ANTIHYPERTENSIVES

β-adrenoceptor antagonistLipid soluble nonselective β blocker

Metoprolol (lopressor)Pindolol (visken) ISA activity (partial agonist): don’t decrease HR as much

Non selective β blocker + α1 selective blocker

ThiazidesHydrochlorothiazideChlrothalidoneMetolazoneindapamide

Block Na+-Cl- symporter in DCT.Arterial vasodilatorsreduced extracellular volume reduced BV reduced CO PVR increases (compensatory) over time PVR comes back to normal and then usually falls below it fall in BP increased PRA (compensatory)

Potassium Sparing SpironolactoneEplerenone

Block aldo receptors. Selective, competitive mineralocorticoid antag.- Inc in renin release/PRA

TriamtereneAmiloride

-block endothelial cell Na current -Inc in renin release/PRA-Effect not seen for 12 to 14 weeks -Block Na current channels..

Propanolol (Inderal)

2nd generation β1 selective blocker (cardioselective)

Labetalol (trandate, normodyne)ACE inhibitors end in “PRIL”Hemodynamic actions : Dec PVR (minimal reflex tachycardia) with balanced vasodilation (increased bradykinin) & by limiting sympathetic stimulation, maximize CO in patients w/CHF (if you decrease the amount going to the heart, then your heart rate never increases)Balanced vasodilator (arterial and venous)

Captopril (capoten)

Long half life

Renin Inhibitors

First orally activeProline derivative

Enalapril (Vasotec) Pro-drug: Hepatic/gut wall esterase metabolism to enalaprilat

Lisinopril (Prinivel, Zestril)

Angiotensin Receptor Blockers end in “SARTAN”Candesartan (atacand)Eprosartan (tevetan)Irbesatan (Avapro)Losartan (Cozaar)Tasosartan (Verdia)Telmisartan (Micardis)Valsartan (Diovan)Almesartan (Benicar)

-ATII receptor antagonists – REVERSIBLE, COMPETITIVE - Decrease remodling of the heart-Orally active-Has no effect on bradykinin: exert effect only on AngII

Vasopeptidase InhibitorsOmapatrilat

Inhibits ACE and blocks NEP-less vasoconstriction-more vasodilation (increased bradykinin)

Aliskiren (Tekturna) First-in-class oral renin inhibitor (2007) Potent and specific in vitro inhibitor of human renin Plasma half-life of ≈24 hours.

Direct Arterial Vasodilators

Calcium Channel Blockers - End in - “IPINE”All block the L type Ca channel (allows transmembrane flux of calcium) decrease PVR, decreased myocardial contractility, decreased HR & cause AV block in some casesArterial vasodilatorDihydropiridinesNifedipineAmlodipine (norvasc)felodipine (Plendil)isradipine (Dynacirc)nicardipine (Cardene)nisoldipine (Sular)lacidipine (Lacipil, Motens)

Only affects peripheral vasculature - mostly arterial (problem with excess vasodilation)Less affinity for s subtype of the L Ca channel found in the heart.

PhenylalkylaminesVerapamil

Affects heart more than vasculature: can cause decr CO, xs vasodilation & problems w/myocardial arrhythmias and HR.

BenzothiazepinesDilitiazem

A1 adrenoceptor antagonists End in –“AZOSIN”Prazosin (Minipress)Doxazosin (Cardura)Terazosin (Hyrtrin)

A1 receptors are on the vasculature everywhere, including the vasculature in and around the male urogenital region.

Balanced vasodilator

Hydralazine (Apresoline)

Endothelial NO release – increases NOInterference with SR Ca++ release Direct acting smooth muscle relaxant Arterial Vasodilation

Centrally Active Antihypertensives

Adrenergic neuron BlockersReserpine (Serpasil)

Guanadrel (hyorel)

Hypertensive Crisis Drugs

Algorithm for HTN Treatment

Minoxidil (Rogaine) Loniten

Active compound = minoxidil sulfateK+ channel agonist – hyperpolarizes VSM - vasodilation

Clonidine (Catapres)GuanabenzGuanfacinea-Methyldopa (Aldomet)

RilmenidineMonoxidine

A2 adrenoceptor, imidazoline agonist (I1): inhibit CV neurons in med. oblongataDirect agonists except for A-MD: replaces NE with alpha-methyl NE (AMNE) in storage vesiclesReduce sympathetic outflow – decr PVR, CO, HR, PRA, RVR

Rilmenidine, Monoxidine I1R selectivea-Methyldopa A2 selective

Irreversible binder of (VMAT) decrease NE release, NE depletionUse (R>>>G)

Guanethidine(lsmelin sulfate)

Blocks release of NE, DA.Displaces NE from vesicles.Entry via Uptake1 transporter.Only has PNS action.

