Pharmacology Notes 2022 PDF

COMPENDIUM PHARMACOLOGIA TABLES MADE BY MAX LEMKE AND ADA OHLSEN Table of Content PHARMACOLOGY COLLOQUIUM 1 3 Definitions 3 Direct acting agonists 5...

COMPENDIUM PHARMACOLOGIA TABLES MADE BY MAX LEMKE AND ADA OHLSEN Table of Content PHARMACOLOGY COLLOQUIUM 1 3 Definitions 3 Direct acting agonists 5 Mixed action agonists 6 Alpha receptors 7 Beta receptors 8 Partial agonist 10 Parasympathetic nervous system - Cholinergic system 12 Cholinergic agonists 13 Anticholinergic 15 PHARMACOLOGY COLLOQUIUM 2 16 Hypertension 16 Antiplatelet 18 Anticoagulants 19 Diabetes 21 Hyperlipidemia 23 PHARMACOLOGY COLLOQUIUM 3 25 Analgesic pain ladder 25 NSAIDs 26 Opioids 27 Antihistamine 29 Glucocorticoids & Mineralocorticoids 31 GI 33 Antiemetics 33 Anti-peptic ulcer agents 35 Laxatives 36 Anti-diarrheal agents 38 Gastric diseases 39 PHARMACOLOGY COLLOQUIUM 4 40 Anti-seizure drugs 40 Antidepressants 43 Alzheimers 45 Parkinsons 46 Antipsychotic 48 PHARMACOLOGY COLLOQUIUM 5 50 Antifungals 50 Antiviral 51 Antibiotics 54 DDIs 59 Impact of Drugs 61 Addictions 62 General anesthesia 63 Local anesthesia 65 2 of 65 Pharmacology Colloquium 1 DEFINITIONS Zero order elimination: Agonist: Pharmacokinetics: Constant rate of elimination (= same amount being lost A molecule capable of binding to and functionally activating a over time) ex. Aspirin, Ethanol target Bodies reaction on the drugs Ex. Phenylephrine (alpha agonist) Relationship between concentration and time (metabolism, First order elimination: absorption, distribution and excretion) Antagonist: Rate of elimination is proportional to amount (= same percen- Pharmacodynamics: tage being lost over time) - most drugs have this A molecule that binds to a target and prevents other molecules 1/2 = 4h (on average); (steady state occurs after 4 half lives are (e.g., agonists) from binding Drugs effect on the body complete) Relationship between concentration and effect Elimination (clearance) Competitive: Volume of drug cleared from body over time Pharmacokinetics: CL = (rate of eliminations) / (plasma concentration) Reversible Ex. Prazosin (alpha blocker), Propranolol and Atenolol (beta Kinetics: blocker), Phentolamine (alpha and ß blocker) IV formulations = 100% bioavailability; PO formulations = 50% Therapeutic index: Non competitive: bioavailability due to first pass effect A quantitative measurement of the relative safety of a drug Irreversible First pass effect: It is a comparison of the amount of a therapeutic agent that Ex. Carvedilol and Labetalol (beta blockers) Phenoxybenzami- causes the therapeutic effect to the amount that causes toxicity ne (alpha blocker) Pre-systemic metabolism of drug (reducing bioavailability) Large TI is better than narrow TI Mostly elimination through kidneys (renal = urine) Synergy: Toxic dose: Metabolism (mechanism by which drugs are converted to Epinephrine and Atropine: Epinephrine will stimulate SNS metabolites): Median toxic dose (TD50) of a drug or toxin is the dose at while Atropine will inhibit PNS enabling muscle relaxation in which toxicity occurs in 50% of cases, LD50 - 50% of test sub- airway smooth muscles in ex. asthma or COPD = better airflow Phase 1: