drugs

Drugs Uses Mechanism of Action

EffectsPharmacokinetics,

Toxicities, Interactions

AdverseReaction

ClinicalApplication

Trade Name

Category: ANGINA PECTORIS

BETA BLOCKERS Cardiac arrhythmias, angina pectoris, hypertension, essential tremor, myocardial infarction, pheochromocytoma

Nonselective competitive antagonist adrenoceptors

Decreased heart rate, cardiac output, and blood pressure, decreases myocardial oxygen demand

Oraland parenteral, duration 4-6 h *Toxicity: asthma, atrioventricular block, acute heart failure; sedation*Interactions: Additive with all cardiac depressants

Fatigue, weaknesses, nausea, vomiting, depression, bradycardia, dizziness, vertigo, rash, decrease libido, hypotension, hyperglycemia, decrease exercise tolerance, proarrhythmic effects

Prophylaxis of angina Inderal, inderal LA, Propranolol, Atenolol

CALCIUM CHANNEL BLOCKERS

Vasospastic angina (Prinzmetal's variant angina), chronic stable angina, hypertension

Block vascular L-type calcium channels > cardiac channels

Like verapamil and diltiazem; less cardiac effects

Oral, duration 4-6 h *Toxicity: Excessive hypotension *Interactions: Additive with other vasodilators

Dizziness, lightheadedness, nervousness, headache, nausea, constipation, peripheral edema, asthenia, bradycardia, atrioventricular block, arrhythmias, flushing

Prophylaxis of angina, hypertension

Nifedipine, Adalat, procardia, procardia XL, dihydropyridine

CALCIUM CHANNEL BLOCKERS

Angina pectoris, arrhythmia, essential hypertension, atrial flutter/fibrillation

Nonselective block of L-type calcium channels in vessels and heart

Reduce vascular resistance, cardiac rate, and cardiac force results in decreased oxygen demand

Oral, IV, duartion 4-8 h *toxicity: Atrioventricular block, acute heart failure; constipation,edema *Interactions: Additive with other cardiac depressants and hypotension

Dizziness, light headedness, nervousness, bradycardia, flushing, rash


Verapamil (Calan, isoptin, verelan), Diltiazem (Cardizem, dilacor XR)

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AdverseReaction

ClinicalApplication

Trade Name

MISCELLANEOUSRanolazine

Inhibit late Na+ current in heart, also may modify fatty acid oxidation, reduce contractility

Reducescardiac oxygen demand, fatty oxidation modification may improve efficiency of cardiac oxygen utilization

Oral, duration 6-8 h * Toxicity: QT interval prolongation, nausea, constipation, dizziness *Interactions: Inhibitors of CYP3A increase ranolazine concentration and duration of action


No significant hemodynamic effects

for angina ivabradine

NITRATES Treatment and prevention of angina pectoris

Release nitrate oxide in smooth muscles, which activate guanylyl cyclase and increased cGMP

Smooth muscle relaxation especially, in vessels, other smooth muscle is relaxed but not as markedly, vasodilation decreases venous return and heart size , may increase coronary flow in some areas and in variant angine

very high first pass effect, so sublingual dose is much smaller than oral, high lipid solubility ensures rapid absorption * Toxicity: Orthostatic hypotension, tachycardia, head ache * Interaction: Synergistic hypotension with phosphodiesterase type 5 inhibitors (Sildenafil, etc.)

headache, hypotension, dizziness, weakness, flushing, restlessness

Angina: Sublingual dose form for acute episodes *oral and transdermal forms for prophylaxis

Nitroquick, nitrostat, nitrolingual, isodril, dilatrate, nitroglycerin, isosorbide dinitrate, isosorbide mononitrate

Category: ANTIARRHYTHMIA

CLASS 1B Ventricular arrhythmia Sodium channels (INa) Blockade

Blocks activated and inactivated channels with fast kinetics *does not prolong and may shorten action potential

IV *First-pass hepatic metabolism *reduces dose in patients with heart failure or liver disease *Toxicity: Neurologic symptoms

Lightheadedness, nervousness, bradycardia, hypotension, drowsiness, proarrhythmic effect

Terminate ventricular tachycardias and prevent ventricular fibrillation after cardioversion

Lidocaine, Mexiletine

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AdverseReaction

ClinicalApplication

Trade Name

CLASS 1B Dofetilide

Conversion of atrial fibrillation, flutter to normal sinus rhythm, maintenance of normal sinus rhythm

Ikr Block Prolongs actions potential ,effective refractory period

Oral *renal excretion *Toxicity: Torsade de pointes (initiate in hospitals) *Interactions: Additive with other QT-prolonging drugs

Headache, chest pain, dizziness, respiratory tract infection, dyspnea, nausea, flu like syndrome, proarrhythmic effect

Maintenance or restoration of sinus rhythm in atrial fibrillation

Sotalol, Ibutilide, Dronedarone, Vernakalant, Dofetilide (Tikosyn)

CLASS 1C Paroxymal atrial fibrillation, flutter and supraventricular tachycardia

Sodium channels (INa) Blockade

Dissociates from channels with slow kinetics *No change in action potential duration

Oral *Hepatic, and Kidney metabolism *half life ~20 h *Toxicity:Proarrhythmic

Dizziness, headache, faintness, blurred vision, headache, nausea, dyspnea, fatigue, palpitations, proarrhythmic effect

Supraventricular arrhythmias in patients with normal heart *do not use in ischemic conditions (post-myocardial infarction)

Flecainide, Propafenone, Moricizine

CLASS 2 Ventricualr arrhythmia, hypertension

- Adrenoceptors blockade

Direct membrane effects (Sodium channel block) and prolongation of action potential duration *slows SA node automaticity and AV nodal conduction velocity

Oral, Parenteral *duration 4-6 h *Toxicity: Asthma, AV blockade, acute heart failure *Interactions: With other cardiac depressants and hypotensive drugs

Hypotension, proarrhythmic effect, nausea, headache, decreased exercise tolerance

Atrial arrhythmias and prevention of recurrent infarction and sudden death

Propanolol (Inderal), Esmolol (Breviloc)

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AdverseReaction

ClinicalApplication

Trade Name

CLASS 3 Amiodarone

Life threatening ventricular arrhythmia

Blocks IKr, INa, ICa-L channels, adrenoceptors

Prolongs actions potential duration and QT interval *slows heart rate and AV node conduction *low incidence of torsade de pointes

Oral, IV, *Variable absorption and tissue accumulation *hepati metabolism, elimination complex and slow *Toxicity: Bradycardia and heart block in diseased heart, peripheral vasodilation, pulmonary and hepatic toxicity *Hyper -or Hypothyroidism *Interactions: Many based on CYP metabolism

Malaise, fatigue, tremor, proarrhythmic effect, nausea, vomiting, constipation, photosensitivity

Serious ventricular arrhythmias and supraventricular arrhythmias

Cordarone, Pacerone

CLASS 4 Supravwentricular tachyarrhythmia, temporary control of rapid ventricular rate in atrial flutter/fibrillation, angina, hypertension

Calcium channels IKr, INa, ICa-L blockade

Slows SA node automaticity and AV nodal conduction velocity *decreases cardiac contractility *reduces blood pressure

Oral, IV, *hepatic metabolism *caution in patients with hepatic dysfunction *toxicity: Atrioventricular block, acute heart failure; constipation, edema *Interactions: Additive with other cardiac depressants and hypotension

Constipation, dizziness, headache, mental depression, proarrhythmic effect, peripheral edema, vomiting, nausea

Supraventricular tachycardia

Verapamil (Colan, Covera HS, Isoptin, Verelan), Diltiazem

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AdverseReaction

ClinicalApplication

Trade Name

CLASS IA Procainamide - life threatening ventricular arrhythmiaQuinidine - premature atrial and ventricular contractions, atrial tachycardia and flutter, paroxysmal

INa (primary) and IKr (secondary) blockade

Slows conduction velocity and pacemaker rate, prolongs action potential duration and dissociates from Ina channel with intermediate kinetics , direct depressant effects on SA & AV nodes

Oral, IV, IM *eliminated by hepatic metabolism to N-acetylprocainamide (NAPA) and renal elimination *NAPA implicated in torsade de pointes in atients with renal failure *Toxicity: Hypotension *Long-term therapy produces reversible lupus-related

Hypotension, disturbances of cardiac rhytthm, proarrhythmic effect

Most atrial and ventricular arrhythmias *drug of second choice for most sustained ventricular arrhythmias associated with acute myocardial infarction

Procainamide, Disopyramide, Quinidine

MISCELLANEOUSAdenosine

Activates inward rectifier IK *Blocks Ica

Very brief, usually complete AV blockade

IV only *duration 10-15 *Toxicity: Chest tightness, dizziness *Interactions: Additive with other cardiac depressants and hypotension

Paroxysmal supraventricular tachycardia

MISCELLANEOUSMagnesium

Seizure associated with eclampsia and acute nephritis in children

Poorly understood *interacts with Na+, K+ ATPase, K+, and Ca2+ channels

Normalizes or increases plasma Mg2+

IV *duration dependent on dosage *Toxicity: Muscle weakness in overdose

Flushing, sweating, depressed reflexes, hypotension, cardiac and CNS depression

Torsade de pointes *digital-is-induced arrhythmias

Magnesium sulfate

MISCELLANEOUS:Potassium

Hypokalemia due to arrhythmia

Increases K+ permeability, K+ currents

Slows ectopic pacemakers *slows conduction velocity in heart

Oral, IV *Toxicity: Reentrant arrhythmias, fibrillation or arrest in overdose

Nausea, vomiting, diarrhea, flatulence, abdominal discomfort

Digitalis-induced arrhythmias *arrhythmias associated with hypokalemia

K-tab, K lyte, Slow-K

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AdverseReaction

ClinicalApplication

Trade Name

Category: ANTICHOLINERGIC

CHOLINERGIC POISONING Atropine

Pylorospasm, reduction of bronchial and oral secretion, excessive vagal-induced bradycardia, ureteral and biliary colic

Nonselective competitive antagonist at all muscarinic receptors in CNS and periphery

Blocks muscarinic excess at exocrine glands, heart, smooth muscle

Intravenous infusion until antimuscarinic signs appear *continue as long as necessary *toxicity: Insignificant as long as AChE inhibition continues

