CCF,antiarrhythmias,ischemic heart disease Drugs Flashcards
How does heart failure occur,name four underlying causes of it,what are the cardinal symptoms of heart failure
HF, there is a decrease in C.O & Increased sympathetic activity
True or false
In ability of the heart to maintain C.O. sufficient to meet the metabolic needs of the body during excercise and ultimately at rest whilst maintaining a normal filling pressure .Its car- dinal symptoms are dyspnea, fatigue, and fluid retention.
HF is due to an impaired ability of the heart to adequately fill with and/or eject blood. It is often accompanied by abnormal increases in blood volume and intersti- tial fluid.
In heart failure there inadequate cardiac output due to systemic vasoconstriction and this occurs due to the RAAS and can also be caused due to the sympathetic nervous system specifically norepinephrine
In the end there’s decreased blood flow to the vital organs,kidneys,skin ,GIT and the cycle continues
Underlying causes of HF include arteriosclerotic heart disease, myocardial infarction, hypertensive heart disease, valvular heart disease, dilated cardiomyopathy, and congenital heart disease.
True
What ar the goals in treating heart failure and state the seven classes of drugs used to treat it
Goals of treatment are to alleviate symptoms, slow disease pro- gression, and improve survival. HF: reduced myocardial work load, decreased extracellular fluid volume, improved cardiac contractility, and a reduced rate of cardiac remodeling,improve cardiac performance,reduce arrhythmias,maintain adequate renal function and electrolyte balance
Accordingly, seven classes of drugs have been shown to be effective: 1) angiotensin-converting enzyme inhibitors, 2) angiotensin-receptor blockers, 3) aldosterone antagonists, 4) β-blockers, 5) diuretics, 6) direct vaso- and venodilators, and 7) inotropic agents (Fi
Or
Diuretics⇒ Mainly Loop diuretics and thiazides
2) Neuro endocrine antagonists:- A.C.E.Inhibitors, Ag II antagonist, Aldosterone antagonists, β-Adrenoceptor antagonist.
3) Positive ionotropic agents : Cardiac glycosides, 1-adrenoceptor agonists,Phosphodiesterase inhibitors.
4) Vasodilators: Organic nitrates, hydrallazine, sodium nitroprusside and α-adrenoceptor antagonists
What’s the the compensatory physiological mechanism of the body in response to heart failure
When there is increased pressure in the heart at end systolic and diastolic due to more blood being left in the heart at the end systole or diastole , it causes increased pressure backwards to pulmonary circulation causing increased fluid shift from capillaries to interstitium and alveoli causing pulmonary edema true or false
Increased sympathetic activity: Baroreceptors sense a decrease in blood pressure and activate the sympathetic nervous system. In an attempt to sustain tissue perfusion, this stimulation of β-adrenergic receptors results in an increased heart rate and a greater force of contraction of the heart muscle. In addition, vaso- constriction enhances venous return and increases cardiac pre- load. An increase in preload (stretch on the heart) increases stroke volume, which, in turn, increases cardiac output. These compen- satory responses increase the work of the heart, which, in the long term, contributes to further decline in cardiac function.
- Activation of the renin–angiotensin–aldosterone system: A fall in cardiac output decreases blood flow to the kidney, prompt- ing the release of renin, and resulting in increased formation of angiotensin II and release of aldosterone. This results in increased peripheral resistance (afterload) and retention of sodium and water. Blood volume increases, and more blood is returned to the heart. If the heart is unable to pump this extra volume, venous pressure increases and peripheral and pulmonary edema occur. Again, these compensatory responses increase the work of the heart, contributing to further decline in cardiac function.
- Myocardial hypertrophy: The heart increases in size, and the chambers dilate and become more globular. Initially, stretching of the heart muscle leads to a stronger contraction of the heart. However, excessive elongation of the fibers results in weaker con- tractions, and the geometry diminishes the ability to eject blood.
True
What will cause the ventricles not to fill properly ,what causes diastolic heart failure and systolic heart failure
excessive elongation of the fibers results in weaker con- tractions, and the geometry diminishes the ability to eject blood. This type of failure is termed “systolic failure” or HF with reduced ejection fraction (HFrEF) and is the result of the ventricle being unable to pump effectively. Less commonly, patients with HF may have “diastolic dysfunction,” a term applied when the ability of the ventricles to relax and accept blood is impaired by structural changes such as hypertrophy.The thickening of the ventricular wall and subsequent decrease in ventricular volume decrease the abil- ity of heart muscle to relax. In this case, the ventricle does not fill adequately, and the inadequacy of cardiac output is termed “dia- stolic HF” or HF with preserved ejection fraction.
