Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

Category: ANGINA PECTORIS BETA BLOCKERS Prophylaxis of angina Cardiac arrhythmias, Nonselective Decreased heart rate, Oraland parenteral, Fatigue, weaknesses, Inderal, inderal angina pectoris, competitive cardiac output, and duration 4-6 h nausea, vomiting, LA, Propranolol, hypertension, antagonist β blood pressure, *Toxicity: asthma, depression, Atenolol essential tremor, adrenoceptors decreases myocardial atrioventricular block, bradycardia, dizziness, myocardial infarction, oxygen demand acute heart failure; vertigo, rash, decrease pheochromocytoma sedation*Interactions: libido, hypotension, Additive with all hyperglycemia, cardiac depressants decrease exercise tolerance, proarrhythmic effects CALCIUM CHANNEL Prophylaxis of Vasospastic angina Block vascular L- Like verapamil and Oral, duration 4-6 h Dizziness, Nifedipine, BLOCKERS angina, hypertension (Prinzmetal's variant type calcium diltiazem; less cardiac *Toxicity: Excessive lightheadedness, Adalat, angina), chronic stable channels > cardiac effects hypotension nervousness, procardia, angina, hypertension channels *Interactions: Additive headache, nausea, procardia XL, with other vasodilators constipation, dihydropyridine peripheral edema, asthenia, bradycardia, atrioventricular block, arrhythmias, flushing CALCIUM CHANNEL Prophylaxis of Angina pectoris, Nonselective block Reduce vascular Oral, IV, duartion 4-8 h Dizziness, light Verapamil BLOCKERS angina, hypertension arrhythmia, essential of L-type calcium resistance, cardiac *toxicity: headedness, (Calan, isoptin, hypertension, atrial channels in vessels rate, and cardiac Atrioventricular block, nervousness, verelan), flutter/fibrillation and heart force results in acute heart failure; bradycardia, flushing, Diltiazem decreased oxygen constipation,edema rash (Cardizem, demand *Interactions: Additive dilacor XR) with other cardiac depressants and hypotension

Page 1 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

MISCELLANEOUS for angina Inhibit late Na+ Reducescardiac Oral, duration 6-8 h * Prophylaxis of angina, No significant ivabradine Ranolazine current in heart, also oxygen demand, Toxicity: QT interval hypertension hemodynamic effects may modify fatty acid fatty oxidation prolongation, nausea, oxidation, reduce modification may constipation, contractility improve efficiency dizziness of cardiac oxygen *Interactions: utilization Inhibitors of CYP3A increase ranolazine concentration and duration of action NITRATES Angina: Sublingual Treatment and Release nitrate Smooth muscle very high first pass headache, Nitroquick, dose form for acute prevention of angina oxide in smooth relaxation especially, effect, so sublingual hypotension, nitrostat, episodes *oral and pectoris muscles, which in vessels, other dose is much smaller dizziness, weakness, nitrolingual, transdermal forms activate guanylyl smooth muscle is than oral, high lipid flushing, restlessness isodril, dilatrate, for prophylaxis cyclase and relaxed but not as solubility ensures nitroglycerin, increased cGMP markedly, rapid absorption * isosorbide vasodilation Toxicity: Orthostatic dinitrate, decreases venous hypotension, isosorbide return and heart size tachycardia, head mononitrate , may increase ache * Interaction: coronary flow in Synergistic some areas and in hypotension with variant angine phosphodiesterase type 5 inhibitors (Sildenafil, etc.) Category: ANTIARRHYTHMIA CLASS 1B Terminate Ventricular arrhythmia Sodium channels Blocks activated and IV *First-pass hepatic Lightheadedness, Lidocaine, ventricular (INa) Blockade inactivated channels metabolism *reduces nervousness, Mexiletine tachycardias and with fast kinetics dose in patients with bradycardia, prevent ventricular *does not prolong heart failure or liver hypotension, fibrillation after and may shorten disease *Toxicity: drowsiness, cardioversion action potential Neurologic symptoms proarrhythmic effect

Page 2 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

CLASS 1B Maintenance or Conversion of atrial Ikr Block Prolongs actions Oral *renal excretion Headache, chest pain, Sotalol, Ibutilide, Dofetilide restoration of sinus fibrillation, flutter to potential ,effective *Toxicity: Torsade de dizziness, respiratory Dronedarone, rhythm in atrial normal sinus rhythm, refractory period pointes (initiate in tract infection, Vernakalant, fibrillation maintenance of hospitals) dyspnea, nausea, flu Dofetilide normal sinus rhythm *Interactions: Additive like syndrome, (Tikosyn) with other QT- proarrhythmic effect prolonging drugs CLASS 1C Supraventricular Paroxymal atrial Sodium channels Dissociates from Oral *Hepatic, and Dizziness, headache, Flecainide, arrhythmias in fibrillation, flutter and (INa) Blockade channels with slow Kidney metabolism faintness, blurred Propafenone, patients with normal supraventricular kinetics *No change *half life ~20 h vision, headache, Moricizine heart *do not use in tachycardia in action potential *Toxicity:Proarrhythmi nausea, dyspnea, ischemic conditions duration c fatigue, palpitations, (post-myocardial proarrhythmic effect infarction) CLASS 2 Atrial arrhythmias Ventricualr β- Adrenoceptors Direct membrane Oral, Parenteral Hypotension, Propanolol and prevention of arrhythmia, blockade effects (Sodium *duration 4-6 h proarrhythmic effect, (Inderal), recurrent infarction hypertension channel block) and *Toxicity: Asthma, AV nausea, headache, Esmolol and sudden death prolongation of blockade, acute heart decreased exercise (Breviloc) action potential failure *Interactions: tolerance duration *slows SA With other cardiac node automaticity depressants and and AV nodal hypotensive drugs conduction velocity

Page 3 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

CLASS 3 Serious ventricular Life threatening Blocks IKr, INa, ICa-L Prolongs actions Oral, IV, *Variable Malaise, fatigue, Cordarone, Amiodarone arrhythmias and ventricular arrhythmia channels, β potential duration absorption and tissue tremor, proarrhythmic Pacerone supraventricular adrenoceptors and QT interval accumulation *hepati effect, nausea, arrhythmias *slows heart rate and metabolism, vomiting, AV node conduction elimination complex constipation, *low incidence of and slow *Toxicity: photosensitivity torsade de pointes Bradycardia and heart block in diseased heart, peripheral vasodilation, pulmonary and hepatic toxicity *Hyper -or Hypothyroidism *Interactions: Many based on CYP metabolism CLASS 4 Supraventricular Supravwentricular Calcium channels Slows SA node Oral, IV, *hepatic Constipation, Verapamil tachycardia tachyarrhythmia, IKr, INa, ICa-L automaticity and AV metabolism *caution dizziness, headache, (Colan, Covera temporary control of blockade nodal conduction in patients with mental depression, HS, Isoptin, rapid ventricular rate velocity *decreases hepatic dysfunction proarrhythmic effect, Verelan), in atrial cardiac contractility *toxicity: peripheral edema, Diltiazem flutter/fibrillation, *reduces blood Atrioventricular block, vomiting, nausea angina, hypertension pressure acute heart failure; constipation, edema *Interactions: Additive with other cardiac depressants and hypotension

Page 4 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

CLASS IA Most atrial and Procainamide - life INa (primary) and Slows conduction Oral, IV, IM Hypotension, Procainamide, ventricular threatening IKr (secondary) velocity and *eliminated by disturbances of Disopyramide, arrhythmias *drug of ventricular arrhythmia blockade pacemaker rate, hepatic metabolism to cardiac rhytthm, Quinidine second choice for Quinidine - premature prolongs action N-acetylprocainamide proarrhythmic effect most sustained atrial and ventricular potential duration (NAPA) and renal ventricular contractions, atrial and dissociates from elimination *NAPA arrhythmias tachycardia and Ina channel with implicated in torsade associated with flutter, paroxysmal intermediate kinetics de pointes in atients acute myocardial , direct depressant with renal failure infarction effects on SA & AV *Toxicity: Hypotension nodes *Long-term therapy produces reversible lupus-related MISCELLANEOUS Paroxysmal Activates inward Very brief, usually IV only *duration 10- Adenosine supraventricular rectifier IK *Blocks complete AV blockade 15 *Toxicity: Chest tachycardia Ica tightness, dizziness *Interactions: Additive with other cardiac depressants and hypotension MISCELLANEOUS Torsade de pointes Seizure associated Poorly understood Normalizes or IV *duration Flushing, sweating, Magnesium Magnesium *digital-is-induced with eclampsia and *interacts with Na+, increases plasma dependent on dosage depressed reflexes, sulfate arrhythmias acute nephritis in K+ ATPase, K+, and Mg2+ *Toxicity: Muscle hypotension, cardiac children Ca2+ channels weakness in overdose and CNS depression MISCELLANEOUS: Digitalis-induced Hypokalemia due to Increases K+ Slows ectopic Oral, IV *Toxicity: Nausea, vomiting, K-tab, K lyte, Potassium arrhythmias arrhythmia permeability, K+ pacemakers *slows Reentrant diarrhea, flatulence, Slow-K *arrhythmias currents conduction velocity in arrhythmias, abdominal discomfort associated with heart fibrillation or arrest in hypokalemia overdose

Page 5 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

Category: ANTICHOLINERGIC CHOLINERGIC Mandatory antidote Pylorospasm, Nonselective Blocks muscarinic Intravenous infusion Drowsiness, blurred AtroPen POISONING for severe reduction of bronchial competitive excess at exocrine until antimuscarinic vision, tachycardia, Atropine cholinesterase and oral secretion, antagonist at all glands, heart, smooth signs appear dry mouth, urinary inhibitor poisoning excessive vagal- muscarinic muscle *continue as long as hesitancy induced bradycardia, receptors in CNS necessary *toxicity: ureteral and biliary and periphery Insignificant as long as colic AChE inhibition continues CHOLINERGIC Usual antidote for Treat Very high affinity for Regenerates active Intravenous every 4-6 Neuromuscular POISONING early stage (48 organophosphorus phosphorus atom AChE; can relieve hours *toxicity: Can weakness Pralidoxime hours) poisoning but does not enter skeletal muscle end cause muscle cholinesterase CNS plate block weakness and inhibitor overdose GASTROINTESTINAL Reduces smooth oral; peptic ulcer, Competitive Reduces smooth Available in oral and Blurred vision, dry Rubinol, DISORDERS muscle and secretory parenteral; antagonist at M3 muscle and secretory parenteral forms mouth, altered taste Dicyclomine, activity of gut inconjunction with receptors activity of gut *short t1/2 but action perception, nausea, Hyoscyamine, aneasthesia to reduce last up to 6 hours vomiting, dysphagia, Glycopyrrolate bronchial and oral *Toxicity:Tachycardia, urinary hesitancy and secretion, to bloch confusion, urinary retention cardiac vagal retention, increased inhibitory reflexes intraocular pressure during induction of *Interactions: With anaesthesia and other antimuscarinics intubation; protection against the pheripheral muscuranic effects of cholinergic agents

