Kristine Knoll Drug List Drug/Class Direct Cholinergic Agonists Muscarine Nicotine Pilocarpine Bethanechol Cevimeline Methacholine Indirect

Cholinergic Agonists (reversible) Tacrine Alzheimer's tx Myasthenia Gravis, Urinary retention, stimulate bladder, paralytic ileus Anticholinesterase Physostigmine Glaucoma, CNS seizures, Myasthenia gravis Myasthenia Gravis, Curariform drug toxicity Crosses BBB Alzheimer's tx Muscarinic Nicotinic Pred. Muscarinic Pred. Muscarinic Muscarinic Glaucoma, Xerostomia Stimulate Bladder, GI, Paralytic ileus Xerostomia, Longer duration Sjogren's syndrome choline ester alkaloid carbomate Mechanism Clinical Uses Side Effects Note: Do not use if Bowel obstruction, Asthma, Peritonitis Miscellaneous

No CNS action

alkaloid

Neostigmine

Reversal of curare Excess can cause Depolarizing Neuromuscular Blockade reversal of atropine, TCA

Pyridostigmine Donepezil Galatamine Rivastigmine Drug/Class Indirect Cholinergic Agonists (irreversible) Nerve Gas (Sarin) Insecticide (Parathion) Acetylcholine Augmenters Sildenafil (Viagra) Inhibit 5-PDE, increase cGMP --> Vasodilation Phosphorylated Esterase that cannot regenerate Mechanism

Clinical Uses

Side Effects Note: Do not use if Bowel obstruction, Asthma, Peritonitis

Miscellaneous

None

Pralidoxime (2-PAM) can help if early (No CNS)

Erectile dysfunction

Headache, nasal congestion, Differences due to duration of dyspepsia, visual action; Metabolized by disturbances (blue vision w/ CYP3A4; Should not be used

Cholinergic Antagonists (Antimuscarinics) Atropine Scopolamine Propantheline Glycopyrrolate Methantheline Cholinergic Antagonists (Antinicotinics-Ganglionic blockers) Hexamethonium Pentolinium Trimethaphan Mecamylamine Cholinergic Antagonists (Antinicotinics-Neuromuscular Junction blockers) Tubocurarine Pancuronium Mivacurium Atracurium Vecuronium Succinylcholine Drug/Class Other "Muscle Relaxers" Dantrolene Botulinum toxin Unknown; Decreases Ca release from SR Blocks Ach vesicle release (for months) Malignant hyperthermia Prevent sweating, cosmetic Hepatotoxicity Depolarizing blockade of Nnmj receptor Mechanism Clinical Uses Malignant hyperthermia Side Effects Non-depolarizing blockade of Nnmj receptor Competes with Ach at receptor Given IV or IM Non-depolarizing blockade of NG receptor Emergency HTN crisis Block both Parasympathetic and SympatheticEffects depend on dominant tone Muscarinic competitor blocks M1, M2, and M3 Eye dilation Motion sickness; mydriasis, cycloplegia Aggravates Glaucoma CNS probs: euphoria, restlessness, delerium Greater CNS effects than Atropine Synthetic

Emergency HTN crisis

short half-life

Some association with Histamine release due to Muscle relaxation before and during surgery, ECT, Tetanus large size (bronchospasm and edema) convulsions, orthopedic procedures

Seizures due to metabolites in CNS Excreted by liver (used in Pts with renal probs) Contract then paralyzed (Pseudocholinesterase) Miscellaneous

Direct Adrenergic Agonists (Sympathomimetics) Epinephrine Norepinephrine Dopamine Dobutamine Phenylephrine Methoxamine Metaproterenol Isoproterenol Clonidine Oxynetazoline Albuterol Salmeterol methyldopa Drug/Class Indirect Adrenergic Agonists Amphetamine Tyramine Cocaine Methylphenidate Imipramine Mixed Adrenergic Agonists Ephedrine Pseudoephedrine Metaraminol Alpha-Adrenergic Antagonists Phenoxybenzamine Non-selective alpha blocker Phentolamine Doxazosin Tamsulosin Alfuzosin Terazosin Prazosin Drug/Class Beta-Adrenergic Antagonists Propranolol Nadolol Timolol Atenolol Selective Beta 1 blocker Metoprolol Agents with Intrinsic Sympathomimetic Activity Pindolol, Acebutolol Beta and Alpha 1 Antagonists Labetatol Blocks B and a1 Carvedilol Other Agents with Adrenergic Agonistic Activity Reserpine inhibits storage of Norepi in vesicles Depletes Norepi with decrease in sympathetic HTN in Pts who cannot tolerate increased TPR HTN, MI; heart failure Inhibits vasoconstriction of pure B blockers Antioxidant and Antiapoptotic activity Not pure B antagonists Partial agonists HTN in Pts who cannot tolerate increased TPR Non-selective beta blocker HTN, glaucoma, migraine, CV, thyroid, stage fright Bronchoconstriction, arrhythmias at withdrawl longer duration Mechanism Clinical Uses Side Effects Miscellaneous Selective Alpha 1 blocker hypertension, urinary retention due to BPH nasal congestion, orthostatic Decreases TPR and blood hypotension, first dose pressure Little effect on syncope CO or RBF Pheochromocytoma orthostatic hypotension Decreases TPR and blood pressure reflex tachycardia can worsen heart condition Direct: a and B Indirect: release of Norepi Direct: a rel. of Norepi Indirect: inhibits re-uptake Beta 1 and alpha mediates Norepi release causes release of Norepi Beta 1 and alpha Reuptake 1 blocks Local anesthetic activity with analogs Metabolized by MAO (careful with inhibitors) Peripheral and CNS effects blocks reuptake of Dopamine and Norepi Cardiac death from build-up of Norepi Mechanism Clinical Uses Side Effects beta 2 beta 2 alpha-methylNE converted into dopa Miscellaneous Low dose: B (dilation) High dose: a (constrict) Beta 1 and alpha Low dose: B1 High dose: a (D1, D2) Asthma, anaphylactic shock, glaucoma Shock, but decrease in RBF Shock-inc. CO w/ maint of renal blood flow Increase CO in CHF (+ inotropic) topical, eye, nasal decongestant Paroxysmal supravent. tachycardia Bronchodilator reflex bradycardia Does not stimulate heart Similar to Albuterol, Ritodrine, Terbutaline CNS effects (tremors, stroke), arrhythmias All adrenergic receptors All receptors but Beta 2

