Class 6 - Cardiac Drugs

Cardiac Output

CO=Heart Rate x Stroke Volume

HR between 60-100 is idealStroke Volume

PRELOADAFTERLOADCONTRACTILITY

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PRELOADPreload is the filling pressure of the

heart

Too much = overloadToo little = not enough

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AFTERLOADAfterload is the amount of pressure

that the heart has to pump againstToo much pressure can ↓COToo little pressure can ↓CO

*Each heart chamber must exceed the pressure in the next chamber for the heart valves to open

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CONTRACTILITYThe strength of the heart muscle

gives it the ability to contract

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Cardiac DrugsAll cardiac drugs are given so that

the patient has a good cardiac output!!!

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Action Sites

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Treatments that affect Preload

Goal= ↓volume & ↓pressure in the left ventricle

Decrease PreloadDiureticsNitrates (venous vasodilators)Morphine SulfateFluid restriction

Increase preloadFluid Intake 8

Treatments that affect Afterload

Vasodilate ArteriolesDecrease Afterload

ACE InhibitorsARB’sAdrenergic Antagonists

Alpha & Beta Blockers & CombinedIndirect-Acting Antiadrenergic

AgentsVasodilators (Arterial)Ca+ Channel Blockers 9

Treatments that affect Afterload

Vasoconstrict ArteriolesIncrease afterload

Vasopressors

10

Treatments that affect Contractility

Inotropes/ cardiac glycosides

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DiureticsLehne (Figure 40-2)↓Cardiac Preload

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DiureticsHigh-Ceiling (Loop) DiureticsThiazide DiureticsPotassium-Sparing Diuretics

Aldosterone AntagonistNonaldosterone Antagonist

Osmotic Diuretics

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High-Ceiling (Loop) DiureticsFurosemide®LasixAction:

Promote urine production by blocking reabsorption of Na+ & Cl- in the Loop of Henle

Prevents passive reabsorption of H2O↓SVR & ↓BP

14

High-Ceiling (Loop) DiureticsFurosemide®LasixTreatment:

Use other diuretics FIRST!Pulmonary Edema associated with CHFEdema of hepatic, cardiac, renal originHTN**Effective diuresis despite renal

insufficiency**

15

High-Ceiling (Loop) DiureticsFurosemide®LasixSide Effect:

Hyponatremia, HypochloremiaDehydrationOrthostaic hypotensionHypokalemia (↓K+)Ototoxicity—reversibleHyperglycemiaHyperuricemia↓HDL, ↑LDL, ↓Magnesium, ↓Ca+

16

Thiazide DiureticsHydrochlorothiazide (HCTZ)

®HydroDIURILAction:

Promote urine production by blocking reabsorption of Na+ & Cl- in the early segment of the distal convoluted tubule

Prevents passive reabsorption of H2O↓SVR & ↓BPSimilar to Loop diuretic but less diuretic

effect & cannot help diuresis during renal insufficiency

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Thiazide DiureticsHydrochlorothiazide (HCTZ)

®HydroDIURILTreatment:

Essential HTNEdemaDiabetes Insipidus

Other Thiazide Diuretics:Chlorthiazide®DiurilChlorthalidone®Hygroton

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Thiazide DiureticsHydrochlorothiazide (HCTZ)

®HydroDIURILSide Effect:

Similar to Loop Diuretic EXCEPT NO Ototoxicity

NSAIDS decrease effect

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Potassium-Sparing DiureticsAction:

Modest ↓urine production↓K+ & Na+ exchange which retains K+

Treatment:Counteract K+ Loss caused by Loop &

Thiazide diureticsTypes:

Aldosterone AntagonistsNonaldosterone Antagonists

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Potassium-Sparing DiureticsAldosterone Antagonists

Spironolactone ®AldactoneBlocks the actions of Aldosterone in

distal nephron (causing Retention of K+ & ↑Excretion of Na+)