Sodium Nitroprusside (Nipride)

NO release balanced vasodilationIV pump, light sensitiveThiocyanate toxicity w/ prolonged infusion

Diazoxide (hyperstat, Proglycem)

Potassium channel opener, IM pushHyperglycemia

Fenoldopam mesylate (Corlopam)

D1 receptor agonist

ACEi & ARBS

Heart Failure ACEi, B blockers, diureticsDiuretics preferred; long-acting DHP Ca blockers

Myocardial Infarction B-blockers (non-ISA) or ACEi (in systolic failure)

Antiarrhythmic Agents

Diabetes mellitus (type 1) w/proteinuria

Isolated systolic HTN (older persons)

Class I (A) - “Quid - Pro - Dis” not quid pro quoNa+ Channel blockade (inward): moderate Phase 0 block (and also Phase III block)Pro-arrhythmic actions (CAST Study)Vagolytic action (Antimuscarinic): Increase QRS, QT, Prolong ERP/APD [End Resting Potential/Action Potential Duration]Suppress accessory pathways and useful in pre-excitation arrhythmias - Wolf-Parkinson-White

Quinidine(Quinaglute, Cardioquin, Quinidex)

(4) AP actions on isolated Purkinje fiber:a. Slowing rise of Phase 0 depolarization (Na channel)b. Reducing the rate of rise of Phase 4 spontaneous depolarizationc. Prolonging Phase 3 repolarization and action potential durationd. raising the threshold for elicitation of a propagated action potential- Quinine isomer*- Prolong QRS, QT :- Tachycardia early: Hypotension, Antimuscarinic effect- Increase ventricular rate in atrial fib/flutter so contraindicated??

Procainamide(Pronestyl)

- Similar to quinidine More hypotension (ganglionic block)- Active metabolite = NAPA (Class III) prolong AP duration

Disopyramide (Norpace)

Oral, decreases abnormal ventricular automaticity by acting on Na/K currents

Mexiletine (Mexitil)

Propafenone (Rythmol)Moricizine (Ethmozine) (IA/IB/IC properties)

Acebutolol (Sectral)Atenolol (Tenormin)

Class I (B) “Take exit IB to Lido’s Mexican Taco stand”Na+ channel (Phase 0) block Shorten APD (Decrease QT interval, Slightly slow Phase 0)Pro-arrhythmic actions (CAST Study)Use-dependence (Na+ channel kinetics): increased Na+ channel blockade as heart rate increasesSelectivity for ventricular arrhythmias (IB)Rapid kinetics

Lidocaine (Xylocaine) Prototype for Class IB agents:Intravenous use only due to extensive first-pass hepatic metabolism

Phenytoin (Dilantin) Orally effective, lidocaine-like agents; (second-line use)Rarely used

Orally effective, lidocaine-like agents that are relegated for second-line use

Class I (C) Marked pro-arrhythmic effectsUsed in severe V. tachyarrhythmiasMarkedly slow Phase 0 Increase PR intervalSlow kinetics (bind avidly to, and only slowly dissociate from, sodium channels) exert effects even on normal HR’s

Flecainide (Tambocor)

relatively toxic Class IC agents used primarily for severe ventricular arrhythmias

Class IIβ-Adrenoceptor blockade: Block pro-arrhythmic actions of catecholaminesLimit tissue death in ischemiaLimiting AV node conduction (useful for slowing ventricular rate in supraventricular arrhythmias)Antihypertensive and antianginal actions (Catecholamines are released in MI)

Esmolol (Brevibloc)

Timolol (Blocadren)

ultra-brief acting agent most often used during acute surgical procedures by IV infusion

Metoprolol (Lopressor)

Contraindication in vasospatic angina, least likely to aggravate substrate underlying syncopedon’t give combo with verapamil