Drowsiness, blurred vision, tachycardia, dry mouth, urinary hesitancy

Mandatory antidote for severe cholinesterase inhibitor poisoning

AtroPen

CHOLINERGIC POISONINGPralidoxime

Treat organophosphorus poisoning

Very high affinity for phosphorus atom but does not enter CNS

Regenerates active AChE; can relieve skeletal muscle end plate block

Intravenous every 4-6 hours *toxicity: Can cause muscle weakness and overdose

Neuromuscular weakness

Usual antidote for early stage (48 hours) cholinesterase inhibitor

GASTROINTESTINAL DISORDERS

oral; peptic ulcer, parenteral; inconjunction with aneasthesia to reduce bronchial and oral secretion, to bloch cardiac vagal inhibitory reflexes during induction of anaesthesia and intubation; protection against the pheripheral muscuranic effects of cholinergic agents

Competitive antagonist at M3 receptors

Reduces smooth muscle and secretory activity of gut

Available in oral and parenteral forms *short t1/2 but action last up to 6 hours *Toxicity:Tachycardia, confusion, urinary retention, increased intraocular pressure *Interactions: With other antimuscarinics

Blurred vision, dry mouth, altered taste perception, nausea, vomiting, dysphagia, urinary hesitancy and retention

Reduces smooth muscle and secretory activity of gut

Rubinol, Dicyclomine, Hyoscyamine, Glycopyrrolate

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AdverseReaction

ClinicalApplication

Trade Name

MOTION SICKNESS DRUGS

Preanaesthetic sedation, motion sickness

Unknown mechanism in CNS

Reduces vertigo, postoperative nausea

Transdermal patch used for motion sickness *IM injection for postoperative use *Toxicity:Tachycardia, confusion, urinary retention, increased intraocular pressure *Interactions: With other antimuscarinics

Confusion, dry mouth, constipation, urinary hesitancy, urinary retention, blurred vision

Prevention of motion sicknessand postoperative nausea and vomiting

Scopolamine

OPHTHALMOLOGYAtropine

Pylorospasm, reduction of bronchial and oral secretion, excessive vagal-induced bradycardia, ureteral and biliary colic

Competitive antagonist at all M receptors

Causes mydriasis and cycloplegia

Used as drops * long (5-6days) action * Toxicity: Increased intraocular pressure in close angle glaucoma * Interactions: With other antimuscarinics

Drowsiness, blurr vision, tachycardia, dry mouth, urinary hesitancy

Retinal examination: prevention of synechiae after surgery

Atropen, Atropine, Scopolamine, Homatropine, Cyclopentolate, Tropicamide

RESPIRATORY(ASTHMA, COPD)

Bronchospasm associated with chronic obstructive pulmonary disease, chronic bronchitis, emphysema and rhinorrhea

Competitive, nonselective antagonist at M receptors

Reduce or prevent bronchospasm

Aerosol canister, up to qid * Toxicity: Xerostomia, cough * Interactions: With other antimuscarinics

Dryness of the oropharynx, nervousness, irritation from aerosol, dizziness, headache, GI distress, dry mouth, nausea, palpitation

Prevention and relief of acute episodes of bronchospasm

Ipratropium, Tiotropium

URINARYOxybutynin

Overactive bladder, neurogenic bladder

Nonselective muscarinic antagonist

Reduces detrusor smooth muscle tone, spasms

Oral, IV, patch formulations *toxicity: Tachycardia, constipation, increased intraocular pressure, xerostomia *Patch: Pruritus *Interactions: With other antimuscarinics

Dry mouth, constipation, nausea, headache, drowsiness, urinary retention

Urge incontinence; postoperative spasms

Enablex, Ditropan, Oxybutynin, Darifenacin, solifenacin, Tolterodine, Trospium

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AdverseReaction

ClinicalApplication

Trade Name

Category: ANTI-DEPRESSANT

5-HT2 ANTAGONIST Depression, alcohol craving

Inhibition of 5HT2A receptors *Nefazodone also blocks SERT weakly

Trazodone forms a metabolite (m-cpp) that blocks 5HT2A, 2C receptors

Relatively short half-lives *active metabolites *Toxicity:Modest - and H1 -Receptor blockade (trazodone) *Interactions:Nefazodone inhibits CYP3A4

Somnolence, insomnia, dizziness, nausea, dry mouth, constipation, headache, weakness, drowsiness, priapism, vomiting, fatigue,

Major depression*sedation and hypnosis (trazodone)

Deseryl, Trazodone, Nefazodone

MONOAMINE OXIDASE INHIBITORS (MAOIs)

Depression, anxiety associated with depression, neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation (Zyban)

Blockade of MAO-A and MAO-B (Phenelzine,nonselective) *MAO-B irreversible selective MAO-B inhibition (low dose selegiline)

Transdermal absorption of selegiline achieves levels that inhibit MAO-A

Very slow elimination *Toxicity: Hypotension, insomnia *Interactions:Hypertensie crisis with tyramine, other indirect sympahtomimetics *serotonin syndrome with serotogenic agents, meperidine

Orthostatic hypotension, vertigo, dizziness, nausea, constipation, dry mouth, diarrhea, headache, restlessness, blurred vision, hypertensive crisis

Major depression unresponsive to the other drugs

Nardil, Parnate, Phenelzine, Tranylcypromine, Selegiline

SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs)

Depression, panic disorder, post traumatic stress disorder (PTSD), premenstrual disorder, generalized anxiety disorder, bulimia

Highly selective blockade of serotonin transporter (SERT) * little effect in norepinephrine transporter (NET)

Acute increase of serotonergic synaptic activity * slower changes in several signaling pathways and neurotrophic activity

Half-lives from 15-75 h * Oral-activity * Toxicity: Well tolerated but cause sexual dysfunction * Interaction: some CYP inhibition or fluoxetine 2D6, 3A4; fluvoxamine 1A2; paroxetine 2D6

Nausea, dry mouth, sweating, somnolence, insomia, anorexia, diarrhea, nervousness, drowsiness, asthenia, tremor, constipation, dyspepsia, ejaculatory disturbances,

Major depression, anxiety disorder * Panic disorder * Obsessive-compulsive disorder * Post-traumatic stress disorder * Perimenopausal vasomotor symptoms * Eating disorder (bulimia)

Celexa, Lexapro, Prozac, Prozac weekly, sarafem, Paxil, Zoloft, Citalopram, Escitalopram, Fluoxetine, Fluvoxamine

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AdverseReaction

ClinicalApplication

Trade Name

SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs)

Depression, diabetic peripheral neuropathy, fibromyalgia, stress incontinence, anxiety disorder, premenstrual disorder

Moderately selective blockade of NET and SERT

Acute increase in serotonergic and adrenergic synaptic activity * otherwise like SSRIs

Toxicity: Anticholinergic sedation, hypertension (venlafaxine) * Interaction: Some CYP2D6 inhibition (duloxetine, desvenlafaxine)

Insomnia, dry mouth, nausea, constipation, headache, dizziness, nervousness, weakness, anorexia, somnolence, sweating

Major depression, chronic pain disorders * fibromyalgia, perimenopausal symptoms

Cymbalta, Effexor, Duloxetine, Venlafaxine, and Desvenlafaxine

TETRACYCLICS, UNICYCLIC

Depression, anxiety associated with depression, neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation (Zyban)

Increaed norepinephrine and dopamine activity (bupropion) *NET>SERT inhibition (amoxapine, maprotiline) *increased relaease of norepinephrine 5-HT (mirtazapine)

Presynaptic release of catecholamines but no effects on 5-HT (bupropion) *amoxapine and maprotiline resemble TCAs

Extensive metabolism in liver *Toxicity:Lower seizure threshold (amoxapine, bupropion); sedation and weight gain (mirtazapine) *Interactions: CYP2D6 inhibitor (bupropion)

Agitation, dizziness, dry mouth, insomnia, sedation, headache, nausea, vomiting, tremor, constipation, weight loss, anorexia, excess sweating

Major depression *smoking cessation (bupropion) *sedation (mirtazapine) *amoxapine and maprotiline rarely used

Wellbutrin, Wellbutrin SR, Zyban (smoking cessation), Remeron, Buprupion, Amoxapine, Maprotiline, Mirtazapine

TRICYCLIC ANTIDEPRESSANT (TCA)

Depression, enuresis, eating disorders

Mixed and variable blockade of NET and SERT

Like SNRIs plus significant blockade of autonomic nervous system and histamine receptors

Long half-lives *CYP substrates *active metabolites *Toxicity:Anticholinergic, -blocking effects, sedation and weight gain, arrhythmias, and seizures in overdose *Interactions:CYP inducers and inhibitors

Sedation, anticholinergic effects (dry mouth, dry eyes, urinary retention), constipation

Major depression not responsive to other drugs *chronic pain disorder *incontinence *obsessive-compulsive disorder

Tofranil, Tofranil PM, Imipramine

Category: ANTIHYPERTENSION

ANGIOTENSIN RECEPTOR BLOCKERS

Block AT1 angiotensin receptors

Same as ACE inhibitors but no increase in bradykinin

Oral *toxicity: Same as ACE inhibitors but no cough,

Hypertension *heart failure,

Losartan, many others

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AdverseReaction

ClinicalApplication

Trade Name

ANGIOTENSIN-CONVERTING ENZYMES (ACE) INHIBITORS

Hypertension HF, LVD, after MI, diabetic nephropathy

Inhibit angiotensin converting enzyme

Reduce angiotensin II levels *reduce vasoconstriction and aldosterone secretion *increase bradykinin

Oral *toxicity: Cough, angioedema *teratogenic

Tachycardia, gastric irritation, peptic ulcer, proteinuria, rash, pruritus, cough

Hypertension *heart failure, diabetes

Captopril, Capoten

DIURETICS Loop diuretics: Furosemide

Edema due to CHF, cirrhosis of the liver, renal disease, acute pulmonary edema plus hypertension

Block Na+, Cl-, K+ transporter in renal loop of Henle

Like thiazides * Greater efficacy

Oral * Duration: 8-12 h * Toxicity: Hypokalemic metabolic alkalosis hyperuricemia, hyperglycemia, hyponatremia

Electrolyte and hematologic imbalances, anorexia, nausea, vomiting, dizziness, rash, photosensivity, ortostatic hypotension, glycosuria

Severe hypertension, heart failure

Lasix

DIURETICS Thiazides: Hydrochlorothiazide

Hypertension, edema due to CHF, cirrhosis, corticosteroid and estrogen therapy

Block Na+ or Cl- transporter in renal distal convoluted tubule

Reduce blood volume plus poorly understood vascular effects

Oral * Duration: 8-12 h * Toxicity: Hypokalemic metabolic alkalosis, hyperuricemia, hyperglycemia, hyponatremia

Orthostatic hypotension, dizziness, vertigo, light-headedness, weakness, anorexia, gastri distress, nausea, diarrhea, constipation, hematologic changes, rash, photosensitivity reaction, hyperglycemia, fluid and electrolyte imbalances, reduced libido

