blockers Timolol Therapeutic Class: Antiglaucoma Agents MOA: Bind BETA 1 + BETA 2 Pharm Action: Reduce intraocular pressure Indication: Ocular hypertension, Glaucoma Adverse Effect: Minimal 20. Non-selective Beta1/Beta2 Blockers Propranolol 21. Non-selective Beta1/Beta2 Blockers with Alpha Blockade Carvedilol Labetalol 22. Cardio-selective (Beta1) Blockers. Atenolol Bisoprolol Metoprolol succinate Metoprolol tartrate Nebivolol For Drugs Listed in 20, 21, and 22. ROA: Oral, Injectable Pharm Action: decreased sympathetic outflow Depending on subclass, these drugs will block: Beta 1 receptors = decrease heart rate (HR) and contractility Beta 2 receptors = smooth muscle relaxation Alpha 1 receptors = decrease Blood Pressure (BP) #1 use = Cardiovascular (CV) disease Angina Arrhythmias Hypertension Myocardial Infarction Heart failure Acute Coronary Syndrome #2 Non-cardiovascular Uses Pheochromocytoma Essential tremor Migraine prophylaxis Parkinson’s disease Acute panic, agitation and stress with schizophrenia and antipsychotic therapy Aggressive behavior Performance anxiety Patient with Asthma or Hyperlipidemia Use cardio-selective Beta1 Blocker → these drugs will not stimulate Beta2 and cause bronchospasm Patient with Bradycardia or Hyperlipidemia Use a beta blocker (NONE ARE FROM TOP MEDS) with intrinsic sympathetic activity (ISA) → these drugs have partial agonist activity that manifests as slight cardiac stimulation Patient with Heart Failure Select Bisoprolol, Carvedilol, and Metoprolol SR because these are clinically-proven to decrease mortality → can change from clinical trail outcomes Patient with Hepatic Disease Use beta blocker that is not hepatically-eliminated (Atenolol) Patient with Renal Disease Use beta blocker not renally-excreted Labetalol Metoprolol Propranolol All are associated with CV depression (Bradycardia and Hypotension) CNS depression associated with Lipophilic beta-blockers (Metoprolol and Propranolol) due to these drugs crossing the Blood Brain Barrier (BBB) Bronchospasm and Dyspnea are associated with Non-specific Beta-Blockers (Propranolol) because they block Beta2 receptors leading to bronchospasm Sexual dysfunction is associated with any Beta blocker with alpha blockade (Carvedilol and Labetalol) → This is the same Adverse Effect associated with Alpha1 blockers used to treat hypertension and BPH Drug Interactions: Any drug that targets beta adrenergic receptors Any drug that targets alpha adrenergic receptors Contraindications: For any drug that blocks Beta1 receptors Pre-existing Bradycardia Pre-existing Heart Block For any drug that blocks Beta2 receptors Respiratory disorder Black Box Warnings DO NOT abruptly withdraw from treatment with: Nadolol Propranolol Atenolol Metoprolol With abrupt withdrawal, these drugs are associated with an increase risk of: Cardiac ischemia Exacerbation of angina Precipitation of myocardial infarction and/or an arrhythmia Block 3 1st generation H1 Antihistamine questions will test knowledge about 1. Anticholinergic activity → SEDATING (More lipophilic) For: Allergy, Insomnia, Sedation/Anxiety, Nausea/Vomiting Select 1st Generation Chlorpheniramine (OTC) Diphenhydramine (Rx, OTC, injectable) Dimenhydrinate (OTC) Doxylamine (OTC) Hydroxyzine (Rx) Meclizine (Rx, OTC) Promethazine (Rx) 2. Beers List inclusion Elderly (Due to anticholinergic activity) due to increase risk for delirium, cognitive impairment, urinary retention (including BPH) 3. Recognize an Rx H1 antihistamine used to treat short-term anxiety and insomnia Doxylamine: short-term insomnia Hydroxyzine: antiemetic, short-term insomnia, alternative 4. Recognize an H1 antihistamine used to treat motion sickness and vertigo Dimenhydrinate: antiemetic, antivertigo Meclizine: antiemetic, antivertigo H1 Antihistamine Important Points Clinical use: Allergies, Insomnia, Sedation/Anxiety, Nausea/Vomiting MOA: Disrupt histamine binding to H1 histamine receptors Pharm Action: Reduce histamine-mediated allergic responses Sedation Antiemesis antivertigo Adverse Effects: chronic use = weight gain SEDATION (related to decreased histamine-to-H1 receptor binding) Anti-SLUDGE-DDUMBELS related to anticholinergic activity Paradoxical CNS stimulation for children less than 6 years old Drug Interactions CNS depressant Anticholinergics H1 antihistamines and H3 histamine receptor antagonist/inverse agonist Cough-cold combination products Patients that are REALLY sensitive to