Oxidation (P450), reduction, hydrolysis jects died Salbutamol and phenylephrine: Salbutamol will stimulate ß Phase 2: Conjugation (Sulfation, Methylation, Acetylation, Glu- adrenergic receptors and Phenylepinephrine will stimulate curonidation) Therapeutic dose: alpha adrenergic receptors = act on different receptor subtypes Geriatric patients have more phase 2 metabolism = ↑ adverse to ↑ HR, cardiac output and peripheral vascular resistance effects if they have slow conjugation The quantity of any substance required to effect the cure of a Neostigmine and Pilocarpine: Neostigmine will ↑ ACh concen- disease tration (prevent breakdown) while Pilocarpine directly stimula- Half life: CD50 = when the dose cures 50% of test subjects (mean cura- tes cholinergic receptors = promotes muscle contraction in ex. tive dose) urinary retention = bladder emptying Time required to reduce the amount of the drug in the body Prazosin and Propranolol: Prazosin will block alpha adrenergic (blood) by half LD50: receptors (relax blood vessels, reduce peripheral resistance) and Propranolol will block ß adrenergic receptors (slow HR, Lethal dose at which 50% of test subjects died reduce cardiac output) = better effect in hypertension or benign prostatic hyperplasia (BPH) 3 of 65 Type Location In The Body Mechanism Of Action Molecular Pathway If Activated α1 Vessels Contraction (↑s vascular resistance) Bind Gq = activates phospholipase C = release Smooth muscles of IP3 and DAG IP3 acts on its receptor = release of Ca2+ Pupil Contraction (mydriasis) Bladder Contraction (erect hairs) Prostatic smooth muscle Contraction α2 CNS Inhibits neurotransmitter release Inhibition of adenylyl cyclase via G protein Vessels Coronary vessels Contraction Pancreas Inhibits insulin release Platelets Stimulates aggregation Adipocytes Inhibits lipolysis ß1 Heart Stimulates rate and force Bind Gs = ↑ in cAMP Juxtaglomerular cells of kidney Stimulates renin release ß2 Heart Stimulates rate and force Bind Gs = ↑ in cAMP Lung Relaxes / Bronchodilation Vessels Vasodilation Liver Stimulates glycogenolysis Uterine Relaxes GI ↓ GI motility Pancreatic ß cells Stimulates insulin release Voluntary muscles Causes tremors ß3 Adipose tissue Stimulates lipolysis Bind Gs = ↑ in cAMP Dopamine 1 Renal vessels Vasodilation Bind Gs = ↑ cAMP (in neurons and vessels) Dopamine 2 Nerve terminals Inhibits adenylyl cyclase Bind Gi = ↓ cAMP synthesis 4 of 65 DIRECT ACTING AGONISTS Group Agent MOA SE Indication Contraindication Direct acting agonist Epinephrine α 1 = Vasoconstriction, ↑ BP Hypertension Anaphylaxis Glaucoma ß1 = ↑ HR, ↑ Force, ↑ AV con- Arrhythmias Non selective duction MI Halothane anesthesia α+ß ß2 = Bronchodilation Pulmonary edema Anxiety Headache Norepinephrine α 1 = Vasoconstriction, ↑ BP Hypertension Cardiac arrest Hypertension ß1 = ↑ HR, ↑ Force, ↑ AV con- Angina Pectoris Hypotensive shock Blood clot duction MI Arrhythmias ↓ Renal blood flow Dopamine Low dose: Angina Acute HF Pheochromocytoma Arrhythmia Hypotensive shock Acidosis D = Vasoconstriction Hypertension Ventricular arrhythmias ↑ BP Nausea High dose: α 1 = Vasoconstriction ↑ BP Even higher dose: ß1 = ↑ HR ↑ Force ↑ AV conduction 5 of 65 MIXED