Hypertension, mild heart failure

HydroDIURIL, esidrix, microzide, oretic

DIURETICSSpironolactone

hypertension, edema due to CHF, cirrhosis, renal disease, hypokalemia, prophylaxis of hypokalemia in at- risk patients, hyperaldosteronism

Blocks aldosterone receptor in a renal collecting tubule

Increase Na+ and decrease K+ * poorly understood reduction in heart failure mortality

Oral * Duration: 8-12 h * Toxicity: Hypokalemic metabolic alkalosis hyperuricemia, hyperglycemia, hyponatremia

Headache, diarrhea, drowsiness, lethargy, hyperkalemia, cramping, gastritis, erectile dysfunction, gynecomastia

Aldosteronism, heart failure, hypertension

Aldactone, Eplerenone

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AdverseReaction

ClinicalApplication

Trade Name

PARENTERAL AGENTSNitroprusside

Hypertensive crisis Releases nitric oxide Powerful vasodilation Parenteral *Short duration *Toxicity: Excessive hypotension, shock

Apprehension headache, restlessness, nausea, vomiting, palpitation, diaphoresis

Hypertensive emergencies

Nitropress

PARENTERAL AGENTS: Fenoldopam

Activates D1 receptors

Powerful vasodilation Parenteral *Short duration *Toxicity: Excessive hypotension, shock


PARENTERAL AGENTS: Diazoxide

Hypertensive emergencies, or crisis

Opens K channels Powerful vasodilation Parenteral *Short duration *Toxicity: Excessive hypotension, shock

Dizziness, weakness, nausea, vomiting, sodium and water retention, hypotension, myocardial ischemia


Hyperstat IV

RENIN INHIBITORS Inhibits enzyme activity of renin

Reduce angiotensin I and II and aldosterone

Oral *toxicity:Hyperkalemia, renal impairment *potential teratogen

Hypertension Aliskiren

SYMPATHATHIC NERVE TERMINAL BLOCKERS Guanethidine

Hypertension Interferes with amine released and replaces norepinephrine in vesicles

Reduces all sympathetic effects, especially cardiovascular, and reduce blood pressure

Guanethidine: Severe orthostatic hypotension *sexual dysfunction

Dizziness, weakness, lassitude, syncope, postural or exertional hypotension diarrhea bradycardia, fluid retention and edema, CHF, inhibition of ejaculation

Hypertension but rarely used

Ismelin

SYMPATHOPLEGICS, CENTRALLY ACTIVE: Clonidine, Methyl DOPA

Hypertension Activates 2 adrenoceptor

Reduce central sympathetic outflow * reduce norepinephrine release from noradrenergic nerve endings

Oral *Clonidine also patch *Toxicity: sedation *methyldopa hemolytic anemia

Drowsiness, sedation, dizziness, headache, fatigue that tends to diminish within 4-6 weeks, dry mouth, constipation, impotence, decrease sexual activity

Hypertension *clonidine also used in withdrawal from abused drugs

Catapres, clonidine

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AdverseReaction

ClinicalApplication

Trade Name

VASODILATORSHydralazine

Essential hypertension (oral), when needed to lower blood pressure (parenteral)

Causes nitric oxide release

Vasodilation *reduce vascular resistance *arterioles more sensitive than veins *reflex tachycardia

Oral *Toxicity: Angina, tachycardia *Hydralazine: Lupus-like syndrome

Dizziness, palpitation, tachycardia, angina, anorexia, nausea, vomiting, headache, hypotension, diarrhea, rash, nasal congestion

Hypertension *Minoxidil also used to treat hair loss

Apresoline

VASODILATORS: Minoxidil

Severe hypertension Metabolite opens K channels in vascular smooth muscle

Vasodilation *reduce vascular resistance *arterioles more sensitive than veins *reflex tachycardia

Minoxidil:Hypertrichosis

Headache, hypotension, electrocardiogram changes, tachycardia, rash, fatigue, sodium and water retention, nausea, hair growth, changes in direction and magnitude of T waves

Hypertension *Minoxidil also used to treat hair loss

Loniten

VASODILATORS:Nifedipine, Amlodipine

Vasospastic angina (Prinzmetal's variant angina), chronic stable angina, hypertension (sustained release only)

Block vascular calcium channels > cardiac calcium channels

*reduce vascular resistance

Oral, duration 4-6 h *toxicity: Excessive hypotension *Interactions: Additive with other vasodilators

Dizziness, light headedness, nervousness, headache, nausea, constipation, peripheral edema, asthenia, bradycardia, atrioventricular block, arrhythmias, flushing

Hypertension Adalat, procardia, procardia XL

VASODILATORS:Verapamil, Diltiazem

Supraventricular tachyarrhythmias, temporary control of rapid ventricular rate in atrial flutter or fribrillation, angina, unstable angina, hypertension

Nonselective block of L-type calcium channels

Reduce cardiac rate and output *reduce vascular resistance

Oral, IV, duration 4-8 h *toxicity: Atrioventricular block, acute heart failure; constipation, edema *Interactions: Additive with other cardiac depressants and hypotension

Constipation, dizziness, light headedness, headache, asthenia, nausea, vomiting, peripheral edema, hypotension, mental depression, aggranulocytosis, proarrythmic effects

Hypertension, angina, arrhythmias

Calan, covera HS, Isoptin, verelan, verelan PM

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AdverseReaction

ClinicalApplication

Trade Name

BLOCKERS Hypertension Selectively block 1 adrenoceptors

Prevent sympathetic vasoconstriction *reduce prostatic smooth muscle tone

Oral *toxicity: Orthostatic hypotension

Dizziness, headache, drowsiness, lack of energy, somnolence, nausea, palpitation, edema, dyspnea, nasal congestion, sinusitis

hypertension *benign prostatic hyperplasia

Prazosin, Terazosin, Doxazosin

BLOCKERS Hypertension, angina pectoris, MI

Blocks 1 receptors: carvedilol also blocks receptor

Prevent sympathetic cardiac stimulation * reduce renin secretion

Oral *Toxicity: Fatigue Dizziness, vertigo, fatigue, bradycardia, CHF, arrhythmias, tachycardia, sinuatrial or atrioventricular block, gastric pain, flatulence, constipation, diarrhea, nausea, vomiting, impotence, decrease libido, decrease exercise tolerance, rash, eye irritation

Hypertension, heart failure

Metoprolol, Carvedilol, Propranolol, atenolol

Category: ANTI-PSYCHOTIC

Atypical Antipsychotics

Psychotic disorders Blockade of 5HT2A receptors > blockadeof D2 receptors

Some blockade (clozapine, risperidone, ziprasidone) and M-receptor blockade (clozapine, olanzapine) *variable H1-receptor blockade (all)

Toxicity: Agranulocytosis (clozapine), diabetes (clozapine, olanzapine), hypercholesterolemia (clozapine, olanzapine), hyperporlactinemia (ziprasidone), QT prolongation (ziprasidone), weight gain (clozapine, olanzapine)

Agitation, anxiety, headache, constipation, dry mpouth, nausea

Schizophrenia improve both positve and negative symptoms *bipolar disorder (olanzapine or risperidone adjunctive with lithium) *agitation in Alzheimer's and Parkinson's (low doses) *major depression (aripiprazole)

aripiprazole, clozapine, olanzapine, Quetiapine, risperidone, Ziprasidone

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AdverseReaction

ClinicalApplication

Trade Name

Butyrophenone Psychotic disorders, Tourette's syndrome, hyperactivity

Blockade of D2 receptors >>5HT2A receptors

Some blockade, but minimal M receptor blockade and much less sedation than the phenothiazines

Oral and parenteral forms with metabolism elimination *Toxicity: Extrapyramidal dysfunction is the major adverse effect

EPS, dystonia, akathisia, drowsiness, headache, orthostatic hypotension

Schizophrenia (alleviates positve symptoms), bipolar disorder (manic phase), Huntington's chorea, Tourette's syndrome

Haloperidol

Lithium Manic episodes of bipolar disorder

Mechanism of action uncertain *Suppresses inositol signaling and inhibits glycogen synthase kinase-3 (GSK-3), a multifunctional protein kinase

No significant antagonistic actions on autonomic nervous system receptors or specific CNS receptors *no sedative effects

Oral absorption, renal elimination *half-life 20 h *narrow therapeutic window (monitor blood levels) *Toxicity: Tremor, edema, hypothyroidism, renal dysfunction, dysrhythmias * pregnancy category D *Interactions: Clearance decreased by thiazides and some NSAIDs

Headache, drowsiness, tremor, nausea, polyuria

Bipolar affective disorder -- prophylactic use can prevent mood swings between mania and depression

Eskalith, Lithobid

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AdverseReaction

ClinicalApplication

Trade Name

Newer Agents for Bipolar Disorder

Bipolar disorder Mechanism of action in bipolar disorder is unclear.

Carbamazepine causes dose-related diplopia and ataxia * lamotrigine causes nausea, dizziness, and headache * valproic acid causes gastrointestinal distress, possible weight gain, alopecia

Oral absorption * once-daily dosing carbamazepine forms active metabolite * lamotrigine and valproic acid form conjugates * Toxicity: Hematotoxicity and induction of P450 drug metabolism (carbamazepine), rash (lamotrigine), tremor, liver dysfunction, weight gain, inhibition of drug metabolism (valproic acid)

Dizziness, nausea, insomnia, headache, lamotrigine Stevens-Johnsons Syndrome rash

Valproic acid is increasingly used as first choice in acute illness * carbamazepine and lamotrigine are also used both in acute mania and for prophylaxis in depressive phase

Carbamazepine (Tegretol, Epitol), Lamotrigine (Lamictal) and Valproic acid (Depakote. Depakene)

Phenothiazines Psychotic disorders, intractable hiccups

Blockade of D2 receptors >>5HT2A receptors

-Receptor blockade (fluphenazine least) *muscarinic (M)-receptor blockade (especially chlorpromazine and thioridazine) *H1-receptor blockade (chlorpromazine and thioridazine) *Central nervous system (CNS) Depression (sedation) *decreased seizure threshold *QT prolongation (thioridazine)

Oral and parenteral forms, long half-lives with metabolism-dependent elimination *Toxicity: Extensions of effects on - and M- receptors *blockade of dopamine receptors may result in akathisia, dystonia, Parkinsonian symptoms, tardive, dyskinesias, and hyperprolactinemia

Hypotension, drowsiness, dyskinesia, dystonia, behavioral changes, photosensitivity