State the signs and symptoms of HF
If the adaptive mechanisms adequately restore cardiac output, HF is said to be compensated. If the adaptive mechanisms fail to main- tain cardiac output, HF is decompensated and the patient develops worsening HF signs and symptoms. True or false
Typical HF signs and symptoms include dyspnea on exertion, orthopnea, paroxysmal nocturnal dys- pnea, fatigue, and peripheral edema.
3.What drugs worsen HF, and 1.how is HF managed and 2.when are ionotropic agents used in Hf
Chronic HF is typically managed by fluid limitations (less than 1.5 to 2 L daily)
low dietary intake of sodium (less than 2000 mg/d);
treat- ment of comorbid conditions;
Judicious use of diuretics, inhibitors of the renin–angiotensin–aldosterone system, and inhibitors of the sympathetic nervous system.
Inotropic agents are reserved for acute HF signs and symptoms in mostly the inpatient setting.
Drugs that may precipitate or exacerbate HF, such as nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, nondihydropyridine calcium channel block- ers, and some antiarrhythmic drugs, should be avoided if possible.
How does Hf cause the activation of the RAAS system
renin–angiotensin–aldosterone system via two mechanisms: 1) increased renin release by juxtaglomerular cells in renal afferent arterioles due to diminished renal perfusion pressure produced by the failing heart and this causes the activation of RAAS causing water and sodium retention by aldosterone
and 2) renin release by juxtaglomerular cells promoted by sympathetic stimulation and activation of β receptors
State the mechanism of action,actions on the heart,indications,rite of administration,which ACE inhibitor must be taken on an empty stomach and is not a prodrug and adverse effects of ACE inhibitors
The potential for symptom- atic hypotension with ACE inhibitors is much more common if used concomitantly with a diuretic. ACE inhibitors are teratogenic and should not be used in pregnant women. True or false
These drugs block the enzyme that cleaves angiotensin I to form the potent vasoconstrictor angiotensin II. They also diminish the inactivation of bradykinin (Figure 19.5). Vasodilation occurs as a result of decreased levels of the vasocon- strictor angiotensin II and increased levels of bradykinin (a potent vasodilator). By reducing angiotensin II levels, ACE inhibitors also decrease the secretion of aldosterone.
- Actions on the heart: ACE inhibitors decrease vascular resis- tance (afterload) and venous tone (preload), resulting in increased cardiac output. ACE inhibitors also blunt the usual angiotensin II–mediated increase in epinephrine and aldosterone seen in HF. ACE inhibitors improve clinical signs and symptoms of HF and have been shown to significantly improve patient survival in HF
- Indications: ACE inhibitors may be considered for patients with asymptomatic and symptomatic HFrEF. Importantly, ACE inhibitors are indicated for patients with all stages of left ventricular failure. Patients with the lowest ejection fraction show the greatest benefit from use of ACE inhibitors. Depending on the severity of HF, ACE inhibitors may be used in combination with diuretics, β-blockers, digoxin, aldosterone antagonists, and hydralazine/isosorbide dinitrate fixed-dose combination. Patients who have had a recent myocardial infarction or are at high risk for a cardiovascular event also benefit from long-term ACE inhibitor therapy. ACE inhibitors are also used for the treatment of hypertension (see Chapter 17).
- Pharmacokinetics: ACE inhibitors are adequately absorbed fol- lowing oral administration. Food may decrease the absorption of captopril [CAP-toe-pril], so it should be taken on an empty stom- ach. Plasma half-lives of active compounds vary from 2 to 12 hours, although the inhibition of ACE may be much longer.
- Adverse effects: These include postural hypotension, renal insufficiency, hyperkalemia, a persistent dry cough, and angio- edema (rare),skin rashes,neutropenia Potassium levels must be monitored, particularly with concurrent use of potassium supplements, potassium-sparing diuretics, or aldosterone antagonists due to risk of hyperkalemia. Serum creatinine levels should also be monitored, particularly in patients with underlying renal disease.
Except for captopril, ACE inhibitors are prodrugs that require activation by hydrolysis via hepatic enzymes. Renal elimination of the active moiety is important for most ACE inhibitors except fosinopril [foe-SIH-no-pril].
True or false
Give five examples of ACE inhibitors
True
Captopril CAPOTEN Enalapril VASOTEC Fosinopril MONOPRIL Lisinopril PRINIVIL, ZESTRIL Quinapril ACCUPRIL Ramipril ALTACE
Only reduced aldosterone causes reduced sodium and water retention true or false
Reduced angiotensin 2 and aldosterone by ACe inhibitors causes increased beadykinin levels,decreased output of sympa and vasodilation of the vascular smooth muscle causing reduced preload and afterload on the heart true or false
False
Both reduced aldosterone and angiotensin 2 (caused by ACe inhibitors) cause reduced sodium and water retention thereby reducing preload and afterload
True
ARBs(Angiotensin receptor blockers ) cause reduced cough and angioedema that is caused by increased levels of bradykinin true or false
State the mechanism of action of ARBs
ARBs are very similar to ACE inhibitors true or false
Which ARB is given twice daily as opposed to the usual once daily ?
