Flashcards 2

Gabapentin Midazolam (Neurontin )

(Versed)

Valproic acid (Valproate)

Carbamazepine

(Tegretol, Carbatrol)

Thiopental Lamotrigine (Pentoth (Lamictal)

Lithium

al)

Atenolol

(Tenormin)

Ergot alkaloids

Methyldopa

Benzodiazepine Intravenous Anesthetic Increases GABAA receptor activity

Anticonvulsant that enhances concentration of presynaptic GABA but molecular target unk. For burning, shooting, stabbing neuropathic pain (esp. postherpetic Slow onset and recovery (Flumazenil reverses effects) neuralgia) & partial seizures Lipid-soluble at physiological pH & can readily cross BBB Minimal adverse effects (drowsiness, tolerance develops Not used to achieve deep sedation usually because prolongs recovery w/in days, sedation induced at high doses) & amnesia Newer drug: simple partial, complex partial, & partial w/ 2ndarily Used in balanced anesthesia & conscious sedation; generalized cardiovascular stability; marked amnesia

Anticonvulsant that inhibits voltage-gated Na channels For shooting, stabbing neuropathic pain, seizures & mood-stabilization with little sedative activity May potentiate GABA-A receptors, stabilizes inactive form of Na channel Side effect: Aplastic anemia (rare but potentially fatal), diplopia & ataxia are common, leukopenia (not usu. clinically significant Conventional Drug: simple partial, complex partial, partial w/ 2ndarily generalized, & tonic-clonic seizures

Anticonvulsant that inhibits voltage-gated Na channels For shooting, stabbing neuropathic pain, seizures, migraine prophylaxis & mood-stabilization with little sedative activity Multi. mechanisms of action that include Na channel inhibition, increase in presynaptic GABA, & inhib. Ca voltage-gated channels in thalamus Side effects : nausea, epigastric distress, liver toxicity Inhibits metabolism of phenytoin Conventional Drug: simple partial, complex partial, partial w/ 2ndarily generalized, absence, myoclonic & tonic-clonic seizures

Barbiturate Intravenous Anesthetic Anticonvulsant that inhibits voltage-gated Na channels Rapid onset and rapid recovery (bolus dose) – Also used as mood-stabilizing drug slow recovery following infusion Inhibits Na channel & voltage-gated Ca channels in thalamus Preanesthetic; standard induction agent; cardiovascular depression; Approved as adjunct for partial seizures in pts. >16yo marked sedation during minor surgical Little sedative activity, but dizziness & headache common procedures avoid in porphyrias Side effect: Stevens-Johnson syndrome/toxic epidermal necrolysis Highly lipid soluble (rapid recovery due to redistrib to fat) (2% of children <16yo; occurs in adults too but rare), rash is common Dose-depend. arterial BP, SV, & CO due to myocardial depression Newer drug: simple partial, complex partial, partial w/ 2ndarily & increase venous capacitance, no major generalized, absence, myoclonic, & tonic-clonic changes in SVR, no increase in intracranial pressure

β1 receptor antagonist - Cardioselective (β 1>>> β 2) Mood Stabilizer & ADH Antagonist Low lipid solubility & metabolized very little by liver; eliminated by Stabilizes mood swings in manic depressive. Depresses NA or 5HT kidneys transmission by formation of IP3 & DAG. Elim by kidney (Na Rx: hypertension, angina excretion opposite of Li excretion) Adverse effects: myocardial contractility, bradyarrhythmias, Narrow TI w/ side effects: GI irritation, edema, bronchospasms, prolong hypoglycemia in pts taking insulin, muscular weakness, tremors, ataxia, drowsiness, triglycerides, HDL-cholesterol, fatigue, sleep disturbance, muscle rigidity, cardiac arrhythmias, seizures, coma, mild depression, hypertensive response in some situations nephrogenic diabetes insipidus, nontoxic goiter (pheochromocytoma), sudden withdrawal – exacerbation of angina Drug Interactions: Diuretics (esp. thiazides) & NSAIDS esp if MI has occurred (increase reabsorption) NSAIDS may reduce BP lowering effect

α2 receptor agonist (prodrug) & Antihypertensive agent Prodrug converted to active agent (α-CH3-NE) in CNS Partial α agonists α-CH3-NE is selective α2 receptor agonist, which decreases sympathetic outflow from CNS Group of compounds w/ mixed α partial agonist & antagonist actions Oral & iv administration at adrenergic receptors & agonist at 5HT receptors Adverse effects: Sedation (esp. during initial), some pts have Produced from fungal contamination of grains persistent mental concentration, depression, or extrapyramidal Previously used in treatment of migraines signs, dry mouth, orthostatic hypotension (esp. in vol. depleted pts), Chronic use assoc. w/ cardiac valvular lesions & retroperitoneal hepatic fxn abnl (uncommon allergic like rxn- can be serious), + fibrosis Coombs test (hemolytic anemia)

Guanethidine Diazepam (Ismelin (Valium)

)

Labetalol Carvedilol (Trandate (Coreg)

)

Diazoxide Clozapine (Proglycem-oral; Hyperstat IV)

Propranolol

(Clozaril)

Aripiprazole

(Indera l)

(Abilify )

Prazosin Cyproheptadine (Minip ress)

Sympatholytic Slow depletion of NE from nerve terminals, which results in decreased release of catecholamines No CNS activity Oral administration Rx: severe hypertension Adverse effects: Orthostatic hypotension

Long acting benzodiazepine sedative-hypnotic Anxiolytic & Centrally-acting muscle relaxant Increases release of GABA in CNS Rapid onset of action Used for acute anxiety, marked sedation during minor surgical procedures, epilepsy, status epilepticus

Some drugs (ex. TCAs) block the transport into nerve endings resulting in blockade or reversal of antihypertensive effect