anticholinergics Elderly (Beers list) Glaucoma Physical GI or genito-urinary tract obstruction With a respiratory disorder Taking any drug that alters cholinergic neurotransmission How to remember Adverse Effects of Anticholinergic Drugs: Hot as a hare (Hyperthermia from no sweating) Dry as a bone (Dry Skin) Red as a beet (Flushed from overheating because no sweating) Blind as a bat (Mydriasis will cause blurred vision) Mad as a hatter (Anytime you affect Acetylcholine in the brain, you alter cognition) 2nd generation H1 Antihistamines 5. Identify 2nd generation H1 antihistamines with mast cells stabilizer activity Azelastine (Rx) Ketotifen (OTC) Olopatadine (Rx) 6. Identify 2nd generation H1 antihistamines without mast cells stabilizer activity Cetirizine (OTC) Fexofenadine (OTC) Levocetirizine (OTC) Loratadine (OTC) 7. General H1 antihistamine pharmacology question (1st or 2nd generation) Low sedation: Cetirizine Levocetirizine Acrivastine Non-sedating: Fexofenadine Loratadine Desloratadine Metabolism: Minor CYP3A4 substrates: Cetirizine, Loratadine, Desloratadine, Fexofenadine Minor CYP2D6 substrate: Loratadine Adverse Effects: Weight gain (with chronic use) Less Adverse Effects than 1st generation H1 antihistamines Drug Interactions Fexofenadine only: no Aluminum- or Magnesium- containing products Histamine combination products for cough, cold, allergy, etc. Both 1st and 2nd generation H1 antihistamines are used for symptomatic Allergy Relief for: Allergic Rhinitis: Nasal turbinate Allergic Asthma: Airways Allergic Conjunctivitis: Conjunctiva Urticaria: Upper dermal layers Angioedema: Deeper dermal layers Anaphylaxis: Whole body Drug Class to treat narcolepsy 8. Histamine H3 receptor Antagonist/Inverse Agonist Pitolisant Therapeutic Class: Narcolepsy Agent MOA: Histamine 3 receptor antagonist and inverse agonist Pharm Action: CNS Stimulation (and thus WAKEFULNESS) Clinical Use: Narcolepsy Metabolism: CYP2D6 and CYP3A4 substrate Adverse Effects: Any symptom associated with CNS stimulation Contraindications: Liver disease Drug Interactions: H1 antihistamines (Histamine binds to H3 receptors and stops histamine release) Drugs to treat gastric acid disorders 9. Muscarinic Antagonists Dicyclomine Glycopyrrolate Hyoscyamine Methscopolamine 10. H2 histamine blockers Famotidine Cimetidine Both Drugs have equal efficacy MOA: Histamine H2 receptor antagonists Pharm Action: decreased histamine-mediated gastric acid production Metabolism: Cimetidine is a non-selective CYP inhibitor Adverse Effects Atrophic gastritis Pneumonia (CAP and HAP) Cytopenia Cimetidine only: Antiandrogenic symptoms (sexual dysfunction, gynecomastia, galactorrhea, hyperprolactinemia) Beers List: Delirium and significant mental status changes Warnings (increased risk for) Vitamin B12 deficiency (>2 years) C. difficile infection (with AB to treat H. pylori) Parasitic infection for immunocompromised patients Drug Interactions pH dependent drugs Proton pump inhibitors 11. Proton Pump Inhibitors Dexlansoprazole Lansoprazole Pantoprazole Esomeprazole Omeprazole Rabeprazole MOA: Inhibit actively secreting H+/K+ -ATPase (proton pump) Pharm: decrease gastric acid production Metabolism: pH-dependent (acid releases active metabolite) CYP3A4 substrates are: Dexlanso-/Lanso-/Rabe-prazole Adverse Effects: Reduce magnesium blood levels Pneumonia (CAP and HAP) SLE (Lupus) Bone fractures Contraindications: Osteoporosis (bone disease) SLE (Lupus) Warnings (increased risk for) Vitamin B12 deficiency (> 2 years) Drug Interactions pH dependent drugs Any other gastric acid-reducing drug classes 12. Mucosal Protectant – Misoprostol Class: Mucosal Protectant and synthetic prostaglandin (PGE1) analog Clinical Use: NSAID-induced ulcer prophylaxis Abortifacient Postpartum hemorrhage MOA: Prostaglandin receptor agonist (it’s a prostaglandin analog) Pharm Action: decreased basal and nocturnal gastric acid secretion to promote mucus production and bicarbonate secretion Adverse Effects: Abdominal cramps due to its oxytocic properties Black Box Warning: Abortifacient properties Contraindications: Pregnancy Drug Interactions: Mg-containing products (together they worsen diarrhea) Another oxytocic 13. Mucosal Protectant - Sucralfate Clinical Use: Duodenal (not peptic) ulcers MOA: utilizes acid to complex with proteins on surface of epithelial cells in duodenum Pharm Action: forms paste-like protective barrier at interface of mucous and