ACTION AGONISTS Group Agent MOA SE Indication Contraindication Mixed action agonist Ephedrine Activate adrenergic receptors Decongestant by binding + release stored NE Vasoconstriction Bronchodilatation Rarely used Pseudoephedrine Activate adrenergic receptors Decongestant by binding + release stored NE Vasoconstriction Bronchodilation ↓ Nasal inflammation ↓ Nasal mucous 6 of 65 ALPHA RECEPTORS Group Agent MOA SE Indication Contraindication α 1 agonist Phenylephrine α 1 = Vasoconstriction, ↑ BP Hypertension Decongestant Acidosis Oxymetazoline Mydriasis Bradycardia Mydriasis Overactive thyroid Arrhythmia Neurogenic hypotension Intestinal ischemia Chest pain Kidney failure Nausea Vomiting Headache Anxiety α 2 agonist Clonidine α 2 = (Oral), ↓ NE release → Hypotension Hypertension Pregnancy Vasodilation, ↓ HR, ↓ CO = ↓ Arrhythmia Glaucoma Dry eyes BP Bradycardia ADHD Heart attack Works peripheral and on CNS Hallucination Spasticity Depression Confusion Drug withdrawal Headache Insomnia Methyldopa α 2 = (Oral), ↓ NE release → RBC breakdown Hypertension (mostly used in Anemia Vasodilation, ↓ HR, ↓ CO, = ↓ Liver problem pregnancy) Liver impairment BP Hypersensitivity MAOIs Primarily on CNS Insomnia Non selective α blockers Phentolamine Block α 1: Tachycardia Hypertensive emergency in HF (Reversible = 4h) (α 2) Pheochromocytoma Coronary disease Vasodilation Orthostatic Hypotension Injection in Penis = Erection Renal impairment Phenoxybenzamine ↓ BP Nasal congestion (Irreversible = 12h) Inhibition ejaculation Block α 2: ↑ NE release ↓ BP α 1 blocker Prazosin Block α 1: Orthostatic hypotension BPH Cataract eye surgery Alfuzosin Tamsulosin Vasodilation P: Hypertension T: Stones under 4 mm and ↓ BP over 10 mm, cataract eye sur- T: Chronic Prostatitis, kidney gery Relax prostate + Bladder stones = ↑ Urinary flow 7 of 65 BETA RECEPTORS Group Agent MOA SE Indication Contraindication ß 1 agonists Dobutamine ß1: Arrhythmia Acute HF Hypokalemia Angina Hypertension ↑ HR Hypertension Heart attack ↑ CO Headache ß2 agonists Salbutamol ß2: ↓ K+ Acute Asthma symptoms Hypokalemia Fenoterol Tachycardia COPD Diabetes SABA Bronchodilation Anxiety Bronchoconstriction Overactive thyroid Arrhythmia ↑ K+ levels Shaky Headache F: Cardiovascular toxicity ß2 agonist Salmeterol ß2: ↓ K+ Asthma attack prevention Hypokalemia Formoterol Dizzy COPD Diabetes LABA Bronchodilation Sinus infect Overactive thyroid Migraine tremors ß3 agonist Mirabegron ß3: Constipation Overactive bladder Pregnancy Diarrhea Hypertension Relax bladder + prevent urina- UTI tion 1st gen ß blocker Propranolol ß1: Bronchoconstriction Hypertension Asthma Timolol Arrhythmia Arrhythmia COPD Non selective Nadolol ↓ HR Sexual dysfunction Thyrotoxicosis AV Block ↓ Force Masking hypoglycemia Tremors Cardiogenic shock ↓ AV conduction Nausea Capillary hemangiomas Hypotension GI disturbances Renal impairment ß2: Constipation P: Migraine prophylaxis (cros- Hepatic impairment ses BBB) Diabetes Bronchoconstriction T: Glaucoma 8 of 65 2nd gen ß blocker Atenolol ß1: Depression Hypertension AV Block Bisoprolol Erectile dysfunction Angina Cardiogenic shock ß1 blocker Metoprolol ↓ HR Bronchospasm Arrhythmia Hypotension ↓ Force Bradycardia