Page 6 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

MOTION SICKNESS Prevention of motion Preanaesthetic Unknown Reduces vertigo, Transdermal patch Confusion, dry mouth, Scopolamine DRUGS sicknessand sedation, motion mechanism in CNS postoperative nausea used for motion constipation, urinary postoperative sickness sickness *IM injection hesitancy, urinary nausea and vomiting for postoperative use retention, blurred *Toxicity:Tachycardia, vision confusion, urinary retention, increased intraocular pressure *Interactions: With other antimuscarinics OPHTHALMOLOGY Retinal examination: Pylorospasm, Competitive Causes mydriasis and Used as drops * long Drowsiness, blurr Atropen, Atropine prevention of reduction of bronchial antagonist at all M cycloplegia (5-6days) action * vision, tachycardia, Atropine, synechiae after and oral secretion, receptors Toxicity: Increased dry mouth, urinary Scopolamine, surgery excessive vagal- intraocular pressure in hesitancy Homatropine, induced bradycardia, close angle glaucoma Cyclopentolate, ureteral and biliary * Interactions: With Tropicamide colic other antimuscarinics RESPIRATORY Prevention and relief Bronchospasm Competitive, Reduce or prevent Aerosol canister, up to Dryness of the Ipratropium, (ASTHMA, COPD) of acute episodes of associated with nonselective bronchospasm qid * Toxicity: oropharynx, Tiotropium bronchospasm chronic obstructive antagonist at M Xerostomia, nervousness, irritation pulmonary disease, receptors cough * from aerosol, chronic bronchitis, Interactions: With dizziness, headache, emphysema and other antimuscarinics GI distress, dry mouth, rhinorrhea nausea, palpitation URINARY Urge incontinence; Overactive bladder, Nonselective Reduces detrusor Oral, IV, patch Dry mouth, Enablex, Oxybutynin postoperative spasms neurogenic bladder muscarinic smooth muscle tone, formulations *toxicity: constipation, nausea, Ditropan, antagonist spasms Tachycardia, headache, drowsiness, Oxybutynin, constipation, urinary retention Darifenacin, increased intraocular solifenacin, pressure, xerostomia Tolterodine, *Patch: Pruritus Trospium *Interactions: With other antimuscarinics

Page 7 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

Category: ANTI-DEPRESSANT 5-HT2 ANTAGONIST Major Depression, alcohol Inhibition of 5HT2A Trazodone forms a Relatively short half- Somnolence, Deseryl, depression*sedation craving receptors metabolite (m-cpp) lives *active insomnia, dizziness, Trazodone, and hypnosis *Nefazodone also that blocks 5HT2A, 2C metabolites nausea, dry mouth, Nefazodone (trazodone) blocks SERT weakly receptors *Toxicity:Modest α- constipation, and H1 -Receptor headache, weakness, blockade (trazodone) drowsiness, priapism, *Interactions:Nefazodo vomiting, fatigue, ne inhibits CYP3A4 MONOAMINE Major depression Depression, anxiety Blockade of MAO-A Transdermal Very slow elimination Orthostatic Nardil, Parnate, OXIDASE INHIBITORS unresponsive to the associated with and MAO-B absorption of *Toxicity: hypotension, vertigo, Phenelzine, (MAOIs) other drugs depression, (Phenelzine,nonselec selegiline achieves Hypotension, insomnia dizziness, nausea, Tranylcypromine, neuropathic pain, tive) *MAO-B levels that inhibit *Interactions:Hyperten constipation, dry Selegiline attention deficit irreversible selective MAO-A sie crisis with mouth, diarrhea, hyperactivity disorder MAO-B inhibition tyramine, other headache, (ADHD), smoking (low dose selegiline) indirect restlessness, blurred cessation (Zyban) sympahtomimetics vision, hypertensive *serotonin syndrome crisis with serotogenic agents, meperidine SELECTIVE Major depression, Depression, panic Highly selective Acute increase of Half-lives from 15-75 h Nausea, dry mouth, Celexa, Lexapro, SEROTONIN anxiety disorder * disorder, post blockade of serotonergic synaptic * Oral-activity * sweating, Prozac, Prozac REUPTAKE Panic disorder * traumatic stress serotonin activity * slower Toxicity: Well somnolence, insomia, weekly, sarafem, INHIBITORS (SSRIs) Obsessive- disorder (PTSD), transporter (SERT) * changes in several tolerated but cause anorexia, diarrhea, Paxil, Zoloft, compulsive disorder premenstrual little effect in signaling pathways sexual dysfunction * nervousness, Citalopram, * Post-traumatic disorder, generalized norepinephrine and neurotrophic Interaction: some CYP drowsiness, asthenia, Escitalopram, stress disorder * anxiety disorder, transporter (NET) activity inhibition or tremor, constipation, Fluoxetine, Perimenopausal bulimia fluoxetine 2D6, 3A4; dyspepsia, ejaculatory Fluvoxamine vasomotor fluvoxamine 1A2; disturbances, symptoms * Eating paroxetine 2D6 disorder (bulimia)

Page 8 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

SEROTONIN- Major depression, Depression, diabetic Moderately Acute increase in Toxicity: Insomnia, dry mouth, Cymbalta, NOREPINEPHRINE chronic pain peripheral selective blockade serotonergic and Anticholinergic nausea, constipation, Effexor, REUPTAKE disorders * neuropathy, of NET and SERT adrenergic synaptic sedation, headache, dizziness, Duloxetine, INHIBITORS (SNRIs) fibromyalgia, fibromyalgia, stress activity * otherwise hypertension nervousness, Venlafaxine, and perimenopausal incontinence, anxiety like SSRIs (venlafaxine) * weakness, anorexia, Desvenlafaxine symptoms disorder, Interaction: Some somnolence, sweating premenstrual disorder CYP2D6 inhibition (duloxetine, desvenlafaxine) TETRACYCLICS, Major depression Depression, anxiety Increaed Presynaptic release Extensive metabolism Agitation, dizziness, Wellbutrin, UNICYCLIC *smoking cessation associated with norepinephrine and of catecholamines in liver dry mouth, insomnia, Wellbutrin SR, (bupropion) depression, dopamine activity but no effects on 5- *Toxicity:Lower sedation, headache, Zyban (smoking *sedation neuropathic pain, (bupropion) HT (bupropion) seizure threshold nausea, vomiting, cessation), (mirtazapine) attention deficit *NET>SERT *amoxapine and (amoxapine, tremor, constipation, Remeron, *amoxapine and hyperactivity disorder inhibition maprotiline resemble bupropion); sedation weight loss, anorexia, Buprupion, maprotiline rarely (ADHD), smoking (amoxapine, TCAs and weight gain excess sweating Amoxapine, used cessation (Zyban) maprotiline) (mirtazapine) Maprotiline, *increased relaease *Interactions: CYP2D6 Mirtazapine of norepinephrine 5- inhibitor (bupropion) HT (mirtazapine) TRICYCLIC Major depression Depression, enuresis, Mixed and variable Like SNRIs plus Long half-lives *CYP Sedation, Tofranil, Tofranil ANTIDEPRESSANT not responsive to eating disorders blockade of NET and significant blockade substrates *active anticholinergic effects PM, Imipramine (TCA) other drugs *chronic SERT of autonomic nervous metabolites (dry mouth, dry eyes, pain disorder system and histamine *Toxicity:Anticholinergi urinary retention), *incontinence receptors c, α-blocking effects, constipation *obsessive- sedation and weight compulsive disorder gain, arrhythmias, and seizures in overdose *Interactions:CYP inducers and inhibitors Category: ANTIHYPERTENSION ANGIOTENSIN Hypertension *heart Block AT1 angiotensin Same as ACE Oral *toxicity: Same as Losartan, many RECEPTOR BLOCKERS failure, receptors inhibitors but no ACE inhibitors but no others increase in cough, bradykinin

Page 9 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

ANGIOTENSIN- Hypertension *heart Hypertension HF, LVD, Inhibit angiotensin Reduce angiotensin II Oral *toxicity: Cough, Tachycardia, gastric Captopril, CONVERTING failure, diabetes after MI, diabetic converting enzyme levels *reduce angioedema irritation, peptic ulcer, Capoten ENZYMES (ACE) nephropathy vasoconstriction and *teratogenic proteinuria, rash, INHIBITORS aldosterone secretion pruritus, cough *increase bradykinin DIURETICS Loop Severe hypertension, Edema due to CHF, Block Na+, Cl-, K+ Like thiazides * Oral * Duration: 8-12 Electrolyte and Lasix diuretics: heart failure cirrhosis of the liver, transporter in renal Greater efficacy h * Toxicity: hematologic Furosemide renal disease, acute loop of Henle Hypokalemic imbalances, anorexia, pulmonary edema metabolic alkalosis nausea, vomiting, plus hypertension hyperuricemia, dizziness, rash, hyperglycemia, photosensivity, hyponatremia ortostatic hypotension, glycosuria DIURETICS Thiazides: Hypertension, mild Hypertension, edema Block Na+ or Cl- Reduce blood volume Oral * Duration: 8-12 Orthostatic HydroDIURIL, Hydrochlorothiazide heart failure due to CHF, cirrhosis, transporter in renal plus poorly h * Toxicity: hypotension, esidrix, corticosteroid and distal convoluted understood vascular Hypokalemic dizziness, vertigo, microzide, oretic estrogen therapy tubule effects metabolic alkalosis, light-headedness, hyperuricemia, weakness, anorexia, hyperglycemia, gastri distress, nausea, hyponatremia diarrhea, constipation, hematologic changes, rash, photosensitivity reaction, hyperglycemia, fluid and electrolyte imbalances, reduced libido DIURETICS Aldosteronism, heart hypertension, edema Blocks aldosterone Increase Na+ and Oral * Duration: 8-12 Headache, diarrhea, Aldactone, Spironolactone failure, hypertension due to CHF, cirrhosis, receptor in a renal decrease K+ * poorly h * Toxicity: drowsiness, lethargy, Eplerenone renal disease, collecting tubule understood reduction Hypokalemic hyperkalemia, hypokalemia, in heart failure metabolic alkalosis cramping, gastritis, prophylaxis of mortality hyperuricemia, erectile dysfunction, hypokalemia in at- risk hyperglycemia, gynecomastia patients, hyponatremia hyperaldosteronism

