Cardiac Output
CO=Heart Rate x Stroke Volume
HR between 60-100 is idealStroke Volume
PRELOADAFTERLOADCONTRACTILITY
2
PRELOADPreload is the filling pressure of the
heart
Too much = overloadToo little = not enough
3
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
4
CONTRACTILITYThe strength of the heart muscle
gives it the ability to contract
5
Cardiac DrugsAll cardiac drugs are given so that
the patient has a good cardiac output!!!
6
Action Sites
7
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
11
DiureticsLehne (Figure 40-2)↓Cardiac Preload
12
DiureticsHigh-Ceiling (Loop) DiureticsThiazide DiureticsPotassium-Sparing Diuretics
Aldosterone AntagonistNonaldosterone Antagonist
Osmotic Diuretics
13
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
17
Thiazide DiureticsHydrochlorothiazide (HCTZ)
®HydroDIURILTreatment:
Essential HTNEdemaDiabetes Insipidus
Other Thiazide Diuretics:Chlorthiazide®DiurilChlorthalidone®Hygroton
18
Thiazide DiureticsHydrochlorothiazide (HCTZ)
®HydroDIURILSide Effect:
Similar to Loop Diuretic EXCEPT NO Ototoxicity
NSAIDS decrease effect
19
Potassium-Sparing DiureticsAction:
Modest ↓urine production↓K+ & Na+ exchange which retains K+
Treatment:Counteract K+ Loss caused by Loop &
Thiazide diureticsTypes:
Aldosterone AntagonistsNonaldosterone Antagonists
20
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
22
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
24
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
26
Organic NitratesAction:
Venous vasodilator (↓Cardiac Preload)Minimal Arterial vasodilator
(↓Cardiac Afterload)Treatment:
Angina PectorisHeart FailureMI
27
Organic NitratesNitroglycerin
Sublingual = Nitrostat, NitrotabTransdermal patches = Nitro-DurTopical Ointment = Nitro-BidIV = Nitro-Bid IV, Tridil
Isosorbide Mononitrate = Imdur, ISMO, Monoket
Isosorbide Dinitrate = Isordil
28
Organic NitratesSide Effects:
HeadacheOrthostatic hypotensionSublingual burningContact dermatitis—patchReflex TachycardiaFlushing
29
Morphine SulfateAction:
Opioid AnalgesicCoronary Vasodilator↓WOB (work of breathing)↓Preload (↓venous return)↓Afterload↓Anxiety
30
Morphine SulfateTreatment:
Heart FailurePulmonary EdemaMI
31
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
33
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
34
EFFECTS of Angiotensin-Converting Enzyme (ACE) Inhibitors
**Inhibits or blocks Angiotensin I from converting to Angiotensin II**
Action:↓Afterload↓Blood Pressure↑Urine VolumePrevents Vasoconstriction
35
EFFECTS of Angiotensin-Converting Enzyme (ACE) Inhibitors
**Inhibits or blocks Angiotensin I from converting to Angiotensin II**
Treatment:HTNCHFDiabetic NephropathyMIPrevent cardiovascular events
36
EFFECTS of Angiotensin-Converting Enzyme (ACE) Inhibitors
**Inhibits or blocks Angiotensin I from converting to Angiotensin II**
“pril”Captopril ®CapotenLisinopril ®ZestrilEnalapril ®Vasotec
37
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
39
EFFECTS of Angiotensin II Receptor Blockers (ARBs)
**Inhibits or blocks action of Angiotensin II**
Treatment:HTNCHFDiabetic NephropathyMI (Valsartan ®Diovan)Stroke prevention (Losartan ®Cozaar)
40
EFFECTS of Angiotensin II Receptor Blockers (ARBs)
**Inhibits or blocks action of Angiotensin II**
“sartan”Losartan ®CozaarCandesartan ®AtacandValsartan ®DiovanTelmisartan ®Micardis
41
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)
43
Adrenergic InhibitorsAdrenergic Antagonists
(Causes direct blockade of adrenergic receptors)Alpha-adrenergic BlockersBeta-adrenergic BlockersCombined α & β Blockers
Indirect-Acting Antiadrenergic Agents
44
Alpha-Adrenergic BlockersAction:
Selective blockade of alpha 1 receptorsTreatment:
HTNBPHPheochromocytoma
(catecholamine/epi. & norepi. -secreting tumor)
Raynaud’s DiseaseReversal of toxicity from Alpha 1 Agonist
45
Alpha-Adrenergic Blockers“osin”
Prazosin ®MinipressTerazosin ®HytrinDoxasosin ®CarduraTamsulosin ®Flomax
46
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
48
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
50
Beta-Adrenergic BlockersSide Effects:
Bradycardia↓COMay exacerbate HFAV BlocksSudden withdrawal→ Rebound Cardiac
Excitation (e.g. Angina, Ventricular dysrhythmias)
51
Beta-Adrenergic BlockersSide Effects: (cont’d)
BronchoconstrictionInhibition of Glycogenolysis
(breakdown of glycogen → glucose)Depression/InsomniaErectile Dysfunction
52
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
54
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
55
Indirect-Acting Antiadrenergic AgentsAction:
Indirectly prevents activation of peripheral adrenergic receptors
Types:Adrenergic Neuron-Blocking AgentsCentrally Acting Alpha 2 Agonists
56
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
58
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
60
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
62
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
63
VasodilatorsTreatment:
Essential HTNHTN CrisisAnginaHeart FailureMIPheochromocytomaPVDPulmonary Arterial HTNControlled hypotension during surgery
64
VasodilatorsSide Effects:
Postural HypotensionReflex TachycardiaExpansion of Blood Volume (thus
concurrent diuretic therapy)HeadacheFlushing
65
Direct VasodilatorsHydralazine®ApresolineMinoxidil®LonitenDiazoxideSodium Nitroprusside-Nipride
66
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
70
Calcium Channel BlockersVerapamil®Isoptin, ®CalanAmlodipine®NorvascDiltiazem®CardizemNifedipine®Adalat, ®Procardia
71
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
73
Adrenergic Agonists/SympathomimeticsEpinephrine ®AdrenalineGiven Injection, Inhalation, IVSide Effect:
HTN CrisisDysrhythmiasAnginaNecrosis following Extravasation
(Counteract with Phentolamine)Hyperglycemia (from Glycogenolysis)
74
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
75
Adrenergic Agonists/SympathomimeticsDopamine ®IntropinActivates Dopamine, β1 & at high doses
α1↑AfterloadTreatment:
ShockHeart Failure
76
Adrenergic Agonists/SympathomimeticsDopamine ®IntropinSide Effect:
TachycardiaDysrhythmiasAnginal pain Necrosis following Extravasation
(Counteract with Phentolamine)
77
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
80
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
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