Beta 1 (some Alpha) Alpha 1 >> Alpha 2 Alpha 1 Beta 2 Beta 1 and Beta 2 Alpha 2 (in CNS)

Control of BZ and opiate withdrawl, HT

Inhibits sympathetic vasomotor centers

Viral and allergic rhinitis

Can cause HTN crisis

Hypotensive states

No CNS-too polar

Topical for glaucoma HTN with impaired pulmonary function Will not block B2 (no added lung problems)

guanadrel guanabenz Guanethidine Drugs for Parkinson's (loss of DA action) Levodopa (L-Dopa) Carbidopa (Sinemet) Selegiline (deprenyl) Entacapone Tolcapone Bromocriptine Pergolide Dopaminergic agonists Pramipexole Ropinirole Drug/Class Other Drugs for Parkinson's Benztropine Trihexyphenidyl Atropine Amantadine Amphetamine Alzheimer Drug/Class Tacrine Reivastigmine Cholinesterase Inhibitors Donepezil Galantamin Memantine Glutamate antagonist at NMDA receptor Mechanism Clinical Uses Side Effects Miscellaneous Synthesis, release, reuptake of DA? stimulates DA release Antiviral, seemingly helpful for PD Livedo reticularis (bluish skin w/ edema) Anticholinergic agents Reduce excitation of GABA neurons Muscarinic blockade: Can't see,spit,pee,shit block Ach receptor Mechanism Clinical Uses Side Effects Miscellaneous Converted to Dopamine Blocks AAAD in Periph. More L-Dopa in CNS Inhibits MAO type B Inhibits COMT Inhibits COMT Preventing DA metabolism Prevent DA metabolism and allow more L-Dopa to enter CNS Parkinson's Disease Similar to DA (but less) Lessens peripherals, may increase CNS ones Adrenergic stimulation NO hepatotoxicity Hepatotoxicity Not used much anymore Large first-pass, to CNS by ACTIVE transport Does NOT cross BBB (prevents --> DA in Per.) Type B more specific to DA at small doses blocks release of stored Norepi

Still active at later stages when DA neurons completely For all DAergic drugs: Per arrythmias (B1), hypotension lost CNS -N/V(emetic center) dyskinesias, agitation, hallucinations (DA receptors in other parts of brain)

Cross BBB

inhibit Ach production

Drugs for Psychiatric Disorders (Antipsychotics)

D2 blockers

Block DA type 2 receptors

Positive symptoms (delusions, craziness) Usually safe, unless combined (EtOH), increased Prolactin with DA blockade, TD, Antipsychotic malignant syndrome Blockade of DA's in other parts of brain, or other receptors (Ach,His) can lead to side effects

5HT2 blockers

Block 5-HT type 2 receptors

Negative symptoms (anergy, depression)

Haloperidol

DA-2 blockers

Low sedation, alphaMost widely used of classical blockade, High EPS, alleviates antipsychotics + symptoms, hyperprolactonemia Requires WBC monitoring Agranulocytosis, EPS/TD Low

Depot preparation for compliance probs Increased antimuscarinic Low Prolactin elevation

Clozapine Risperidone quetuapine aripiprazole Olanzapine Drug/Class Lithium Antiepileptic Drugs Carbamazepine Phenytoin Fosphenytoin (1 )
o

EPS at high doses, More Prolactin elevation Atypicals: Moderate D2, High D4, High 5-HT2 Similar to Clozapine Do not require WBC monitoring

Very low agranulocytosis Mechanism Most likely interferes with IP3 and DAG paths Clinical Uses Bi-Polar disorder Possible birth defects, OC interactions Like Phenytoin; + DOC for Trigeminal Neuralgia Block Na channels in brain; reduce neuron firing
+

Side Effects Fatigue, hand tremor Neph. diabetes insipidus

Miscellaneous

Behaves similarly to Na+ Compete 4 reabsorption Also used for pain control, diabetic neuropathies, and withdrawl symptoms control NOT used for Absence (petit mal) seizures; zero-order at [high] More hydrophilic IM/IV; ER for FAST action In

Drowsiness, vertigo, ataxia Gingival hyperplasia, nystagms,atxia,hirsutsm

Tonic-clonic (GM), Psychomotor, and Focal

Valproic acid Phenobarbital Ethosuximide Clonazepam Diazepam

(2 ) (Valproate)

Prolongs GABA, Blocks Na+ 2+ and T-type Ca

Anticonvulsant and moodstabilizer GM, Psychomotor, and Focal; also (EtOH w/x)

Liver failure in kids overdose)

(with Least toxic; --> Children to avoid gum growth Contra in tonic-clonics Potential to exacerbate seizures; yes Tolerance Medical emergency

Sedation or hyperactivity Extended depression (GI, drowsiness, lazy) Drowsiness, ataxia, aggressiveness

(1 )

Blocks T-type Ca channels

2+

Absence (petit mal) ONLY -usually children Useful in all, esp. myoclonic and akinetic Status epilepticus

Stimulates GABA

Therapeutic Adjuncts (some can be used alone) Gabapentine Drug/Class Lamotrigine Topiramate Levetiracetam Zonisamide Oxcarbazepine Opioid Agonists Presynapse: close Ca2+ + Postsynapse: open K Resp. depression, Sedation, Constipation, Nausea/vomiting (CNS), Addiction Effects of receptors (Mu, Delta, Kappa) Histamine release due to large size; Pharmacodynamic tolerance 2-3 wks; High dependence; Changed to M-3-G (les) and M-6-G (more active) Some people lack CYP2D6 (no pain relief) Increase GABA release? Mechanism Inactivates Na channels Blocks Na+ channels, augments GABA
+

Partial sz; Pain control (more common use) Clinical Uses Partials, some GM, atonic, and absence Partial sz (approved for monothrpy), migraines Partial sz Newer agents Partial sz Side Effects Cerebellar dys, drowsiness, and rash Ataxia, drowsiness Miscellaneous Possibly leading to StevensJohnson syn. Also inhibits glutamate at certain receptors

Morphine

Stimulation of Mu, kappa receptors

Analgesia (Mu), Diarrhea, Cough, Surgery

Codeine Opium Heroin Hydromorphine

Metabolized in liver to morphine by CYP2D6

Cough, Pain relief (w/ NSAIDs)