Page 10 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

PARENTERAL AGENTS Hypertensive Hypertensive crisis Releases nitric oxide Powerful vasodilation Parenteral *Short Apprehension Nitropress Nitroprusside emergencies duration *Toxicity: headache, Excessive hypotension, restlessness, nausea, shock vomiting, palpitation, diaphoresis PARENTERAL Hypertensive Activates D1 Powerful vasodilation Parenteral *Short AGENTS: emergencies receptors duration *Toxicity: Fenoldopam Excessive hypotension, shock PARENTERAL Hypertensive Hypertensive Opens K channels Powerful vasodilation Parenteral *Short Dizziness, weakness, Hyperstat IV AGENTS: emergencies emergencies, or crisis duration *Toxicity: nausea, vomiting, Diazoxide Excessive hypotension, sodium and water shock retention, hypotension, myocardial ischemia RENIN INHIBITORS Hypertension Inhibits enzyme Reduce angiotensin Oral Aliskiren activity of renin I and II and *toxicity:Hyperkalemia aldosterone , renal impairment *potential teratogen SYMPATHATHIC Hypertension but Hypertension Interferes with Reduces all Guanethidine: Severe Dizziness, weakness, Ismelin NERVE TERMINAL rarely used amine released and sympathetic effects, orthostatic lassitude, syncope, BLOCKERS replaces especially hypotension *sexual postural or exertional Guanethidine norepinephrine in cardiovascular, and dysfunction hypotension diarrhea vesicles reduce blood pressure bradycardia, fluid retention and edema, CHF, inhibition of ejaculation SYMPATHOPLEGICS, Hypertension Hypertension Activates α2 Reduce central Oral *Clonidine also Drowsiness, sedation, Catapres, CENTRALLY ACTIVE: *clonidine also used adrenoceptor sympathetic outflow patch *Toxicity: dizziness, headache, clonidine Clonidine, Methyl in withdrawal from * reduce sedation *methyldopa fatigue that tends to DOPA abused drugs norepinephrine hemolytic anemia diminish within 4-6 release from weeks, dry mouth, noradrenergic nerve constipation, endings impotence, decrease sexual activity

Page 11 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

VASODILATORS Hypertension Essential hypertension Causes nitric oxide Vasodilation *reduce Oral *Toxicity: Angina, Dizziness, palpitation, Apresoline Hydralazine *Minoxidil also used (oral), when needed release vascular resistance tachycardia tachycardia, angina, to treat hair loss to lower blood *arterioles more *Hydralazine: Lupus- anorexia, nausea, pressure (parenteral) sensitive than veins like syndrome vomiting, headache, *reflex tachycardia hypotension, diarrhea, rash, nasal congestion VASODILATORS: Hypertension Severe hypertension Metabolite opens K Vasodilation *reduce Minoxidil:Hypertrichosi Headache, Loniten Minoxidil *Minoxidil also used channels in vascular vascular resistance s hypotension, to treat hair loss smooth muscle *arterioles more electrocardiogram sensitive than veins changes, tachycardia, *reflex tachycardia rash, fatigue, sodium and water retention, nausea, hair growth, changes in direction and magnitude of T waves VASODILATORS: Hypertension Vasospastic angina Block vascular *reduce vascular Oral, duration 4-6 h Dizziness, light Adalat, Nifedipine, (Prinzmetal's variant calcium channels > resistance *toxicity: Excessive headedness, procardia, Amlodipine angina), chronic stable cardiac calcium hypotension nervousness, procardia XL angina, hypertension channels *Interactions: Additive headache, nausea, (sustained release with other vasodilators constipation, only) peripheral edema, asthenia, bradycardia, atrioventricular block, arrhythmias, flushing VASODILATORS: Hypertension, Supraventricular Nonselective block Reduce cardiac rate Oral, IV, duration 4-8 h Constipation, Calan, covera Verapamil, Diltiazem angina, arrhythmias tachyarrhythmias, of L-type calcium and output *reduce *toxicity: dizziness, light HS, Isoptin, temporary control of channels vascular resistance Atrioventricular block, headedness, verelan, verelan rapid ventricular rate acute heart failure; headache, asthenia, PM in atrial flutter or constipation, edema nausea, vomiting, fribrillation, angina, *Interactions: Additive peripheral edema, unstable angina, with other cardiac hypotension, mental hypertension depressants and depression, hypotension aggranulocytosis, proarrythmic effects

Page 12 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

α BLOCKERS hypertension Hypertension Selectively block α1 Prevent sympathetic Oral *toxicity: Dizziness, headache, Prazosin, *benign prostatic adrenoceptors vasoconstriction Orthostatic drowsiness, lack of Terazosin, hyperplasia *reduce prostatic hypotension energy, somnolence, Doxazosin smooth muscle tone nausea, palpitation, edema, dyspnea, nasal congestion, sinusitis β BLOCKERS Hypertension, heart Hypertension, angina Blocks β1 receptors: Prevent sympathetic Oral *Toxicity: Fatigue Dizziness, vertigo, Metoprolol, failure pectoris, MI carvedilol also cardiac stimulation * fatigue, bradycardia, Carvedilol, blocks α receptor reduce renin CHF, arrhythmias, Propranolol, secretion tachycardia, sinuatrial atenolol or atrioventricular block, gastric pain, flatulence, constipation, diarrhea, nausea, vomiting, impotence, decrease libido, decrease exercise tolerance, rash, eye irritation Category: ANTI-PSYCHOTIC Atypical Schizophrenia Psychotic disorders Blockade of 5HT2A Some α blockade Toxicity: Agitation, anxiety, aripiprazole, Antipsychotics improve both positve receptors > (clozapine, Agranulocytosis headache, clozapine, and negative blockadeof D2 risperidone, (clozapine), diabetes constipation, dry olanzapine, symptoms *bipolar receptors ziprasidone) and M- (clozapine, mpouth, nausea Quetiapine, disorder (olanzapine receptor blockade olanzapine), risperidone, or risperidone (clozapine, hypercholesterolemia Ziprasidone adjunctive with olanzapine) *variable (clozapine, lithium) *agitation in H1-receptor blockade olanzapine), Alzheimer's and (all) hyperporlactinemia Parkinson's (low (ziprasidone), QT doses) *major prolongation depression (ziprasidone), weight (aripiprazole) gain (clozapine, olanzapine)

Page 13 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

Butyrophenone Schizophrenia Psychotic disorders, Blockade of D2 Some α blockade, but Oral and parenteral EPS, dystonia, Haloperidol (alleviates positve Tourette's syndrome, receptors >>5HT2A minimal M receptor forms with akathisia, drowsiness, symptoms), bipolar hyperactivity receptors blockade and much metabolism headache, orthostatic disorder (manic less sedation than the elimination *Toxicity: hypotension phase), Huntington's phenothiazines Extrapyramidal chorea, Tourette's dysfunction is the syndrome major adverse effect Lithium Bipolar affective Manic episodes of Mechanism of No significant Oral absorption, renal Headache, Eskalith, Lithobid disorder -- bipolar disorder action uncertain antagonistic actions elimination *half-life drowsiness, tremor, prophylactic use can *Suppresses inositol on autonomic 20 h *narrow nausea, polyuria prevent mood signaling and nervous system therapeutic window swings between inhibits glycogen receptors or specific (monitor blood levels) mania and depression synthase kinase-3 CNS receptors *no *Toxicity: Tremor, (GSK-3), a sedative effects edema, multifunctional hypothyroidism, renal protein kinase dysfunction, dysrhythmias * pregnancy category D *Interactions: Clearance decreased by thiazides and some NSAIDs

Page 14 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

Newer Agents for Valproic acid is Bipolar disorder Mechanism of Carbamazepine Oral absorption * Dizziness, nausea, Carbamazepine Bipolar Disorder increasingly used as action in bipolar causes dose-related once-daily dosing insomnia, headache, (Tegretol, first choice in acute disorder is unclear. diplopia and ataxia * carbamazepine forms lamotrigine Stevens- Epitol), illness * lamotrigine causes active metabolite * Johnsons Syndrome Lamotrigine carbamazepine and nausea, dizziness, and lamotrigine and rash (Lamictal) and lamotrigine are also headache * valproic valproic acid form Valproic acid used both in acute acid causes conjugates * Toxicity: (Depakote. mania and for gastrointestinal Hematotoxicity and Depakene) prophylaxis in distress, possible induction of P450 drug depressive phase weight gain, alopecia metabolism (carbamazepine), rash (lamotrigine), tremor, liver dysfunction, weight gain, inhibition of drug metabolism (valproic acid) Phenothiazines Psychiatric: Psychotic disorders, Blockade of D2 α-Receptor blockade Oral and parenteral Hypotension, Chlorpromazine, Schizophrenia intractable hiccups receptors >>5HT2A (fluphenazine least) forms, long half-lives drowsiness, Fluphenazine (alleviate positive receptors *muscarinic (M)- with metabolism- dyskinesia, dystonia, and Thioridazine symptoms), bipolar receptor blockade dependent elimination behavioral changes, disorder (manic (especially *Toxicity: Extensions photosensitivity phase) chlorpromazine and of effects on α- and *nonpsychiatric: thioridazine) *H1- M- receptors antiemesis, receptor blockade *blockade of preoperative (chlorpromazine and dopamine receptors sedation thioridazine) *Central may result in (promethazine) nervous system (CNS) akathisia, dystonia, *Pruritus Depression (sedation) Parkinsonian *decreased seizure symptoms, tardive, threshold *QT dyskinesias, and prolongation hyperprolactinemia (thioridazine)

Page 15 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

Thioxanthene Psychiatric: Schizophrenia Blockade of D2 α-Receptor blockade Oral and parenteral Extrapyramidal Thiothixene Schizophrenia receptors >>5HT2A (fluphenazine least) forms, long half-lives syndrome (EPS), (Navane) (alleviate positive receptors *muscarinic (M)- with metabolism- drowsiness, nausea, symptoms), bipolar receptor blockade dependent elimination diarrhea disorder (manic (especially *Toxicity: Extensions phase) chlorpromazine and of effects on α- and *nopsychiatric: thioridazine) *H1- M- receptors antiemesis, receptor blockade *blockade of preoperative (chlorpromazine and dopamine receptors sedation thioridazine) *Central may result in (promethazine) nervous system (CNS) akathisia, dystonia, *Pruritus Depression (sedation) parkinsonian *decreased seizure symptoms, tardive threshold *QT dyskinesias, and prolongation hyperprolactinemia (thioridazine) Category: ANTI-SEIZURE BENZODIAZEPINES Absence seizures, Seizure disorder, panic Potentiates GABA Documented efficacy >80% bioavailabilty Drowsiness, Klonopin Clonazepam myoclonic seizures, disorder responses against absence *extensively depression, ataxia, infantile spasms seizure metabolized but no anorexia, diarrhea, active metabolites *t constipation, dry 1/2 20-50 h mouth, palpitations, visual disturbances, rash BENZODIAZEPINES Status epilepticus, Status epilepticus, Potentiates GABA Stops continuous Well absorbed orally, Drowsiness, Valium, diastat Diazepam seizures clusters seizures disorders (all responses seizure *rectal administration depression, ataxia, forms), anxiety gives peak anorexia, diarrhea, disorder, alcohol concentration in ~1 h constipation, dry withdrawal with 90% mouth, palpitations, bioavailability *IV for visual disturbances, status epilepticus rash *highly protein-bound *extensively metabolized to several active metabolites *t 1/2 ~2 d

