CONGESTIVE HEART FAILURE

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CONGESTIVE HEART FAILURE

• MA. LENY ALDA G. JUSAYAN, MD

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HEART FAILURE

• Inability of the heart to pump an adequate amount
  of blood to the bodys needs
• CONGESTIVE HEART FAILURE refers to the state in
  which abnormal circulatory congestion exists a
  result of heart failure

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CAUSES OF HEART FAILURE

• Final common pathway of many kinds of heart
  diseases
• Ischemic, alcoholic, restrictive, hypertrophic
• Optimal treatment requires identification of
  primary secondary factors leading to CHF
• HELPFUL RESULT of dilatation increases cardiac
  output
• HARMFUL RESULT of dilation more wall tension,
  more oxygen is needed to produce any given stroke
  volume

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CLASSIFICATION

• SYSTOLIC DYSFUNCTION
• Inadequate force is generated to eject blood
  normally
• Reduce cardiac output, ejection fraction (lt 45)
• Typical of acute heart failure
• Secondary to AMI
• Responsive to inotropics

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CLASSIFICATION

• DIASTOLIC DYSFUNCTION
• Inadequate relaxation to permit normal filling
• Hypertrophy and stiffening of myocardium
• Cardiac output may be reduced
• Ejection fraction is normal
• Do not respond optimally to inotropic agents

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CLASSIFICATION

• HIGH OUTPUT FAILURE
• Increase demand of the body with insufficient
  cardiac output
• Hyperthyroidism, beri-beri, anemia, AV shunts
• Treatment is correction of underlying cause

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CLASSIFICATION

• ACUTE HEART FAILURE
• Sudden development of a large myocardial
  infarction or rupture of a cardiac valve in a
  patient who previously was entirely well, usually
  predominant systolic dysfunction

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CLASSIFICATION

• CHRONIC HEART FAILURE
• Typically observed in patients with dilated
  cardiomyopathy or multivalvular heart diseases
  that develops or progresses slowly

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PRECIPITATING CAUSES OF HEART FAILURE

• Infection
• Anemia
• Thyrotoxicosis pregnancy
• Arrythmias
• Rheumatic, viral other forms of myocarditis
• Infective endocarditis
• Systemic hypertension
• Myocardial infarction
• Physical, dietary, fluid, environmental
  emotional excesses
• Pulmonary embolism

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PULMONARY CONGESTION RESPIRATORY SYMPTOMS

• Result of dilatation increasing left
  ventricular end diastolic pressure, left atrial
  pressure capillary pressures
• Results to pulmonary vascular congestion
  symptoms associated with cough with blood tinged
  sputum

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Cont.

• EDEMA OF THE BRONCHIAL MUCOSA
• Increases resistance to airflow producing
  respiratory distress similar to asthma (cardiac
  asthma)

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Cont

• DYSPNEA
• Results from reflexes initiated by vascular
  distention
• Increased rigidity of lungs impaired gas
  exchange resulting from interstitial edema
• Accumulation of fluid in ALVEOLARS SACS
  (pulmonary edema)

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Cont.

• TACHYCARDIA
• An early compensatory response mediated by
  increased sympathetic tone
• EDEMA
• compensatory response mediated by the renin
  angiotensin aldosterone system by increased
  sympathetic outflow
• CARDIOMEGALY
• a compensatory structural response

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SYMPTOMS

• Due to inadequate perfusion of peripheral tissues
  (fatigue, dyspnea)
• Elevated intracardiac filling pressures
  (orthopnea, PND, peripheral edema)

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PHYSICAL EXAM

• Jugular venous distention
• S3
• Rales
• Pleural effusion
• Edema
• Hepatomegaly
• Ascites

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All the signs of CHF are the consequences of
inadequate force of contraction"
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PATHOPHYSIOLOGY

• STARLINGS LAW
• Within limits, the force of ventricular
  contraction is a function of the end-diastolic
  length of the cardiac muscle, which in turn is
  closely related to the ventricular end-diastolic
  volume.