Psychiatric: Schizophrenia (alleviate positive symptoms), bipolar disorder (manic phase) *nonpsychiatric: antiemesis, preoperative sedation (promethazine) *Pruritus

Chlorpromazine, Fluphenazine and Thioridazine

Page 15 of 41




AdverseReaction

ClinicalApplication

Trade Name

Thioxanthene Schizophrenia Blockade of D2 receptors >>5HT2A receptors

-Receptor blockade (fluphenazine least) *muscarinic (M)-receptor blockade (especially chlorpromazine and thioridazine) *H1-receptor blockade (chlorpromazine and thioridazine) *Central nervous system (CNS) Depression (sedation) *decreased seizure threshold *QT prolongation (thioridazine)

Oral and parenteral forms, long half-lives with metabolism-dependent elimination *Toxicity: Extensions of effects on - and M- receptors *blockade of dopamine receptors may result in akathisia, dystonia, parkinsonian symptoms, tardive dyskinesias, and hyperprolactinemia

Extrapyramidal syndrome (EPS), drowsiness, nausea, diarrhea

Psychiatric: Schizophrenia (alleviate positive symptoms), bipolar disorder (manic phase) *nopsychiatric: antiemesis, preoperative sedation (promethazine) *Pruritus

Thiothixene (Navane)

Category: ANTI-SEIZURE

BENZODIAZEPINESClonazepam

Seizure disorder, panic disorder

Potentiates GABA responses

Documented efficacy against absence seizure

>80% bioavailabilty *extensively metabolized but no active metabolites *t 1/2 20-50 h

Drowsiness, depression, ataxia, anorexia, diarrhea, constipation, dry mouth, palpitations, visual disturbances, rash

Absence seizures, myoclonic seizures, infantile spasms

Klonopin

BENZODIAZEPINESDiazepam

Status epilepticus, seizures disorders (all forms), anxiety disorder, alcohol withdrawal

Potentiates GABA responses

Stops continuous seizure

Well absorbed orally, *rectal administration gives peak concentration in ~1 h with 90% bioavailability *IV for status epilepticus *highly protein-bound *extensively metabolized to several active metabolites *t 1/2 ~2 d

Drowsiness, depression, ataxia, anorexia, diarrhea, constipation, dry mouth, palpitations, visual disturbances, rash

Status epilepticus, seizures clusters

Valium, diastat

Page 16 of 41




AdverseReaction

ClinicalApplication

Trade Name

CYCLIC UREIDES Ethosuximide

Partial seizures Reduces low threshold Ca2+ currents (T-type)

effective against pentylenetetrazol seizures

Well absorbed orally, with peak levels in 3-7 h *not protein-bound *completely metabolized to inactive compounds *t 1/2 typically 40 h

Drowsiness, ataxia, dizziness, nausea, vomiting, urinary frequency, pruritus, urticaria, gingival hyperplasia

Absence seizures Zarontin

CYCLIC UREIDES Phenobarbital

Status epilepticus, cortical focal seizures, tonic-clonic seizures

Enhances phasic GABA receptor responses *reduces excitatory synaptic responses

Decrease excitatory response, selectively suppress abnormal neurons

nearly complete absorption *not significantly bound to plasma proteins *peak concentration in 1/2 to 4 h *no active metabolites *t 1/2 varies from 75 to 125 h

Somnolence, agitation, confusion, ataxia, CNS depression, nervousness, nausea, vomiting, constipation, diarrhea

generalized tonic-clonic seizures, partial seizure, myoclonic seizures, neonatal seizures, status epilepticus

Phenobarbital sodium (Luminal sodium)

CYCLIC UREIDESPhenytoin, fosphenytoin

Status epilepticus Blocks high frequency firing of neurons through action on voltage-gated (VG) Na+ channels * decrease of synaptic release of glutamate

Inhibit a variety of calcium induced secretory processes

Absorption is formulation dependent, highly bound plasma proteins, no active metabolites *dose-dependent elimination, t 12-36 hours *fosphenytoin is IV, IM routes

Ataxia, CNS depression, hypotension, mental confusion, slurred speech, dizziness, drowziness, gingival hyperplasia, rash

generalized tonic-clonic seizures, partial seizure

Cerebyx, Dilantin

CYCLIC UREIDESPrimidone

Epilepsy Similar to phenytoin but converted to phenobarbital

Effective in controlling seizures in newborn infants

Well absorbed orally, not highly bound to plasma proteins *peak concentrations in 2-6 h * t 10-25 hours *two active metabolites (phenobarbital and phenylethymalonamide)

Dizziness, somnolence, nausea, vomiting


Mysoline

Page 17 of 41




AdverseReaction

ClinicalApplication

Trade Name

GABA DERIVATIVEPregabalin

Partial seizure (adults), postherpetic neuralgia, neuropathic pain

Decreases excitatory transmission by acting on VG Ca2+ channels presynaptically (2 subunit)

Act presynaptically to decrease glutamate

Well absorbed orally * not bound to plasma proteins * not metabolized * t1/2 6-7 h

Dizziness and somnolence

Partial seizures Lyrica

GABA DERIVATIVES Gabapentin

Partial seizure (adults) postherpetic neuralgia

Decreases excitatory transmission by acting on VG Ca2+ channels presynaptically (2 subunit)

Act presynaptically to decrease the release of glutamate

Bioavailability 50%, decreasing with increasing doses * not bound to plasma proteins * not metabolized * t 1/2 6-8 h

Somnolence, dizziness, ataxia

Generalized tonic-clonic seizures, partial seizures, generalized seizures

Neurontin

GABA DERIVATIVESVigabatrin

Partial seizures and West's syndrome

Irreversably inhibits GABA-transaminase

Produces sustained increase in the intracellular concentration of GABA in the brain

70% bioavailable * not bound to plasma proteins *not metabolized, *t 1/2 5-7 h (not relevant because of mechanism of action)

Irreversible visual field defects, drowsiness, dizziness and weight gain

Partial seizures, infantile spasms

Levetiracetam Effective against partial seizure in adults and children, ineffective when caused by maximum electric shock

Action on synaptic protein SV2A

Modify the synaptic release of glutamate and GABA

Well absorbed orally * no significant protein binding * extensively metabolized but no active metabolite * t1/2 6-11 h

Somnolence, asthenia, ataxia and dizziness, agitation, anxiety

Generalized tonic-clonic seizures, partial seisures, generalized seizures

Keppra

MISCELLANEOUS Lacosamide

pain syndrome and partial seizure

Enhances slow inactivation of Na+ channels * Blocks effect of neurotrophins (via CRMP-2)

Adjunctive therapy in partial onset seizure with or without secondary generalizations in patients with epilepsy 16 years and older

well absorbed *minimal protein binding *one major nonactive metabolite * t1/2 12-14 h

Dizziness, headache, nausea and diplopia

Generalized tonic-clonic seizures, partial seisures

Vimpat

Page 18 of 41




AdverseReaction

ClinicalApplication

Trade Name

MISCELLANEOUS Valproate

Epilepsy, migraine, headache, mania

Blocks high-frequency firing of neurons * modifies amino acid metabolism

Inhibits GABA transaminase in the brain blocking its degradation, potent inhibitor of histone deacetylase and changes transcription of many genes

Well absorbed from several formulations * highly bound to plasma proteins * extensively metabolized * t 1/2 9-16 h

Headache, somnolence, dizziness, tremor, nausea, vomiting, diplopia

Generalized tonic-clonic seizures, partial seisures, generalized seizures, absence seizures, myoclonic seizures

Depakote, depakene

MISCELLANEOUS Lamotrigine

Partial seizure (used with other anticonvulsants), bipolar disorder

Prolongs inactivation of VG-Na+ channels * acts presynaptically on VG-Ca+ channels, decreasing glutamate release

Decrease synaptic release of glutamate

Well absorbed orally * no significant protein binding * extensively metabolized, but no active metabolites * t 1/2 25-35 h

Dizziness, somnolence, insomia, ataxia, nausea, vomiting, diplopia, headache, Steven's-Johnsons syndrome, rash

Generalized tonic-clonic seizures, generalized seizures, partial seisures, absence seizures

Lamictal

Tiagabine Partial seizures Blocks GABA reuptake in forebrain by selective blockade of GAT-1

Inhibit GABA uptake, prolong inhibitory action of synaptically released GABA and potentiate tonic inhibition

Well absorbed * Highly bound to plasma protein * Extensively metabolized but no active metabolite * t1/2 4-8 h

Dizziness, somnolence, asthenia, nervousness, nausea

Partial seizures Gabitril

Topiramate Partial/ tonic-clonic seizures, migraine, headache

Multiple actions on synaptic function, primary action on kinases altering the phosphorylation of voltage-gated and ligand-gated ion channels

Potentiate the inhibitory effect of GABA acting at site different from benzodiazepine, depress the excitatory action of kainate on glutamate receptor,

Well absorbed * not bound to plasma protein * Extensively metabolized but 40% excreted unchanged in the urine * no active metabolite * t1/2 20 h, but decreases with concomitant drugs

Fatigue concentration problems, somnolence, anorexia

Generalized tonic-clonic seizures, partial seisures, generalized seizures, absence seizures, migraine

Topamax

Page 19 of 41




AdverseReaction

ClinicalApplication

Trade Name

TRICYCLICS Carbamazepine

Epilepsy, bipolar disorder, trigeminal/ postherpetic neuralgia

Blocks high-frequency firing of neurons through the action on VG Na+ cahnnels *decreases synaptic release of glutamate

Treats bipolar depression, trigeminal neuralgia and epilepsy

Well absorbed orally, with peak levels in 6-8 h *no significant protein binding *metabolized in part to active 10-11-epoxide *t1/2 of parent ranges from 8-12 h in treated patients to 36 h in normal subjects

Dizziness, nausea, drowsiness, unsteady gait, aplastic anemia and blood cells abnormality


Tegretol, epitol

Zonisamide Partial seizures of epilepsy

Blocks high-frequency firing via action on VG-Na+ channels

Effect on sodium channels, may also act on voltage-gated calcium channel

Approximately 70% bioavailable orally * minimally bound to plasma proteins * > 50% metabolites * t1/2 20 h

Somnolence, anorexia, headache, dizziness, rash, heat stroke

Generalized tonic-clonic seizures, partial seisures, myoclonic seizures

Zonegran

Category: ASTHMA

BETA AGONISTS Epinephrine

Asthma, bronchospasm Nonselective and agonist

Bronchodilation plus all other sympathomimetic effects on cardiovascular and other organ systems

Aerosol, nebulizer, or parenteral

palpitation, tachycardia, hypertension, arrhythmias, dizziness, vertigo, shakiness, nervousness, headache, insomnia, nausea, vomitting, anxiety, fear, pallor