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CYCLIC UREIDES Absence seizures Partial seizures Reduces low effective against Well absorbed orally, Drowsiness, ataxia, Zarontin Ethosuximide threshold Ca2+ pentylenetetrazol with peak levels in 3-7 dizziness, nausea, currents (T-type) seizures h *not protein-bound vomiting, urinary *completely frequency, pruritus, metabolized to urticaria, gingival inactive compounds *t hyperplasia 1/2 typically 40 h CYCLIC UREIDES generalized tonic- Status epilepticus, Enhances phasic Decrease excitatory nearly complete Somnolence, Phenobarbital Phenobarbital clonic seizures, cortical focal seizures, GABA receptor response, selectively absorption *not agitation, confusion, sodium (Luminal partial seizure, tonic-clonic seizures responses *reduces suppress abnormal significantly bound to ataxia, CNS sodium) myoclonic seizures, excitatory synaptic neurons plasma proteins depression, neonatal seizures, responses *peak concentration nervousness, nausea, status epilepticus in 1/2 to 4 h *no vomiting, active metabolites *t constipation, diarrhea 1/2 varies from 75 to 125 h CYCLIC UREIDES generalized tonic- Status epilepticus Blocks high Inhibit a variety of Absorption is Ataxia, CNS Cerebyx, Dilantin Phenytoin, clonic seizures, frequency firing of calcium induced formulation depression, fosphenytoin partial seizure neurons through secretory processes dependent, highly hypotension, mental action on voltage- bound plasma confusion, slurred gated (VG) Na+ proteins, no active speech, dizziness, channels * metabolites *dose- drowziness, gingival decrease of synaptic dependent hyperplasia, rash release of glutamate elimination, t½ 12-36 hours *fosphenytoin is IV, IM routes CYCLIC UREIDES generalized tonic- Epilepsy Similar to phenytoin Effective in Well absorbed orally, Dizziness, Mysoline Primidone clonic seizures, but converted to controlling seizures in not highly bound to somnolence, nausea, partial seizure phenobarbital newborn infants plasma proteins *peak vomiting concentrations in 2-6 h * t½ 10-25 hours *two active metabolites (phenobarbital and phenylethymalonamid e)

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GABA DERIVATIVE Partial seizures Partial seizure Decreases excitatory Act presynaptically to Well absorbed orally * Dizziness and Lyrica Pregabalin (adults), postherpetic transmission by decrease glutamate not bound to plasma somnolence neuralgia, neuropathic acting on VG Ca2+ proteins * not pain channels metabolized * t1/2 6-7 presynaptically (α2δ h subunit) GABA Generalized tonic- Partial seizure (adults) Decreases excitatory Act presynaptically to Bioavailability 50%, Somnolence, Neurontin DERIVATIVES clonic seizures, postherpetic neuralgia transmission by decrease the release decreasing with dizziness, ataxia partial seizures, acting on VG Ca2+ of glutamate increasing doses * not generalized seizures channels bound to plasma Gabapentin presynaptically (α2δ proteins * not subunit) metabolized * t 1/2 6- 8 h GABA DERIVATIVES Partial seizures, Partial seizures and Irreversably inhibits Produces sustained 70% bioavailable * not Irreversible visual field Vigabatrin infantile spasms West's syndrome GABA-transaminase increase in the bound to plasma defects, drowsiness, intracellular proteins *not dizziness and weight concentration of metabolized, *t 1/2 5- gain GABA in the brain 7 h (not relevant because of mechanism of action) Levetiracetam Generalized tonic- Effective against Action on synaptic Modify the synaptic Well absorbed orally * Somnolence, asthenia, Keppra clonic seizures, partial seizure in protein SV2A release of glutamate no significant protein ataxia and dizziness, partial seisures, adults and children, and GABA binding * extensively agitation, anxiety generalized seizures ineffective when metabolized but no caused by maximum active metabolite * electric shock t1/2 6-11 h MISCELLANEOUS Generalized tonic- pain syndrome and Enhances slow Adjunctive therapy in well absorbed Dizziness, headache, Vimpat clonic seizures, partial seizure inactivation of Na+ partial onset seizure *minimal protein nausea and diplopia Lacosamide partial seisures channels * Blocks with or without binding *one major effect of secondary nonactive metabolite neurotrophins (via generalizations in * t1/2 12-14 h CRMP-2) patients with epilepsy 16 years and older

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MISCELLANEOUS Generalized tonic- Epilepsy, migraine, Blocks high- Inhibits GABA Well absorbed from Headache, Depakote, clonic seizures, headache, mania frequency firing of transaminase in the several formulations * somnolence, dizziness, depakene Valproate partial seisures, neurons * modifies brain blocking its highly bound to tremor, nausea, generalized seizures, amino acid degradation, potent plasma proteins * vomiting, diplopia absence seizures, metabolism inhibitor of histone extensively myoclonic seizures deacetylase and metabolized * t 1/2 9- changes transcription 16 h of many genes MISCELLANEOUS Generalized tonic- Partial seizure (used Prolongs Decrease synaptic Well absorbed orally * Dizziness, Lamictal clonic seizures, with other inactivation of VG- release of glutamate no significant protein somnolence, insomia, Lamotrigine generalized seizures, anticonvulsants), Na+ channels * acts binding * extensively ataxia, nausea, partial seisures, bipolar disorder presynaptically on metabolized, but no vomiting, diplopia, absence seizures VG-Ca+ channels, active metabolites * t headache, Steven's- decreasing 1/2 25-35 h Johnsons syndrome, glutamate release rash Tiagabine Partial seizures Partial seizures Blocks GABA Inhibit GABA uptake, Well absorbed * Dizziness, Gabitril reuptake in prolong inhibitory Highly bound to somnolence, asthenia, forebrain by action of synaptically plasma protein * nervousness, nausea selective blockade released GABA and Extensively of GAT-1 potentiate tonic metabolized but no inhibition active metabolite * t1/2 4-8 h Topiramate Generalized tonic- Partial/ tonic-clonic Multiple actions on Potentiate the Well absorbed * not Fatigue concentration Topamax clonic seizures, seizures, migraine, synaptic function, inhibitory effect of bound to plasma problems, partial seisures, headache primary action on GABA acting at site protein * Extensively somnolence, anorexia generalized seizures, kinases altering the different from metabolized but 40% absence seizures, phosphorylation of benzodiazepine, excreted unchanged in migraine voltage-gated and depress the the urine * no active ligand-gated ion excitatory action of metabolite * t1/2 20 channels kainate on glutamate h, but decreases with receptor, concomitant drugs

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TRICYCLICS generalized tonic- Epilepsy, bipolar Blocks high- Treats bipolar Well absorbed orally, Dizziness, nausea, Tegretol, epitol Carbamazepine clonic seizures, disorder, trigeminal/ frequency firing of depression, with peak levels in 6-8 drowsiness, unsteady partial seizure postherpetic neuralgia neurons through the trigeminal neuralgia h *no significant gait, aplastic anemia action on VG Na+ and epilepsy protein binding and blood cells cahnnels *decreases *metabolized in part abnormality synaptic release of to active 10-11- glutamate epoxide *t1/2 of parent ranges from 8- 12 h in treated patients to 36 h in normal subjects Zonisamide Generalized tonic- Partial seizures of Blocks high- Effect on sodium Approximately 70% Somnolence, anorexia, Zonegran clonic seizures, epilepsy frequency firing via channels, may also bioavailable orally * headache, dizziness, partial seisures, action on VG-Na+ act on voltage-gated minimally bound to rash, heat stroke myoclonic seizures channels calcium channel plasma proteins * > 50% metabolites * t1/2 20 h Category: ASTHMA BETA Anaphylaxis, asthma, Asthma, bronchospasm Nonselective α and β Bronchodilation plus Aerosol, nebulizer, or palpitation, Adrenaline, AGONISTS others *rarely used agonist all other parenteral tachycardia, Epinephrine for asthma (β2- sympathomimetic hypertension, mist, primatene Epinephrine selective agents effects on arrhythmias, dizziness, mist preferred) cardiovascular and vertigo, shakiness, other organ systems nervousness, headache, insomnia, nausea, vomitting, anxiety, fear, pallor BETA AGONISTS Asthma, chronic Bronchospasm, Selective β2 agonist Prompt, efficacious Aerosol inhalation palpitation, Proventil, Albuterol obstructive prevention of EIB bronchodilation *duration several tachycardia, Ventulin, Volmax pulmonary disease hours *also available hypertension, tremor, (COPD) *Drug of for nebulizer and dizziness, shakiness, choice in acute parenteral use nervousness, nausea, asthmatic *Toxicity: Tremor, vomiting bronchospasm tachycardia *overdose:arrhythmias

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BETA AGONISTS Asthma, but β2- Bronchospasm during β1 and β2 agonist Bronchodilation plus Aerosol, nebulizer, or Palpitation, Isuprel Isoproterenol selective agents anaesthesia, powerful parenteral tachycardia, chest preferred vasopressor during cardiovascular effects tightness, angina, shock shakiness, nervousness, weakness, hyperactivity, headache, nausea, vomiting, flushing, sweating BETA AGONISTS Asthma prophylaxis Asthma, Selective β2 agonist Slow onset, primarily Aerosol inhalation palpitation, Serevent, diskus, Salmeterol bronchospasm, preventive action; *duration several tachycardia, tremor, metaproterenol, prevention of EIB potentiates hours *Toxicity: nervousness, terbutaline, corticosteroid effects Tremor, tachycardia headache, nausea, formoterol *overdose:arrhythmias vomitting, heartburn, GI distress, diarrhea, cough rhinitis CORTICOSTEROIDS, Asthma * adjunct in Prophylactic Alters gene Reduces mediators of Aerosol * duration Oral laryngeal, Flovent, flovent INHALED COPD maintenance and expression inflammation * hours * Toxicity: pharyngeal irritation, rotadisk, flovent Fluticasone treatment of asthma powerful prophylaxis limited by aerosol fungal infection, diskus of exacerbations application * candidal suppression of HPA infection, vocal cord function changes. CORTICOSTEROIDS, Asthma * adjunct in Endocrine, rheumatic, Like fluticasone Reduces mediators of Oral * duration hours Fluid and electrolyte, Methylprednisol SYSTEMIC COPD collagen, inflammation, * Toxicity: Multiple masculoskeletal, one: Parenteral Prednisone dermatologic, powerful prophylaxis cardiovascular, agent like allergies, ophthalmic, of exacerbations gastrointestinal, prednisone respiratory, dermatology, hematologic, neurology, endocrine, edematous, ophthalmic, metabolic gastrointestinal, nervous system diseases