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PATHOPHYSIOLOGY

• Heart failure results in DEPRESSION of the
  ventricular function curve
• COMPENSATION in the form of stretching of
  myocardial fibers results
• Stretching leads to cardiac dilatation which
  occurs when the left ventricle fails to eject its
  normal end diastolic volume

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CARDIAC FAILURE
? VENOUS PRESSURE
? CARDIAC OUTPUT
? BLOOD PRESSURE
? SYMPATHETIC ACTIVITY
? RENAL BLOOD FLOW
? RENIN ANGIOTENSIN II
? ALDOSTERONE
? CAPILLARY FILTRATION
? SODIUM RETENTION
EDEMA
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NEUROHUMORAL ACTIVATION DURING MYOCARDIAL FAILURE
MYOCARDIAL FAILURE
? CARDIAC OUTPUT
? BLOOD PRESSURE/TISSUE PERFUSION
ACTIVATION OF ADRENERGIC SYSTEM
ARTERIOLAR CONSTRICTION
INCREASED SYSTEMIC VASCULAR RESISTANCE
INCREASED RESISTANCE TO EJECTION
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COMPENSATORY RESPONSES DURING HEART FAILURE
? CARDIAC OUTPUT
? CAROTID SINUS FIRING
? RENAL BLOOD FLOW
? SYMPATHETIC DISCHARGE
? RENIN RELEASE
? FORCE
? RATE
? PRELOAD
? AFTERLOAD
REMODELING

• CARDIAC OUTPUT
• (VIA COMPENSATION)

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Pathophysiology of Cardiac Performance
Factor Mechanism Therapeutic Strategy
1. Preload (work or stress the heart faces at the end of diastole) increased blood volume and increased venous tone---gtatrial filling pressure -salt restriction-diuretic therapy-venodilator drugs
2. Afterload (resistance against which the heart must pump) increased sympathetic stimulation activation of renin-angiotensin system ---gt vascular resistance ---gt increased BP - arteriolar vasodilators-decreased angiotensin II(ACE inhibitors)
3. Contractility decreased myocardial contractility ---gt decreased CO -inotropic drugs (cardiac glycosides)
4. Heart Rate decreased contractility and decreased stroke volume ---gt increased HR (via activation of b adrenoceptors)
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CLINICAL MANAGEMENT OF CONGESTIVE HEART FAILURE

• OBJECTIVES
• Increase cardiac contractility
• Decrease preload ( left ventricular pressure)
• Decrease afterload (systemic vascular resistance)
• Normalize heart rate and rhythm

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• ApproachesReduce workload of heart
• 1.Limit activity level reduce weight control
  hypertension
• 2. Restrict sodium (low salt diet)3. Give
  diuretics (removal of retained salt and
  water)4. Give angiotensin-converting enzyme
  inhibitors(decreases afterload and retained salt
  and water)5. Give digitalis (positive inotropic
  effect on depressed heart)6. Give vasodilators
  (decreases preload afterload)

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DRUGS USED TO TREAT CONGESTIVE HEART DISEASE

• VASODILATORS
• Reduce the preload (through venodilatation), or
  reduction in afterload (through arteriolar
  dilatation) or both
• Decrease the load of the myocardium

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DIURETIC AGENTS

• Reduce salt water retention, thereby reducing
  ventricular preload
• INOTROPIC AGENTS
• Increase the strength of contraction of cardiac
  muscles

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DRUGS USED TO TREAT CONGESTIVE HEART FAILURE
VASODILATORS
INOTROPIC AGENTS

• CAPTOPRIL
• ENALAPRIL
• FOSINOPRIL
• LISINOPRIL
• QUINAPRIL
• HYDRALAZINE
• ISOSORBIDE
• MINOXIDIL
• SODIUM NIITROPRUSSIDE

-DIGOXIN -DIGITOXIN -DOBUTAMINE -AMRINONE -MILRI
NONE
DIURETICS
-BUMETANIDE -FUROSEMIDE -HYDROCHLOROTHIAZIDE -META
LAZONE
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BASIC PHARMACOLOGY OF DRUGS USED IN CONGESIVE
HEART FAILURE