Mixed β>α1 receptor antagonist & Antihypertensive agent Mixed β>α1 receptor antagonist & Antihypertensive agent Has intrinsic sympathomimetic activity, local anesthetic effect, & High lipid solubility & metabolized by liver & kidneys moderate lipid solubility Rx: HTN & heart failure in certain pts Metabolized by liver (1st pass effect) Adverse effects: myocardial contractility, bradyarrhythmias, Adverse effects: myocardial contractility, bradyarrhythmias, bronchospasms, prolong hypoglycemia in pts taking insulin, fatigue, bronchospasms, prolong hypoglycemia in pts taking insulin, sleep disturbance, depression, hypertensive response in some triglycerides, HDL-cholesterol, fatigue, sleep disturbance, situations (pheochromocytoma), hepatotoxicity, sudden withdrawal – depression, hypertensive response in some situations exacerbation of angina esp if (pheochromocytoma), sudden withdrawal – exacerbation of angina MI has occurred esp if MI has occurred NSAIDS may reduce BP lowering effect NSAIDS may reduce BP lowering effect

Atypical Antipsychotic Acts peripherally by opening K+ channels Blocks 5HT2 receptors > D2 receptors. Also blocks D4 receptors, Parenteral arteriolar dilator that has been used in hypertensive 5HT1C, 5HT2A, α1, Muscarinic, & Histamine emergencies (Admin. mini-bolus via iv; duration ~4-12 hrs) Effective in individuals suffering from disorganization, loose BP w/ reflex sympathetic stim & elim by hepatic associations, inappropriate affect, incoherence & reduction in metabolism & urinary excretion of unchanged drug rational thought processes & relieves many negative symptoms. Less Adverse effects: Excessive lowering of BP, angina, ischemic ECG extrapyramidal side effects changes, heart failure in pts w/ ischemic heart dz, fluid retention, st Causes agranulocytosis (req. weekly blood tests for 1 4-5 mths. & hyperglycemia. CI in hypertensive encephal. monthly thereafter), sedation, hypotension, tachycardia, fever, salivation, dizziness, & weight gain

Atypical Antipsychotic Partial agonist at D2 (antagonist at postsynaptic & weak agonist at presynaptic) & 5-HT1A receptors & antagonist at 5-HT2A receptor. Also D3, D4, 5-HT2C, 5-HT7, α 1, H1 receptors Appears to be activation of receptor in states of low dopaminergic tone & inhibition at high tone Has higher affinity for 5-HT1A * 5-HT2A receptors than D2 receptors Side effects: Orthostatic hypotension & somnolence

Nonselective (β 1~ β 2) β receptor antagonist HR & contractility CO; renal renin release; CNS effects not major mech (although used for stage fright) Produces local anesthetic, high lipid sol., & metabol by liver Adverse effects: myocardial contractility, bradyarrhythmias, bronchospasms, prolong hypoglycemia in pts taking insulin, Triglycerides, HDL-cholesterol, fatigue, sleep disturbance, depression, hypertensive response in some situations (pheochromocytoma), sudden withdrawal –exacerbation of angina esp if MI has occurred NSAIDS may BP lowering effect

α1 adrenergic receptor antagonist & Antihypertensive agent Dilates arterioles & veins; NE can still act on presynaptic a2 neurons to do neg. feedback on NE release (may explain less reflex tachycardia than phentolamine) Oral admin. & mainly eliminated by liver Rx: HTN, BPH Adverse effects: First dose phenomenon – symptomatic orthostatic hypotension w/ syncope possible (min. by starting low dose at bedtime); dizziness; headache

Antagonist of 5HT2, 5HT2, and H1 receptors Reduces GI mobility in pts w/ severe post-gastrectomy dumping syndrome & antihistamine that has some anticholinergic activity, moderate sedation

Ziprasidone Risperidone (Geodo (Risperdal)

Quetiapine

n)

Olanzapine

(Seroqu

(Zyprex

el)

a)

Clonidine

Reserpine

(Catapres

(Serpasil

)

)

Metoprolol

Terazosin

(Lopressor, Toprol XL)

(Hytri n)

Phenoxybenzamine Phentolamine (Dibenzyline (Rogitine)

)

Atypical Antipsychotic

Atypical Antipsychotic

Unlikely to cause weight gain or raise prolactin, but may increase QT interval & has been assoc w/ cardiac arrhythmias

Recommended for pts experiencing 1st episode of schizophrenia, where negative symptoms predominate Potent blocker of D2 & 5-HT2a receptors As effective as haloperidol in reducing positive symptoms but w/out extrapyramidal effects at low doses

Considered 2nd line drug

Atypical Antipsychotic Potent 5-HT2 receptor antagonism with moderate D2 receptor antagonism. Also 5HT1a, D1, H1, α1 and α 2. No cholinergic & Exhibits higher affinity for D2 receptors and lower benzodiazepine receptor activity for 5-HT2a receptors, blocks acetylcholine Improves positive & potentially negative symptoms of schizophrenia No extrapyramidal side effects at a level equivalent to haloperidol w/out producing extrapyramidal Improves both positive & negative symptoms. Similar to clozapine side effects or persistent elevation of serum prolactin. No assoc. w/ but doesn’t cause agranulocytosis agranulocytosis. May have orthostatic hypotension or somnolence. Significant risk of excessive weight gain & type 2 diabetes Effective as monotherapy for bipolar mania & may be combined w/ standard mood stabilizers Atypical Antipsychotic

Inhibits transport of monoamine transmitters into synaptic vesicles, which causes depletion of synaptic vesicle monoamine stores sympatholytic effects Crosses BBB CNS depression Has peripheral & central actions Oral or iv administration Rx: HTN Adverse effects: Sedation, depression

α1 adrenergic receptor antagonist & Antihypertensive agent

Selective α2-receptor agonist that acts in the brain Decrease sympathetic outflow to the peripheral NS & interacts w/ imidazoline receptors in CNS, which may contribute to BP lowering effect Oral, transdermal preparations, & iv (get initial pressor response after iv due to α -receptors in arterioles) Adverse effects: Sedation, depression, dry mouth, orthostatic hypotension, and if sudden withdrawal can get rebound hypertension, HR, sweating, headache, hypertensive crisis

β1 receptor antagonist - Cardioselective (β 1>>> β 2)