Usually ARBs are highly plasma protein bound which ARB is the exception?
ARBs also have high volume of distribution
Which ARB undergoes extensive first pass metabolism and has an active metabolite ?
ARBs are not contraindicated in pregnancy true or false
Give some examples of ARBs
True
The effects on symptoms and haemodynamics in patients with heart failure is similar to that of A.C.E. Inhibitors.
•It has the advantage of being free of cough with A.C.E.Inhibitors. & thus may be used as an alternative to A.C.E. Inhibitors in those who cannot tolerate the cough side effect
Valsartan
Candesartan
Losartan
False
ANGIOTENSIN RECEPTOR BLOCKERS Candesartan ATACAND Losartan COZAAR Telmisartan MICARDIS Valsartan DIOVAN ALDOSTERONE AN
Give two examples of aldosterone antagonists
State the function of each
Difference between the two examples
And indications of aldosterone antagonists
Eplerenone INSPRA Spironolactone ALDACTONE
Spironolactone [spy-ro-no-LAC-tone] is a direct antag- onist of aldosterone, thereby preventing salt retention, myocardial hypertrophy, and hypokalemia. Eplerenone [eh-PLEH-reh-none] is a competitive antagonist of aldosterone at mineralocorticoid receptors.
Although similar in action to spironolactone at the mineralocorticoid receptor, eplerenone has a lower incidence of endocrine-related side effects due to its reduced affinity for glucocorticoid, androgen, and progesterone receptors.
Aldosterone antagonists are indicated in patients with more severe stages of HFrEF or HFrEF and recent myocardial infarction.
State the functions of beta blockers in Hf
State the three beta blockers that are used in Hf
How each of them work
Which of the beta blockers are beta1 selective
Which of the blockers protects against recurrent MI and why
Contraindications of beta blockers in HF
Treatment of beta blockers should be started at low doses and gradually titrated to target doses based on patient tolerance and vital signs.true or false
The benefit of β-blockers is attributed, in part, to their ability to prevent the changes that occur because of chronic activation of the sympathetic nervous system. These agents decrease heart rate and inhibit release of renin in the kidneys. In addition, β-blockers prevent the deleterious effects of norepinephrine on the cardiac muscle fibers, decreasing remodeling, hypertrophy, and cell death.
Three β-blockers have shown benefit in HF: bisoprolol [bis-oh-PROE-lol], carvedilol [KAR- ve-dil-ol], and long-acting metoprolol succinate [me-TOE-proe-lol SUK- si-nate] (Figure 19.7).
Carvedilol is a alpha 1 and nonselective β-adrenoreceptor antagonist
Metoprolol succinate
reduces mortality in patients
antagonist that also blocks α-adrenoreceptors, whereas bisoprolol and metoprolol succinate are β1-selective antagonists.β-Blockade is rec- ommended for all patients with chronic, stable HF. Bisoprolol, carvedilol, and metoprolol succinate reduce morbidity and mortality associated with HFrEF.
Carvedilol also has antioxidant properties and thus protects against recurrent MI .
Contraindications
Both carvedilol and metoprolol are metabolized by the cytochrome P450 2D6 isoenzyme, and inhibitors of this metabolic pathway may increase levels of these drugs and increase the risk of adverse effects. In addition, carvedilol is a substrate of P-glycoprotein (P-gp). Increased effects of carvedilol may occur if it is coadministered with P-gp inhibitors. β-Blockers should also be used with caution with other drugs that slow AV conduction, such as amiodarone, verapamil, and diltiazem.
How do diuretics work on HF
WhT kind of diuretics are used in HF
As diuret- ics have not been shown to improve survival in HF, they should only be used to treat signs and symptoms of volume excess.
True or false
Why are loop diuretics given IV during heart failure
Loop diuretics have rapid onset of action and short duration of action.
•Depending on the Patients condition, the loop diuretics may be administered once daily or 2 or 3 times daily to reduce the plasma volume .true or false
Loop diuretics increase the nephrotoxic effect of?
What enhances the risk of digoxin toxicity?