• DIGITALIS
• PHARMACOKINETICS
• DIGOXIN DIGITOXIN
• LIPID SOLUBILITY MEDIUM HIGH
• ORAL AVAILABILITY 75 gt90
• HALF-LIFE 40 HRS 168 HRS
• PLASMA PROTEIN BINDING 20-40 HRS gt90 HRS
• PERCENTAGE METABOLIZED lt20 gt80
• VOLUME OF DISTRIBUTION 6.3 L/KG 0.6 L/KG

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• PHARMACOKINETICS
• -T1/2 is long (40 hrs)-Therapeutic plasma
  concentration 0.5-2 ng/ml-Toxic plasma
  concentration gt2 ng/ml
• digitalis must be present in the body in certain
  "saturating" amount before any effect on
  congestive failure is noted
• this is achieved by giving a large initial dose
  in a process called "digitalization"
• -after intial dosages, digitalis is given in
  "maintenance" amounts sufficient to replace that
  which is excreted
• to avoid exceeding therapeutic range during
  digitalization- the loading dose should be
  adjusted according to the health of the patient-
  slow digitalization (over 1 week) is the safest
  technique- plasma digoxin levels should be
  monitored

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METABOLISM EXCRETION

• Digoxin not extensively metabolized, 2/3
  excreted unchanged in the kidneys
• Digitoxin metabolized in the liver and excreted
  into the gut via the bile

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MECHANISM OF ACTION

• Inhibit the monovalent cation transport enzyme
  coupled Na, K ATPase increased intracellular
  Na content ? increases intracellular Ca2
  through a Na - Ca2 exchange carrier mechanism.
• Increased myocardial uptake of Ca2 augments Ca2
  release to the myofilaments during excitation ?
  invokes a positive inotropic response

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MECHANISM OF ACTION

• Produce alterations in the electrical properties
  of both contractile cells and the specialized
  automatic cells, leading to increased
  automaticity ectopic impulse activity
• Prolong the effective refractory period of the AV
  node ? slow ventricular rate in atrial flutter
  fibrillation

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PROPERTIES OF CARDIAC GLYCOSIDES
OUABAIN DIGOXIN DIGITOXIN
Lipid solubility (oil/water coefficient) Low Medium High
Oral availability ( absorbed) 0 75 gt 90
Half-life in the body (hrs) 21 40 168
Plasma protein binding ( bound) 0 lt20 gt80
Volume of distribution 18 6.3 0.6
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EFFECTS IN HEART FAILURE

• Stimulates myocardial contractility
• Improves ventricular emptying
• Increase cardiac output
• Augments ejection fraction
• Promotes diuresis
• Reduces elevated diastolic pressure volume
  end systolic volume
• Reduces symptoms resulting from pulmonary
  vascular congestion elevated systemic venous
  pressure

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DIGITALIS INTOXICATION

• Serious potentially fatal complication
• Anorexia, nausea vomiting earliest signs of
  digitalis intoxication
• Arrythmias ventricular premature beats,
  bigeminy, ventricular atrial tachycardia w/
  variable AV block
• Chronic digitalis intoxication exacerbations of
  heart failure, weight loss, cachexia, neuralgias,
  gynecomastia, yellow vision, delirium

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TREATMENT OF DIGITALIS INTOXICATION

• Tachyarrythmias withdrawal of the drug,
  treatment with beta blocker or lidocaine
• Hypokalemia potassium administration by the oral
  route

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OTHER POSITIVE INOTROPIC DRUGS USED IN HEART
FAILURE

• BIPYRIDINES
• Amrinone Milrinone
• Parenteral forms only
• Half-life 2-3 hrs
• 10-40 excreted in the urine
• MOA increase inward calcium influx in the heart
  during action potential inhibits
  phosphodiesterase
• ADVERSE EFFECTS nausea, vomiting,
  thrombocytopenia, liver enzyme changes

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BETA ADRENOCEPTOR STIMULANTS

• DOBUTAMINE
• Increases cardiac output
• Decrease in ventricular filling pressure
• Given parenterally
• CONTRAINDICATIONS pheochromocytoma,
  tachyarrythmias
• ADVERSE EFFECTS precipitation or exacerbation of
  arrythmia