Produces local anesthetic effect, has moderate lipid solubility, & Dilates arterioles & veins; NE can still act on presynaptic a2 neurons metabolized by liver to do neg. feedback on NE release (may explain less reflex Adverse effects: myocardial contractility, bradyarrhythmias, tachycardia than phentolamine) bronchospasms, prolong hypoglycemia in pts taking insulin, Oral admin. & mainly eliminated by liver triglycerides, HDL-cholesterol, fatigue, sleep disturbance, Rx: HTN, BPH depression, hypertensive response in some situations Adverse effects: First dose phenomenon – symptomatic orthostatic (pheochromocytoma), sudden withdrawal – exacerbation of angina hypotension w/ syncope possible (min. by starting low dose at esp if MI has occurred bedtime); dizziness; headache NSAIDS may reduce BP lowering effect Longer acting than prazosin

α receptor antagonist α receptor antagonist prodrug Long-acting irreversible (suicide) inhibitor Treatment of pheochromocytoma

Nonselective (α1~ α2) Presynaptic & postsynaptic antagonist Competes with NE so decreases total peripheral resistance & venous return to heart Rx: HTN

Flurazepam

Paraldehyde

(Dalmane)

Doxazosin

Zolpidem

(Cardura)

(Ambien)

Zaleplon Phenobarbital (Sonata )

(Luminal)

Temazepam

Triazolam

(Restoril)

(Ativan)

Amobarbital Chlordiazepoxide (Amytal (Librium)

Sodium)

Long acting benzodiazepine sedative-hypnotic T1/2 = 50-100 hrs Marketed primarily for treatment of insomnia

Non-barbiturate sedative-hypnotic Formerly used in alcohol withdrawal Characteristic disagreeable odor

α1 adrenergic receptor antagonist & Antihypertensive agent Novel Benzodiazepine-Receptor Agonist

Dilates arterioles & veins; NE can still act on presynaptic a2 neurons to do neg. feedback on NE release (may explain less reflex Hypnotic Agents tachycardia than phentolamine) Low tolerance & dependence Oral admin. & mainly eliminated by liver Assumed to bind to GABA subtype Rx: HTN, BPH May have stimulating effect in elderly when used for insomnia, but Adverse effects: First dose phenomenon – symptomatic orthostatic less residual mental impairment & less abuse potential hypotension w/ syncope possible (min. by starting low dose at bedtime); dizziness; headache Longer acting than prazosin

Long acting barbiturate sedative-hypnotic Novel Benzodiazepine-Receptor Agonist Enhances GABA-mediated Cl flux Prominent sedative activity (usu. not at anti-seizure dose) Hypnotic Agents Used in management of seizure disorders (1st line drug; highly Low tolerance & dependence effective against partial & generalized) & daytime sedation in severe Assumed to bind to GABA subtype anxiety states May have stimulating effect in elderly when used for insomnia, but Rare fatal toxic epidermolysis bullosum from hypersensitivity less residual mental impairment & less abuse potential Conventional drug: Partial w/ 2ndarily generalized & tonic-clonic

Short acting benzodiazepine sedative-hypnotic

Intermediate acting benzodiazepine sedative-hypnotic

T1/2= 2-6 Marketed primarily for treatment of insomnia

T1/1 – 10-2 hrs Marketed primarily for treatment of insomnia

Short-intermediate acting barbiturate sedative-hypnotic

Long acting benzodiazepine sedative-hypnotic

(3-6 hrs)

(>6hours)

Levetiracetam

Ethosuximide

(Keppra

(Zaronti

)

n)

Phenytoin

Effects of Barbiturates

(Dilantin)

Zonisamide

Barbiturates

(Zonegran)

Tiagabine

Topiramate

(Gabitril)

Primidone

(Topamax)

Felbamate

(Mysoli ne)

(Felbato l)

Anticonvulsant with unk. Mech. Anticonvulsant that blocks voltage-gated channels in thalamus only (ONLY drug known to act exclusively this way) Highly effect & well-tolerated (side effect mild epigastric distress) Conventional Drug & 1st line for absence seizures

Used as adjunct against partial seizures Sedation & dizziness may occur Newer drug: simple partial, complex partial, & partial w/ 2ndarily generalized

Anticonvulsant that inhibits voltage-gated Na channels Reversibly depress all excitable tissues but CNS most sens (esp. Depolarization inhib. b/c voltage-gated Na channel retic. activating sys. in brain stem & limbic system) partially closed Side effects: Nystagmus, frank Induces tolerance & addiction, hepatic P450 enzymes, all levels CNS diplopia (req. dose reduction), hirsutism, gingival depression, low TI, rxn to pain, depresses auto. ganglia & NMJ, hyperplasia, facial coarsening w/ long-term use, fetal hydantoin resp. neurogenic drive at hypnotic dose & abolished at 3Xdose, syndrome , no gen. CNS depress chemo. resp. drives fail at 10X, hypotension in CHF pts (anesthesia Drug Interactions: Phenobarbital & carbamazepine plasma level; dose) & depress cardiac conduction (toxic), No direct renal sulfonamides & phenylbutazone plasma level (hypotension 2nd to CV collapse. Induces sleep that has reduced REM May exacerbate absence seizures sleep (withdrawal from chronic may cause rebound in REM = Conventional Drug: simple partial, complex partial, partial w/ nightmares) 2ndarily generalized, & tonic-clonic seizures

Allosteric binds to GABA-A receptor – potentiates action; at high Anticonvulsant that inhibits voltage-gated Na channels (toxic) doses, directly stimulates receptor. Toxicity causes: paradoxical excitement (inebriation common), subj. perception of Inhibition of Na and Ca channels in thalamus pain, hypersensitivity common in atopic pts. Approved only as adjunct in refractory partial seizures but appears to Drug Interactions: Other sedatives, EtOH, antihistamines, isoniazid, have broad spectrum methylphenidate, MAO-Is CNS depressant effects due to Somnolence & fatigue are common. Depression & psychosis less metabolism of barb.; barbs. metabolism Vit. D & K, anticoagulants common. Skin rashes are common & renal calculi in 4% & steroids. Contra. in porphyria Newer drug: simple partial, complex partial, & Uses: anesthesia induction, seizures, therapeutic coma, & partial w/ 2ndarily generalized metabolism of hyperbilirubinemia in neonates