HF Renal impairment ↓ AV conduction HF Glaucoma Hepatic impairment Masking hypoglycemia Diabetes High dose = ↓ Selectivity Dizzy Raynaud's phenomenon Fatigue Asthma COPD → ↑ Dose 3rd gen Carvedilol Block ß1: Hypotension Hypertension Asthma Labetalol Bradycardia Pregnancy COPD Non-selective ß blocker ↓ HR ↑ Weight Left ventricle dysfunction AV Block ↓ Force Masking hypoglycemia Cardiogenic shock ↓ AV conduction Dizzy C: HF (because of antioxidant Hypotension Fatigue effect) Renal impairment Block ß2: Diarrhea Hepatic impairment Weak Diabetes Bronchoconstriction Block α1: Vasodilation ↓ BP 3rd gen Nebivolol N: Vasodilation by NO release Eye stinging Hypertension Pregnancy Betaxolol Blurry vision Angina ß1 blocker B: Vasodilation by blocking Masking hypoglycemia AV Block Ca2+ ch Dizzy N: HF (because of Antioxidant Cardiogenic shock Headache effect) Hypotension Renal impairment Hepatic impairment Diabetes Raynaud's phenomenon 9 of 65 PARTIAL AGONIST Group Agent MOA SE Indication Contraindication Partial agonist Pindolol Non-selective ß blocker: Bronchoconstriction Hypertension Hypotension Arrhythmia Pregnancy Renal impairment ß1: Sexual dysfunction Left ventricle dysfunction Hepatic impairment Nausea Diabetes ↓ HR GI disturbances Patients with … but still in Raynaud’s phenomenon ↓ Force Constipation need of ß blocker: ↓ AV conduction Asthma ß2: Bradycardia Heart block Bronchoconstriction → But less because also: ß1 + ß2 agonist: ß1: ↑ HR ↑ CO ß2: Bronchodilation 10 of 65 Acebutolol ß1 blocker: Depression Hypertension Hypotension Erectile dysfunction Angina Renal impairment ß1: Bronchospasm Arrhythmia Hepatic impairment Bradycardia HF Diabetes ↓ HR HF Glaucoma Raynaud's phenomenon ↓ Force Dizzy ↓ AV conduction Fatigue Patients with … but still in need of ß blocker: → But less because also: Asthma ß1 + ß2 agonist: Bradycardia Heart block ß1: ↑ HR ↑ CO ß2: Bronchodilation 11 of 65 PARASYMPATHETIC NERVOUS SYSTEM - CHOLINERGIC SYSTEM Type Location In The Body Mechanism Of Action Molecular Pathway If Activated M1 Gastric glands Secretion of gastric acid Gq = Phospholipase C release = release of 2nd CNS Pro cognitive messenger (DAG and IP3) DAG modulates protein kinase C IP3 causes Ca2+ release M2 Cardiac cells ↓ HR and ↓ contraction force Gi = opens K+ channels = hyperpolarization = ↓s HR (couple adenyl cyclase via Gi = ↓ cAMP syn- thesis) M3 Smooth muscle in eye Miosis Gq = phospholipase C release = release of 2nd Lungs Bronchoconstriction messenger (DAG and IP3) GI ↑ Peristalsis DAG modulates protein kinase C Urinary tract Bladder contraction IP3 causes Ca2+ release Exocrine glands (sweat and salivary) ↑ Secretion M4 CNS Regulates neurotransmission GI = ↓ cAMP synthesis M5 CNS Regulates neurotransmission Gq = phospholipase C release = release of 2nd messenger (DAG and IP3) DAG modulates protein kinase C IP3 causes Ca2+ release Nm Neuromuscular junction Muscle contraction Na+/K+ channel is activated = Na+ influx = exci- tatory postsynaptic potential (EPSP) = action potential propagation Nn Nervous system and autonomic ganglia Transmission of cholinergic signals Na+/K+ channel is activated = Na+ influx = exci- tatory postsynaptic potential (EPSP) = action