Propranolol (Inderal) Prototype of the Class II antiarrhythmic agents reduces pro-arrhythmic actions of catecholamines at β-adrenoceptors, including: a. reducing pacemaker activity in SA and AV nodal tissueb. limiting conduction through the AV node/Bundle of Hisc. blocking catecholamine-enhanced automaticity in atrial/ventricular tissue

Class III - Ends in DARONEK+ Channel blockade Prolong APD and refractory period (all block K+ channels EXCEPT ibutilide)Reverse use dependence: bind best at slower rates (EXCEPT amiodarone); Complex actions; Very efficacious; Highly toxic

Amiodarone (Cordarone)

Prototype Class III agent, (4) major membrane blockades:a. K+ channels: prolong APD (Class III action)b.Na+ channels: slow conduction & widen QRS (Class I action)c. Ca++ channel: prolong PR intervals and prolong AV node conduction (Class IV action)d. β-adrenoceptor block to decrease sinus rate (Class II action) most prominent when admin IV- Supercedes lidocaine in ACLS VF/pulseless VT and wide-complex tachycardia management- Does not prolong APD (QT interval) Both A and metabolite (desethylamiodarone) ↑ defib threshold

Dronedarone

Bretylium (Bretylol)

Dofetilide

Bepridil (Vascor) Prolongs APD; Not labeled for antiarrhythmic useNon-DHP Ca+ blocker

Magnesium sulfate

Newer, gentler Amiodarone More rapid onset, less severe side effects

Sotalol (Betapace) β-adrenoceptor block & Class III APD actionL-isomer: Non-selective β-adrenoceptor blockD-isomer = prolongs APDadrenergic neuron blockade, recently discontinued from ACLS protocols.

Blocks delayed rectified K channels (Ikr), and causes APD prolongation in atrial and ventricular muscle

Ibutilide (Corvert) Unique because APD prolongation results from STIMULATION of slow inward Na+ current & BLOCKS IK1 currents

Class IV: Ca++ Channel blockadeprimary utility in management of supraventricular (atrial and AV nodal) tachyarrhythmias w/ virtually no efficacy against ventricular arrhythmias prolonging PR interval (Slow heart rate) Caution in WPWVerapamil (Calan, Isoptin)

Oral or IV; prolongs AV node conduction solely by actions on Ca currents

Dilitiazem (Cardizem, Dilacor)Class V (Other)Digoxin (Lanoxin) - Slow ventricular rate by increasing vagal tone & dec

AV node conduction - High levels result in 3rd degree AV blockuseful agent in treatment of les torsades de pointes (IV), even in patients with normal circulating magnesium levels.

Anti-anginal Agents

Nitrite; volatile liquid-inhalation

Nitrates

Adenosine (Adenocard)

- Identical to the endogenous vasodilating myocardial metabolite- possess very short action (T1/2 = 10 sec) transiently increase AV node effective refractory period by:blocking AV conduction, causing brief periods of asystole (adenosine pause) & terminating supraventricular tachyarrhythmias dependent upon AV node conduction Increases AV node ERP, Immediate conversion of PSVT- Endogenous nucleoside

Nitrovasodilators- induce moderate coronary dilation by inc. intracellular cGMPtarget a soluble guanyl cyclase to increase cGMP vasodilation (does not inhibit platelet aggregation)selective venodilators reduce preload (venous return) on the myocardiumNVD have to be nitrated by reductases found in liver and glutathionepoorly bioavailable when taken by mouth and absorbed through the GI systemDifferential Dx of chest pain relieved by nitroglycerin: biliary and esophageal spasms

Amyl nitrate (Aspirols, Vaporole)

Nitroglycerin -sublingual tablet and nasal spray -Preparations: buccal tablets, oral sustained release, intravenous solution, 2% ointment, and transdermal patch -sublingual: onset of 2-4 min, duration of 20-40 min; volatile, adsorbs to plastic; 3 month shelf life; active drug-aerosol: 3 year shelf life

“organic nitrate”

“organic nitrate”-orally active, longer acting

Bepridil (Vascor)

Propranolol (Inderal)

Ivabradine

pentaerythritol tetranitrate erythrityl tetranitrate

Isosorbide dinitrate (Isordil, Sorbitrate)Isosorbide mononitrate (Ismo)

Calcium Channel Blockers - Help with reducing “After Load” Work on Arterioles>>veins.