Anticonvulsant that inhibits voltage-gated Na channels Inhibits Na channel; binds to postsynaptic GABA receptors & potentiates activity Often used in partial seizures. Little sedative activity Side effects: fatigue, decreased mental acuity, anxiety, confusion, paresthesias are common, glaucoma w/ vision changes uncommon but require stopping drug Newer drug: simple partial, complex partial, partial w/ 2ndarily generalized, myoclonic, & tonic-clonic

Anticonvulsant with unk. mechanism (mech may include blockade of NMDA receptor subtype) 3rd line drug for refractory partial seizures Toxicity may result in aplastic anemia & hepatitis

Anticonvulsant that inhibits GABA reuptake Used as adjunct in partial seizures Sedation may occur with dose escalation & cases of psychosis have been reported Generally well-tolerated, major side effect is tremor. Psychosis (requires drug removal), anxiety, & depression may occur. Newer drug: simple partial, complex partial, & partial w/ 2ndarily generalized

Metabolized to phenobarbital, but may have independent anti-seizure activity Conventional drug: tonic-clonic

Captopril

Amiloride

(Capoten )

(Midam or)

Guanadrel Guanabenz (Hylorel )

(Wytensin)

Ethacrynic acid

β blockers with partial β agonist activity

(Edecrin )

Sumatriptan

Triamterene

(Imitrex)

(Dyrenium)

Ondansetron Ketanserin (Zofran (Sufrexal)

)

K-Sparing Diuretic - Sodium Channel Blocker Inhibit Na channels in luminal mb causing Na reabsorption and K & H excretion in late distal tubule & collecting duct. Used in combo w/ thiazide or loop diuretics (helps offset their hypokalemia effects) Rx: HTN & heart failure Adverse effects: Hyperkalemia (may be life threatening & risk is increased in renal dz, or when also taking K supplements, ACE inhibitors, Angiotensin II receptor blockers, β blockers, NSAIDS)

Selective α2-receptor agonist Acts on α2-receptors in the brain Decrease sympathetic outflow to the peripheral NS Rx: HTN Adverse effect: Sedation, depression, dry mouth

Inhibitor of ACE/kininase II (NOT a prodrug) Inhibits conversion of angiotensin I to II ( vasoconstrict & aldosterone); plasma renin activity; breakdown of vasodilator bradykinin PVR, but little change in HR. Elim. by kidney W/ RAS, renal perfusion pres b/c angiotensin II-depend. constriction of efferent arteriole which maintains GFR In diabetic nephropathy, may albuminuria & stabilize renal function ( Glom cap press) NSAIDS may reduce antihypertensive effects

Slow depletion of NE from nerve terminals, which results in decreased release of catecholamines No CNS activity Oral administration Rx: Severe HTN Adverse effects: Orthostatic hypotension Some drugs (ex. TCAs) block the transport into nerve endings resulting in blockade or reversal of antihypertensive effect

Loop diuretic Blocks salt reabsorption in TAL by inhibiting Na-K-2Cl symporter in luminal mb; In pts. w/ heart failure, in vent. filling press. & improvement in pulmonary congestion –beneficial in acute pulm. Edema; urinary Ca excretion ( Ca reabsorption in ascending limb) Adverse effects: hypokalemia (cardiac arrhythmias, potentiates effects of digitalis), metabolic alkalosis, hyperuricemia, hyperglycemia, some lipid h, volume depletion, hyponatremia, ototoxicity, allergic rxn.

Acebutolol (cardioselective – β1 antagonist), Carteolol, Celiprolol (cardioselective – β1 antagonist), Labetalol, Penbutolol, Pindolol Has intrinsic sympathomimetic activity

K-Sparing Diuretic - Sodium Channel Blocker Inhibit Na channels in luminal mb causing Na reabsorption and K & H excretion in late distal tubule & collecting duct. Used in combo w/ thiazide or loop diuretics (helps offset their hypokalemia effects) Rx: HTN, heart failure, cirrhosis, nephrotic syndrome Adverse effects: Hyperkalemia (may be life threatening & risk is increased in renal dz, or when also taking extra K+, ACE inhibitors, Angiotensin II receptor blockers, β blockers, NSAIDS); in kidney stones esp. if pt. has hx of kidney stones)

5-HT1B & 5HT1D Receptor Agonist Antimigraine agent (presumed action is constricting meningeal vessels) 1st line treatment of migraine Constriction of coronary arteries & heart block can occur in pts w. advanced coronary artery dz.

Antagonist of 5HT1C, 5HT2, alpha and H1 receptors Antagonist of 5HT3 receptors Principally used to control nausea & vomiting in cancer chemo pts. Primary mech is prob combo of receptor antagonism in emetic center in brainstem & GI tract

In Phase 3 clinical studies Effective antihypertensive presumably due to α blockade Toxicity: sedation

β blockers with local anesthetic effect

Fosphenytoin

(Cerebyx)

Benazepril (Notes table only)

Thiazides

(Lotensin)

Torsemide Loop diuretics (Demad ex)

Furosemide

Bumetanide

(Lasix)

(Bumex)

Buspirone Mannitol (BuSpa r)

High concentrations of these beta blockers alter depolarization of nerve & muscle cell membranes producing “local anesthetic” effect Newer drug used to treat status epilepticus

Acebutolol (cardioselective – β1 antagonist), Labetalol, Metoprolol Considered safer than IV phenytoin because it is more water-soluble (cardioselective – β1 antagonist), Pindolol, Propranolol, Betaxolol & doesn’t require glycol (assoc. with renal & cardiac toxicity) (slight effect)

Blocks salt reabsorption in distal convoluted tubule (DCT) inhibiting NaCl symporter in luminal membrane Decreases peripheral vascular resistance & often reduces urinary calcium excretion Rx for HTN, idiopathic hypercalciuria Unlikely to be effective if GFR <30mL/min Adverse effects: Hypokalemia, metabolic alkalosis, hyperuricemia, hyperglycemia, some lipid , volume depletion, hyponatremia, allergic rxn., NOT assoc. w/ ototoxicity Less effect than loop diuretics but greater than K-sparing