potential propagation 12 of 65 CHOLINERGIC AGONISTS Group Agent MOA SE Indication Contraindication Direct acting Bethanechol Carbachol: GI disturbances C: ↓ Intraocular pressure in COPD Carbachol Hypotension glaucoma Asthma Pilocarpine M3 = Contraction of sphincter Bradycardia Bradycardia of iris P: Sjörgens syndrome, dry Peptic ulcer disease ACh (Not used because it’s Bethanechol: eyes Hypotension quickly degradation by AChE) Pilocarpine: Bronchoconstriction B: Urinary retention M1, M2, M3 = Contracting ciliary muscle C & P: Bethanechol: Miosis ↓ Ocular pressure M2, M3 = ↑ Bladder contrac- tion and GI motility Pilocarpine: ↑ Sweating ↑ Salivation Indirect acting reversible Physostigmine Inhibit AChE = Inhibit ACh DUMBBELSS: Physostigmine: Atropine over- Phy, P & N: Rivastigmine degradation = ↑ ACh = ↑ Sti- dose Donepezil mulation of cholinergic recep- Diarrhea Urinary obstruction Galantamine tor Urination Py, P & N: myasthenia gravis Asthma Pyridostigmine Miosis (MG) COPD Neostigmine Bronchoconstriction Bradycardia Edrophonium Bradycardia D & R: Alzheimer's Epilepsy Excitation (skeletal muscles & CNS) E: Rapid reversal of non depo- Physostigmine: Peptic ulcer Lacrimation larizing neuromuscular block disease Salivation + MG diagnosis Sweating E: History of asthma Nicotinic agonist Depolarizing: 1. Binds Nm (neuromuscular Muscle pain Added to anesthesia for mus- Family history or susceptibility junction) in skeletal muscles Hyperkalemia cle relaxation to malignant hyperthermia Succinylcholine causing Na+/K+ channel to ↑ Intraocular pressure open = depolarization for a Malignant hyperthermia longer period of time 2. Receptor repolarizes but is desensitized = no AP can be triggered 13 of 65  Non depolarizing: Competitively binds Nm = Hypotension Added to anesthesia for mus- Low Mg2+, K+ and Ca2+ inhibits ACh from activating Tachycardia cle relaxation Myasthenia gravis Pancuronium receptor = inhibition of mus- Prolonged respiratory Depres- cle contraction sion Varenicline Partial agonist of subtype Nausea Smoking cessation History of psychiatric illness a4ß2 nicotine receptor Headache Seizures Insomnia Abnormal dreams Drugs which treat glaucoma: Carbachol AChE inhibitors: Neostigmine & Physostigmine, Atropine (can dilate pupil but also ↑ Intraocular pressure which causes glaucoma) 14 of 65 ANTICHOLINERGIC Group Agent MOA SE Indication Contraindication Antimuscarinic Scopolamine Non selectively blocks musca- Dry mouth Motion sickness Glaucoma rinic receptor Blurred vision Urinary retention Constipation Urinary retention Atropine Non selectively blocks M re- Dry mouth Bradycardia Glaucoma ceptors Blurred vision Antidote for AChE inhibitor Urinary retention Antidote: M1 = GI = Constipation Constipation overdose Myasthenia gravis M2 = Heart = ↑ HR Urinary retention Induce mydriasis Physostigmine M3 = Exocrine gland = Dries Ipratropium Block M3 receptor in lungs = Dry mouth COPD Glaucoma Tiotropium Bronchodilation Blurred vision Chronic bronchitis Obstruction in GI and urinary Constipation Emphysema tract Urinary retention Asthma Throat irritation Headache Oxybutynin Blocks M1, M2, M3 receptors Dry mouth Overactive bladder Glaucoma in bladder Blurred vision