DihydropiridinesNifedipineAmlodipine (norvasc)felodipine (Plendil)

Arterioles>> veins

Diltiazem (Cardizem)

Arterioles>> veins

β-Adrenoceptor blockers (Many available) Beneficial: reduce mortality in angina a. Decrease myocardial O2 demand--decrease HR, contractile force, BP (Decrease afterload, increase preload) b. Increase O2 supply by improving diastolic perfusion of cardiac tissue (increased diastolic interval) c. Reduce ventricular arrhythmias- decreased AV node conduction (Phase IV depolarization), inc V Fib thresholdPotentially detrimental actions: a. Increase left ventricular end diastolic volume (preload) by reducing contractility—inc O2 demand b. unmask α-adrenoceptor mediated constriction—potential for aggravation of Prinzmetals angina (CI)Use with nitrates: prevent reflex tachycardia, less increase in left ventricular filling pressure (preload) together, they reduce myocardial oxygen consumption and increase subendocardial blood flow

Ranolazine (Ranexa) Blocks late sodium current in ischemic myocardium and reduces calcium overload, Inhibits “Late” Ina current and reduces Ca++ overload in ischemic myocardium, also inhibits IKr

-Selective inhibitor of If channel in the sino-atrial node and slows heart rate, reducing myocardial oxygen consumption

Fasudil Rho-Kinase inhibitorsLisinopril Tx: Left ventricular dysfunction & mild nocturnal dyspnea;Nicorandil

Heart FailureInamrinone Acute Heart Failure crisis only!

Digitalis

AntifungalsAmphoterocin B

Flucytosine

Ketoconazole Block the synthesis of ergosterol

Griseofulvin Binds microtubules prevents mitosisTerbinafine Inhibitor of ergosterol biosynthesisNystatin Sim to Amphotericin B

-Nitrate derivative of nicotinamide-Also activates KATP channels in vascular smooth muscle and ischemic myocardium

Nesiritide (Natrecor) Human recombinant brain natriuretic peptide (BNP) - Balanced vasodilation; natriuresis, diuresis, reduced renin, aldosterone, and norepinephrine levels. Acts through NPR A receptor.

Na+/K+-ATPase - Positive Inotropic action

Binds ergosterol and alters membrane and modifies permeability/transport

Acc. In fungal cells, converted to 5FU and 5dUMP, inhibit thymidylate synthase

ANTIHYPERTENSIVES

β-adrenoceptor antagonist

Reduce stroke, LVH, cardiac ischemic events.More effective in blacks, elderly.Useful for AHTN therapy in elderly.

Can strengthen bones (hypercalcemia)

Electrolyte excretion (Na, K, Mg)Uric acid & Ca are increased-Dec in Glucose Tolerance (secondary to hypokalemia)-Incr. in serum lipids-transient, mildCI: severe renal failure (GFR<30mL/min), lithium therapy (decreased clearance), hypokalemia, gout, diabetes mellitus

-Reduce LVH that occurs w/longstanding HTN and also reduce/delay the progression of CHF.-More effective in blacks, elderly.-Eplerenone – more selective and has 1 a day dosing; less gynecomastia, menstrual disruption, impotence

Hyperkalemia

Immediate: Decr in cardiac contractility & HR. Decreased renal renin release (unlike thiazides)Takes weeks to see drop in BP (compensatory inc. in PVR before eventual decrease)

More effective in young Caucasians.

Bradycardia/exercise intoleranceDyspnea/bronchoconstriction/vasoconstrictionRxn to hypoglycemiaFatigue/sleep disturbances (CNS)Hypersympathetic withdrawal response (particularly in CAD)CI: asthma/bronchospasm; high degree heart block, bradycardia; precipitated CHF, hypotension; psychoses/CNS depression; hypoglycemia/DiabeticOD therapy: glucagon, isoproterenol, dobutamine, atropine

Hemodynamic actions : Dec PVR (minimal reflex tachycardia) with balanced vasodilation (increased bradykinin) & by limiting sympathetic stimulation, maximize CO in patients w/CHF (if you decrease the

Hypertension

Renin Inhibitors

HTN – all stagesCongestive Heart FailureDiabetic NephropathyPost Myocardial infarction

Cough – buildup of bradykinin around nerve endings in bronchioles or lung tissue (ACEi only)Excessive hypotension (Fluid, Na restricted)Azotemia/renal failure (RAS)Possible hyperkalemia Angioedema – inc tissue bradykininDysgeusia/Ageusia Rash, Proteinuria, Neutropenia – usually seen w/captopril at high dosesCI –Pregnancy (Ang II needed in developing fetus, same problem seen w/ARBs); Renal Artery Stenosis (decr clearance since Ang II is primary controller of GFR).