Prodrug Inhibitor of ACE/kininase II Inhibits conversion of angiotensin I to II ( vasoconstrict & aldosterone); plasma renin activity; breakdown of vasodilator bradykinin PVR, but little change in HR. Elim. by kidney W/ RAS, renal perfusion pres b/c angiotensin II-depend. constriction of efferent arteriole which maintains GFR In diabetic nephropathy, may albuminuria & stabilize renal function ( Glom cap press) NSAIDS may reduce antihypertensive effects

Blocks salt reabsorption in thick ascending limb (TAL) by inhibiting Loop diuretic Na-K-2Cl symporter in luminal mb; In pts. w/ heart failure, in vent. filling press. & improvement in pulmonary congestion –beneficial in Blocks salt reabsorption in TAL by inhibiting Na-K-2Cl symporter in luminal mb.; In pts. w/ heart failure, in vent. filling press. & acute pulm edema; urinary Ca excretion ( Ca reabsorption in improvement in pulmonary congestion –beneficial in acute pulm. ascending limb) Rx for HTN, hypercalcemia, heart failure Edema; urinary Ca excretion ( Ca reabsorption in ascending limb) Adverse effects: hypokalemia (cardiac arrhythmias, potentiates Adverse effects: hypokalemia (cardiac arrhythmias, potentiates effects of digitalis), metabolic alkalosis, hyperuricemia, effects of digitalis), metabolic alkalosis, hyperuricemia, hyperglycemia, some lipid h, volume depletion, hyponatremia, hyperglycemia, some lipid , volume depletion, hyponatremia, ototoxicity, allergic rxn.(less common than w/ other loop diuretics) ototoxicity, allergic rxn. Greater diuretic effect than thiazide & K-sparing diuretics

Loop diuretic

Loop diuretic

Blocks Na reabsorb in TAL - inhibits Na-K-2Cl symporter in Blocks salt reabsorption in TAL by inhibiting Na-K-2Cl symporter luminal mb.; In pts. w/ heart failure, vent filling press. & improves in luminal mb.; In pts. w/ heart failure, in vent. filling press. & pulm congestion –beneficial in acute pulm. Edema; urinary Ca improvement in pulmonary congestion –beneficial in acute pulm. excretion ( Ca reabsorb in ascending limb) rationale for use w/ Edema; urinary Ca excretion ( Ca reabsorption in ascending limb) saline in therapy of hypercalcemia Adverse effects: hypokalemia (cardiac arrhythmias, potentiates Adverse effects: hypokalemia (cardiac arrhythmias, potentiates effects of digitalis), metabolic alkalosis, hyperuricemia, effects of digitalis), metabolic alkalosis, hyperuricemia, hyperglycemia, some lipid h, volume depletion, hyponatremia, hyperglycemia, some lipid h, volume depletion, hyponatremia, ototoxicity, allergic rxn. ototoxicity, allergic rxn.

Osmotic Diuretic 5-HT1A Receptor Agonist Increases osmolality of tubular fluid & decreases osmotic reabsorption of water & Na; Causes movement of water out of cells, which increases renal blood flow & medullary flow, which decreases medullary hypertonicity & fluid reabsorption Not widely used as diuretic. One use is to decrease intracranial pressure in pts. w/ certain neurological problems.

Used for alleviating chronic anxiety symptoms & for smoking cessation No sedation, euphoria or dependence. No additive effects w/ other CNS depressants Requires 1-2wks for therapeutic effects

Acetazolamide

Ritanserin

(Diamox)

Spironolactone Eplerenone (Aldactone )

(Inspra)

Hydrochlorothiazide (HCTZ)

Chlorthalidone

Metolazone K-Sparing Diuretics (Zaroxolyn, Mykrox)

Pentobarbital Chloral Hydrate (Nembutal Sodium)

Carbonic Anhydrase Inhibitor Selective 5HT2 antagonist Currently in clinical trials to prevent thromboembolism

Inhibits carbonic anhydrase, which decreases NaHCO3 reabsorption in PCT of kidney Infrequently used as diuretic. One use is treatment of glaucoma (decreases intraorbital pressure) Adverse effects: metabolic acidosis

K-Sparing Diuretic - Mineralocorticoid Receptor Antagonist

K-Sparing Diuretic - Mineralocorticoid Receptor Antagonist

Synthetic steroid that binds to cytoplasmic aldo receptor, preventing Selective synthetic steroid that binds to cytoplasmic aldosterone binding of aldo which Na reabsorption and K & H secretion in receptor, preventing the binding of aldosterone which Na late DT & CD reabsorption and K & H secretion in late distal tubule & collecting Rx: dz states assoc. w/ plasma aldo levels (1º & 2 º duct hyperaldosteronism), nephrotic syndrome, heart failure, cirrhosis w/ Used to treat dz states assoc. w/ plasma aldo levels (1º & 2 º ascites & in combo w/ thiazide or loop diuretics in pts w/ edema & hyperaldosteronism) & in combo w/ thiazide or loop diuretics in pts hypertension w/ edema & hypertension Adverse effects: Hyperkalemia, metabolic acidosis (possible), Adverse effects: Hyperkalemia, metabolic acidosis (possible) other endocrine effects (gynecomastia in males)

Thiazide Diuretic Blocks salt reabsorption in DCT by inhibiting NaCl symporter in luminal membrane Decreases peripheral vascular resistance & often reduces urinary calcium excretion (Rx for idiopathic hypercalciuria) Unlikely to be effective if GFR <30mL/min Adverse effects: Hypokalemia, metabolic alkalosis, hyperuricemia, hyperglycemia, some lipid , volume depletion, hyponatremia, allergic rxn., NOT assoc. w/ ototoxicity