Decreased dependence

Semi-synthetic derivatives Oxycodone Hydrocodone Propoxyphene Diphenylheptanes Methadone Fentanyl Meperidine Sufentanil,Alfentanil,Remifentanil Tramadol Drug/Class Nalbuphine Pentazocine Synthetic Non-Analgesic dextromethorphan Diphenoxylate/Atropine Looperamide Opioid Antagonists Naloxone Naltrexone Sedative-Hypnotic and Anxiolytic Drugs Barbiturates Phenobarbital Miscellaneous Buspirone Zolpidem (Ambien), Zaleplon Chloral hydrate promethazine Partial agonist at 5-HT1a receptors Selective for BZ1 receptor (sleep) Rapid onset, short duration Anxiety only Hypnotic similar to BZ's Does not interact with EtOH, motor skills Less tolerance, dependency, amnesia Low TI Unpleasant taset/smell 1-4 weeks to start working Enhances duration GABA Primarily for binding to receptor --> Clanticonvulsants/ anesthetics influx --> hyperpolarization Longer-acting Tolerance --> Smaller Therapeutic index Can produce anesthesia and even death; Withdrawl sx can be fatal Pure antagonist (mainly at Mu receptors) Opioid toxicity (Resp. depression, coma) Opioid, EtOH addiction Can try in ER with comatose pt. Talwin-NX (no absorption orally) Longer onset, T1/2, duration of action Partial agonist (Mu, delta, sigma) Analgesia (kappa) Withdrawl sx when given with morphine Talwin-NX to prevent IV abuse Mechanism Clinical Uses Side Effects Miscellaneous Phenylpiperidines Withdrawl from heroin or morphine Anesthesia (sedative, analgesic) Mild to moderate pain; Avoid chronic use Less euphoria, slow withdrawl 80x better analgesic potency than morphine Neurotoxicity, seizures from metabolite Slower onset, longer duration of action Transdermal form - slower onset, long DOA No cough suppression, NO miosis (abuse!) Pain control

Drug/Class Benzodiazepines Alprazolam Midazolam Clonazepam Diazepam (Valium) Lorazepam Triazolam Flumazenil Drugs for Depression Monoamine Oxidase Inhibitors Selegilline Phenelzine Isocarboxazid Tranylcypromine Drug/Class Tricyclic Antidepressants

Mechanism BZ1 = sleep, BZ2 = memory/motor function

Clinical Uses

Side Effects Anterograde amnesia, few outside of CNS

Miscellaneous Will NOT produce anesthesia or death All of these can cross placenta --> probs.

Enhances frequency GABA binding to receptor --> Cl influx resulting in hyperpolarizatioin (inhibitory effect in brain) GABA must be present to show any effect (cannot affect Cl- conductance alone)

Varied: some anticonvulsants, muscle relaxors in addition to anxiolytic/sedative/ hypnotics

Overdose similar to EtOH intoxication; all can develop dependence

All these only toxic when combined (EtOH)

Oral form for kids

For starting sleep BZ receptor antagonist Hasten recovery, overdose

Daytime anxiety, morning insomnia

Shorter-acting Also antagonizes zolpidem and zaleplon No CNS stimulation for normal patients MAOa = NE, 5-HT MAOb = DA

Also used for Panic disorder, Enuresis, Chronic pain, Eating disorders, Attention Deficit disorder Nasty drugs also for parkinsons (MAOb) Increase vesicular stores of NE and 5-HT, via MAOa

Low TI; hypotension, sexual dysfunction, insomnia, OD sx's, Tyramine crisis, potentiates meperidine

Hepatotoxicity

Mechanism

Clinical Uses

Side Effects

Miscellaneous

Amitriptyline

Block reuptake of 5-HT and NE

Higher incidence of anticholinergic

Very low TI; OD can be fatal (treat symptoms); potentiate amphetamines (block reuptake); counter Guanethidine and Clonidine (HTN), and L-dopa due to delayed gastric emptying (antimuscarinic) Requires downregulation of autoreceptor 4 activity

Selective Serotonin Reuptake Inhibitors Fluoxetine (Prozac) Paroxetine Sertraline (Zoloft) escitalopram Atypical- Tricyclics duloxetine Bupropion Venlafaxine Drug/Class Drugs of Abuse Amphetamine Methamphetamine "speed" Caffeine Cocaine Ephedrine hydroxybutyrate Flunitrazepam Nicotine Ethanol Ketamine Lysergic acid diethyl-amide (LSD) Phencyclidine (PCP) Marijuana (THC) Growth Hormone Erythropoietin Increase in 5-HT activity Inhibit NMDA channels, block reuptake DA, NE G-protein receptor in CNS CNS depressant (GABA, Na, NMDA, 5-HT3???) Social Blocks DA reuptake (also NE) Beta 1, alpha, releases NE and DA Mechanism Clinical Uses Inhibits reuptake of NE and also for smoking 5-HT Block reuptake of 5-HT selectively

High TI (death only with combos)

Long T1/2 of metabolite (least CNS stimulation, sexual w/x sx) dysfunction; inhibition of P450 (esp. fluoxetine, paroxetine); Serotonin syndrome (esp. w/ MAOIs/meperidine)

Side Effects

Miscellaneous

CV, psychosis, lowered seizure threshold

Alcoholic hallucinosis (DT's), suppressed ADH

W/drawl CAN be fatal - CV collapse from ANS

NO withdrawl syndrome; chemically like 5-HT

Androgenic Hormones Barbituates Benzodiazepines Nalaxone Opiod Antagonist Methadone Opiods Meperidine

Anti-Hypertensive Drugs CHF Coronary Heart dz Arrhythmias Anti-anginal DIURETICS- excretion of Na and H20 Drug/Class Thiazide Diuretics Hydrochlorothiazide Chlorothiazide Indapamide Loop Diuretics (High-Ceiling)

1st line- Diuretics, b-blockers, ace inhibitors, Ca chnl blockers, and a-blockers. Others: lipid-lowering RAAs system, diuretic, cardiac glycosides, nitrates, ionotropic agents, b-blockers,lipid lowering sympth, RAAS, nitrates, ca chnl blockers, antithrombotic, lipid lowrering sympth,glycosides,ca chnl blockers, antithrombotic, antiarrhythmic organic nitrates, ca chnl blockers, b-blockers,