Anaphylaxis, asthma, others *rarely used for asthma (2-selective agents preferred)

Adrenaline, Epinephrine mist, primatene mist

BETA AGONISTSAlbuterol

Bronchospasm, prevention of EIB

Selective 2 agonist Prompt, efficacious bronchodilation

Aerosol inhalation *duration several hours *also available for nebulizer and parenteral use *Toxicity: Tremor, tachycardia *overdose:arrhythmias

palpitation, tachycardia, hypertension, tremor, dizziness, shakiness, nervousness, nausea, vomiting

Asthma, chronic obstructive pulmonary disease (COPD) *Drug of choice in acute asthmatic bronchospasm

Proventil, Ventulin, Volmax

Page 20 of 41




AdverseReaction

ClinicalApplication

Trade Name

BETA AGONISTSIsoproterenol

Bronchospasm during anaesthesia, vasopressor during shock

1 and 2 agonist Bronchodilation plus powerful cardiovascular effects

Aerosol, nebulizer, or parenteral

Palpitation, tachycardia, chest tightness, angina, shakiness, nervousness, weakness, hyperactivity, headache, nausea, vomiting, flushing, sweating

Asthma, but 2- selective agents preferred

Isuprel

BETA AGONISTSSalmeterol

Asthma, bronchospasm, prevention of EIB

Selective 2 agonist Slow onset, primarily preventive action; potentiates corticosteroid effects

Aerosol inhalation *duration several hours *Toxicity: Tremor, tachycardia *overdose:arrhythmias

palpitation, tachycardia, tremor, nervousness, headache, nausea, vomitting, heartburn, GI distress, diarrhea, cough rhinitis

Asthma prophylaxis Serevent, diskus, metaproterenol, terbutaline, formoterol

CORTICOSTEROIDS, INHALEDFluticasone

Prophylactic maintenance and treatment of asthma

Alters gene expression

Reduces mediators of inflammation * powerful prophylaxis of exacerbations

Aerosol * duration hours * Toxicity: limited by aerosol application * candidal infection, vocal cord changes.

Oral laryngeal, pharyngeal irritation, fungal infection, suppression of HPA function

Asthma * adjunct in COPD

Flovent, flovent rotadisk, flovent diskus

CORTICOSTEROIDS, SYSTEMICPrednisone

Endocrine, rheumatic, collagen, dermatologic, allergies, ophthalmic, respiratory, hematologic, edematous, gastrointestinal, nervous system diseases

Like fluticasone Reduces mediators of inflammation, powerful prophylaxis of exacerbations

Oral * duration hours * Toxicity: Multiple

Fluid and electrolyte, masculoskeletal, cardiovascular, gastrointestinal, dermatology, neurology, endocrine, ophthalmic, metabolic

Asthma * adjunct in COPD

Methylprednisolone: Parenteral agent like prednisone

Page 21 of 41




AdverseReaction

ClinicalApplication

Trade Name

IGE ANTIBODYOmalizumab

Moderate to severe persistent asthma

Humanized IgE antibody reduces circulating IgE

Reduces frequency of asthma exacerbations

Parenteral * duration 2-4 d *Toxicity: Injection site reactions (anaphylaxis extremely rare)

Injection site reaction, viral infection, sinusitis, headache, pharyngitis, anaphylaxis, malignant cyst

Severe asthma inadequately controlled by above agents

Xolair

LEUKOTRIENE ANTAGONISTSMontelukast, zafirlukast

Prophylaxis and treatment of chronic asthma in adults and pediatric patients 12 months of age and older, seasonal allergic rhinitis in adults and pediatric patients 2 years of age and older

Block leukotriene D4 receptors

Block airway response to exercise and antigen challenge

Oral * duration hours * Toxicity: Minimal

Headache, dizziness, dyspepsia, gastroenteritis, influenza like symptoms, cough, abdominal pain, fatigue

Headache (usually mild), flatulence, abdominal pain, cramps, constipation, nausea, dyspepsia, rhabdomyolysis with acute renal failure

Singulair, Zileuton (Zyflo): Inhibits lypoxygenase, reduces synthesis of leukotrienes

METHYLXANTHINESTheophylline

Symptomatic relief or prevention of bronchial asthma and reversible bronchospasm of chronic bronchitis and emphysema

Uncertain * phosphodiesterase inhibiton * adenosine receptor antagonist

Bronchodilation, cardiac stimulation, increased skeletal muscle strength (diaphragm)

Oral * duration 8-12 h but extended-release preparations often used * Toxicity: Multiple

Nausea, vomitting, restlessness, vomiting, tachycardia, tremor, headache, palpitation, hyperglycemia, electrocardiographic changes, cardiac arrhythmias

Asthma, COPD Theo-24, Theo-DUR, elixophyllin, slo-phyllin, uniphyl

STABILIZERS OF MAST AND OTHER CELLSCromolyn, nedocromil

Bronchial asthma, prevention of bronchospasm; prevention of EIA, nasal preparation: prevention and treatment of allergic rhinitis

Alters function of delayed chloride channels * inhibits inflammatory cell activation

Prevents acute bronchospasms

Aerosol * duration 6-8 h * Toxicity: Cough * not absorbed so other toxicities are minimal

Dizziness, headache, nausea, dry and irritated throat, rash, joint swelling and pain

Asthma (other routes used for ocular, nasal, and gastrointestinal allergy)

Intal, nasalcrom, gastrocrom

Page 22 of 41




AdverseReaction

ClinicalApplication

Trade Name

Category: CHOLINOMIMETIC

DIRECT ACTING CHOLINE ESTERS

Urinary cholinergics, acute non obstructive urinary retention

Muscarinic agonist *negligible effects at nicotinic receptors

Activate M1 through M3 receptors in all peripheral tissue , cause increased secretion, smooth muscle contraction (except vascular smooth muscle relaxes,) and changes in heart rate

Oral and parenteral, duration ~30 mins *does not enter central nervous system (CNS) *Toxicity: Excessive parasympathomimetic effects especially bronchospasm in asthmatics * Interactions: Additive with other parasympathomimetics

Abdominal discomfort, headache, diarrhea, nausea, salivation, urgency

Postoperative and Neurogenic ileus and urinary retention

Bethanechol (Duvoid, urecholine), Carbachol (Miostat)

DIRECT ACTING NICOTINIC AGONIST

Varenicline - for cessation of smoking

Agonist at both NN and NM receptors

Activates autonomic postganglionic neurons (both sympathetic and parasympathetic) and skeletal muscle neuromuscular end plates *Enters CNS and activities NN receptors

Oral gum, patch for smoking cessation *toxicity:Increased gastrointestinal (GI) activity, nausea, vomiting, diarrhea acutely, Increase in blood pressure *high dose causes seizures *long-term GI and cardiovascular risk factor *Interactions: Additive with CNS stimulants varenicline has long half life

Excess nicotine - convulsion, coma, respiratory arrest, nausea and insomnia

*Medical use in smoking cessation *non medical use in smoking and insecticides

Nicotine, Varenicline

Page 23 of 41




AdverseReaction

ClinicalApplication

Trade Name

DIRECT-ACTING MUSCARINIC ALKALOIDS OR SYNTHETICS

Glaucoma Muscarinic agonist *negligible effects at nicotinic receptors, partial agonist

Activate M1 through M3 receptors in all peripheral tissue , cause increased secretion, smooth muscle contraction (except vascular smooth muscle relaxes,) and changes in heart rate

Oral lozenge and topical *toxicity &interactions: Like Bethanechol

Temporary reduction in visual acuity, headache

Glaucoma:Sjgren's syndrome

Pilocarpine, Cevimeline

INTERMIDIATE-ACTING CHOLINESTERASE INHIBITORS

Therapeutic uses in myasthenia gravis, physostigmine for glaucoma

Forms covalent bond with AChE, but hydrolyzed and released

Like edrophonium, but longer-acting

Oral and parenteral *quaternary amine, does not enter CNS. duration 2-4 h *toxicity &interactions:Like Edrophonium

Prolonged duration of effect

Myasthenia gravis *Postoperative and Neurogenic ileus and urinary retention

Neostigmine, Pyridostigmine, Physostigmine

LONG-ACTING CHOLINESTERASE INHIBITORS

as insecticides Like Neostigmine, but released more slowly

Like Neostigmine, but longer-acting

Topical only *Toxicity:Brow ache, uveitis, blurred vision

Central nervous system toxicity

Obsolete *was used in glaucoma

Echothiophate, Malathion, Parathion, Sarin,

SHORT-ACTING CHOLINESTERASE INHIBITOR

Diagnosis of myasthenia gravis

Alcohol, binds briefly to active site of acetylcholinesterase (AChE) and prevents access of acetylcholine (Ach)

Amplifies all actions of ACh *increases parasympathetic activity and somatic neuromuscular transmission

Parenteral *quaternary amine *does not enter CNS *Toxicity: Parasympathomimetic excess *Interactions: Additive with parasympathomimetics

Increased bronchial secretions, cardiac arrhythmias, muscle weakness, urinary frequency

Diagnosis and acute treatment of myasthenia gravis

Edrophonium (Enlon, Tensilon)

Page 24 of 41




AdverseReaction

ClinicalApplication

Trade Name

Category: DIURETICS

CARBONIC ANHYDRASE INHIBITORS Acetazolamide

Open angle glaucoma, secondary glaucoma, drug-induced edema, edema due to CHF

Inhibition of the enzyme prevents of dehydration of H2CO3 and hydration of CO2

Reduces reabsorption of HCO3- in kidney , causing self-limited diuresis *Hyperchloremic metabolic acidosis reduces body pH, reduces intraocular pressure

Oral and topical preparations available *Duration of action~ 8-12 h *Toxicity: Metabolic acidosis, renal stones, hyperammonemia in cirrhotics

Weakness, fatigue, anorexia, vomiting, paresthesias, photosensitivity

Glaucoma, mountain sickness, edema with alkalosis

Brinzolamide, dorzolamide

LOOP DIURETICS Furosemide

Edema due to CHF, cirrhosis of the liver, renal disease, acute pulmonary edema

Inhibition of the Na/K/2Cl transporter in the ascending limb of Henle's loop

Marked increase in NaCl excretion, some K wasting hypokalemic metabolic alkalosis, increased urine Ca and Mg

Oral and parenteral preparations *Duration of action 2-4 hours *Toxicity: Ototoxicity, Hypovolemia, K wasting, Hyperuricemia, hypomagnesemia

Electrolyte and hematologic imbalance, anorexia, vomiting, dizziness, photosensitivity, glycosuria