Two Types: Sodium Channel Blockers & Mineralocorticoid Receptor Antagonists Sodium channel blockers inhibit Na channels in luminal mb causing Na reabsorption and K & H excretion in late distal tubule & collecting duct. Used in combo w/ thiazide or loop diuretics (helps offset their hypokalemia effects) Mineralocorticoid Receptor Antagonists binds to cytoplasmic aldosterone receptor, which Na reabsorption and K & H secretion in late distal tubule & collecting duct

Thiazide Diuretic Blocks salt reabsorption in DCT by inhibiting NaCl symporter in luminal membrane peripheral vascular resistance & often urinary Ca excretion (Rx for idiopathic hypercalciuria). Rx: HTN, nephrogenic diabetes insipidus Unlikely to be effective if GFR <30mL/min Adverse effects: Hypokalemia, metabolic alkalosis, some lipid , hyperuricemia, hyperglycemia, volume depletion, hyponatremia, allergic rxn., NOT assoc. w/ ototoxicity

Thiazide Diuretic Blocks salt reabsorption in DCT by inhibiting NaCl symporter in luminal membrane Decreases peripheral vascular resistance & often reduces urinary calcium excretion (Rx for idiopathic hypercalciuria) Unlikely to be effective if GFR <30mL/min Adverse effects: Hypokalemia, metabolic alkalosis, hyperuricemia, hyperglycemia, some lipid , volume depletion, hyponatremia, allergic rxn., NOT assoc. w/ ototoxicity

Non-barbiturate sedative-hypnotic Short-intermediate acting barbiturate sedative-hypnotic Usual use is for sedation in children (3-6 hours) Liquid is irritating to skin & mucous mbs

Vasopressin Conivaptan (Pitressin )

(Vaprisol)

Demeclocycline

Desmopressin

(Declomycin)

Aliskiren

(DDAVP)

Quinapril (Notes table only) (Tekturna

)

(Accupril )

Enalapril ACE Inhibitors (Vasote c)

Fenoldopam

Hydralazine

(Corlop am)

(Apresoline )

Decreases renal water reabsorption ADH Antagonist

Arginine vasopressin= antidiuretic hormone

Decreases effects of ADH on renal CD cells Rx: SIADH in certain situations Adverse effects: possible nephrogenic diabetes insipidus

perm. of renal CD cells to H2O (V2 receptor) via insertion of H2O channels into luminal mb; vasoconstriction (V1 receptor) Rx: Central diabetes insipidus Adverse effects: Water intoxication (V2 mediated); vascular & GI effects (V1 mediated); allergic rxn

ADH Antagonist Decreases renal water reabsorption V1A & V2 receptor antagonist; V2 antagonism results in free H2O excretion Rx: euvolemic hyponatremia (ex SIADH in hospitalized pts - short term iv), NOT approved for heart failure CI in hypovolemic hyponatremia or w/ potent CYP3A4 inhibitors Metabolized by & inhibits CYP3A4 Adverse effects: Infusion site rxn, correction of low serum Na concentration too rapidly can cause serious problems

Prodrug Inhibitor of ACE/kininase II

1-deamino-8-D-arginine vasopressin (DDAVP) Longer duration of action than vasopressin Increased antidiuretic to pressor activity perm. of renal CD cells to H2O (V2 receptor) via insertion of H2O channels into luminal mb; vasoconstriction (V1 receptor) Rx: Central diabetes insipidus Adverse effects: H2O intoxication (V2); vascular & GI effects (V1) – less than vasopressin; allergic rxn

Renin Inhibitor

Inhibits conversion of angiotensin I to II ( vasoconstriction & Decreases plasma renin activity, Angiotensin I & Angiotensin II aldosterone); plasma renin activity; breakdown of vasodilator activity bradykinin Increases plasma renin concentration PVR, but little change in HR. Elim. by kidney Has not been shown to improve clinical outcome yet W/ RAS, renal perfusion pres b/c angiotensin II-depend. constriction of efferent arteriole which maintains GFR Adverse effects: Diarrhea, cough, angioedema, Potassium, In diabetic nephropathy, may albuminuria & stabilize renal function Creatine, Fetal toxicity & birth defects – DO NOT USE DURING ( Glom cap press) PREGNANCY!! NSAIDS may reduce antihypertensive effects

Inhibitor of ACE/kininase II (NOT a prodrug) Prodrug Inhibitor of ACE/kininase II Inhibits conversion of angiotensin I to II ( vasoconstriction & Inhibits conversion of angiotensin I to II ( vasoconstriction & aldosterone); hypertensive response to angiotensin I, but not aldosterone); plasma renin activity; breakdown of vasodilator angiotensin II injection; plasma renin activity; breakdown of bradykinin vasodilator bradykinin PVR, but little change in HR. Elim. by kidney PVR, but little change in HR. Elim. by kidney W/ RAS, renal perfusion pres b/c angiotensin II-depend. W/ renal a. stenosis (RAS), renal perfusion pres b/c angiotensin constriction of efferent arteriole which maintains GFR II-depend. constriction of efferent arteriole which maintains GFR. In diabetic nephropathy, may albuminuria & stabilize renal function In diabetic nephropathy, may albuminuria & stabilize renal function ( Glom cap press) ( Glom cap press) NSAIDS may reduce antihypertensive effects NSAIDS may reduce antihypertensive effects

Arterial vasodilator via direct relaxation Vasodilator via stimulation of D1 receptors Periph vasc resistance & lowers BP, but activates compens. resp. Parenteral drug for hypertensive emergencies (Admin. continuous iv (sympathetic stim, salt & water retention) infusion – rapid onset; duration of action 30 min) Can use w/ β-blocker & diuretic, or w/ organic nitrate in heart failure Hepatic metabolism Oral & iv administration, but metabolized partly by acetylation Adverse effects: Palpitations, angina, headache, drug-induced lupus Adverse effects: headache, flushing, HR, intraocular pressure Use w/ caution in pts. w/ glaucoma (greatest in slow acetylators), fluid retention

Flumazenil

Secobarbital

(Romazicon)

Lisinopril Losartan (Prinivil, Zestril)

(Cozaar)

Adverse effects of ACE/kinase II Inhibitors

Minoxidil

(Rogaine)

Ramipril Benzodiazepines (Altace )