Treatment:HTNEdemaUse concurrently with Loop/thiazide

diuretics to counteract K+ wasting effect 21

Potassium-Sparing DiureticsAldosterone Antagonists

Spironolactone ®AldactoneSide Effect:

HyperkalemiaBenign & Malignant TumorsEndocrine effects

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Potassium-Sparing DiureticsNonaldosterone AntagonistsTriamterene®Dyrenium /

Amioride®MidamorDirectly inhibits the Na+ & K+ exchange in

distal nephron (causing Retention of K+ & ↑Excretion of Na+)

Treatment:HTNEdemaUse concurrently with Loop/thiazide

diuretics to counteract K+ wasting effect 23

Potassium-Sparing DiureticsNonaldosterone AntagonistsTriamterene®Dyrenium /

Amioride®MidamorSide Effect:

Hyperkalemia

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Osmotic DiureticsMannitol®Osmitrol

Action:Promotes diuresis by creating an

osmotic force within the lumen of the nephron

Inhibits passive reabsorption of H2OTreatment:

Prophylaxis of Renal Failure↓ICP (Intracranial pressure)↓IOP (Intraocular pressure) 25

Osmotic DiureticsMannitol®Osmitrol

Side Effect:EdemaFluid & Electrolyte Imbalance

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Organic NitratesAction:

Venous vasodilator (↓Cardiac Preload)Minimal Arterial vasodilator

(↓Cardiac Afterload)Treatment:

Angina PectorisHeart FailureMI

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Organic NitratesNitroglycerin

Sublingual = Nitrostat, NitrotabTransdermal patches = Nitro-DurTopical Ointment = Nitro-BidIV = Nitro-Bid IV, Tridil

Isosorbide Mononitrate = Imdur, ISMO, Monoket

Isosorbide Dinitrate = Isordil

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Organic NitratesSide Effects:

HeadacheOrthostatic hypotensionSublingual burningContact dermatitis—patchReflex TachycardiaFlushing

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Morphine SulfateAction:

Opioid AnalgesicCoronary Vasodilator↓WOB (work of breathing)↓Preload (↓venous return)↓Afterload↓Anxiety

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Morphine SulfateTreatment:

Heart FailurePulmonary EdemaMI

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Morphine SulfateSide Effect:

Respiratory DepressionSedation/Euphoria/Dysphoria (Anxiety)Orthostatic HypotensionBradycardiaConstipationUrinary RetentionCough SuppressionBiliary Colic (spasm of common bile duct)Emesis↑ICP

(↓RR → ↑CO2 → dilation of cerebral vasculature) 32

Drugs Affecting the Renin-Angiotensin-Aldosterone System (RAAS)Angiotensin-Converting Enzyme

(ACE) InhibitorsAngiotensin II Receptor Blockers

(ARBs)

Reminder:↓Afterload

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Renin-Angiotensin-Aldosterone System (RAAS)

Kidneys release Renin when triggered by ↓BP, ↓blood volume, ↓renal profusion, Na+ depletion, β1 stimulation

→ Angiotensinogen activates Angiotensin I→ Angiotensin I converts to Angiotensin II in the lungs→ Angiotensin II causes

→ Systemic Vasoconstriction (↑BP)→ Increase Aldosterone secretion

(Na+ & H2O Retention & loss of K+)(↑blood volume)

→ Renal vasoconstriction, ↓renal blood flow, ↓GFR

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EFFECTS of Angiotensin-Converting Enzyme (ACE) Inhibitors

**Inhibits or blocks Angiotensin I from converting to Angiotensin II**

Action:↓Afterload↓Blood Pressure↑Urine VolumePrevents Vasoconstriction

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EFFECTS of Angiotensin-Converting Enzyme (ACE) Inhibitors

**Inhibits or blocks Angiotensin I from converting to Angiotensin II**

Treatment:HTNCHFDiabetic NephropathyMIPrevent cardiovascular events

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EFFECTS of Angiotensin-Converting Enzyme (ACE) Inhibitors