Mechanism "Breaking phenomenon " with all Na excretors

Clinical Uses Some allergies to sulfur in structure

Side Effects Passive Na exchange distally can --> K loss Caution with renal insufficiency, xerostomia Can --> hypokalemia, hyperuricemia, hypercalcemia, metabolic alkalosis, post HypoT, lichenoid Vasodilation following IV

Miscellaneous Increase LDL, TGs, and total cholesterol

Blocks NaCl symporter in early distal convoluted tubule

HTN (first-line), CHF, edema, nephrolithiasis, diabetes insipidus

Rapid onset, relatively short DOA, Also DECREASE Ca2+ in urine

increase NaCl excretion

Furosemide

Inhibit Na,K,Cl symporter in thick ascending limb

Edema, acute renal failure, hypercalcemia, chemical intoxication (increases excretion)

Hypovolemia, hypokalemia, hypocalcemia, hyperuricemia, Also INCREASE Ca2+ in urine ototoxicity (esp. E. acid), impaired platelet aggregation Weak diuretics, usually given with thiazides to prevent hypokalemia

Potassium-sparing Diuretics Amiloride Triamterene Spironolactone Eplerenone (more potent) Inhibit Na reabsorption in collecting duct and late distal convoluted tubule Aldosterone antagonist Aldosterone antagonist

CHF (3rd-line), cirrhosis w/ ascites, nephritic syndrome, o HTN, 1 aldosteronism

hyperkalemia, gynecomastia Lack of Na in cell to exchange prevents excretion of K (spiro), loss of libido, renal stones (Triam), gluc. Intolerance (Amil) RAAS system

Drug/Class Carbonic Anhydrase Inhibitors

Mechanism

Clinical Uses

Side Effects

Miscellaneous Minor diuretics

Acetazolamide

Prox. Tubule: Reversibly inhibit CA --> inhibit NaHCO3 reabsorption

Glaucoma (main), acute mountain sickness Increase GFR, reduce eye pressure (eye surgery) intracranial pressure (neurosurg.), cerebral edema, toxin excretion hyponatremia Clinical Uses decrease CO, HR

Fatigue, parasthesias, metabolic acidosis, hypokalemia, hyperglycemia

Rapid tolerance

Osmotic Diuretics Prox. Tubule: Osmotic pull of H2O Pharmacologically inert ADH (vasopressin) antagonist Drug/Class Beta-adrenergic Antagonists Propranolol Nadolol Metoprolol Atenolol Mechanism

Minor diuretics Fatal cellular dehyrdation (large doses), ionic imbalances Filtered at glomerulus, minimally reabsorbed prevents water reabsorption Side Effects Miscellaneous

Mannitol

Conivaptan

Reduce CO, and plasma renin activity; also inhibit presynaptic beta receptors, CNS effects, PNS effects

b1b2 HTN Bronchoconstriction (except with metoprolol) b1b2 b1 b1 post hypoT, receptor upregulation: neuronal blockers, beta adrenergic blockers decrease PR HTN, BPH

Labetalol

a1b1b2

Alpha-adrenergic Antagonists Prazosin Doxazosin Terazosin Inhibitors of Renin-Angiotensin System Captopril Lisinopril Enalapril Angiotensin Converting Enzyme (ACE) inhibitors Alpha-1 blocker

Non-peptide (orally active)

HTN, CHF, MI Valsartan Olmesartan Angiotensin II receptor antagonist

Renal failure (reversible), loss of taste, cough, allergy, angioedema, hyperkalemia, fetal malformatioin

HTN, CHF, MI

Renal failure (reversible), loss of taste, cough, allergy, angioedema, hyperkalemia, fetal malformatioin

Angiotensin II receptor antagonist Losartan Aliskiren Spironolactone Aldosterone antagonist Eplerenone Centrally-acting Drugs Clonidine alpha- Methyldopa Guanabez Other Agents: Neuronal Blocker Guanathidine Guanadrel Reserpine Drug/Class Vasodilators Diltiazem Nifedipine Verapamil Nitroglycerin (IV) Nitroprusside Minoxidil Activation of guanylyl cyclase --> inc. cGMP and NO Activation of ATP-sensitive K channels increase cGMP, NO direct effect, possible K agonist and inhibit Ca release blockade of PDE-5, cGMP stays increased K chnl activator Calcium channel blockerHTN, Arrythmias (slow negative inotropic, slow AV conduction through AV node, node, VD, block influx Ca DECREASE contractility) inhibits storage of NE in vesicles Mechanism Clinical Uses blocks release of stored NE HT increase GI, nasal congest, sedation, resp depression, sex dysfx, post hypoT Alpha-2 agonist: reduces sympathetics HTN, insomnia, opiate w/dx, Tourette's Preeclampsia HT Decreases LDL, and total cholesterol Renin Inhibitor hyperkalemia, gynecomastia (spiro), headache (epler)

K+ sparing diuretics

Side Effects

Miscellaneous

Combined therapy with diuretics & beta blockers to prevent adverse reflexes to vasodilators Reflex tachycardia may worsen heart condition, effects on AV conduction, hypoT, edema

Gingival Hyperplasia (also with phenytoin & cyclosporine) Avoid in those with conduction disturbances

Excessive dilation --> coronary artery dz, CHF, Raynaulds Hypotension, flushing, angina after w/drawal, HT emergencies, acute CHF methemoglobinemia HT Na retention, hypertrichosis

Releases nitric oxide, can cause cyanide accum.