Balanced vasodilation without causing increased inotropic effect.

Few adverse effects (i.e.. Cramping)CI: pregnancy, lactation

Direct Arterial Vasodilators

All block the L type Ca channel (allows transmembrane flux of calcium) decrease PVR, decreased myocardial contractility, decreased HR & cause AV block in some cases

All stages of HTNIschemic heart disease-Prinzmetals anginaAntiatherosclerotic actionsDifferential antiarrhythmic (V+D only)Cerebral vasospasm (migraine, raynauds phenomenon, renal protection in hypertensive diabetics.)

ActionsArterial vasodilation (DHPs >> V > D)Negative inotropic,chronotropic & dromotropic action (V>D>>>>DHPs)Reflex tachycardia (DHPs only)

Hypotension (particularly w/IV use)dizziness, headache, flushing (vasodilation)peripheral (ankle) edema (vasodilation)

V>D>>>>DHPsnegative intropism/ dromotropism/ chronotropyexacerbated by B blockersverapamil increases plasma digoxin levelsGingival hyperplasia (DHPs)Constipation (V)Tachycardia (DHPs)

Mild/moderate HTN (+/- diuretic or B blocker)Initial mono therapy use discouraged by ALLHATNo block of presynaptic a2 adrenoceptors = less reflexive tachycardia than w/non-selective blockImproved CO in CHFIncr HDL, decr total chol (LDL) and decr TG.

“First-Dose” Syncope – xs hypotension and orthostatic hypotensionReflex cardiac stimulation because of orthostatic hypotension (palpitations, angina)Orthostatic complaints (edema, dizziness, fatigue)Retrograde ejaculation, priapism

CHFModerate severe HTN (w/diuretic & sympatholytic) -Marked Pseudotolerance (reflex cardiac stimulation & renal fluid & Na retention): use with with B blocker or sympatholytic drug or a diuretic (block renal response)

Drug Induced Lupus“Slow Acetylator” phenotype specific Vascular headache (cerebral dilation)Reflex tachycardiaMyocardial ischemiaWeight gain and edema

Centrally Active Antihypertensives

Adrenergic neuron BlockersHTN – use limited by CNS effects.

Severe HTN – last resort drug.

Hypertensive Crisis Drugs

HirsutismPericardial effusion

Moderate/severe HTNAnalgesiaETOH, opiod, tobacco cessationPost-trauma stress syndromeCHFClonidine:adjunctive analgesic actions (CNS alpha2-effect)limits sympathetic components of withdrawal from drugs Calming in severe ADHD

For all drugsDry mouth, sedation, ImpotenceWithdrawal (C>>GB=GF>>aMD): hypersymp. and MI

A-MD onlyFatigue, sedation, depression, nightmaresGalactorrhea (increase prolactin)Autoimmune related (+Coombs, hemolytic anemia, abnormal LFT)

Sedation, decr concentration.Diarrhea, incr acid secretion.Pseudotolerance (incr renin).Major depression (high doses)

Othostatic hypotension.GI – diarrhea, gastric a. secretion.Inhibition of ejaculation.Incr sensitivity to adrenergic agonists (receptor up regulation).

Severe elevation in BP with evidence of ongoing target organ damageReduce mean BP by no more than 25% or to ~160/100 mm Hg (min to 2h)Generally in ICUAttention to fluid status

Antiarrhythmic Agents

Hypotension may occur by direct negative inotropic effect

Na+ Channel blockade (inward): moderate Phase 0 block (and also Phase III block)

Vagolytic action (Antimuscarinic): Increase QRS, QT, Prolong ERP/APD [End Resting Potential/Action Potential Duration]Suppress accessory pathways and useful in pre-excitation arrhythmias - Wolf-Parkinson-White