Page 21 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

IGE ANTIBODY Severe asthma Moderate to severe Humanized IgE Reduces frequency of Parenteral * duration Injection site reaction, Xolair Omalizumab inadequately persistent asthma antibody reduces asthma exacerbations 2-4 d *Toxicity: viral infection, controlled by above circulating IgE Injection site reactions sinusitis, headache, agents (anaphylaxis pharyngitis, extremely rare) anaphylaxis, malignant cyst LEUKOTRIENE Headache (usually Prophylaxis and Block leukotriene Block airway Oral * duration hours Headache, dizziness, Singulair, ANTAGONISTS mild), flatulence, treatment of chronic D4 receptors response to exercise * Toxicity: Minimal dyspepsia, Zileuton (Zyflo): Montelukast, abdominal pain, asthma in adults and and antigen challenge gastroenteritis, Inhibits zafirlukast cramps, constipation, pediatric patients 12 influenza like lypoxygenase, nausea, dyspepsia, months of age and symptoms, cough, reduces rhabdomyolysis with older, seasonal allergic abdominal pain, synthesis of acute renal failure rhinitis in adults and fatigue leukotrienes pediatric patients 2 years of age and older METHYLXANTHINES Asthma, COPD Symptomatic relief or Uncertain * Bronchodilation, Oral * duration 8-12 h Nausea, vomitting, Theo-24, Theo- Theophylline prevention of phosphodiesterase cardiac stimulation, but extended-release restlessness, vomiting, DUR, bronchial asthma and inhibiton * increased skeletal preparations often tachycardia, tremor, elixophyllin, slo- reversible adenosine receptor muscle strength used * Toxicity: headache, palpitation, phyllin, uniphyl bronchospasm of antagonist (diaphragm) Multiple hyperglycemia, chronic bronchitis and electrocardiographic emphysema changes, cardiac arrhythmias STABILIZERS OF Asthma (other routes Bronchial asthma, Alters function of Prevents acute Aerosol * duration 6-8 Dizziness, headache, Intal, nasalcrom, MAST AND OTHER used for ocular, prevention of delayed chloride bronchospasms h * Toxicity: Cough * nausea, dry and gastrocrom CELLS nasal, and bronchospasm; channels * inhibits not absorbed so other irritated throat, rash, Cromolyn, nedocromil gastrointestinal prevention of EIA, inflammatory cell toxicities are minimal joint swelling and pain allergy) nasal preparation: activation prevention and treatment of allergic rhinitis

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Category: CHOLINOMIMETIC DIRECT ACTING Postoperative and Urinary cholinergics, Muscarinic agonist Activate M1 through Oral and parenteral, Abdominal Bethanechol CHOLINE ESTERS Neurogenic ileus and acute non obstructive *negligible effects M3 receptors in all duration ~30 mins discomfort, headache, (Duvoid, urinary retention urinary retention at nicotinic receptors peripheral tissue , *does not enter diarrhea, nausea, urecholine), cause increased central nervous salivation, urgency Carbachol secretion, smooth system (CNS) (Miostat) muscle contraction *Toxicity: Excessive (except vascular parasympathomimetic smooth muscle effects especially relaxes,) and changes bronchospasm in in heart rate asthmatics * Interactions: Additive with other parasympathomimetics DIRECT ACTING *Medical use in Varenicline - for Agonist at both NN Activates autonomic Oral gum, patch for Excess nicotine - Nicotine, NICOTINIC AGONIST smoking cessation cessation of smoking and NM receptors postganglionic smoking cessation convulsion, coma, Varenicline *non medical use in neurons (both *toxicity:Increased respiratory arrest, smoking and sympathetic and gastrointestinal (GI) nausea and insomnia insecticides parasympathetic) and activity, nausea, skeletal muscle vomiting, diarrhea neuromuscular end acutely, Increase in plates *Enters CNS blood pressure *high and activities NN dose causes seizures receptors *long-term GI and cardiovascular risk factor *Interactions: Additive with CNS stimulants varenicline has long half life

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DIRECT-ACTING Glaucoma:Sjögren's Glaucoma Muscarinic agonist Activate M1 through Oral lozenge and Temporary reduction Pilocarpine, MUSCARINIC syndrome *negligible effects M3 receptors in all topical *toxicity in visual acuity, Cevimeline ALKALOIDS OR at nicotinic peripheral tissue , &interactions: Like headache SYNTHETICS receptors, partial cause increased Bethanechol agonist secretion, smooth muscle contraction (except vascular smooth muscle relaxes,) and changes in heart rate INTERMIDIATE- Myasthenia gravis Therapeutic uses in Forms covalent Like edrophonium, Oral and parenteral Prolonged duration of Neostigmine, ACTING *Postoperative and myasthenia gravis, bond with AChE, but but longer-acting *quaternary amine, effect Pyridostigmine, CHOLINESTERASE Neurogenic ileus and physostigmine for hydrolyzed and does not enter CNS. Physostigmine INHIBITORS urinary retention glaucoma released duration 2-4 h *toxicity &interactions:Like Edrophonium LONG-ACTING Obsolete *was used as insecticides Like Neostigmine, Like Neostigmine, but Topical only Central nervous Echothiophate, CHOLINESTERASE in glaucoma but released more longer-acting *Toxicity:Brow ache, system toxicity Malathion, INHIBITORS slowly uveitis, blurred vision Parathion, Sarin, SHORT-ACTING Diagnosis and acute Diagnosis of Alcohol, binds Amplifies all actions Parenteral Increased bronchial Edrophonium CHOLINESTERASE treatment of myasthenia gravis briefly to active site of ACh *increases *quaternary amine secretions, cardiac (Enlon, Tensilon) INHIBITOR myasthenia gravis of parasympathetic *does not enter CNS arrhythmias, muscle acetylcholinesterase activity and somatic *Toxicity: weakness, urinary (AChE) and prevents neuromuscular Parasympathomimetic frequency access of transmission excess *Interactions: acetylcholine (Ach) Additive with parasympathomimetics

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Category: DIURETICS CARBONIC Glaucoma, mountain Open angle glaucoma, Inhibition of the Reduces reabsorption Oral and topical Weakness, fatigue, Brinzolamide, ANHYDRASE sickness, edema with secondary glaucoma, enzyme prevents of of HCO3- in kidney , preparations available anorexia, vomiting, dorzolamide INHIBITORS alkalosis drug-induced edema, dehydration of causing self-limited *Duration of action~ 8- paresthesias, edema due to CHF H2CO3 and diuresis 12 h *Toxicity: photosensitivity Acetazolamide hydration of CO2 *Hyperchloremic Metabolic acidosis, metabolic acidosis renal stones, reduces body pH, hyperammonemia in reduces intraocular cirrhotics pressure LOOP DIURETICS Pulmonary edema, Edema due to CHF, Inhibition of the Marked increase in Oral and parenteral Electrolyte and Bumetanide, Furosemide peripheral edema, cirrhosis of the liver, Na/K/2Cl NaCl excretion, some preparations hematologic Torsemide, Hypertension, acute renal disease, acute transporter in the K wasting *Duration of action 2- imbalance, anorexia, Ethacrynic acid hypercalcemia or pulmonary edema ascending limb of hypokalemic 4 hours *Toxicity: vomiting, dizziness, hyperkalemia, acute Henle's loop metabolic alkalosis, Ototoxicity, photosensitivity, renal failure, anion increased urine Ca Hypovolemia, K glycosuria overdose and Mg wasting, Hyperuricemia, hypomagnesemia OSMOTIC DIURETICS Renal failure due to Promote diuresis in Physical osmotic Marked increase in IV administration Edema, fluid and Osmitrol Mannitol increased solute load acute renal failure, effect on tissue urine flow, rduced *Toxicity: Nausea, electrolyte imbalance, (rhabomyolysis, reduce IOP, treatment water distribution brain volume, vomiting, headache headache, blurred chemotheraphy), of cerebral edema because it is decreased intraocular vision, nausea, increased retained in the pressure, initial vomiting, urinary intracranial pressure, vascular hyponatremia, then retention glaucoma compartment hypernatremia OTHER AGENTS Hyponatremia reduce objective signs Antagonist at V1a Reduces water IV only *Toxicity: Can not be Conivaptan of hyponatremia and and V2 ADH reabsorption, Infusion site reactions administered for heart failure receptors increases plasma Na those with congestive associated with concentration heart faiulure elevated concentration of vasspressin

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POTASSIUM-SPARING Hypokalemia from CHF, hypertension, Blocks epithelial Reduces Na retention Orally active *duration Headache, diarrhea, Eplerenone, DIURETICS other diuretics prevention of sodium channels in and K wasting 24 h *Toxicity: dizziness, nausea, Triamterene Amiloride *reduces lithium- hypokalemia in at- collecting tubules *Increases lithium Hyperkalemic fatigue, weakness, induced polyuria riskpatients, polyuria clearance metabolic acidosis hypotension prevention with lithium use POTASSIUM-SPARING Aldosteronism from Edema due to CHF, Pharmacologic Reduces Na retention Slow onset and offset Headache, diarrhea, DIURETICS any cause cirrhosis of the liver, antagonist of and K wasting in of effects *Duration lethargy, Spironolactone *Hypokalemia due to acute renal disease, aldosterone *weak kidney *poorly 24-48 h *Toxicity: hyperkalemia, other diuretics hypokalemia, antagonism of understood Hyperkalemia, cramping, gastritis, *postmyocardial hyperaldosteronism androgen receptors antagonism of gynecomastia erectile dysfunction, infarction aldosterone in heart (spironolactone, not gynecomastia and vessels eplerenone) *additive interaction with other K-retaining drugs THIAZIDES Hypertension,mild Edema due to CHF, Inhibition of the Modest increase in Oral *Duration 8-12 h Electrolyte and Metolazone, Hydrochlorothiazides heart failure, cirrhosis of the liver, Na/Cl transported in NaCl excretion *some *Toxicity: hematologic Chlorothiazide nephrolithiasis, acute renal the distal K wasting Hypokalemic imbalance, anorexia, nephrogenic dysfunction convoluted tubule *Hypokalemic metabolic alkadosis, vomiting, dizziness, diabetes insipidus metabolic alkadosis hyperuricemia, photosensitivity, *Decreases urine Ca hyperglycemia, glycosuria hyponatremia

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Category: DYSLIPIDEMIA BILE ACID Elevated LDL, Hyperlipidemia Binds bile acids in Decreases LDL oral, taken with meals, Constipation (may colestid, SEQUESTRANT digitalis toxicity, gut, prevent not absorbed, toxicity: lead to fecal cholestryramine, Colestipol pruritus reabsorption, constipation, bloating, impaction), colesevalam increases interferes with exacerbation of cholesterol absorption of some hemorrhoids, catabolism, up- drugs and vitamins abdominal pain, regulates LDL distention, cramping, receptor nausea, increase bleeding related to vitamin K, malabsorption, vitamin A and D deficiency FIBRATES Hypertriglyceridemia, Hyperlipidemia, Peroxisome Decrease secretion of Oral *duration 3-24 h Dyspepsia, abdominal Lopid Fenofibrate, low HDL hypertri- glyceridemia, proliferator- very-low-density *Toxicity: Myopathy, pain, diarrhea, gemfibrozil reduction of CAD risk activated receptor lipoproteins (VLDL) hepatic dysfunction nausea, vomiting, alpha (PPAR-α) *increase lipoprotein rash, vertigo, agonists lipase activity headache, *increase high- cholecystitis,cholelithia density lipoproteins sis (HDL) NIACIN Low HDL *elevated Adjunctive treatment Decreases Increases HDL Oral *large doses Generalized flushing Niaspan, Niacor, VLDL, LDL, Lp(a) for hyperlipidemia catabolism of apo *decreases *Toxicity: Gastric sensation of warmth, extended A1 *reduces VLDL lipoprotein a [Lp(a)], irritation, flushing, low severe itching and release niacin secretion from liver LDL and triglycerides incidence of hepatic tingling, nausea, toxicity *may reduce vomiting, abdominal glucose tolerance pain