Hydralazine

HT, CHF

Sildenafil Diazoxide Ionotropic Agents

Male Impotence

color vision

Digoxin

Inhibits Na/K ATPase -> lowered intracellular K, increased intracell Ca, increased release of Ach increaes Ca influx

CHF, Atrial flutter/fibrillation (slows conduction through AV node) CHF (IV) CHF (fixed, high grade coronary occlusion)

Nausea, vomiting, diarrhea, visual disturbances, various arrythmias Tachyarrythmias (NOT bradycardia)

Increases automaticity and conduction in atrial muscle; toxic levels can increase catecholamines Potent, but questionable efficacy Increases CO, and decreases VFP

Milrinone

Dobutamine

Beta 1 agonist

Anti-Arrythmic Drugs Drug/Class Class 1A Block membrane Na channels, slow Phase 0; ALSO block K channels, prolongs AP and ERP Atrial, AV junction, ventricular tachyarrys., including Wolff-ParkinsonWhite V.tach in those that cannot tolerate first two Hypotension, syncope (QT elongation) from Torsades de Pointes, cinchonism, SLE-like Sx Greater anti-muscarinic, ionotropic, Torsades IV; Anti-muscarinic effects can -> tachyarr. Oral; aggravates Myasthenia Gravis Mechanism Clinical Uses Side Effects Miscellaneous

Procainamide

Disopyramide Class 1B Lidocaine Phenytoin Class 1C Flecainide Class 3 Bretylium Amiodarone Sotalol

Block membrane Na channels, slow Phase 0

V.tach in depolarized tissues (ischemic, dig. toxicity), including WPW

CNS effects, respond to diazepam; Low Torsades, hepatotoxic

IV; ineffective in normal polarized (Aflutter, Afib)

Long-term Na blocker, increased threshhold

Decreased ionotropy, CHF, V.tach, Torsades

Oral; No anti-muscarinic Inc [] w/ Amiodarone

K channel blocker, prolongs Life-threatening V.tach (old) AP, ERP

nausea/vomiting with rapid IV

Painful parotid enlrgemnt, HTN in some Active metabolite, NOT reverse rate dependent Reverse rate dependent

Na block, K block, Ca block, SV/V.tach, also WPW (major Pulmonary fibrosis, corneal a/b block DOC) deposits, thyroid Beta blocker, increases AP & ERP in all tissues SV/V.tach Bradycardia, Torsades

Drugs that Alter Hemostasis Antiplatelet Drugs Acetylsalicylic acid (aspirin) Ibuprofen (and other NSAIDs) Dipyridamole Abciximab Ticlopidine Clopidogrel Inhibitors of Clotting Factor Synthesis Warfarin Sodium (coumarin) Inhibitors of Clotting Factors Hirudin leech 65aa inhibits 2a and 10a Anticoagulant - activates antithrombin III (& LPL), inhibits 2a and 10a Low molecular weight Heparin - inhibit factor Xa (less activation of antithrombin III) hemorrhage, low platelets, osteoporosis, thrombocytopenia, teratog, Reye's in kids Prevents carboxylation of Vitamin K - prevents synthesis of II, VII, IX, and X Bleeding, allergy;Contra in pregnancy, liver dx Oral; genetic variations in susceptibility metabolized CYP450 Irreversible inhibition of Cyclooxygenase Reversible inhibition of Cyclooxygenase Inhb phosphodiesterase -> increased cAMP Binds to IIb/IIIa adhesion molecule Platelet ADP receptor antagonist (irreversible) Anticoagulation, pain control, antipyretic Used in combination with aspirin During & after coronary artery procedures Anticoagulation in those who cannot tolerate aspirin Hemorrhage, thrombocytpenia TTP, neutropenia, less blood cells, increased LDL, VLDL (Clopidogrel less) Platelets may be more sensitive than vessel wall Potentiates PGI2, inhibts Adenosine uptake Monoclonal antibody

Dose dependent

Heparin

Also for asthma, growth factor, antiviral

Inhibits factors II, IX, X, and XII

Enoxaparin

Anticoagulation, DVT prophylaxis, PE

Less capacity to bind platelet, Higher bioavailability, longer plasma proteins, or half-life osteoblasts

Fibrinolytic Agents Altepase Antifibrinolytic Agents (Preserves clots) Tranexamic acid Pentoxifylline Drugs for Hyperlipidemia Nicotinic acid (niacin) Lovastatin Simvastatin Atorvastatin Ezetimibe (Zetia) Inhibits cholesterol absrp. (at brush border) Bile acid sequestrants prevent enterohepatic recirculation (LDL now used to make more) Activate peroxisome proliferators-activated receptor alpha (PPARs) Inhibit VLDL synthesis, induce LPL, inc. HDL Decrease triglycerides HMG CoA reductase inhibitors; prevents synthesis of cholesterol Overdose of fibrinolytic agents, stroke, hyphema (blood in ant. chamber of vascular dementia, prevents claudication, xanthine derivative obstructive arteries decreases rate of fibrinolysis increase HDL, decrease TAG & LDL Inhibits mobilization of free Inhibit VLDL synthesis, fatty acids (FFAs) induce LPL; inc. HDL Also: plaque stability, antiinflam., sepsis, stroke, osteoporosis, arthritis, DM, dementia, MS, transplants, kidney dz, cancer, blindness Often used with statin Gastric probs, Diabetes, mylgia, rhabd., flushing Hepatitis, myalgia, rhabdomyolysis (esp. with niacin); slight increase in [warfarin] Gall stones? Inc. hepatic enzymes; hedche, URIs 100% bioavailability plasminogen activator Dissolution of formed clots, evolving MI

Lovastatin - prodrug/crosses BBB All increase hepatic LDL receptors; eliminated via CYP3A4 (big 1st pass) Eliminated via glucoronidation

Cholestyramine

Rash, fecal impaction, Increase hepatic LDL constipation Can receptors (need cholesterol to also bind drugs or vitamins -make new bile acids) > deficiency Allergy, RBC def., myalgia, rhabdo. (esp with HMG-CoA inhib. & niacin) Fibrates (fibric acid derivatives)

Gemfibrozil Clofibrate

PGE2 and PGI2 TXA2 and PGF2a

Vasodilation, Bronchodilation, DEC platelet agg, INC renal blood flow, GI (dec acid, inc HCO3&mucus) Vasoconstriction, Bronchoconstriction, INC platelet agg (TXA2)

Histamine

Constricts Bronchi (H1) Constricts Gut (H1) Inc Gastric Acid (H2) Vascular dilation (H1,2)

CNS neurotransmitter (H1 and H2) Nerve endings (Pain, itch) (H1) BP drop (H1 rapid, H2 slow effect)

Drug/Class 1st Gen. Antihistamines Diphenhydramine (Benadryl) Dimenhydrinate (Dramamine) Chlorpheniramine (Chlor-Trimeton) 2nd Gen. Antihistamines Fexofenadine (Allegra)