Pulmonary edema, peripheral edema, Hypertension, acute hypercalcemia or hyperkalemia, acute renal failure, anion overdose

Bumetanide, Torsemide, Ethacrynic acid

OSMOTIC DIURETICSMannitol

Promote diuresis in acute renal failure, reduce IOP, treatment of cerebral edema

Physical osmotic effect on tissue water distribution because it is retained in the vascular compartment

Marked increase in urine flow, rduced brain volume, decreased intraocular pressure, initial hyponatremia, then hypernatremia

IV administration *Toxicity: Nausea, vomiting, headache

Edema, fluid and electrolyte imbalance, headache, blurred vision, nausea, vomiting, urinary retention

Renal failure due to increased solute load (rhabomyolysis, chemotheraphy), increased intracranial pressure, glaucoma

Osmitrol

OTHER AGENTSConivaptan

reduce objective signs of hyponatremia and heart failure associated with elevated concentration of vasspressin

Antagonist at V1a and V2 ADH receptors

Reduces water reabsorption, increases plasma Na concentration

IV only *Toxicity: Infusion site reactions

Can not be administered for those with congestive heart faiulure

Hyponatremia

Page 25 of 41




AdverseReaction

ClinicalApplication

Trade Name

POTASSIUM-SPARING DIURETICSAmiloride

CHF, hypertension, prevention of hypokalemia in at-riskpatients, polyuria prevention with lithium use

Blocks epithelial sodium channels in collecting tubules

Reduces Na retention and K wasting *Increases lithium clearance

Orally active *duration 24 h *Toxicity: Hyperkalemic metabolic acidosis

Headache, diarrhea, dizziness, nausea, fatigue, weakness, hypotension

Hypokalemia from other diuretics *reduces lithium-induced polyuria

Eplerenone, Triamterene

POTASSIUM-SPARING DIURETICSSpironolactone

Edema due to CHF, cirrhosis of the liver, acute renal disease, hypokalemia, hyperaldosteronism

Pharmacologic antagonist of aldosterone *weak antagonism of androgen receptors

Reduces Na retention and K wasting in kidney *poorly understood antagonism of aldosterone in heart and vessels

Slow onset and offset of effects *Duration 24-48 h *Toxicity: Hyperkalemia, gynecomastia (spironolactone, not eplerenone) *additive interaction with other K-retaining drugs

Headache, diarrhea, lethargy, hyperkalemia, cramping, gastritis, erectile dysfunction, gynecomastia

Aldosteronism from any cause *Hypokalemia due to other diuretics *postmyocardial infarction

THIAZIDESHydrochlorothiazides

Edema due to CHF, cirrhosis of the liver, acute renal dysfunction

Inhibition of the Na/Cl transported in the distal convoluted tubule

Modest increase in NaCl excretion *some K wasting *Hypokalemic metabolic alkadosis *Decreases urine Ca

Oral *Duration 8-12 h *Toxicity: Hypokalemic metabolic alkadosis, hyperuricemia, hyperglycemia, hyponatremia

Electrolyte and hematologic imbalance, anorexia, vomiting, dizziness, photosensitivity, glycosuria

Hypertension,mild heart failure, nephrolithiasis, nephrogenic diabetes insipidus

Metolazone, Chlorothiazide

Page 26 of 41




AdverseReaction

ClinicalApplication

Trade Name

Category: DYSLIPIDEMIA

BILE ACID SEQUESTRANT Colestipol

Hyperlipidemia Binds bile acids in gut, prevent reabsorption, increases cholesterol catabolism, up-regulates LDL receptor

Decreases LDL oral, taken with meals, not absorbed, toxicity: constipation, bloating, interferes with absorption of some drugs and vitamins

Constipation (may lead to fecal impaction), exacerbation of hemorrhoids, abdominal pain, distention, cramping, nausea, increase bleeding related to vitamin K, malabsorption, vitamin A and D deficiency

Elevated LDL, digitalis toxicity, pruritus

colestid, cholestryramine, colesevalam

FIBRATESFenofibrate, gemfibrozil

Hyperlipidemia, hypertriglyceridemia, reduction of CAD risk

Peroxisome proliferator-activated receptor alpha (PPAR-) agonists

Decrease secretion of very-low-density lipoproteins (VLDL) *increase lipoprotein lipase activity *increase high-density lipoproteins (HDL)

Oral *duration 3-24 h *Toxicity: Myopathy, hepatic dysfunction

Dyspepsia, abdominal pain, diarrhea, nausea, vomiting, rash, vertigo, headache, cholecystitis,cholelithiasis

Hypertriglyceridemia, low HDL

Lopid

NIACIN Adjunctive treatment for hyperlipidemia

Decreases catabolism of apo A1 *reduces VLDL secretion from liver

Increases HDL *decreases lipoprotein a [Lp(a)], LDL and triglycerides

Oral *large doses *Toxicity: Gastric irritation, flushing, low incidence of hepatic toxicity *may reduce glucose tolerance

Generalized flushing sensation of warmth, severe itching and tingling, nausea, vomiting, abdominal pain

Low HDL *elevated VLDL, LDL, Lp(a)

Niaspan, Niacor, extended release niacin

Page 27 of 41




AdverseReaction

ClinicalApplication

Trade Name

STATINSAtorvastatin, simvastatin, rosuvastatin

Primary hyperlipidemia, reduction of elevated total and LDL cholesterol levels and serum triglycerides

Inhibit HMG-CoA reductase

Reduce cholesterol synthesis and up-regulate low-density lipoprotein (LDL) receptors on hepatocytes * modest reduction in triglycerides

Oral *duration 3-24 h *Toxicity: Myopathy, hepatic dysfunction *Interactions:CYP-dependent metabolism (3A4, 2C9) Interacts with CYP inhibitors

Headache (usually mild), flatulence, abdominal pain, cramps, constipation, nausea, dyspepsia, rhabdomyolysis with acute renal failure

Atherosclerotic vascular disease (primary and secondary prevention) *acute coronary syndrome

Lipitor, fluvastatin, pravastatin, lovastatin

STEROL ABSORPTION INHIBITOR Ezetimibe

Primary hypercholesterolemia

Blocks sterol transporter NPCL1L in intestine brush border

Inhibits reabsoption of cholesterol excreted in bile, decreases LDL and phytoesterols

Oral, duration 24 h, Diarrhea, back pain, sinusitis, dizziness, abdominal pain, arthralgia, cough, fatigue

Elevated LDL, phytosterolemia

Zetia

Category: GASTROINTESTINAL CONDITIONS

ANTIDIARRHEAL DRUGSLoperamide

Nausea, diarrhea, abdominal cramps, H. pylori infection with duodenal ulcer

Activates -opioid receptors in enteric nervous system

Slows motility in gut with negligible CNS effects

Mild cramping but little or no CNS toxicity

Dry skin and mucus membranes, nausea, constipation, light headedness

Nonspecific, noninfectious diarrhea

Immodium, kaopectate, Maalox, Diphenoxylate,

ANTIEMETIC DRUGS Aprepitant

Prevent acute and delayed nausea and vomiting from highly emetogenic chemotherapeutic regimens

NK1-receptors blocker in CNS

Interferes with vomiting reflex *Noeffects on 5-HT, dopamine or steroid receptors

Given orally *IV fosaprepitant available *fatigue, dizziness, diarrhea *CYP interactions

Fatigue, dizziness and diarrhea

Effective in reducing both early and delayed emesis in cancer chemotheraphy

Emend, Corticosteroids, Antimuscarinics (scopolamine), Antihistaminiccs, Phenothiazines,

ANTIEMETIC DRUGSOndansetron, other 5 HT3 antagonists

Prevention of chemotheraphy induced and postoperative nausea vomitting, bulimia, spinal analgesia-induced pruritus, levodopa-induced psychosis

5-HT3 blockade in gut and CNS with shorter duration of binding than alosetron

Extremely effective in preventing chemotheraphy-induced and post-operative nausea and vomiting

Usually given Headache, fatigue, drowsiness, sedation, constipation, hypoxia

First-line agents in cancer chemotheraphy; also useful for postop emesis

Zofran

Page 28 of 41




AdverseReaction

ClinicalApplication

Trade Name

BILE ACID THERAPHY FOR GALLSTONESUrsodiol

Dissolution of small cholesterol gallstones in patients with asymptomatic gallbladder disease who refuse cholecystectomy

Reduces cholesterol secretion into bile

Dissolve gallstones May cause diarrhea HepatotoxicityGallstones in patients refusing or not eligible for surgery

Actigall, URSO

DRUG STIMULATING MOTILITYMetoclopramide

Diabetic gastroparesis, GERD, prevention of nausea and vomiting

D2-receptor blocker * removes inhibition of acetylcholine neurons in enteric nervous system

Increases gastric emptying and intestinal motility

Parkinsonian symptoms due to block of central nervous system (CNS) D2 receptors

Restlessness, dizziness, fatigue, extrapyramidal effects

Gastri paresis (eg, in diabetes) *antiemetic

Reglan, Domperidone, Cholinomimetics, Macrolides

DRUGS FOR IRRITABLE BOWEL SYNDROME (IBS)Alosetron

For severe IBS with diarrhea

5-HT3 antagonist of high potency and duration of binding

Reduces smooth muscle activity in gut

Rare but serious constipation *ischemic colitis *infarction

Ischemic colitis, serious complication of constipation requiring hospitalization or surgery

Approved for severe diarrhea-predominants IBS in women

Lotronex

DRUGS USED IN ACID-PEPTIC DISEASES Proton pump inhibitors (PPIs)

Errosive esophagitis, GERD, H.pylori, erradication, NSAID-associated gastric ulcer, hypersecretory condition, heartburn, reduce risk of upper GI bleeding

Irreversible blockade of H+, K+-ATPase pump in active parietal cells of stomach

Long-lasting reduction of stimulated and nocturnal acid secretion

Half-lives much shorter than duration of action * low toxicity *reduction of stomach acid may reduce absorption of some drugs and increase that of others

Headache, nausea, diarrhea

Peptic ulcer, gastroesophageal reflux disease, erosive gastritis

Prilosec, zegerid, omeprazole, Iansoprazole

DRUGS USED IN INFLAMMATORY BOWEL DISEASE (IBD) Anti-TNF antibodies, eg, infliximab others,

Crohn's disease, ulcerative colitis and rheumatoid arthritis

Bind tumor necrosis factor and prevent it from binding to its receptors

Suppression of severalaspects of immune function, especially TH1

Infusion reactions *reactivation of latent tuberculosis *Increased risk of dangerous systemic fungal and bacterial infections