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STATINS Atherosclerotic Primary Inhibit HMG-CoA Reduce cholesterol Oral *duration 3-24 h Headache (usually Lipitor, Atorvastatin, vascular disease hyperlipidemia, reductase synthesis and up- *Toxicity: Myopathy, mild), flatulence, fluvastatin, simvastatin, (primary and reduction of elevated regulate low-density hepatic dysfunction abdominal pain, pravastatin, rosuvastatin secondary total and LDL lipoprotein (LDL) *Interactions:CYP- cramps, constipation, lovastatin prevention) *acute cholesterol levels and receptors on dependent nausea, dyspepsia, coronary syndrome serum triglycerides hepatocytes * metabolism (3A4, 2C9) rhabdomyolysis with modest reduction in Interacts with CYP acute renal failure triglycerides inhibitors STEROL ABSORPTION Elevated LDL, Primary Blocks sterol Inhibits reabsoption Oral, duration 24 h, Diarrhea, back pain, Zetia INHIBITOR phytosterolemia hypercholesterolemia transporter NPCL1L of cholesterol sinusitis, dizziness, Ezetimibe in intestine brush excreted in bile, abdominal pain, border decreases LDL and arthralgia, cough, phytoesterols fatigue Category: GASTROINTESTINAL CONDITIONS ANTIDIARRHEAL Nonspecific, Nausea, diarrhea, Activates μ-opioid Slows motility in gut Mild cramping but Dry skin and mucus Immodium, DRUGS noninfectious abdominal cramps, H. receptors in enteric with negligible CNS little or no CNS toxicity membranes, nausea, kaopectate, Loperamide diarrhea pylori infection with nervous system effects constipation, light Maalox, duodenal ulcer headedness Diphenoxylate, ANTIEMETIC DRUGS Effective in reducing Prevent acute and NK1-receptors Interferes with Given orally *IV Fatigue, dizziness and Emend, Aprepitant both early and delayed nausea and blocker in CNS vomiting reflex fosaprepitant diarrhea Corticosteroids, delayed emesis in vomiting from highly *Noeffects on 5-HT, available *fatigue, Antimuscarinics cancer emetogenic dopamine or steroid dizziness, diarrhea (scopolamine), chemotheraphy chemotherapeutic receptors *CYP interactions Antihistaminiccs, regimens Phenothiazines, ANTIEMETIC DRUGS First-line agents in Prevention of 5-HT3 blockade in Extremely effective in Usually given Headache, fatigue, Zofran Ondansetron, other 5 cancer chemotheraphy gut and CNS with preventing drowsiness, sedation, HT3 antagonists chemotheraphy; also induced and shorter duration of chemotheraphy- constipation, hypoxia useful for postop postoperative nausea binding than induced and post- emesis vomitting, bulimia, alosetron operative nausea and spinal analgesia- vomiting induced pruritus, levodopa-induced psychosis

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BILE ACID THERAPHY Gallstones in Dissolution of small Reduces cholesterol Dissolve gallstones May cause diarrhea Hepatotoxicity Actigall, URSO FOR GALLSTONES patients refusing or cholesterol gallstones secretion into bile Ursodiol not eligible for in patients with surgery asymptomatic gallbladder disease who refuse cholecystectomy DRUG STIMULATING Gastri paresis (eg, in Diabetic gastroparesis, D2-receptor blocker Increases gastric Parkinsonian Restlessness, Reglan, MOTILITY diabetes) *antiemetic GERD, prevention of * removes inhibition emptying and symptoms due to dizziness, fatigue, Domperidone, Metoclopramide nausea and vomiting of acetylcholine intestinal motility block of central extrapyramidal effects Cholinomimetics, neurons in enteric nervous system (CNS) Macrolides nervous system D2 receptors DRUGS FOR Approved for severe For severe IBS with 5-HT3 antagonist of Reduces smooth Rare but serious Ischemic colitis, Lotronex IRRITABLE BOWEL diarrhea- diarrhea high potency and muscle activity in gut constipation *ischemic serious complication SYNDROME (IBS) predominants IBS in duration of binding colitis *infarction of constipation Alosetron women requiring hospitalization or surgery DRUGS USED IN ACID- Peptic ulcer, Errosive esophagitis, Irreversible Long-lasting Half-lives much Headache, nausea, Prilosec, PEPTIC DISEASES gastroesophageal GERD, H.pylori, blockade of H+, K+- reduction of shorter than duration diarrhea zegerid, Proton pump reflux disease, erradication, NSAID- ATPase pump in stimulated and of action * low toxicity omeprazole, inhibitors (PPIs) erosive gastritis associated gastric active parietal cells nocturnal acid *reduction of stomach Iansoprazole ulcer, hypersecretory of stomach secretion acid may reduce condition, heartburn, absorption of some reduce risk of upper drugs and increase GI bleeding that of others DRUGS USED IN Infliximab: Crohn's disease, Bind tumor necrosis Suppression of Infusion reactions Sore throat, cough, Remicade, INFLAMMATORY Moderately severe ulcerative colitis and factor and prevent it severalaspects of *reactivation of latent sinus infection, gastric Corticosteroids BOWEL DISEASE (IBD) to severe Crohn's rheumatoid arthritis from binding to its immune function, tuberculosis distress Anti-TNF antibodies, disease and receptors especially TH1 *Increased risk of eg, infliximab others, ulcerative colitis dangerous systemic *others approved in fungal and bacterial Crohn' disease infections

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DRUGS USED IN Mild to moderately Chronic inflammatory Mechanism Generalized GI upset, mucositis Bone marrow INFLAMMATORY severe Crohn's diseases, Crohn's uncerain *may suppression of *myelosuppression depression, BOWEL DISEASE (IBD) disease and disease and promote apoptosis immune processes *purine analogs may megaloblastic anemia, Purine analogs and ulcerative colitis rheumatoid arthritis of immune cells cause hepatotoxicity, alopecia, for patients antimetabolites, eg, *Methotrexate but rare with with psoriasis, hepatic 6-mercaptopurine, blocks dihydrofolate methotrexate at low damage is common methotrexate reductase doses used DRUGS USED IN Mild to moderately Ulcerative colitis, Mechanism Topical therapeutic Sulfasalazine causes Headache, nausea, Azulfidine, INFLAMMATORY severe Crohn's rheumatoid arthritis uncerain *may be action *systemic sulfonamide toxicity anorexia, vomitting, Sulfasalazine BOWEL DISEASE (IBD) disease and inhibtion of absorption may cause and may cause GI gastric distress, 5-Aminosalicylates, ulcerative colitis eicosanoid toxicity upset, reduced sperm count eg, mesalamine in inflammatory myalgias,arthralgias, many formulations mediators myelosuppression *other aminosalicylates much less toxic DRUGS USED TO Patients with Inhibit intestinal Somatostatin analog May alter portal Reduced endocrine Steatorrhea, nausea, TREAT VARICEAL bleeding varices or secretion and ixhibit *mechanism not blood flow and and exocrine abdominal pain, HEMORRHAGE at high risk of repeat dose related effect on certain variceal pressure pancreatic activity flatulence Octreotide bleeding bowel motility,Inhibit *other endocrine pancreatic secretion in abnormalities *GI patients with upset pancreatic fistula LAXATIVES Simple constipation; Symptomatic relief of Osmotic agents Usually causes Magnesium may be Diarrhea, bone loss in Milk of Magnesium bowel prep for peptic ulcer and increase water evacuation within 4-6 absorbed and caused patients with chronic Magnesia, Bulk hydroxide, and other endoscopy stomach hyperacidity, content of stool h, sooner in large toxicity in renal renal failure forming non-absorbable salts (especially PEG constipation doses impairment laxatives: and sugars solutions) Methylcellulose, PANCREATIC Pancreatic Treat pancreatic Replacement Improves digestion of Taken with every meal Oropharyngeal Pancreatin SUPPLEMENTS insufficiency due to enzyme insufficiency enzymes from dietary fat, protein, *may increase mucositis, diarrhea, Pancrelipase cystic fibrosis, animal pancreatic and carbohydrates incidence of gout abdominal pain, renal pancreatitis, extracts stones, colonic pancreatectomy strictures

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Category: MOVEMENT DISORDER ANTUMUSCARINIC Parkinson's disease Parkinson's disease, Antagonist at M Reduces tremor and Oral * Toxicity: Typical Dry mouth, blurred Cogentin, AGENTS drug-induced EPS receptors in basal rigidity * little effect antimuscarinic effects: vision, dizziness, Biperiden Benztropine ganglia on bradykinesia sedation, mydriasis, nausea, nervousness, (Akineton), urinary retention, dry skin rash, urinary orphenadrine, mouth retention, dysuria, procycline, tachycardia, muscle trihexyphenidyl weakness, disorientation, confusion COMT INHIBITORS Parkinson's disease adjunct to Inhibits COMT in Reduces metabolism Oral Dyskinesis, nausea, Tolcapone Entacapone levodopa/carbidopa periphery *does of levodopa and *Toxicity:increased diarrhea, urine (Tasmar), not enter CNS prolongs its action levodopa toxicity discoloration Entacapone *nausea, dyskinesias, (Comtan) confusion DOPAMINE AGONISTS Parkinson's disease: Parkinson's disease Direct agonist at D3 Reduces symptoms of Oral *~8 h effect Dizziness, Ropinirole Pramipexole Can be used as initial receptor, nonergot Parkinsonism * *Toxicity: Nausea and hallucination, (Requip), therapy, also smooths out vomiting, postural dyspepsia, syncope, Bromocriptine effective in on-off fluctuations in hypotension, confusion, insomnia (Parlodel, Snap phenomenon levodopa reponse dyskinesias Tabs), DRUGS USED Huntington's disease Deplete cerebral Deplete amine Reduce chorea Oral * Toxicity: Hypotension, Haloperidol HUNTINGTON'S dopamine transmitters, severity Hypertension, depression, sedation, DISEASE especially sedation, depression, diarrhea, nasal Tetrabenazine dopamine, from diarrhea * congestion nerve endings Tetrabenazine somewhat less toxic DRUGS USED IN Tourette's syndrome Deplete cerebral Blocks central D2 Reduces vocal and Oral * Toxicity: Hypotension, Clonidine, TOURETTE'S dopamine receptors motor frequency, Parkinsonism, other depression, sedation, Phenothiazines, SYNDROME severity dyskinesias * sedation diarrhea, nasal Benzodiazepines, Haloperidol congestion Carbamazepine