Mechanism

Clinical Uses

Side Effects

Miscellaneous

Block H1

Minor Allergic reactions (edema, rash, itch), Allergic rhinitis (hayfever, hives), Motion sickness, Sedative OTC

CNS effects: Sedation, Antitussive, Dec motion sickness (antiAch?), dryness

Contraindicated in asthma due to drying effect on lungs

Block H1

Minor Allergic reactions (edema, rash, itch), Allergic rhinitis

Little/NO sedation

Do NOT cross BBB (NO CNS) NOT antiAch NO motion sickness help

Loratadine (Claritin) Cetirizine (Zyrtec) H2 Receptor Antagonists Cimetidine (Tagamet) Ranitidine (Zantac) Famotidine (Pepcid) Nizatidine (Axid) Classification of NSAIDS

Block H1

Minor Allergic reactions (edema, rash, itch), Allergic rhinitis

Little/NO sedation

Do NOT cross BBB (NO CNS) NOT antiAch NO motion sickness help

Block H2 - Decrease gastric acid secretion (volume and acidity)

GERD, Ulcers

Drug/Class

Mechanism

Clinical Uses

Side Effects

Miscellaneous

Salicylates (Aspirin, etc)

Inhibit COX - ASA irrev. All others reversibly... Blocks TXA2 required for platelet aggregation

Fever, headache, myalgia, neuralgia, dysmenorrhea, osteoarth., rheumatoid, prophylaxis for heart, Gout (high dose)

Cleared by conjugation - Low dose (1st order) High dose (0 order); High dose -> uncouples oxidative phosphorylation > Hyperventilation and respiratory alkalosis; dose can -> acidosis; Gastric bleeding (->Fe def?), GI probs, Ulcers?, Salicylism: tinnitus, hache, N/V, dizzy, vision High frequency hearing loss (reversible), Lipooxygenase activation may -> Hypersensitivity (asthma/nasal polyps) Also Reye's syndrome (w/ viral infxn)

Methyl salicylate (Ben-Gay) Salicylic acid Keratolytic

Topical use only Acne, seborrhea, warts Little/NO anti-inflammatory, Low GI, No effect bleeding/resp Not uricosuric Hepatic necrosis (esp. EtOH, fasting) Renal tubular necrosis

Acetominophen

Weak inhibitor of COX

Analgesic, Antipyretic

NOT an NSAID Peroxides->Inactive Can affect ASA binding Greater effect in CNS? Free radical metabolite

Celecoxib (Celebrex) Rofecoxib (Vioxx)

Selective COX-2 Inhibitors (reversible) (Little effect on COX1)

Osteoarthritis, Acute pain, Menstrual pain Same as ASA (better for dysmenorrhea) Intractable fever (Hodgkins), ankylosing spond., OA, RA, GoutA close patent ductus Short-term analgesic (compare opioids, etc) Clinical Uses

Gastric bleeding? Heart attacks, Stroke GI (N/V), CNS - dizzy, headache, etc. Frontal headache, GI ulcers, blood loss

Contains Sulfa

Ibuprofen, naproxen, fenprofen, flurbiprofen COX inhibitor (NSAID) COX inhibitor (Most potent one)

Cross sensitive ASA Naproxen - long acting Sulindac - prodrug with less toxicity Contraindicated: Ulcers Pregnancy, Psychiatric Only IM NSAID evidence of abuse Miscellaneous Poor entry to CNS May also block PG receptors Long T1/2 No

Indomethacin

Ketorolac Drug/Class Diflunisal Meclofenamate Piroxicam Anti-Gout Drugs NSAIDs (NOT ASA) Colchicine Allopurinol Probenecid (and other "-cams")

COX inhibitor Mechanism

Hepatic, renal toxicity Side Effects NO antipyretic

COX inhibitors (NSAIDs)

Tx: Reduce inflam/production of uric acid; increase excretion Decrease pain/inflammation, Dec phagocytosis of urate crystals -> more excreted Binds to tubulin, inhibits polymerization Inhibits Xanthine Oxids Reduces uric acid syn. Weak organic acids increase excretion of UA Acute Gout (1st line) - 1224hrs till effect Chronic Gout (often in combo to start) Compete w/UA for transport (reabsorption) Initial Tx, or sub. for Colchicine Diarrhea, N/V Uncommon Indomethacin most common Reduces leukocyte migration/inflammation Prolongs T1/2 of 6mercaptopurine Contains Sulfa

Drugs for Asthma and other Inflammatory Pulmonary Diseases Beclomethasone Triamcinolone Drug/Class Adrenocorticosteroids Decreases inflam. and secretions/mucus/ cytokines; increases B receptors in lungs Mechanism Clinical Uses Systemic: Adrenal sup, Growth retard, Osteo, Cataracts, Blood changes, Weight gain, HTN Side Effects Side effects much less with aerosol route and alternateday method Miscellaneous

Theophylline phenyl & psuedophrine Albuterol Salmeterol Fluticasone Cromolyn Sodium Guaifenisin Acetylcysteine Zarfirlukast Montelukast Zileuton

Methylxanthines - PDE action, Ca action, Catecholamines, endogenus B-adrenergic agonists - 1) Relax bronchial SM 2) Stimulate mucocilia 3) Dec. SM hypertrophy 4) Inhibit inflam. cells

Reduce LT actions, Dilates, Inc work able, CNS stimulant, diuretic

GI upset, anxiety, arrhythmias, seizures Most cardiac effects

Anti-inflammatory effects via effects on eosinophils

Asthma, Bronchitis, Emphysema (more effective in COPD)

Least cardiac effects, Tremor

(more B2 selective)

Inhibits cellular actvaton (Cl channels)

Mast cell stabilizer, inhibits cough

Inhibits eosinophil infiltration

Splits disulfide bonds less viscosity Leukotriene receptor Antagonist (nonspecific)