Ethchlorvynol

Meprobamate

Competitive Benzodiazepine-receptor antagonist Only benzodiazepine antagonist in US Used for reversing sedative effects in anesthesia or overdose (admin. via iv) Rapid onset, short duration May precipitate withdrawal symptoms in depend. individuals

Short-intermediate acting barbiturate (3-6 hours)

Angiotensin II receptor blockers (ARB) Inhibitor of ACE/kininase II (Not a Prodrug) Inhibits type 1 angiotensin II receptors (AT1) – along w/ its active Inhibits conversion of angiotensin I to II ( vasoconstriction & metabolite (EXP3174) aldosterone); plasma renin activity; breakdown of vasodilator pressor response to infused angiotensin I & II; plasma renin bradykinin activity & plasma angiotensin II levels PVR, but little change in HR. Elim. by kidney Oral admin. W/ RAS, renal perfusion pres b/c angiotensin II-depend. Adverse effects: Hypotension (esp if vol depleted), dizziness (low constriction of efferent arteriole which maintains GFR incidence), K+ can occur, angioedema (less freq than w/ ACE In diabetic nephropathy, may albuminuria & stabilize renal function inhibitors), BUN & Cr in pts w/ bilateral RAS (same as ACE ( Glom cap press) inhib), fetal toxicity & birth defects (same as ACE inhib), less likely NSAIDS may reduce antihypertensive effects to cause cough

Highly efficacious arteriolar dilator Prodrug that is converted by a sulfotransferase to minoxidil sulfate (active metabolite), which opens K+ channel hyperpolarization of Hypotension (esp w/ initial dose in pts w/ salt/volume depletion, smooth muscle cell relaxation multi. antihypertensives, or w/ congestive heart failure), cough, Compensatory sympathetic stim and salt & water retention angioedema, hyperkalemia (risk w/ renal insufficiency, K+ Used w/ b-blocker & loop diuretic supplements, K-sparing diuretics, b blockers, NSAIDs), renal fxn Oral admin (HTN), topical (hair growth) (esp pts w/ bilateral renal artery stenosis), skin rash, neutropenia (pts Adverse effects: palpitations, angina, headache, hypertrichosis (hair w/ renal dz or collagen-vascular dz), reversible diminution or loss of growth), pericardial effusion (not common), ECG changes (T-wave taste, fetal toxicity, birth defects flattening or inversion; not ischemic, freq. on initiation of drug), fluid retention

Prodrug Inhibitor of ACE/kininase II Replaced barbiturates for sedation & hypnosis Inhibits conversion of angiotensin I to II ( vasoconstriction & High TI b/c doesn’t depress resp. drive or cardiovasc system Enhance GABA-mediated chloride flux, causing hyperpolarization. aldosterone); plasma renin activity; breakdown of vasodilator bradykinin Do NOT directly activate the receptor Produces resp. acidosis in COPD pts. PVR, but little change in HR. Elim. by kidney By itself, can only cause coma NOT Death so OD W/ RAS, renal perfusion pres b/c angiotensin II-depend. by itself is rarely fatal constriction of efferent arteriole which maintains GFR Toxicity: ataxia, confusion, amnesia, dependence In diabetic nephropathy, may albuminuria & stabilize renal function & abuse. More common in geriatrics ( Glom cap press) Used w/ psychotherapy for chronic anxiety, insomnia NSAIDS may reduce antihypertensive effects

Non-barbiturate sedative-hypnotic High abuse potential

Non-barbiturate sedative-hypnotic

Indigestible filler in tablets can result in gastric bezoars

Occasionally used as an anticonvulsant

Active metabolite of carisoprodol (Soma), a muscle relaxant

Eszopiclone

Rohypnol

Candesartan (Not bolded in notes)

Trandolapril (Notes table only)

(Atacan (Mavik)

Valsartan (Not bolded in notes)

d)

Telmisartan (Not bolded in notes) (Diovan)

(Micardis)

Partial with Secondarily Generalized Seizures

Eprosartan (Not bolded in notes) (Teveten)

Absence Generalized Seizures

Myoclonic Generalized Seizures

Novel Benzodiazepine-Receptor Agonist Illegal benzodiazepine

Hypnotic Agents Low tolerance & dependence Assumed to bind to GABA subtype

Angiotensin II receptor blockers (ARB) Inhibits type 1 angiotensin II receptors (AT1) – along w/ its active metabolite (EXP3174) pressor response to infused angiotensin I & II; plasma renin activity & plasma angiotensin II levels Oral admin. Adverse effects: Hypotension (esp if vol depleted), dizziness (low incidence), K+ can occur, angioedema (less freq than w/ ACE inhibitors), BUN & Cr in pts w/ bilateral RAS (same as ACE inhib), fetal toxicity & birth defects (same as ACE inhib), less likely to cause cough

Prodrug Inhibitor of ACE/kininase II Inhibits conversion of angiotensin I to II ( vasoconstrict & aldosterone); plasma renin activity; breakdown of vasodilator bradykinin PVR, but little change in HR. Elim. by kidney & liver W/ RAS, renal perfusion pres b/c angiotensin II-depend. constriction of efferent arteriole which maintains GFR In diabetic nephropathy, may albuminuria & stabilize renal function ( Glom cap press) NSAIDS may reduce antihypertensive effects

Angiotensin II receptor blockers (ARB) Inhibits type 1 angiotensin II receptors (AT1) – along w/ its active metabolite (EXP3174) pressor response to infused angiotensin I & II; plasma renin activity & plasma angiotensin II levels Oral admin. Adverse effects: Hypotension (esp if vol depleted), dizziness (low incidence), K+ can occur, angioedema (less freq than w/ ACE inhibitors), BUN & Cr in pts w/ bilateral RAS (same as ACE inhib), fetal toxicity & birth defects (same as ACE inhib), less likely to cause cough