Sore throat, cough, sinus infection, gastric distress

Infliximab: Moderately severe to severe Crohn's disease and ulcerative colitis *others approved in Crohn' disease

Remicade, Corticosteroids

Page 29 of 41




AdverseReaction

ClinicalApplication

Trade Name

DRUGS USED IN INFLAMMATORY BOWEL DISEASE (IBD) Purine analogs and antimetabolites, eg, 6-mercaptopurine, methotrexate

Chronic inflammatory diseases, Crohn's disease and rheumatoid arthritis

Mechanism uncerain *may promote apoptosis of immune cells *Methotrexate blocks dihydrofolate reductase

Generalized suppression of immune processes

GI upset, mucositis *myelosuppression *purine analogs may cause hepatotoxicity, but rare with methotrexate at low doses used

Bone marrow depression, megaloblastic anemia, alopecia, for patients with psoriasis, hepatic damage is common

Mild to moderately severe Crohn's disease and ulcerative colitis

DRUGS USED IN INFLAMMATORY BOWEL DISEASE (IBD) 5-Aminosalicylates, eg, mesalamine in many formulations

Ulcerative colitis, rheumatoid arthritis

Mechanism uncerain *may be inhibtion of eicosanoid inflammatory mediators

Topical therapeutic action *systemic absorption may cause toxicity

Sulfasalazine causes sulfonamide toxicity and may cause GI upset, myalgias,arthralgias, myelosuppression *other aminosalicylates much less toxic

Headache, nausea, anorexia, vomitting, gastric distress, reduced sperm count

Mild to moderately severe Crohn's disease and ulcerative colitis

Azulfidine, Sulfasalazine

DRUGS USED TO TREAT VARICEAL HEMORRHAGEOctreotide

Inhibit intestinal secretion and ixhibit dose related effect on bowel motility,Inhibit pancreatic secretion in patients with pancreatic fistula

Somatostatin analog *mechanism not certain

May alter portal blood flow and variceal pressure

Reduced endocrine and exocrine pancreatic activity *other endocrine abnormalities *GI upset

Steatorrhea, nausea, abdominal pain, flatulence

Patients with bleeding varices or at high risk of repeat bleeding

LAXATIVES Magnesium hydroxide, and other non-absorbable salts and sugars

Symptomatic relief of peptic ulcer and stomach hyperacidity, constipation

Osmotic agents increase water content of stool

Usually causes evacuation within 4-6 h, sooner in large doses

Magnesium may be absorbed and caused toxicity in renal impairment

Diarrhea, bone loss in patients with chronic renal failure

Simple constipation; bowel prep for endoscopy (especially PEG solutions)

Milk of Magnesia, Bulk forming laxatives: Methylcellulose,

PANCREATIC SUPPLEMENTSPancrelipase

Treat pancreatic enzyme insufficiency

Replacement enzymes from animal pancreatic extracts

Improves digestion of dietary fat, protein, and carbohydrates

Taken with every meal *may increase incidence of gout

Oropharyngeal mucositis, diarrhea, abdominal pain, renal stones, colonic strictures

Pancreatic insufficiency due to cystic fibrosis, pancreatitis, pancreatectomy

Pancreatin

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AdverseReaction

ClinicalApplication

Trade Name

Category: MOVEMENT DISORDER

ANTUMUSCARINIC AGENTSBenztropine

Parkinson's disease, drug-induced EPS

Antagonist at M receptors in basal ganglia

Reduces tremor and rigidity * little effect on bradykinesia

Oral * Toxicity: Typical antimuscarinic effects: sedation, mydriasis, urinary retention, dry mouth

Dry mouth, blurred vision, dizziness, nausea, nervousness, skin rash, urinary retention, dysuria, tachycardia, muscle weakness, disorientation, confusion

Parkinson's disease Cogentin, Biperiden (Akineton), orphenadrine, procycline, trihexyphenidyl

COMT INHIBITORSEntacapone

adjunct to levodopa/carbidopa

Inhibits COMT in periphery *does not enter CNS

Reduces metabolism of levodopa and prolongs its action

Oral *Toxicity:increased levodopa toxicity *nausea, dyskinesias, confusion

Dyskinesis, nausea, diarrhea, urine discoloration

Parkinson's disease Tolcapone (Tasmar), Entacapone (Comtan)

DOPAMINE AGONISTSPramipexole

Parkinson's disease Direct agonist at D3 receptor, nonergot

Reduces symptoms of Parkinsonism * smooths out fluctuations in levodopa reponse

Oral *~8 h effect *Toxicity: Nausea and vomiting, postural hypotension, dyskinesias

Dizziness, hallucination, dyspepsia, syncope, confusion, insomnia

Parkinson's disease: Can be used as initial therapy, also effective in on-off phenomenon

Ropinirole (Requip), Bromocriptine (Parlodel, Snap Tabs),

DRUGS USED HUNTINGTON'S DISEASETetrabenazine

Deplete cerebral dopamine

Deplete amine transmitters, especially dopamine, from nerve endings

Reduce chorea severity

Oral * Toxicity: Hypertension, sedation, depression, diarrhea * Tetrabenazine somewhat less toxic

Hypotension, depression, sedation, diarrhea, nasal congestion

Huntington's disease Haloperidol

DRUGS USED IN TOURETTE'S SYNDROME Haloperidol

Deplete cerebral dopamine

Blocks central D2 receptors

Reduces vocal and motor frequency, severity

Oral * Toxicity: Parkinsonism, other dyskinesias * sedation

Hypotension, depression, sedation, diarrhea, nasal congestion

Tourette's syndrome Clonidine, Phenothiazines, Benzodiazepines, Carbamazepine

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AdverseReaction

ClinicalApplication

Trade Name

LEVODOPA AND COMBINATIONSLevodopa

Parkinson's disease Transported into the central nervous system (CNS) and converted to dopamine (which does not enter he CNS); also converted to dopamine in the periphery

Ameliorates all symptoms of Parkinson's disease and causes significant peripheral dopaminergic effects

Oral *6-8 h effect *Toxicities: Gastrointestinal upset, arrhythmias, dyskinesias, on-off and wearing-off phenomena, behavioral disturbances *Interactions: Use with carbidopa greatly diminishes required dosage *use with COMT or MAO-B inhibitors prolong duration of effects

Anorexia, vomiting, abdominal pain, mental changes, headaches, dizziness, increased hand tremor dystonic movements

Parkinson's disease: Most efficacious therapy but not always used as the first drug due to development of disabling response fluctuations over time

Levodopa+Carbidopa (SINEMET), Levodopa+Carbidopa+ Entacapone (STALEVO)

MONOAMINE OXIDASE (MAO) INHIBITORSRasagiline

Agonist for levodopa/carbidopa in parkinson's disease

Inhibits MAO-B selectively, higher doses also inhibits MAO-A

Increases dopamine stores in neurons; may have neuroprotective effects

Oral *Toxicity & interactions: may casue serotonin syndrome with meperidine, and theoretically also with selective serotonin reuptake inhibitors, tricyclic anti depressants

Nausea, dizzinessPakinson's disease; adjunctive to levodopa; smooths levodopa response

Selegiline (Eldepryl)

Category: OPIOID

ANTITUSSIVE Moderate to severe pain, antitussive, anesthetic adjunct

Poorly understood but strong and partial and agonist are also effective

Reduces cough reflex 30-60 mins. Duration * Toxicity: Minimal when taken as directed

Respiratory depression, skeletal muscle rigidity, constipation, nausea, vomiting, lightheadedness,

Severe pain, adjunct in anesthesia (fentanyl, morphine), Pulmonary edema (morphine only), maintenance in rehabilitation programs (methadone only)

Roxanol, Dolophine, Sublimaze, Dilaudid, Numorphan, Demerol, Sufenta, Alfentha, Ultiva

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AdverseReaction

ClinicalApplication

Trade Name

MIXED OPIOID AGONIST-ANTAGONISTS Buprenorphine

Moderate to severe pain, chronic pain, treatment of opioid dependence

Partial agonist * antagonist

Like strong agonist but can antagonize their effects * also reduces craving for alcohol

Long duration of action 4-8 h * May precipitate abstinence syndrome

light headedness, sedation, dizziness, respiratory depression, nausea, vomiting

Moderate pain * Some maintenance rehabilitation programs

Buprenex, Suboxone, Subutex

MIXED OPIOID AGONIST-ANTAGONISTSNalbuphine

Moderate to severe pain, anesthetic adjunct

agonist * antagonist

Like strong agonist but can antagonize their effects * also reduces craving for alcohol

Long duration of action 4-8 h * May precipitate abstinence syndrome

lightheadedness, sedation, dizziness, respiratory depression,nausea, vomiting,

Moderate pain Nubain

OPIOID ANTAGONIST Moderate to severe pain, anesthetic adjunct

Antagonist at , and receptors

Rapidly antagonizes all opioid effects

Duration 1-2 h (may have to be repeated when treating overdose) * Toxicity: Precipitates abstinence syndrome in dependent users

light headedness, sedation, dizziness, respiratory depression, nausea, vomiting

Opioid overdose Naloxone, naltroxone, nalmefene, alvimopan, methylnatrexone bromine

OTHERS ANALGESIC USED IN MODERATE PAIN

Moderate to severe pain, anesthetic adjunct

Mixed effects: weak agonist, moderate SERT inhibitor, weak NET inhibitor

Analgesia Duration: 4-6 h Toxicity: seizures

Sedation, sweating, headache, dizziness, lethargy, confusion

Moderate pain, adjunct to opioid in chronic pain syndrome

Ultram, Tramadol

PARTIAL AGONIST Moderate to severe pain, antitussive, anesthetic adjunct

Less efficacious than morphine * can antagonize strong agonists

Like strong agonist * weaker effects

Like strong agonists, toxicity dependent on genetic variation of metabolism

Sedation, sweating, headache, dizziness, lethargy, confusion

Mild moderate pain * cough (codeine)

STRONG OPIOID AGONIST

Anesthetic adjunct, moderate to severe pain, preoperative sedation, obstetric analgesia

Strong -receptor agonists *variable affinity for and receptors

Analgesia *relief of anxiety *sedation *slowed gastrointestinal transit

First-pass effect *duration 1-4 h except methadone, 4-6 h *Toxicity:Respiratory depression *severe constipation *addiction liability *convulsion

Respiratory depression, skeletal muscle rigidity, constipation, nausea, vomiting, lightheadedness,

Severe pain *adjunct in anesthesia (fentanyl, morphine) *Pulmonary edema (morphine only) *maintenance in rehabilitation programs (methadone only)

Roxanol, Dolophine, Sublimaze, Dilaudid, Numorphan, Demerol, Sufenta, Alfentha, Ultiva