- Wide spectrum of efficacy limited by high incidence of G.I. and cardiac toxicity (pro-arrhythmia)- Chronic suppression of atrial fibrillation/flutter, including WPW- Chronic suppression of some ventricular tachycardias- efficacy against supraventricular and ventricular arrhythmias

hypotension may occur by α-adrenoceptor blockade- G.I.: Nausea, diarrhea frequently seen- Cinchonism (CNS): Headache, Dizziness, Tinnitus; see double- Allergic: Rash, Fever, Thrombocytopenia- Hypotension due to alpha-blocking vasodilation- Quinidine syncope

Drug interactions: Digoxin levels increased by quinidine _ Prolong QRS, QT : Avoid in patients with “Long QT” syndrome - Torsades de pointes

- Conversion of SVTs to sinus rhythm- Control of ventricular rate in atrial arrhythmias due to accessory path conduction (e.g.., WPW) - Wide complex tachycardias of unknown origin- prolongs effective refractory period in ventricular/atrial cells

Hypotension may occur by ganglionic block, Drug-induced lupus (esp. in “slow acetylators”), Agranulocytosis (0.2% incidence; 25% lethal); joint pain, fever

Significant anti-muscarinic effectsMyocardial depression = reduced cardiac output

Effective against DADs in digitalis glycoside intoxication

Only for chronic ventricular tachycardias

Decrease QT interval, Slightly slow Phase 0)

Use-dependence (Na+ channel kinetics): increased Na+ channel blockade as heart rate increases

Useful only against ventricular tachyarrhythmias (particularly after acute MI)- Hemodynamically stable VT- Hemodynamic compromised PVC- Persistent VF/pulseless VT- Digitalis-induced VT

Significant local anesthetic CNS toxicities in greater than therapeutic doses (>9 μg/ml) may cause excessive cardiac slowing/asystole after acute MI & HypoTN in CHF- Paresthesias, tremor, nausea, light-headedness, hearing difficulty, slurred speech, convulsions, respiratory arrestLow incidence of toxicity

- CNS toxicities common- Ataxia, nystagmus- GI distress-Nausea, dyspepsia, Gingival hyperplasia

Adverse effects common - Nausea, Local anesthetic-like CNS toxicities

Slow kinetics (bind avidly to, and only slowly dissociate from, sodium channels) exert effects even on normal HR’s

Marked pro-arrhythmic effects

Block pro-arrhythmic actions of catecholamines

(useful for slowing ventricular rate in supraventricular arrhythmias)antianginal actions (Catecholamines are released in MI)

-optimal management of hyperthyroidism and ventricular arrhythmias

K+ Channel blockade Prolong APD and refractory period (all block K+ channels EXCEPT ibutilide)Reverse use dependence: bind best at slower rates (EXCEPT amiodarone); Complex actions; Very efficacious; Highly toxic

-Broad spectrum anti-arrhythmic Sustained, life-threatening ventricular tachycardias-Atrial tachycardias (incl. Atrial fibrillation)-Suppresses Wolff-Parkinson-White accessory pathways-Compromised LV function -May ↓ sudden death after MI, in CHF due to acute tachycardia

-ECG EffectsDecrease sinus rate (Ca; β-block)Prolong PR, AV node ERP (Ca block)Widen QRS (Na+ block)Prolong QT (K+ block)

Multiple and serious adverse effects compromise chronic oral therapy with :-pulmonary fibrosis (irreversible and life-threatening)-photosensitivity- skin discolor-hypo/hyperthyroidism (iodine in drug)-GI distress, constipation-corneal micro-deposits,-lengthy, complex tissue distribution and elimination (sequestration)-kinetics leading to frequent drug interactions-CNS & peripheral nerve disorders.-Ataxia, tremor, sleep, disturbances

Prolong APD, but least likely to result in les torsades de pointes among Class III agents can show use-dependence (due to its Na+-channel blockade), rather than reverse use-dependence

Persistent atrial fibrillation - QT prolongation & les torsades de pointes

can ENHANCE conduction through accessory pathways (WPW)

Reserved for refractory arrhythmias, severe angina les torsades de pointessupraventricular arrhythmias involving the AV node

Can cause les torsades de pointes β-adrenoceptor blocker side effects

IV for acute cardioversion of atrial flutter and fibrillation

Can cause les torsades de pointes

supraventricular (atrial and AV nodal) tachyarrhythmias w/ virtually no efficacy against ventricular arrhythmias

supraventricular arrhythmias involving the AV node

can ENHANCE conduction through accessory pathways (WPW)