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LEVODOPA AND Parkinson's disease: Parkinson's disease Transported into the Ameliorates all Oral *6-8 h effect Anorexia, vomiting, Levodopa+Carbid COMBINATIONS Most efficacious central nervous symptoms of *Toxicities: abdominal pain, opa (SINEMET), Levodopa therapy but not system (CNS) and Parkinson's disease Gastrointestinal upset, mental changes, Levodopa+Carbid always used as the converted to and causes significant arrhythmias, headaches, dizziness, opa+ first drug due to dopamine (which peripheral dyskinesias, on-off and increased hand Entacapone development of does not enter he dopaminergic effects wearing-off tremor dystonic (STALEVO) disabling response CNS); also converted phenomena, movements fluctuations over to dopamine in the behavioral time periphery disturbances *Interactions: Use with carbidopa greatly diminishes required dosage *use with COMT or MAO-B inhibitors prolong duration of effects MONOAMINE Pakinson's disease; Agonist for Inhibits MAO-B Increases dopamine Oral *Toxicity & Nausea, dizziness Selegiline OXIDASE (MAO) adjunctive to levodopa/carbidopa in selectively, higher stores in neurons; interactions: may (Eldepryl) INHIBITORS levodopa; smooths parkinson's disease doses also inhibits may have casue serotonin Rasagiline levodopa response MAO-A neuroprotective syndrome with effects meperidine, and theoretically also with selective serotonin reuptake inhibitors, tricyclic anti depressants Category: OPIOID ANTITUSSIVE Severe pain, adjunct Moderate to severe Poorly understood Reduces cough reflex 30-60 mins. Duration * Respiratory Roxanol, in anesthesia pain, antitussive, but strong and Toxicity: Minimal depression, skeletal Dolophine, (fentanyl, morphine), anesthetic adjunct partial and μ agonist when taken as directed muscle rigidity, Sublimaze, Pulmonary edema are also effective constipation, nausea, Dilaudid, (morphine only), vomiting, Numorphan, maintenance in lightheadedness, Demerol, rehabilitation Sufenta, programs Alfentha, Ultiva (methadone only)

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MIXED OPIOID Moderate pain * Moderate to severe Partial μ agonist * κ Like strong agonist Long duration of light headedness, Buprenex, AGONIST- Some maintenance pain, chronic pain, antagonist but can antagonize action 4-8 h * May sedation, dizziness, Suboxone, ANTAGONISTS rehabilitation treatment of opioid their effects * also precipitate abstinence respiratory Subutex Buprenorphine programs dependence reduces craving for syndrome depression, nausea, alcohol vomiting MIXED OPIOID Moderate pain Moderate to severe κ agonist * μ Like strong agonist Long duration of lightheadedness, Nubain AGONIST- pain, anesthetic antagonist but can antagonize action 4-8 h * May sedation, dizziness, ANTAGONISTS adjunct their effects * also precipitate abstinence respiratory Nalbuphine reduces craving for syndrome depression,nausea, alcohol vomiting, OPIOID ANTAGONIST Opioid overdose Moderate to severe Antagonist at μ, δ Rapidly antagonizes Duration 1-2 h (may light headedness, Naloxone, pain, anesthetic and κ receptors all opioid effects have to be repeated sedation, dizziness, naltroxone, adjunct when treating respiratory nalmefene, overdose) * Toxicity: depression, nausea, alvimopan, Precipitates vomiting methylnatrexone abstinence syndrome bromine in dependent users OTHERS ANALGESIC Moderate pain, Moderate to severe Mixed effects: weak Analgesia Duration: 4-6 h Sedation, sweating, Ultram, USED IN MODERATE adjunct to opioid in pain, anesthetic μ agonist, moderate Toxicity: seizures headache, dizziness, Tramadol PAIN chronic pain adjunct SERT inhibitor, weak lethargy, confusion syndrome NET inhibitor PARTIAL AGONIST Mild moderate pain Moderate to severe Less efficacious than Like strong agonist * Like strong agonists, Sedation, sweating, * cough (codeine) pain, antitussive, morphine * can weaker effects toxicity dependent on headache, dizziness, anesthetic adjunct antagonize strong genetic variation of lethargy, confusion agonists metabolism STRONG OPIOID Severe pain *adjunct Anesthetic adjunct, Strong μ-receptor Analgesia *relief of First-pass effect Respiratory Roxanol, AGONIST in anesthesia moderate to severe agonists *variable anxiety *sedation *duration 1-4 h except depression, skeletal Dolophine, (fentanyl, morphine) pain, preoperative affinity for δ and κ *slowed methadone, 4-6 h muscle rigidity, Sublimaze, *Pulmonary edema sedation, obstetric receptors gastrointestinal transit *Toxicity:Respiratory constipation, nausea, Dilaudid, (morphine only) analgesia depression *severe vomiting, Numorphan, *maintenance in constipation lightheadedness, Demerol, rehabilitation *addiction liability Sufenta, programs *convulsion Alfentha, Ultiva (methadone only)

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Category: SKELETAL MUSCLE RELAXANT CENTRALLY ACTING Spasm due to Spasticity due to α2-Adrenoceptor Presynaptic and Renal and hepatic Somnolence, fatigue, Zanaflex SPASMOLYTIC DRUG nultiple sclerosis, spinal cord injury agonist in the spinal postsynaptic elimination *Duration dizziness, dry mouth, Tizanidine stroke, amyotrophic cord inhibition of reflex ~3-6 h urinary tract infections lateral sclerosis motor output *toxicities:Weakness, sedation *hypotension CENTRALLY ACTING severe spasticity due Spasticity due to GABA agonist, Pre- and postsynaptic Oral, intrathecal Drowsiness, dizziness, Lioresal SPASMOLYTIC to cerebral palsy, multiple sclerosis, facilitates spinal inhibition of motor *Toxicities: Sedation, tachycardia, nausea, DRUGS Baclofen multiple sclerosis, spinal cord injuries inhibition of motor output weakness, vomiting stroke (intrathecal neurons administration) CENTRALLY ACTING Acute spasm due to Relief of discomfort Poorly understood Reduction in Hepatic metabolism Drowsiness, dizziness, Flexeril SPASMOLYTIC DRUGS muscle injury due to acute, painful inhibition of muscle hyperactive muscle *duration ~4-6 h dry mouth, nausea, Cyclobenzaprine *inflammation musculoskeletal stretch reflex in reflexes * *strong antimuscarinic constipation conditions spinal cord antimuscarinic effects effects CENTRALLY ACTING Chronic spasm due Relief of skeletal Facilitates Increases interneuron Hepatic metabolism Drowsiness, sedation, Valium SPASMOLYTIC DRUGS to cerebral palsy, muscle spasm, GABAergic inhibition of primary *Duration ~12-24 h sleepiness, lethargy, Diazepam stroke, spinal cord spasticity due to transmission in motor afferents in *toxicities: Strong constipation, diarrhea, injury *acute spasm cerebral palsy, central nervous spinal cord *Central antimuscarinic effects bradycardia, due to muscle injury epilepsy, paraplegia, system sedation tachycardia, rash anxiety DEPOLARIZING Placement of Prototypical Agonist at nicotinic Initial depolarization Rapid metabolism by Can cause cardiac Anectine NEUROMUSCULAR tracheal tube at the depolarizing blocking acetylcholine (Ach) causes transient plasma arrhythmia when BLOCKING AGENT start of anesthetic drug receptors especially contractions, cholinesterase* administered during Succinylcholine procedure* Rarely at the followed by prolong normal duration ~ halothane anesthesia, control of muscle neuromuscular flaccid paralysis * 5min * Toxicities: may cause contractions in status junctions * depolarization is then Arrhythmias * bradycardia when epilepticus depolarizes * may followed by Hyperkalemia * second dose is given stimulate ganglionic repolarization that is Transient increase less than 5 minutes nicotinic Ach and also accompanied by intraabdominal, after the initial dose cardiac muscarinic paralysis intraocular pressure * Ach receptors postoperative muscle pain

Page 34 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

DIRECT-ACTING IV: Malignant Spasticity due to Blocks RyR1 Ca2+- Reduces actin-myosin IV, oral *Duration 4-6 Drowsiness, diizziness, Dantrium MUSCLE RELAXANTS hyperthermia *Oral: spinal cord injury, release channels in interaction *weakens h *Toxicities: Muscle weakness, Dantrolene Spasm due to stroke, cerebral palsy, the sarcoplasmic skeletal muscle weakness constipation, cerebral palsy, spinal multiple sclerosis reticulum of skeletal contraction tachycardia, malaise cord injury, multiple muscle sclerosis NON DEPOLARIZING Prolongs relaxation Non depolarizing drug Competitive Prevents Renal excretion * Initially cause muscle NEUROMUSCULAR for surgical antagonist at nACh depolarization by Duration ~ 40-60 mins. weakness, hypotension BLOCKING AGENT : procedures * as receptor, ACh, causes flaccid * Toxicities: Histamine d-Tubocurarine superseded by especially at the paralysis * can cause release * Hypotension newer non neuromuscular histamine release * Prolonged apnea depolarizing agents junction with hypotension * weak block of cardiacmuscarinic ACh receptor NON DEPOLARIZING Like cisatracurium * Neromuscular Similar to Like cisatracurium Hepatic metabolism * Minimal, if any Zemuron NEUROMUSCULAR Useful in patients blocking drug Cisatracurium but slight Duration ~ 20-35 mins. cardiovascular effect BLOCKING AGENT : with renal antimuscarinic effects Toxicities: Like Rocuronium impairment Cisatracurium NON DEPOLARIZING Prolongs relaxation Neuromuscular Similar to Light tubocurarine Non dependent on Minimal, if any Nimbex NEUROMUSCULAR for surgical blocking drug tubocurarine but lacks histamine renal or hepatic cardiovascular effect BLOCKING AGENT: procedures * release and function * Duration ~ Cisatracurium relaxation of antimuscarinic effects 25-45 mins. * respiratory muscles Toxicities: Prolonged to facilitate apnea but less toxic mechanical than atracurium ventilation in intensive care unit Category: SYMPATHETIC ALPHA- Benign prostatic Tamsulosin is α1A Blockade may Orthostatic ADRENORECEPTOR hyperplasia slightly selective for relax prostatic hypotension may be ANTAGONIST α1A smooth muscles less common with this more than vascular subtype TAMSULOSIN smooth muscles