Page 33 of 41




AdverseReaction

ClinicalApplication

Trade Name

Category: SKELETAL MUSCLE RELAXANT

CENTRALLY ACTING SPASMOLYTIC DRUGTizanidine

Spasticity due to spinal cord injury

2-Adrenoceptor agonist in the spinal cord

Presynaptic and postsynaptic inhibition of reflex motor output

Renal and hepatic elimination *Duration ~3-6 h *toxicities:Weakness, sedation *hypotension

Somnolence, fatigue, dizziness, dry mouth, urinary tract infections

Spasm due to nultiple sclerosis, stroke, amyotrophic lateral sclerosis

Zanaflex

CENTRALLY ACTING SPASMOLYTIC DRUGS Baclofen

Spasticity due to multiple sclerosis, spinal cord injuries (intrathecal administration)

GABA agonist, facilitates spinal inhibition of motor neurons

Pre- and postsynaptic inhibition of motor output

Oral, intrathecal *Toxicities: Sedation, weakness,

Drowsiness, dizziness, tachycardia, nausea, vomiting

severe spasticity due to cerebral palsy, multiple sclerosis, stroke

Lioresal

CENTRALLY ACTING SPASMOLYTIC DRUGSCyclobenzaprine

Relief of discomfort due to acute, painful musculoskeletal conditions

Poorly understood inhibition of muscle stretch reflex in spinal cord

Reduction in hyperactive muscle reflexes * antimuscarinic effects

Hepatic metabolism *duration ~4-6 h *strong antimuscarinic effects

Drowsiness, dizziness, dry mouth, nausea, constipation

Acute spasm due to muscle injury *inflammation

Flexeril

CENTRALLY ACTING SPASMOLYTIC DRUGSDiazepam

Relief of skeletal muscle spasm, spasticity due to cerebral palsy, epilepsy, paraplegia, anxiety

Facilitates GABAergic transmission in central nervous system

Increases interneuron inhibition of primary motor afferents in spinal cord *Central sedation

Hepatic metabolism *Duration ~12-24 h *toxicities: Strong antimuscarinic effects

Drowsiness, sedation, sleepiness, lethargy, constipation, diarrhea, bradycardia, tachycardia, rash

Chronic spasm due to cerebral palsy, stroke, spinal cord injury *acute spasm due to muscle injury

Valium

DEPOLARIZING NEUROMUSCULAR BLOCKING AGENT Succinylcholine

Prototypical depolarizing blocking drug

Agonist at nicotinic acetylcholine (Ach) receptors especially at the neuromuscular junctions * depolarizes * may stimulate ganglionic nicotinic Ach and cardiac muscarinic Ach receptors

Initial depolarization causes transient contractions, followed by prolong flaccid paralysis * depolarization is then followed by repolarization that is also accompanied by paralysis

Rapid metabolism by plasma cholinesterase* normal duration ~ 5min * Toxicities: Arrhythmias * Hyperkalemia * Transient increase intraabdominal, intraocular pressure * postoperative muscle pain

Can cause cardiac arrhythmia when administered during halothane anesthesia, may cause bradycardia when second dose is given less than 5 minutes after the initial dose

Placement of tracheal tube at the start of anesthetic procedure* Rarely control of muscle contractions in status epilepticus

Anectine

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AdverseReaction

ClinicalApplication

Trade Name

DIRECT-ACTING MUSCLE RELAXANTSDantrolene

Spasticity due to spinal cord injury, stroke, cerebral palsy, multiple sclerosis

Blocks RyR1 Ca2+-release channels in the sarcoplasmic reticulum of skeletal muscle

Reduces actin-myosin interaction *weakens skeletal muscle contraction

IV, oral *Duration 4-6 h *Toxicities: Muscle weakness

Drowsiness, diizziness, weakness, constipation, tachycardia, malaise

IV: Malignant hyperthermia *Oral: Spasm due to cerebral palsy, spinal cord injury, multiple sclerosis

Dantrium

NON DEPOLARIZING NEUROMUSCULAR BLOCKING AGENT : d-Tubocurarine

Non depolarizing drug Competitive antagonist at nACh as receptor, especially at the neuromuscular junction

Prevents depolarization by ACh, causes flaccid paralysis * can cause histamine release with hypotension * weak block of cardiacmuscarinic ACh receptor

Renal excretion * Duration ~ 40-60 mins. * Toxicities: Histamine release * Hypotension * Prolonged apnea

Initially cause muscle weakness, hypotension

Prolongs relaxation for surgical procedures * superseded by newer non depolarizing agents

NON DEPOLARIZING NEUROMUSCULAR BLOCKING AGENT : Rocuronium

Neromuscular blocking drug

Similar to Cisatracurium

Like cisatracurium but slight antimuscarinic effects

Hepatic metabolism * Duration ~ 20-35 mins. Toxicities: Like Cisatracurium

Minimal, if any cardiovascular effect

Like cisatracurium * Useful in patients with renal impairment

Zemuron

NON DEPOLARIZING NEUROMUSCULAR BLOCKING AGENT: Cisatracurium

Neuromuscular blocking drug

Similar to tubocurarine

Light tubocurarine but lacks histamine release and antimuscarinic effects

Non dependent on renal or hepatic function * Duration ~ 25-45 mins. * Toxicities: Prolonged apnea but less toxic than atracurium

Minimal, if any cardiovascular effect

Prolongs relaxation for surgical procedures * relaxation of respiratory muscles to facilitate mechanical ventilation in intensive care unit

Nimbex

Category: SYMPATHETIC

ALPHA-ADRENORECEPTOR ANTAGONIST TAMSULOSIN

Tamsulosin is slightly selective for 1A

1A Blockade may relax prostatic smooth muscles more than vascular smooth muscles

Orthostatic hypotension may be less common with this subtype

Benign prostatic hyperplasia

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AdverseReaction

ClinicalApplication

Trade Name

ALPHA-ADRENORECEPTOR ANTAGONIST

Blocks 1 but not 2 Lower BP Larger depressor effect with first dose may cause orthostatic hypotension

Hypertension * Benign prostatic hyperplasia

Doxazosin, Terazosin

ALPHA-ADRENORECEPTOR ANTAGONIST YOHIMBINE

Blocks 2 * elicits increased central sympathetic activity * Increase norepinephrine release

Raises BP and HR May cause anxiety * excess pressor effect if norepinephrine transporter is blocked

Male erectile dysfunction * Hypotension

ALPHA-ADRENORECEPTOR ANTAGONIST: LABETALOL

Hypertension > 1 block Lowers BP with limited HR increase

Oral, parentheral * Toxicity: Less tachycardia than other 1 agents

Fatigue, drowsiness, insomnia, hypotension, impotence, diarrhea

Hypertension Trandate

ALPHA-ADRENORECEPTOR ANTAGONIST:PHENOXYBENZAMINE

Irreversibly block 1 and 2 * indirect baroreflex activation

lowers blood pressure (BP) * But heart rate (HR) rises due to baroreflex activation

Irreversible blocker * half-life > than 1 day * Toxicity: Orthostatic hypotension * Tachycardial * Myocardial ischemia

Pheochromo- cytoma * high catecholamine states

BETA-ADRENORECEPTOR ANTAGONIST ESMOLOL

Rapid, short term treatment of ventricular in supraventricular arrhythmia, sinus, tachycardia

1 > 2 Intravenous used * Half-life ~ 10 mins.

Parentheral only * Toxicity: Bradycardia * hypotension

Dizziness, headache, hypotension, nausea, cold, extremities, bradycardia, urinary retention, proarrythmic effect

Rapid control of BP and arrhythmias, thyrotoxicosis and myocardial ischemia intraoperatively

Brevibloc

BETA-ADRENORECEPTOR

Blocks 2 > 1 receptors

Increases peripheral resistance

Toxicity: Asthma provocation

No clinical indication

BETA-ADRENORECEPTOR ANTAGONISTCARVEDILOL

Hypertension, CHF, left ventricular dysfunction

> 1 block Long half-life Oral * Toxicity: fatigue Bradycardia, hypotension, cardiac insufficiency, fatigue, dizziness, diarrhea

Heart failure Coreg, Medroxalol, Bucindolol

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AdverseReaction

ClinicalApplication

Trade Name

BETA-ADRENORECEPTOR ANTAGONISTPINDOLOL

Hypertension 1,2 with intrinsic sympathomimetic (partial agonist) effects

Lowers BP * Modestly lower HR

Oral * Toxicity: fatigue * vivid dreams * cold hands

Bradycardia, dizziness, hypotension, nausea, vomiting, diarrhea

Hypertension, Arrhythmias, Migraine * May avoid worsening of bradycardia

Acebutolol, Carteolol, Bopindol, Penbutolol, Oxprenolol,Viske

BETA-ADRENORECEPTOR ANTAGONIST: METOPROLOL

Hypertension, angina, MI, CHF

Blocks 1 > 2 receptors

Lower HR and BP * Reduce renin may safer than asthma

Oral, 100-450 mg/d, extended release products are given once daily

Bradycardia * fatigue * vivid dreams * cold hands

Angina pectoris * Hypertension * Arrhythmias

Atenolol, alprenolol, betaxolol, nebivolol,

BETA-ADRENORECEPTOR ANTAGONIST: PROPRANOLOL

Cardiac arrhythmias, angina pectoris, hypertension, essential tremor, myocardial infarction, migraine headache, pheochromocytoma

Blocks 1 and 2 receptors

Lower HR and BP * Reduce renin

Oral, parentheral * Toxicity: bradycardia * worsened asthma * fatigue * vivid dreams * cold hands

Dizziness, vertigo, fatigue, bradycardia, CHF, arrhythmia, tachycardia, sinoatrial or atrioventricular block,gastric pain, flatulence, constipation, diarrhea, nausea, vomiting, impotence, decreased libido, decreased exercise tolerance, rash, eye irritation

Hypertension * Angina pectoris * arrhythmias * migraine, hyperthyroidism

Inderal, inderal LA, Nadolol, timolol

TYROSINE HYDROXYLASE INHIBITOR

Blocks tyrosine hydroxylase * reduces synthesis of dopamine, norepinephrine and epinephrine

Lowers BP * in the central nervous system may elicit extrapyramidal effects due to low dopamine

Extrapyramidal symptoms * Orthostatic hypotension * Crystalluria

Pheochromocytoma Metyrosine

Category: SYMPATHOMIMETIC

DOPAMINE D1 AGONISTS

Peripheral arteriolar dilator for hypertensive emergencies and post operative hypertension

Activates adenylyl cyclase

Vascular smooth muscle relaxation

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