Atrial flutter & fibrillationMost useful in CHF with atrial fibrillation

Shortens effective refractory periods in accessory pathways lead to ventricular fibrillation in WPW syndrome (CI)

- Treatment of choice for Torsades de Pointes- Also digitalis arrhythmias, particularly in hypomagnesemia - Pre-eclampsia

Given IV to treat paroxysmal intervals of tachycardia w/ narrow QRS (acute supraventricular tachyarrhythmias)

“Adenosine Pause,” Flushing, Dyspnea, Care in WPW, Bradycardia, AV block, can lead to ventricular fibrillation, if used in WPW with atrial fibrillation Remember to push into proximal vein!

intracellular cGMPtarget a soluble guanyl cyclase to increase cGMP vasodilation (does not inhibit platelet aggregation)selective venodilators reduce preload (venous return) on the myocardium

poorly bioavailable when taken by mouth and absorbed through the GI systemDifferential Dx of chest pain relieved by nitroglycerin: biliary and esophageal spasms

DOC for stable exertional angina- Rapid onset, short duration- Little tolerance to occasional use

-reflex tachycardia and increase in MCF-headache, facial flushing, postural hypotension-syncope, -and in special situations, nausea (oral agents, transderm patch), and methemoglobinemia (overdosage in infants).-Chronic administration : NVD toleranceContraindicated with PDE 5 inhibitors like Sildenafil (Viagra) and in cases of increased intracranial pressure- would make the prob worse

Angina (Stable, Unstable, Prinzmetel’s) - vasodilator: veins>arteries>>>arterioles & pre-capillary sphincters

Headache, mild burning sensation in mouth -Orthostatic hypotension - Tachycardia - -Contraindicated with PDE 5 inhibitors like Sildenafil (Viagra) and in cases of increased intracranial pressure- would make the prob worse

Women are more sensitive than men to the hypotensive actions

antiarrhythmic; reduce MCF, HR

Use in severe, refractory angina only prolongs APD and can precipitate les torsades de pointes

decrease HR, contractile force, BP (Decrease afterload, increase preload)b. Increase O2 supply by improving diastolic perfusion of cardiac tissue (increased diastolic interval)c. Reduce ventricular arrhythmias- decreased AV node conduction (Phase IV depolarization), inc V Fib threshold

Increase left ventricular end diastolic volume (preload) by reducing contractility—inc O2 demandb. unmask α-adrenoceptor mediated constriction—potential for aggravation of Prinzmetals angina (CI)

Use with nitrates: prevent reflex tachycardia, less increase in left ventricular filling pressure (preload) together, they reduce myocardial oxygen consumption and increase subendocardial blood flow

Approved in 2006 for chronic angina patients who remain symptomatic on β-blockers, Ca++-blockers or nitrates

Constipation, nausea, asthenia, dizziness-Contraindicated in hepatic failure (CYP3A4 metabolism) or with drugs that prolong QT interval

-For chronic stable angina in patients with normal sinus rhythm, with contraindication or intolerance for beta blockers

Visual adverse effects of luminous phenomena or phosphenes (Inhibits retinal current Ih, which participates in visual responses)

Renal failure if preexisting renal art. stenosisexcess hypotension and headache

Heart Failure

Incompatible with: heparin, insulin, furosemide, ethacrynic acid,

Antifungals

Candida albicans and cryptococcal infections Bone marrow depression GI dist, and hepatotoxic

GI, skin, liver, CYP450

Only used to treat infections caused by dermatophytes GI, hepatic, renal, hematologicalTreat Dermatophytes Used topically for Candida or to suppress GI fungus in

Use for Acute decompensated heart failure with dyspnea at rest.

LV systolic failure and A. fib. S3 gallop, LV ejection fraction < 40%

Hyperkalemia reduces digitalis binding to enzyme Toxicity can be managed with Stopping drug and administer digoxin-specific Fab (Digibind) Can treat arrhythmias with Lidocaine

Wide antifungal spectrum- synergic vs candida and crypto w/ flucytosine

Chills, fever, electrolyte dysfunction, shock-like syndrome, renal

Wide spectrum- blasto, coccidioides, histo, candida, dermatophytes