Angiotensin II receptor blockers (ARB) Inhibits type 1 angiotensin II receptors (AT1) – along w/ its active metabolite (EXP3174) pressor response to infused angiotensin I & II; plasma renin activity & plasma angiotensin II levels Oral admin. Adverse effects: Hypotension (esp if vol depleted), dizziness (low incidence), K+ can occur, angioedema (less freq than w/ ACE inhibitors), BUN & Cr in pts w/ bilateral RAS (same as ACE inhib), fetal toxicity & birth defects (same as ACE inhib), less likely to cause cough

Conventional Drugs: Carbamazepine, Phenytoin, Valproate, & Phenobarbital Newer Drugs: Gabapentin, Lamotrigine, Levetiracetam, Tiagabine, Topiramate, & Zonisamide

Conventional Drugs: Valproate Newer Drugs: Lamotrigine, Topiramate

Angiotensin II receptor blockers (ARB) Inhibits type 1 angiotensin II receptors (AT1) – along w/ its active metabolite (EXP3174) pressor response to infused angiotensin I & II; plasma renin activity & plasma angiotensin II levels Oral admin. Adverse effects: Hypotension (esp if vol depleted), dizziness (low incidence), K+ can occur, angioedema (less freq than w/ ACE inhibitors), BUN & Cr in pts w/ bilateral RAS (same as ACE inhib), fetal toxicity & birth defects (same as ACE inhib), less likely to cause cough

Conventional Drugs: Ethosuximide, Valproate Newer Drugs: Lamotrigine, Topiramate

Tonic-Clonic Generalized Seizures

Dolasetron (Anzemet) & Granisetron (Kytril) (Note: not bolded in notes)

Status Epilepticus

Sodium nitroprusside

Moexipril (Notes table only)

Irbesartan (Not bolded in notes)

(Univas (Avapro)

Fosinopril (Notes table only)

c)

Enalaprilat (Monopri

l)

Clonazepam

Complex Partial Seizures

Antagonist of 5HT3 receptors Principally used to control nausea & vomiting in cancer chemo pts. Primary mech is prob combo of receptor antagonism in emetic center in brainstem & GI tract

Conventional Drugs: Carbamazepine, Phenobarbital, Phenytoin, Primidone, & Valproate Newer Drugs: Lamotrigine, Topiramate

Arterial & venous dilator Stim. guanylyl cyclase cGMP either release of NO or by direct stimulation of the enzyme Continuous iv infusion; rapid onset & offset of action = close monitoring necessary Aq. solution photosensitive Elimination: Na2Fe(CN)5NO CN SCN urine Adverse effects: Hypotension, Cyanide & thiocyanate toxicity Used n hypertensive emergencies. Caution in pts w/ intracranial pressure or azotemia

Continuous tonic-clonic seizures that requires aggressive intervention including respiratory, cardiovascular & metabolic support Seizure activity usually stopped with IV diazepam followed by IV phenytoin (assoc. w/ renal & cardiac toxicity prob. Due to propylene glycol in IV formulation) Newer agent (fosphenytoin, Cerebyx) is more water-soluble, doesn’t require glycol,& considered safer

Angiotensin II receptor blockers (ARB) Prodrug Inhibitor of ACE/kininase II Inhibits type 1 angiotensin II receptors (AT1) – along Inhibits conversion of angiotensin I to II ( vasoconstrict w/ its active metabolite (EXP3174) & aldosterone); plasma renin activity; pressor response to infused angiotensin I & II; plasma breakdown of vasodilator bradykinin renin activity & plasma angiotensin II levels PVR, but little change in HR. Elim. by kidney Oral admin. W/ RAS, renal perfusion pres b/c angiotensin II-depend. Adverse effects: Hypotension (esp if vol depleted), constriction of efferent arteriole which maintains GFR dizziness (low incidence), K+ can occur, angioedema In diabetic nephropathy, may albuminuria & stabilize renal function (less freq than w/ ACE inhibitors), BUN & Cr in pts w/ bilateral ( Glom cap press) RAS (same as ACE inhib), fetal toxicity & birth defects (same as NSAIDS may reduce antihypertensive effects ACE inhib), less likely to cause cough

Inhibitor of ACE/kininase II (Active metabolite of enalapril) Prodrug Inhibitor of ACE/kininase II Inhibits conversion of angiotensin I to II ( vasoconstrict Inhibits conversion of angiotensin I to II ( vasoconstrict & aldosterone); plasma renin activity; & aldosterone); plasma renin activity; breakdown of vasodilator bradykinin breakdown of vasodilator bradykinin PVR, but little change in HR. Elim. by kidney PVR, but little change in HR. Elim. by liver & kidney W/ RAS, renal perfusion pres b/c angiotensin II-depend. W/ RAS, renal perfusion pres b/c angiotensin II-depend. constriction of efferent arteriole which maintains GFR constriction of efferent arteriole which maintains GFR In diabetic nephropathy, may albuminuria & stabilize renal function In diabetic nephropathy, may albuminuria & stabilize renal function ( Glom cap press) ( Glom cap press) Available for iv use NSAIDS may reduce antihypertensive effects NSAIDS may reduce antihypertensive effects

Conventional Drugs: Carbamazepine, Phenytoin, Valproate Newer Drugs: Gabapentin, Lamotrigine, Levetiracetam, Tiagabine, Topiramate, & Zonisamide

Benzodiazepine Used in epilepsy

Simple Partial Seizures

Hydroxyzine

Olmesartan (Not bolded in notes) (Benicar )

Antihistamine Causes marked sedation but used for alleviating anxiety symptoms

Conventional Drugs: Carbamazepine, Phenytoin, Valproate Newer Drugs: Gabapentin, Lamotrigine, Levetiracetam, Tiagabine, Topiramate, & Zonisamide

Angiotensin II receptor blockers (ARB) Inhibits type 1 angiotensin II receptors (AT1) – along w/ its active metabolite (EXP3174) pressor response to infused angiotensin I & II; plasma renin activity & plasma angiotensin II levels Oral admin. Adverse effects: Hypotension (esp if vol depleted), dizziness (low incidence), K+ can occur, angioedema (less freq than w/ ACE inhibitors), BUN & Cr in pts w/ bilateral RAS (same as ACE inhib), fetal toxicity & birth defects (same as ACE inhib), less likely to cause cough