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ALPHA- Hypertension * Blocks α1 but not α2 Lower BP Larger depressor Doxazosin, ADRENORECEPTOR Benign prostatic effect with first dose Terazosin ANTAGONIST hyperplasia may cause orthostatic hypotension ALPHA- Male erectile Blocks α2 * elicits Raises BP and HR May cause anxiety * ADRENORECEPTOR dysfunction * increased central excess pressor effect if ANTAGONIST Hypotension sympathetic activity norepinephrine * Increase transporter is blocked YOHIMBINE norepinephrine release ALPHA- Hypertension Hypertension β > α1 block Lowers BP with Oral, parentheral * Fatigue, drowsiness, Trandate ADRENORECEPTOR limited HR increase Toxicity: Less insomnia, ANTAGONIST: tachycardia than other hypotension, LABETALOL α1 agents impotence, diarrhea ALPHA- Pheochromo- Irreversibly block α1 lowers blood Irreversible blocker * ADRENORECEPTOR cytoma * high and α2 * indirect pressure (BP) * But half-life > than 1 day * ANTAGONIST: catecholamine states baroreflex activation heart rate (HR) rises Toxicity: Orthostatic PHENOXYBENZAMINE due to baroreflex hypotension * activation Tachycardial * Myocardial ischemia BETA- Rapid control of BP Rapid, short term β1 > β2 Intravenous used * Parentheral only * Dizziness, headache, Brevibloc ADRENORECEPTOR and arrhythmias, treatment of Half-life ~ 10 mins. Toxicity: Bradycardia * hypotension, nausea, ANTAGONIST thyrotoxicosis and ventricular in hypotension cold, extremities, myocardial ischemia supraventricular bradycardia, urinary ESMOLOL intraoperatively arrhythmia, sinus, retention, tachycardia proarrythmic effect BETA- No clinical indication Blocks β2 > β1 Increases peripheral Toxicity: Asthma ADRENORECEPTOR receptors resistance provocation BETA- Heart failure Hypertension, CHF, β > α1 block Long half-life Oral * Toxicity: fatigue Bradycardia, Coreg, ADRENORECEPTOR left ventricular hypotension, cardiac Medroxalol, ANTAGONIST dysfunction insufficiency, fatigue, Bucindolol CARVEDILOL dizziness, diarrhea

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BETA- Hypertension, Hypertension β1,β2 with intrinsic Lowers BP * Oral * Toxicity: fatigue Bradycardia, dizziness, Acebutolol, ADRENORECEPTOR Arrhythmias, sympathomimetic Modestly lower HR * vivid dreams * cold hypotension, nausea, Carteolol, ANTAGONIST Migraine * May (partial agonist) hands vomiting, diarrhea Bopindol, PINDOLOL avoid worsening of effects Penbutolol, bradycardia Oxprenolol,Viske BETA- Angina pectoris * Hypertension, angina, Blocks β1 > β2 Lower HR and Oral, 100-450 mg/d, Bradycardia * fatigue Atenolol, ADRENORECEPTOR Hypertension * MI, CHF receptors BP * Reduce extended release * vivid dreams * cold alprenolol, ANTAGONIST: Arrhythmias renin may safer than products are given hands betaxolol, METOPROLOL asthma once daily nebivolol, BETA- Hypertension * Cardiac arrhythmias, Blocks β1 and β2 Lower HR and Oral, parentheral * Dizziness, vertigo, Inderal, inderal ADRENORECEPTOR Angina pectoris * angina pectoris, receptors BP * Reduce Toxicity: bradycardia * fatigue, bradycardia, LA, Nadolol, ANTAGONIST: arrhythmias * hypertension, renin worsened asthma * CHF, arrhythmia, timolol PROPRANOLOL migraine, essential tremor, fatigue * vivid dreams tachycardia, sinoatrial hyperthyroidism myocardial infarction, * cold hands or atrioventricular migraine headache, block,gastric pain, pheochromocytoma flatulence, constipation, diarrhea, nausea, vomiting, impotence, decreased libido, decreased exercise tolerance, rash, eye irritation TYROSINE Pheochromocytoma Blocks tyrosine Lowers BP * in the Extrapyramidal Metyrosine HYDROXYLASE hydroxylase * central nervous symptoms * INHIBITOR reduces synthesis of system may elicit Orthostatic dopamine, extrapyramidal hypotension * norepinephrine and effects due to low Crystalluria epinephrine dopamine Category: SYMPATHOMIMETIC DOPAMINE D1 Hypertension Peripheral arteriolar Activates adenylyl Vascular smooth Requires dose titration Headache, flushing, Fenoldopam AGONISTS dilator for cyclase muscle relaxation to desired effect reflex tachycardia hypertensive emergencies and post operative hypertension

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DOPAMINE D2 Parkinson's Disease, for patients with Inhibits adenylyl Restores dopamine Oral * Toxicity: Nausea, headache, Bromocriptine AGONISTS Prolactinemia hyperprolactinemia to cyclase and actions in the central Nausea, head ache, light headedness, suppress prolactin interacts with other nervous system hypotension, fatigue release intracellular orthostatic pathways hypotension α1 AGONIST Orthostatic Orthostatic Activates Vascular smooth Oral *Prodrug Nasal burning, Pro Amantine, hypotension hypotension, only phospholipase C, muscle contraction converted to active stinging, dryness, Midodrine, when patient is resulting in increasing blood drug with a 1-h peak rebound nasal Phenylephrine considerably impaired increased pressure (BP) effect *Toxicity: congestion intracellular calcium Produces supine and vasoconstriction hypertension, piloerection (goosebumps), and urinary retention α2 AGONIST Hypertension Hypertension, severe Inhibits adenylyl Vasoconstriction is Oral *transdermal Drowsiness, dizziness, Clonidine, α- pain in patients with cyclase and masked by central *peak effect 1-3 h sedatioin, dry mouth, methyldopa, cancer interacts with other sympatholytic effects, *half-life of oral constipation, dreams, guanfacine, intracellular which lowers (BP) drug~12 h *produces rash, syncope guanabenz, pathways dry mouth and Dexmedetomidin sedation e, tizanidine, β1 AGONIST Cardiogenic shock, Cardiac Activates adenylyl Positive inotropic IV * requires dose Headache, nausea, Dobutamine acute heart failure decompensation due cyclase, increase in effects titration to desired increased heart rate, to depressed myocardial effect increase in systolic contractility caused by contractility blood pressure, organic heart disease palpitations, anginal or cardiac surgical and non specific chest procedures pain β2 AGONIST Asthma Bronchospasm, Activates adenylyl Bronchial smooth Inhalation * Duration: Palpitation, Albuterol prevention of EIB cyclase muscle dilation 4-6 h * Toxicity: tachycardia, Tremor and hypertension, tremor, tachycardia shakiness, dizziness, nervousness, nausea, vomiting

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Category: VASOACTIVE PEPTIDES ANGIOTENSIN Hypertension Hypertension, CHF Selective Arteriolar dilation Oral Headache, dizziness, Eprosartan, RECEPTORS competitive *decreased diarrhea, abdominal Irbesartan, ANTAGONISTS antagonist of aldosterone secretion pain, nausea, URI Candesartan, Valsartan angiotensin AT1 *Increased sodium symptoms, cough Olmesartan, receptors and water excretion telmisartan CALCITONIN GEN- Migraine Antagonist of Blocks some central REALTED PEPTIDE calcitonin gene- and peripheral ANTAGONISTS related peptide (vasodilators) actions BIBN4096BS of CGRP CONVERTING Hypertension *Heart Hypertension, CHF, Inhibits conversion Arteriolar dilation Oral as single dose or Headache, dizziness, Vasotec, ENZYME INHIBITORS failure asympptomatic LVD of angiotensin I to *decreased in 2 divided doses fatigue, nausea, Eprosartan, Enalapril angiotensin II aldosterone secretion diarrhea, decreased Irbesartan, *Increased sodium hematocrit and Candesartan, and water excretion hemoglobin, cough Olmesartan, ENDOTHELIN Pulmonary arterial Non selective receptor Nonselective Vasodilation and Intra-arterial systemic hypotension Sitaxsentan, ANTAGONISTS hypertension blocker antagonist of decrease arterial administration causes facial flushing, edema, Ambrisentan Bosentan endothelin ETA and pressure in humans slow onset of forearm headaches ETB receptors vasodilation NATRIURETIC heart failure in patients with severe Agonist of *Increased sodium IV infusion Fatal renal damage PEPTIDES heart failure natriuretic peptide and water excretion Nesiritide receptors *vasodilation NEUROPEPTIDE None identified Selective antagonist Blocks ANTAGONISTS of neuropeptide Y1 vasoconstrictor BIBP3226 receptors response to neurotensin NEUROTENSIN Potential treatment Schizophrenia, Agonist of central interacts with central can cross the blood AGONISTS PD149163 of schizophrenia and parkinson's disease, neurotensin dopamine systems brain barrier parkinson's disease smoking cessation and receptors weight loss

Page 39 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

NEUROTENSIN None identified Antagonist of Blocks some central ANTAGONISTS central and and peripheral Meclinertant peripheral (vasodilators) actions neurotensin of neurotensin receptors RENIN INHIBITORS Hypertension Hypertension Inhibits catalytic Arteriolar dilation Dose related Aliskiren activity of renin *decreased reduction in blood aldosterone secretion pressure similar to *Increased sodium that of ACE inhibitors, and water excretion, safety and tolerability suppress plasma are comparable to renin activity and angiotensin antagonist reduction in blood and placebo pressure RENIN INHIBITORS Potential use for Selective antagonist Blocks effects of Aliskiren inflammatory pain of kinin B2 kinins on pain, and inflammation receptors hyperalgesia, and inflammation SUBSTANCE P Prevention of Selective antagonist Blocks several central ANTAGONISTS chemotherphy- of tachykinin NK1 nervous system Aprepitant induced nausea and receptors efffects of Substance vomiting P UROTENSIN Diabetic renal failure Peptide antagonist Blocks potent ANTAGONISTS of urotensin vasoconstrictor Palosuran receptors response of endothelin VASOACTIVE Type2 diabetes Therapeutic agent for Selective and Vasodilation poor oral availability, Hypotension INTESTINAL PEPTIDE *chronic obstructive cardiovascular, nonselective *multiple metabolic, rapid metabolism AGONISTS pulmonary disease pulmonary, agonists of VPAC1 endocrine, and other gastrointestinal, AND VPAC2 effects nervous system receptors diseases

Page 40 of 41 Pharmacokinetics, Drugs Clinical Uses Mechanism Effects Toxicities, Adverse Trade Application of Action Interactions Reaction Name

VASOPEPTIDASE Hypertension *heart Vasopeptidase Decreases Vasodilation Angioedema, cough INHIBITORS failure inhibitor, lowers blood metabolism of *increased sodium and dizziness Omapatrilat pressure natriuretic peptides and water excretion inhypertensive and formation of patients and improves angiotensin II cardiac function in patients with heart failure VASOPRESSIN Vasodilatory shock Antioxytoxic activity Agonist of Vasoconstriction More selective for V1 under study Terlipressin AGONISTS but does not vasopressin V1 and receptor and has Arginine vasopressin antagonize the V2 receptors longer half life antidiuretic action of vasopressin, Arg vasopressin is used in sytemic vasoconstriction and decreases pulmonary hypertension. Terlipressin is used for fluid catecholamine refractory septic shock, V1 rceptor agonist VASOPRESSIN Potential use in Dual antagonist of Antagonist of Vasoconstriction non linear safe if IV route, under Relcovaptan ANTAGONISTS hypertension and arginine vasopressin vasopressin V1 and pharmacokinetics study Conivaptan heart failure V2 receptors following intravenous *hyponatremia infusion and oral adminstration, inter action with CYP A34

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