->

Bronchitis, COPD, Acetominophen OD Food decreases bioavailability

Increase theophylline and warfarin Met. by CYP2C9,3A4

5-lipooxygenase inhibitor

Headache, hep. toxic Dyspepsia

Drugs for Gastrointestinal Disorders Peptic-acid Disorders & GERD: H2 antag, PPI, AB, & Adjunctive Omeprazole (Prilosec) Lansoprazole (Prevacid) Rabeprazole Esomeprazole Cimetidine (Tagamet) Ranitidine (Zantac) Misoprostol Sucralfate H2-receptor antagonists (usually combo with antibiotics for H.pylori ) PGE1 analog - Decreases cAMP not clear Reacts w/ HCl -> (increase mucous and bicarb prod) salicylate; H.pyloricidal Antispasmodic (anticholinergic) AB: H.plyori Headache, dizziness, GI, low sperm, gynecomstia, menstrual, halluc, agitation, apnea, renal failure Lacks the hormonal adverse effects Diarrhea, N/V, uterotonic -> abortion Rare; may impair absorption of others Black stool/tongue Uses EP3 recps, gastrin mucus/HCO3 secretion NOT in combo with antacids/indomethacin (Pepto-Bismol) decrease TTC, salicylate hypersenstivity contra: pregos Inhibits CYP450 Proton-pump inhibitors (PPIs): inhibit gastric acid secretion via H/K ATPase, decrease volume gastric juices Zollinger-Ellison syndrome DOC*, GERD N/V diarrhea,rash, somnolence

Inhibit CYP450

GERD

Prevent ulcer

Mucosal protection for chronic NSAIDs Mucosal Protection, ulcer short-term Ulcer, mucosal protection

Bismuth Subsalicylate

Glycopyrrolate Amoxicillin, TTC, Clarithromycin, Metronidazole

decrease motility, parastalsis before surgery, IBS

Ulcer

Ohters: promility drugs, Slt-T4 musc. Agonist, Ach inhibitors, D2 blockers (antipsych) PARATHYROID & THYROID DRUGS Drug/Class Levothyroxine Liothyronine Liotrix calcitrol vitamin A hormone, increase Ca and PO4 Hypoparathyroidism Hyperparathyroidism; pagets, Vit D toxicity, hypercalcemia from malginancy or pregnancy, post-men osteoporosis destroys gland inhibit thyroid peroxidase to decrease hormone production and peripheral conversion T4-T3 inhibit iodide uptake Hyperthyroidism- Goiter (Grave's) hypothroidism rashes, loss of taste, parathesia, agranulocytosis Prego, infections, bone marrow depression CI: pregos Replacement hormone therapy Hypothyroidism- iodine deficiency, Hashimoto (AI) Tachy, palpations, dysrhythmias, caridac arrest, insomnia Mechanism Clinical Uses Side Effects Miscellaneous

calcitonin

Radioactive Iodine propylthiouracil methimazole SCN-, ClO4DIABETES INSULIN Drug/Class Lispro-ultraset Aspart Glulisine Semilente Regular Insulin Lente Isophane NPH Ultralente Glargine

Mechanism

Clinical Uses

Side Effects

Miscellaneous

ORAL HYPOGLYCEMICS/ANTIHYPERGLYCEMIA Drug/Class Tolbutamide Acteohexamide Glyburide Glimepiride Repaglinide Mechanism Clinical Uses Side Effects Miscellaneous

Nateglinide Metformin Acarbose Miglitol Pioglitazone Rosiglitazone Sitagliptin phosphate sitagliptin and metformin exenatide pramlintide acetase Adrenal Drugs/Hormones Hydrocortisol (cortisol) Dexamethasone Prednisolone Synthetic glucocorticoids Prednisone Triamcinolone Fludrocortisone Aldosterone spirolactone Drug/Class Gonadal Drugs/Hormones Tamoxifen Raloxifene Clomiphene Fulvestran Anastrozole Exemestane Letrozole Bicalutamide Finasteride Flutamide ethinyl ester estrone estradiol Mifepristone Progesterone Norethidrone Norethidrone acetate Norgestrel Medroxyprogesterone Testosterone Methyltestosterone fluoxymesterone Pancreatic Drugs/Hormones Insulin Lispro Sulfonylureas Repaglinide (1o) (Glyburide) Recombinant insulin Act on K+ channel to make B cell release insulin Disulfiram-like rxn Type II diabetes Hypoglycemia, Drug interactions (EtOH) Short-acting; target postprandial glucose spikes (RU-486) Binds to glucocorticoid, progesterone receptors Cushing Syn., Postcoital contraceptive Antagonist anti-androgen Blocks 5alpha-reductase Androgen receptor antagonist Prostate cancer Aromatase inhibitors Selective estrogen receptor modulator Selective estrogen receptor modulator Ovulating inducing agent SERD Breast cancer Binds to receptor Acts only on bone receptors (not others) aldosterone antagonist Mechanism Clinical Uses Side Effects Miscellaneous Synthetic mineralocorticoid 20x more mineralC. vs. glucoC. effects Converted to Prednisolone Glucocorticoid Mostly Non-adrenal Many uses (Hypofxn=Addison's, fetal lung maturation) Acts like cortisol Cannot bind to aldosterone receptor due to actions of 11betaHSD-2 --> cortisone (inactive) Adrenal suppression (must taper drugs when discontinuing), hyperglycemia, hypertension/Na retention, edema, Iatrogenic Cushings

Intermediate-acting

Hypoglycemia, Drug interactions (EtOH) Biguanides (1 ) (Metformin)

o

Decrease gluconeo-genesis, increase usage Reduces peripheral insulin resistance Glucosidase inhibitor reduces uptake frm gut

Mainly Type II (if no hepatic/renal disease) P450 inducer, edema, volume expansion Flatulence

Glucose enters SM and adipocytes Activated PPAR-gamma

Thiazolidinediones (TZD) (Pioglitazone) Acarbose Osteoporosis Drug/Class Calcium acetate,carbate,citrate,glubionate Vitamin D3 calcitriol paricalcital teriparatide Raloxifene hormone replacement therapy alendronate ibandronate pamidronate disodium zoledronic acid denosumab

Mechanism

Clinical Uses

Side Effects

Miscellaneous

ANTIBIOTICS Drug/Class Mechanism beta-lactam ring NS; inhibit transpeptidase, cw synthesis= cidal g+,g-cocci,non-beta lactamase anaerobes acid-stable, oral infect Clinical Uses Side Effects Miscellaneous synergistic with aminoglycosides

Penicillins and classification Penicillin G (PENTIDS, PFIZERPEN) Penicillin V (PEN-VEE K, VEETIDS, V-CILLIN) Oxacillin (BACOCIL) Nafcillin (NALLPEN) Dicloxacillin (DYNAPEN) Ampicillin (PRINCIPEN) Amoxicillin (MOXIL< POLYMOX< TRIMOX)