**Inhibits or blocks Angiotensin I from converting to Angiotensin II**

“pril”Captopril ®CapotenLisinopril ®ZestrilEnalapril ®Vasotec

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EFFECTS of Angiotensin-Converting Enzyme (ACE) Inhibitors

**Inhibits or blocks Angiotensin I from converting to Angiotensin II**

Side Effects:HypotensionDizzinessHyperkalemiaRashCough—inhibit bradykinin breakdown in

lungsAcute Renal FailureAngioedema (↑capillary permeability

causing edema of tongue, glottis, pharynx) 38

EFFECTS of Angiotensin II Receptor Blockers (ARBs)

**Inhibits or blocks action of Angiotensin II**

Action:↓Blood Pressure↑Urine VolumePrevents Vasoconstriction

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EFFECTS of Angiotensin II Receptor Blockers (ARBs)

**Inhibits or blocks action of Angiotensin II**

Treatment:HTNCHFDiabetic NephropathyMI (Valsartan ®Diovan)Stroke prevention (Losartan ®Cozaar)

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EFFECTS of Angiotensin II Receptor Blockers (ARBs)

**Inhibits or blocks action of Angiotensin II**

“sartan”Losartan ®CozaarCandesartan ®AtacandValsartan ®DiovanTelmisartan ®Micardis

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EFFECTS of Angiotensin II Receptor Blockers (ARBs)

**Inhibits or blocks action of Angiotensin II**

Side Effects:HyperkalemiaRenal FailureDizzinessHypotensionAngioedema (↑capillary permeability

causing edema of tongue, glottis, pharynx) 42

Cholinergic Vs. Adrenergic ReceptorsLehne (Table 13-2 & 13-2)

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Adrenergic InhibitorsAdrenergic Antagonists

(Causes direct blockade of adrenergic receptors)Alpha-adrenergic BlockersBeta-adrenergic BlockersCombined α & β Blockers

Indirect-Acting Antiadrenergic Agents

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Alpha-Adrenergic BlockersAction:

Selective blockade of alpha 1 receptorsTreatment:

HTNBPHPheochromocytoma

(catecholamine/epi. & norepi. -secreting tumor)

Raynaud’s DiseaseReversal of toxicity from Alpha 1 Agonist

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Alpha-Adrenergic Blockers“osin”

Prazosin ®MinipressTerazosin ®HytrinDoxasosin ®CarduraTamsulosin ®Flomax

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Alpha-Adrenergic BlockersSide Effects:

Orthostatic HypotensionReflex TachycardiaDry MouthSedationDepressionErectile problemsNa+ Retention & ↑Blood Volume

(***Combined with diuretics to prevent kidneys from “neutralizing” hypotensive actions***) 47

Beta-Adrenergic BlockersAction:

Selective blockade of Beta 1 receptors (esp. heart)

β-Adrenergic antagonist effects:↓HR, ↓Force of contraction, ↓AV

conduction velocity (↓O2 demand)↓Renin secretion (↓BP, ↓Blood volume)↑Vasoconstriction (heart, lung, skeletal

muscle)Bronchoconstriction

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Beta-Adrenergic BlockersTreatment:

Angina PectorisHTNCardiac DysrhythmiasMIHeart Failure (carvedilol, bisoprolol, metoprolol)HyperthyroidismPrevent MigraineStage FrightPheochromocytoma (catecholamine/epi. & norepi.

-secreting tumor)Glaucoma

49

Beta-Adrenergic Blockers“olol”

Atenolol ®TenorminMetoprolol®Lopressor, Toprol XLNadolol®CorgardPropranolol®Inderal

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Beta-Adrenergic BlockersSide Effects:

Bradycardia↓COMay exacerbate HFAV BlocksSudden withdrawal→ Rebound Cardiac

Excitation (e.g. Angina, Ventricular dysrhythmias)

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Beta-Adrenergic BlockersSide Effects: (cont’d)

BronchoconstrictionInhibition of Glycogenolysis

(breakdown of glycogen → glucose)Depression/InsomniaErectile Dysfunction

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Combined α & β BlockersAction:

Peripheral vasodilation↓HR, ↓BP, ↓CO, ↓SVR

Treatment:HTNAnginaMI

Carvedilol®CoregLabetalol®Normodyne 53

Combined α & β BlockersSide Effects:

Postural hypotensionBradycardiaAV heart blockHFBronchoconstriction

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Combined α & β BlockersSide Effects: (cont’d)

Inhibition of Glycogenolysis (breakdown of glycogen → glucose)

Sudden withdrawal→ Rebound Cardiac Excitation (e.g. Angina, Ventricular dysrhythmias)

Erectile dysfunctionDepression/Insomnia

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Indirect-Acting Antiadrenergic AgentsAction:

Indirectly prevents activation of peripheral adrenergic receptors

Types:Adrenergic Neuron-Blocking AgentsCentrally Acting Alpha 2 Agonists

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Indirect-Acting Antiadrenergic AgentsAdrenergic Neuron-Blocking Agents

Reserpine®SerpasilAct presynaptically to reduce the

release of norepinephrine (NE) from sympathetic neurons to produce similar effects to combined α & β Blockers:Peripheral vasodilation↓HR, ↓BP, ↓CO, ↓SVR

Treat: HTN57

Indirect-Acting Antiadrenergic AgentsAdrenergic Neuron-Blocking Agents

Reserpine®SerpasilSide Effect:

Severe depressionBradycardia, Orthostatic hypotension,

Nasal congestionUlcer formation, Cramps, Diarrhea

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Indirect-Acting Antiadrenergic AgentsCentrally Acting Alpha 2 Agonists

Act within the CNS to reduce the firing of sympathetic neurons (i.e. ↓ release of NE from sympathetic nerve thus ↓ activation of peripheral adrenergic receptors) to produce similar effects to combined α & β Blockers:Peripheral vasodilation↓HR, ↓BP, ↓CO, ↓SVR

Treatment: HTN59

Indirect-Acting Antiadrenergic AgentsCentrally Acting Alpha 2 Agonists

Clonidine®CatapresTreatment:

HTNSevere cancer pain via epidural infusion(®Duraclon)

Side Effects: DrowsinessXerostomia (dry mouth)Rebound HTN

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Indirect-Acting Antiadrenergic AgentsCentrally Acting Alpha 2 Agonists

Methyldopa®AldometTreatment:

HTNSide Effect:

(+)Coombs’ Test (detects the presence of antibodies directed against the patient’s own RBCs) → Hemolytic Anemia

Hepatic Necrosis 61

VasodilatorsDiffers with regards to which vessels

are affected:Arterioles (Arterial vasodilation) = ↓SVR, ↓Cardiac Afterload→ ↑CO & ↑tissue perfusion→ ↓BP

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VasodilatorsDiffers with regards to which vessels

are affected:Veins (Peripheral vasodilation) = ↓Force of blood returning to the heart → ↓Ventricular filling → ↓Cardiac Preload → ↓Force of Ventricular Contraction → ↓CO & ↓tissue perfusion

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VasodilatorsTreatment:

Essential HTNHTN CrisisAnginaHeart FailureMIPheochromocytomaPVDPulmonary Arterial HTNControlled hypotension during surgery

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VasodilatorsSide Effects:

Postural HypotensionReflex TachycardiaExpansion of Blood Volume (thus

concurrent diuretic therapy)HeadacheFlushing

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Direct VasodilatorsHydralazine®ApresolineMinoxidil®LonitenDiazoxideSodium Nitroprusside-Nipride

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Direct VasodilatorsHydralazine®Apresoline

Arterial vasodilator

Minoxidil®LonitenArterial vasodilatorMore severe adverse reactions thus

concurrent β-Adrenergic Blockers & Diuretics

SE: Hypertrichosis (excessive hair growth), Pericardial Effusion 67

Direct VasodilatorsDiazoxide®Hyperstat IV

Arterial vasodilatorHTN EmergencySE: Hyperglycemia, Hyperuricemia

Sodium Nitroprusside-NiprideArterial & Venous vasodilatorHTN EmergencyFastest acting antihypertensive agentSE: Excessive hypotension, cyanide poisoning,

thoicyanate toxicity68

Calcium Channel BlockersAction:

Block movement of extracellular calcium into cells of the Vascular Smooth Muscle (VSM)↓ContractilityVasodilation of the arterioles of the heart & peripheral arterioles

↓HR↓SVR 69

Calcium Channel BlockersTreatment:

HTNAnginaCardiac Dysrhythmias

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Calcium Channel BlockersVerapamil®Isoptin, ®CalanAmlodipine®NorvascDiltiazem®CardizemNifedipine®Adalat, ®Procardia

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Calcium Channel BlockersSide Effects:

ConstipationBradycardia & Heart blocks

(Caution concurrent use of Digoxin, β-Blockers)FlushingRashHeadacheDizzinessEdemaGingival Hyperplasia (Overgrowth of gum

tissue)Nifedipine—avoid grapefruit 72

Adrenergic Agonists/SympathomimeticsEpinephrine ®AdrenalineActivates α1, α2, β1, β2 receptors:

Vasoconstrictor (Arterial & Venous)↑Afterload

Treatment: AV Heart BlockCardiac ArrestHypotensionControl superficial bleedingAsthma with bronchodilationAnaphylactic Shock

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Adrenergic Agonists/SympathomimeticsEpinephrine ®AdrenalineGiven Injection, Inhalation, IVSide Effect:

HTN CrisisDysrhythmiasAnginaNecrosis following Extravasation

(Counteract with Phentolamine)Hyperglycemia (from Glycogenolysis)

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Adrenergic Agonists/SympathomimeticsNorepinephrine ®LevophedActivates α1, α2, β1 receptors:

Vasoconstrictor (Arterial & Venous)↑Afterload

Treatment: Similar to Epinephrine EXCEPT NO β2

receptor responseSide Effect:

Similar to Epinephrine EXCEPT NO β2 receptor adverse effect responses

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Adrenergic Agonists/SympathomimeticsDopamine ®IntropinActivates Dopamine, β1 & at high doses

α1↑AfterloadTreatment:

ShockHeart Failure

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Adrenergic Agonists/SympathomimeticsDopamine ®IntropinSide Effect:

TachycardiaDysrhythmiasAnginal pain Necrosis following Extravasation

(Counteract with Phentolamine)

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Inotropic Agents/Digitalis GlycosidesDigoxin- ®Digitek, ®LanoxinAction:

(+) Inotropic action of heart↑Force of ventricular contractions↑CO (↓Sympathetic Tone, ↑Urine

Production, ↓Renin release)Treatment:

HFDysrhythmiasCardiogenic Shock 78

Inotropic Agents/Digitalis GlycosidesDigoxin- ®Digitek, ®LanoxinSide Effect:

Ventricular DysrhythmiasHypokalemia Elevated serum Digoxin level

(Counteract with Fab antibody fragments ®Digibind)

Anorexia, Nausea, VomitingFatigueVisual disturbances

79

Anti-Platelet DrugsAspirin/ASAAction:

Suppress Platelet AggregationTreatment:

Prevent arterial thrombosisPrimary prevention of MI

Side Effect: GI Bleeding (Counteract with Proton

Pump Inhibitor)Hemorrhagic Stroke

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Anti-Platelet DrugsAspirin/ASADosing:

Initial Treatment = 325 mg/dayMaintenance Therapy = 81 mg/day

81

Anti-Platelet DrugsClopidogrel ®PlavixAction:

Irreversible blockade of ADP receptors on platelets thus prevents ADP-stimulated aggregation

Treatment:Secondary prevention of MI, Ischemic

stroke, other vascular events

82

Anti-Platelet DrugsClopidogrel ®PlavixSide Effect;

Abdominal painDyspepsiaDiarrheaRash

83