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DRUGS WITHOUT POSITIVE INOTROPIC EFFECTS USED IN
HEART FAILURE

• DIURETICS
• Reduce salt water retention ? reduce
  ventricular preload
• Reduction in venous pressure ? reduction of edema
  its symptoms, reduction of cardiac size ?
  improved efficiency of pump function

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ANGIOTENSIN-CONVERTING ENZYME INHIBITORS

• Reduce peripheral resistance ? reduce afterload
• Reduce salt water retention ( by reducing
  aldosterone secretion) ? reduce preload
• Reduce the long term remodelling of the heart
  vessels ( maybe responsible for the observed
  reduction in the mortality morbidity)

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VASODILATORS

• HYDRALAZINE, ISDN
• Reduction in preload through venodilatation or
  reduction in afterload through arteriolar
  dilation or both

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BETA-ADRENOCEPTOR BLOCKERS

• BISOPROLOL, CARVEDILOL, METOPROLOL
• Reduction in mortality in patients with stable
  Class II Class III heart failure

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DIURETICS
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RENAL TRANSPORT MECHANISM

• PROXIMAL CONVOLUTED TUBULE
• Carries out isosmotic reabsorption of amino
  acids, glucose and cations
• Bicarbonate reabsorption
• 40-50 Na reabsorption

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THICK PORTION OF ASCENDING LIMB OF THE LOOP OF
HENLE

• Pumps Na, K Cl out of the lumen into the
  interstitium
• Provides the concentration gradient for the
  countercurrent concentrating mechanism
• Ca Mg reabsorption

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DISTAL CONVOLUTED TUBULE

• Actively pumps Na Cl out of the lumen nephron
• 10 Na reabsorbed
• Ca Mg reabsorption

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COLLECTING TUBULE

• Primary site of acidification of urine
  aldosterone regulated reabsorption of Na
• 2-4 reabsorbed filtered Na
• H2O reabsorption under ADH control

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DIURETICS

• Drugs that increase the rate of urine flow
• Increase the rate of Na Cl excretion
• Decrease reabsorption of K, Ca Mg

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DIURETICS

• SITE OF ACTION
• Proximal tubule
• Proimal tubule, Loop of Henle, Collecting tubule
• Ascending limb of the loop of Henle
• Distal convoluted tubule
• Collecting ducts

• CLASSIFICATION
• CARBONIC ANHYDRASE INHIBITORS
• OSMOTIC DIURETICS
• LOOP DIURETICS
• THIAZIDE DIURETICS
• POTASSIUM SPARING DIURETICS

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CARBONIC ANHYDRASE INHIBITORS

• CLASSIFICATION PROTOTYPES ACETAZOLAMIDE
  (Diamox) a sulfonamide derivative
• MECHANISM OF ACTION
• Inhibits carbonic anhydrase w/c slows the ff.
  rxn
• H HCO3 ? H2O CO2
• Necessary for maximum reabsorption of HCO3 from
  the glomerular filtrate
• Drug effect occurs throughout the body

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PHARMACOKINETICS

• Well absorbed after oral administration
• Onset of action 30 minutes
• Duration 12 hrs
• Excretion proximal tubule

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CLINICAL USES

• Treatment of glaucoma major application
• Urinary alkalinization
• Epilepsy
• Acute mountain sickness
• Correction of metabolic alkalosis

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TOXICITY

• Hyperchloremic metabolic acidosis
• Renal stones
• Renal potassium wasting
• Drowsiness paresthesias large doses

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LOOP DIURETICS

• CLASSIFICATION PROTOTYPES Furosemide
  prototype sulfonamide derivative
• Bumetanide- sulfonamide
• Ethacrynic Acid phenoxyacetic acid

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PHARMACOKINETICS

• Rapidly absorbed
• Diuretic response is extremely rapid following IV
  injection
• Duration of effect 2-3 hrs
• Half life dependent on renal function
• Excreted in the kidney

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MECHANISM OF ACTION

• Inhibit the coupled Na/K/2Cl transport system
  in the luminal membrane of the thick asceding
  limb of the loop of henle ?reduce NaCl
  reabsorption
• Increase Mg Ca excretion