Resistant, NS

staph aures

pseudomemb colitis prophylaxis- 2g 1 hr po extended BS, g-rods mixed infection, dont give to those with renal impairment

Ampicillin Sulbactm (UNASYN) Amoxicillin clavulanate (AUGMENTIN) Ticarcillin (TICAR) Piperacillin (PIPRACIL)
extended BS pseudomonas,enterobacter, indole, proteus

Ticarcillin clavulnate (TIMENTIN) Piperacillin tazobactam (ZOSYN) Cephalosporins Cephalexin (KEFLEX, KEFLET) Cefazolin ( ANCEF, KEFZOL) Cefaclor (CECLOR) Cefoxitin (MEFOXIN) Ceftriaxone (ROCEPHIN) Cefepime (MAXIPIME) Aztreonam (AZACTAM) Imipenem-cilastin (PRIMAXIN) Vancomycin (VANOCIN, VANCOLED) Bacitracin (BACIGUENT, AK-TRACIN) Macrolides Erythromycin Erythromycin + sulfisoxazole (PEDIAMYCIN, ERYZOLE) Azithromycin (ZITHROMAX, Z-PAC) Clarithromycin (BIAXIN) Clindomycin (CLEOCIN)
metronidazole inhibits translocation of tRNA, inhibits aa synths (50s) diarrhea, pseudom colitis 3rd generation, increase g4th generation,bs impinem atypica b-lactam peptidoglycan precursor, inhibits transglycosylase in cw synth inhibits bactoprenol in cw synth translocation of ribo aa synth (50s) BS inhibits cyp450 penetrate tissue well; csf fluid increase b-lactamase resistance b-lactam aerobic g-rod, pseudomonas, resistant to b-lactamase 2nd generation increase ginhibit transpeptidase, cw synthesis= cidal 1st generation g-

Tetracyclines (5) Tetracycline (ACHROMYCIN, SUMYCIN) Doxycycline (DORYX) Doxycycline Ca+2 (VIBRAMYCIN) Minocycline (MINOCIN) Tigecycline (TYAGEL) Aminoglycosides Streptomycin Amikacin (AMIKIN) Gentamicin (GARAMYCIN, G-MYTICIN) Kanamycin (KANTREX) Tobramycin (NEBCIN)

Drug/Class

Mechanism

Clinical Uses

Side Effects

Miscellaneous

Sulfonamides and Trimethoprim Sulfamethoxazole (GANTANOL) Sulfadiazine Mafenide (SULFAMYLON) Trimethoprim (PROTOPRIM, TRIMPEX) Sulfamethaoxazole+trimethoprim (BACTIM, SEPTRA etc) Fluoroquinolones (5) Ciprofloxacin (CIPRO) Levofloxacin (LEVAQUIN) Norfloxin (NOROXIN) Ofloxacin (FLOXIN) Nitrofurantoin (MACROBID, MACRODANTIN) Nitrofurazone (FURACIN) Polymyxin B Polymyxin E (COLISTIN) Chloramphenicol (CHLOROMYCETIN) Quinupristin dalfopristin (SYNERCID) Lenizolid (ZYVOX) Anti TB drugs Isoniazid Rifamycins Rifampin (RIMACTANE) Rifabutin (MYCOBUTIN) Pyrazinamide Ethambutol (MYAMBUTOL) CIPRO and strptomycins are 2nd line for TB TB treatment Mycobacterium Avium (MAC) Dapsone Clofazamin (LAMPRENE) Polyenes Amphotericin B (FUNGIZONE) Liposomal mphoericin (AMBISOME) Nystatin (MYCOSTATIN, NYSTEX, NILSTAT) Azoles (4) Ketoconazole (NIZORAL) Fluconazole (DIFLUCAN) Itraconazole (SPORANOX) Miconazole (MONISTAT, LOTRIMIN) Terbinafine (LAMISIL) Caspofungin (CANCIDAS) Micafungin (MYCAMINE) Flucytosine or 5-fluorocytosine (ANCOBON) Griseofulvin (GRIFULVIN)
inhibits transferase in aa synth (50s) ihibits attachment of tRNA to site (50s) MRSA, vancomycin RSA b.marrow, CNS toxic, aplastic inhibits cyp450 anemia, gray baby syndrom inhibits cyp450 ihibits DNA gyrase + topiosomerase for transcription aerobes, g+/kids-tendon rupture

Drug/Class

Mechanism

Clinical Uses

Side Effects

Miscellaneous

Antivirals (11) Acyclovir (ZOVIRAX) Ganciclovir (CYTOVENE) Foscarnet (FOSCAVIR) Docanosol (ABREVA) Enfuvirtide (FUZEON) Zidovudine (AZT, RETROVIR) Efavirapine (VIRAMUNE) Ritonavir (NORVIR) Amantadine (SYMMETREL) Oseltamivir (TAMIFLU) Ribaverin (REBETOL)
Drug/Class Mechanism Clinical Uses Side Effects Miscellaneous

Antiparasitics Quinine Quinidine Metronidazole (FLAGYL)

Drug/Class Mechanism Clinical Uses Side Effects Miscellaneous

Immunosuppressants (10) Azathioprine (AZA) Methotrexate (MTX) Mycophenolic Acid (MPA) Mycophenolate Mofetil (MMF, CELLCEPT) prednisone hydrocortisone Cyclophosphamide (CYTOXAN) Cyclosporine (SANDIMMUNE, NEORAL) Tacrolimus (PROGRAF) Sirolimus RAPAMMUNE muromonab-CD3 (ORTHOCLONE-OKT3
Drug/Class Mechanism Clinical Uses Side Effects Miscellaneous

Antineoplastic Agents (12) imatinib (GLEEVAC) Vincristine (ONCOVIN) Paclitaxel (TAXOL) Doxorubicin (ADRIAMYCIN) Tamoxifen (NOLVADEX) Flutamide (EULEXIN) bevacizumab ( AVASTIN) cetuximab (ERBITUX) Erythropoietin (EPOGEN, PROCRIT) Filgrastim (NEUPOGEN) Sargramostim (LEUKINE) Ondansetron (ZOFRAN)

nytoin & cyclosporine)

ease TTC, salicylate hypersenstivity