gastric lumen layers of damaged gastric mucosa Adverse Effects: Respiratory complications Contraindications: Respiratory disorders Dysphagia (anyone with difficulty swallowing) Drug Interactions Antacids (due to the drug utilizing acids) Increased aluminum absorption with aluminum-containing products (like Mylanta) Chelation with quinolone antibiotics Select GI Drugs - Prokinetics → enhance smooth muscle contractions Prokinetics: also known as Propulsive, GI stimulant, GI motility agent Pharm Action: Enhance GI transit and motility Accelerate gastric emptying Clinical Use: GI motility disorders (especially severe constipation due to disease such as IBS) Examples: Gastroparesis Reduced GI motility after abdominal surgery 14. Secretory Agent – Cl- channel activator Drug name: Lubiprostone MOA: Chloride Ion Channel Activator 15. Secretory Agent – GCC agonist Drug names: Plecanatide, Linaclotide MOA: Guanylate Cyclase C (GCC) agonist Black Box Warning - GCC AGONISTS ONLY: Use caution with children due to increased dehydration risk ALL 3 drugs (Channel activator and GCC Agonists) Clinical uses: Chronic constipation disorders (such as chronic idiopathic constipation, IBS-constipation) Net Pharm Action: Promote intestinal fluid secretions containing chloride and/or bicarbonate which in turn regulate bowel movements by encouraging GI motility Adverse Effects: Significant GI distress acute and severe DIARRHEA Abdominal pain cramps distention Flatulence Contraindications: Avoid with bowel impaction or physical obstruction Drug interactions Muscarinic Antagonists (which cause constipation) Any drug class that reduces GI motility (Antidiarrheals) Select GI Drugs - Antidiarrheal 16. Somatostatin Analogs Drug names: Octreotide, Lanreotide, Pasireotide Clinical use/Indication: Diarrhea associated with gastric neuro-endocrine tumors MOA: Somatostatin receptor agonists (because they are synthetic somatostatin analogs) Pharm: Support regulation of gastrointestinal neuroendocrine hormones to assist with regulation of gastric mobility Metabolism: Octreotide is a CYP3A4 substrate Drug-Food Interaction: Dietary fats (altered absorption) Select GI Drugs - Laxatives → promote stool evacuation 17. Bulk-forming Drug names: Calcium Polycarbophil Psyllium Methylcellulose Wheat Dextrin Pharm Action: Promote stool water retention and bulk to improve consistency of bowel movements Other: Improves consistency of bowel movements 18. Stool-softeners → Acute constipation relief Drug names: Docusate Glycerin Mineral oil Pharm Action: Promote water and lipid penetration into stool lowers the surface tension at the oil-water interface of the feces, allowing water and lipids to penetrate the stool. Indication: occasional constipation relief Drug Interactions: Mineral Oil → increased absorption with stool softener laxatives 19. Osmotic → Acute constipation relief and prepare bowel for diagnostic procedures Drug names: Lactulose Mg Citrate/Hydroxide Polyethylene Glycol Na-phosphate/sulfate Sorbitol Mg sulfate K+ chloride Pharm Action: Osmotically drawing water into the intestinal lumen to induce increased peristalsis Drug interactions: Tetracycline and Quinolone antibiotics 20. Stimulant → Acute constipation relief Drug names: Aloe Bisacodyl Castor Oil Senna Pharm Action: Directly stimulate peristaltic movement of the intestine via local mucosal irritation Adverse Effects: cause abdominal pain and/or cramps Cannabinoids 21. For treatment-resistant epilepsy Drug name: Anandamide → endocannabinoid Bind inhibitory G-protein coupled receptors: CB1, CB2 Clinical use: Rx = drug-resistant pediatric epilepsy OTC = natural supplement for CNS depression MOA: Unknown; does not bind CB receptors but shown to prevent the degradation of anandamide Adverse Effects: None besides CNS depression Drug interactions: CNS depression 22. For treatment of N/V and anorexia Subclass: Appetite Stimulants, Antiemetics Drug names: Dronabinol Nabilone MOA: Cannabinoid receptor agonists Dronabinol: non-selective (CB1 and CB2) Nabilone: CB1-selective Pharm Action: Appetite stimulation and decreased emesis Clinical use: Anorexia-associated weight loss (with AIDS); chemotherapy-induced N/V (aka CINV) Metabolism: several minor CYP interactions Warnings: Cardiac disease Contraindications Seizure disorder History of substance abuse Psychiatric disorder Psychological Adverse Effects Associated with CB agonists Affective Sensory Somatic Cognitive