Urinary retention Constipation Gastric retention Urinary retention 15 of 65 Pharmacology Colloquium 2 HYPERTENSION Group Agent MOA SE Indication Contraindication Diuretics D: Carbonic anhydrase inhibi- Acetazolamide EC: NaCl ↓, NaHCO3 ↓↓↓, Hypokalemia Hypertension Hypokalemia tors K+↓ Metabolic acidosis Glaucoma Metabolic acidosis Inhibits carbonic anhydrase Congestive heart failure Renal insufficiency enzyme Pregnancy Bicarbonate gets retained in lumen Reduction in proximal tubule Na+ reabsorption D: Loop Diuretics Furosemide EC: NaCL ↓↓↓↓, K+ ↓, Ca2+ Hypovolemia Hypertension Anuria ↓↓↓ Hyperuricemia Liver cirrhosis Hypokalemia Greatest diuretic effect Torsemide In ascending loop of henle Hypokalemia Congestive heart failure Hypocalcemia Inhibit Na+ K+ cotransporter Hypocalcemia Renal disease Hepatic coma Greatest diuretic effect Pregnancy Remove water so reduce peri- pheral resistance (SVR) D: Thiazides Hydrochlorothiazide EC: Na+ ↓, Mg2+ ↓, K+ ↓, NaCl Hypokalemia Hypertension Gout ↓, Ca2+ ↑↑ Hyperuricemia Heart failure Diabetes Most common Indapamide Early part of distal tubule Hypercalcemia Diabetes insipidus Hyperlipidemia NaCl excretion by inhibiting Hyperlipidemia Hypokalemia Weak diuresis Chlorothiazide NaCl cotransporter Photosensitivity Pregnancy Vasodilation so reduced SVR Erectile dysfunction D: K+ sparring Agents Amiloride EC: K+ ↑↑, NaCl ↓, NaHCO3 ↓ Hyperkalemia Congestive HF Anuria Spironolactone In collecting tubule Metabolic acidosis Liver failure Renal insufficiency Mostly used in combination Inhibit Na+ reabsorption and GI upset To prevent hypokalemia Hyperkalemia with other diuretic K+ excretion In Spiro: Gynecomastia Pregnancy Amiloride: block Na+ channel Menstrual irregularities Weak Spironolactone: Antagonise Aldosterone Ca2+ channel blockers Dihydropyridines Amlodipine Inhibit L-Type Ca2+ channels Peripheral edema Hypertension HF Felodipine in vascular smooth muscle = Gum swell Angina pectoris Hypotension SVR - Headache Dizzy Flushing 16 of 65 Non-Dihydropyridines Verapamil Non selective Bradycardia Hypertension 2/3 AV Block Diltiazem Inhibit L-Type Ca2+ channels Arrhythmia Arrhythmia HF in vascular smooth muscle AV block Stable angina Hypotension and heart (AV/ SA node) Verapamil: Constipation ß blocker Contractility ↓ HR ↓, conduction ↓ Antiarrhythmics RAAS Inhibitors ACE inhibitors Perindopril Inhibit ACE Dry cough (because of brady- Hypertension Pregnancy Lisinopril No ANG2 production kinin) HF Hyperkalemia Captopril Bradykinin ↑: Dilation SVR ↓ Hyperkalemia Ramipril (ACE is killing Bradykinin) Angioedema Renal blood flow ↑ so less renal injury ARBs Telmisartan Block AT1 receptor so no Al- Hyperkalemia Hypertension Hyperkalemia (Angiotensin receptor blockers) Losartan dosterone release Leg swelling Congestive HF Pregnancy Candesartan SVR ↓ Dizzy Diabetic nephropathy ANG2 ↑ Headache Less ANG1 than in ACE inhibi- tors No bradykinin impact Renal blood flow ↑ so less renal injury 17 of 65 ANTIPLATELET Group Agent MOA SE Indication Contraindication TxA2 inhibitor Aspirin Irreversible inhibition of Cox 1 Bleeding Antiplatelet Stomach ulcers and Cox 2 Chest pain Fever Asthma Disrupt platelet regulation Pain Allergy Antidote: Children