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CLINICAL USES

• Treatment of edematous states (CHF ascites)
• Acute pulmonary edema in w/c a separate pulmonary
  vasodilating action may play a useful additive
  role
• Sometimes used in hypertension if response to
  thiazide is inadequate but their short duration
  of action is a disadvantage
• Treatment of severe hypercalcemia induced by a
  carcinoma less common
• Acute renal failure
• Hyperkalemia

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TOXICITY

• Hypokalemic metabolic alkalosis
• Hyperuricemia
• Hypovolemia cardiovascular complications
• Ototoxicity important toxic effect of the loop
  agents
• hypomagnesemia

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THIAZIDE DIURETICS

• CLASSIFICATION PROTOTYPE
• HYDROCHLOROTHIAZIDE sulfonamide derivative
• INDAPAMIDE new thiazide like agent with a
  significant vasodilating effect than Na diuretic
  effect

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MECHANISM OF ACTION

• Inhibit NaCl transport in the early segment of
  the distal convoluted tubule ( a site w/c
  significant dilution of urine takes place)

REDUCE THE DILUTING CAPACITY OF THE NEPHRON
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EFFECTS

• Urinary excretion
• Full doses produce a moderate Na Cl diuresis
  ?hypokalemic metabolic alkalosis
• Reduced the blood pressure by reduction of the
  blood volume but with continued use these agents
  appear to reduce vascular resistance

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CLINICAL USE

• Hypertension major application, for w/c their
  long duration of action moderate intensity of
  action are useful
• Chronic therapy for edematous conditions (CHF)
  another common application
• Recurrent renal calcium stone formation can
  sometimes be controlled with thiazides

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TOXICITY

• Hypokalemic metabolic alkalosis hyperuricemia
• Chronic therapy is often associated with
  potassium wasting
• hyperlipidemia

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POTASSIUM SPARING DIURETICS

• CLASSIFICATION PROTOTYPES
• SPIRINOLACTONE antagonist of aldosterone in the
  collecting tubules
• Has a slow onset offset of action (24-72 hrs)
• TRIAMTERENE AMILORIDE inhibitors of Na flux
  in this portion of the tubule

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ADVERSE EFFECTS

• Decrease K H ion excretion and may cause
  hyperchloremic metabolic acidosis
• Interfere with steroid biosynthesis

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CLINICAL USE

• Hyperaldosteronism important indication
• Potassium wasting caused by chronic therapy with
  loop diuretic or thiazide if not controlled by
  dietary K supplements
• Most common use is in the form of products that
  combine a thiazide with a K sparing agent

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TOXICITY

• Hyperkalemia most important toxic effect
• Metabolic acidosis in cirrhotic patients
• Gynecomastia antiandrogenic effects

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OSMOTIC DIURETICS

• CLASSIFICATION PROTOTYPE
• MANNITOL prototype osmotic diuretic given
  intravenously

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MECHANISM OF ACTION

• Holds water in the lumen by virtue of its osmotic
  effect
• Major location for this action is the proximal
  convoluted tubule, where the bulk of isosmotic
  reabsorption takes place
• Reabsorption of H2O is also reduced in the
  descending limb of the loop of henle the
  collecting tubule

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EFFECTS

• Volume or urine is increased
• Most filtered solutes will be excreted in larger
  amounts unless they are actively reabsorbed

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CLINICAL USES

• Maintain high urine flow (when renal blood flow
  is reduced in conditions of solute overload
  from severe hemolysis or rhabdomyolysis)
• Useful in reducing intraocular pressure in acute
  glaucoma increase intracranial pressure in
  neurologic conditions

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TOXICITY

• Hyponatremia pulmonary edema due to removal of
  water from the intracellular compartment
• Headache, nausea, vomiting
• dehydration

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Asymptomatic LV Dysfubction Mild to moderate CHF Moderate to severe CHF
ACE inhibitor Digoxin Digoxin
Beta blocker Diuretics Diuretics
  ACE inhibitor ACE inhibitor
  Beta blocker Beta blocker
  Spironolactone  
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