What happens when the loop diuretics are used for a long time w NSAIDs
State the difference between loop and thiazides diuretics
Name two examples of thiazides like diuretics
Diuretics decrease plasma volume and, subsequently, decrease venous return to the heart (preload). The mechanism is by decreasing preload and thus reducing circulating blood volume
This decreases cardiac workload and oxygen demand
Diuretics may also decrease afterload by reducing plasma vol- ume, thereby decreasing blood pressure. Loop diuretics are the most commonly used diuretics in HF. .]
True
Both loop and thiazide diuretics are well absorbed after oral administration but in heart failure absorption may be erratic so the loop diuretics are administered by i.v administration.
True
Gentamicin and cephalosporins.
•
Decreased plasma concentration K+ associated with the potent diuretics enhances the risk of digoxin toxicity.
•Concurrent use with NSAIDS may impair diuresis, provoke hyperkalaemia and renal failure.
They act by inhibiting Na+/K+/Cl_-transporter in the thick ascending segment of the loop of Henle while thiazides They act by inhibiting Na+/Cl- co-transporter in the distal convuluted tuble
Chlorthalidone, indapamide, xipamide & metolazone
Give some examples of vaso and venodilators and how they work in HF
Dilation of venous blood vessels leads to a decrease in cardiac preload by increasing venous capacitance. Nitrates are commonly used venous dila- tors to reduce preload for patients with chronic HF. Arterial dilators, such as hydralazine [hye-DRAL-a-zeen] reduce systemic arteriolar resistance and decrease afterload.
Hydralazine APRESOLINE
Isosorbide dinitrate DILATRATE-SR, ISORDIL
FDC (fixed dose combination)Hydralazine/Isosorbide dinitrate BIDIL
If the patient is intolerant of ACE inhibitors or β-blockers, or if additional vasodilator response is required what combination should be done?
Name some adverse effects of this combination
Rarely, hydralazine has been associated with drug-induced lupus.true or false
a combination of hydralazine and isosorbide dinitrate [eye-soe-SOR-bide dye-NYE-trate] may be used. A fixed-dose combination of these agents has been shown to improve symptoms and survival in black patients with HFrEF on standard HF treatment (β-blocker plus ACE inhibitor or ARB).
Headache, hypoten- sion, and tachycardia are common adverse effects with this combination.
Name some Inotropic agents and how they work
All positive inotropes in HFrEF that increase intracellular calcium concen- tration have been associated with reduced survival, especially in patients with HFrEF due to coronary artery disease. For this reason, these agents, with the exception of digoxin, are only used for a short period mainly in the inpatient setting.true or false
Digoxin LANOXIN
Dobutamine DOBUTREX Milrinone PRIMACOR
Positive inotropic agents enhance cardiac contractility and, thus, increase cardiac output. Although these drugs act by different mecha- nisms, the inotropic action is the result of an increased cytoplasmic
calcium concentration that enhances the contractility of cardiac muscle.
True
Name the three classes of inotropic agents used in treating HF
Digitalis glycosides
Beta adrenergic agonists
Phosphodiesterase inhibitors
State the three mechanisms of action of digitalis glycosides,
Regulation of cytosolic calcium concentration: By inhibit- ing the Na+/K+-adenosine triphosphatase (ATPase) enzyme, digoxin reduces the ability of the myocyte to actively pump Na+ from the cell .This decreases the Na+ con- centration gradient and, consequently, the ability of the Na+/ Ca2+-exchanger to move calcium out of the cell. Further, the higher cellular Na+ is exchanged for extracellular Ca2+ by the Na+/Ca2+-exchanger, increasing intracellular Ca2+. A small but physiologically important increase occurs in free Ca2+ that is available at the next contraction cycle of the cardiac muscle, thereby increasing cardiac contractility. When Na+/K+-ATPase is markedly inhibited by digoxin, the resting membrane potential may increase (−70 mV instead of −90 mV), which makes the membrane more excitable, increasing the risk of arrhythmias (toxicity).
b. Increased contractility of the cardiac muscle: Digoxin increases the force of cardiac contraction, causing car- diac output to more closely resemble that of the normal heart (Figure 19.9).Vagal tone is also enhanced, so both heart rate and myocardial oxygen demand decrease. Digoxin slows conduction velocity through the AV node, making it useful for atrial fibrillation. [Note: In the normal heart, the positive inotropic effect of digitalis glycosides is counteracted by compensatory autonomic reflexes.]
c. Neurohormonal inhibition: Although the exact mechanism of this effect has not been elucidated, low-dose digoxin inhibits sympathetic activation with minimal effects on contractility. This effect is the reason a lower serum drug concentration is tar- geted in HFrEF.
State the therapeutic uses or indicators ,route of administration and adverse effects and contraindications of digitalis glycosides
Why does digoxin which is a digitalis glycoside have a large volume of distribution and what does its dosage depend on,when is the loading dose of digoxin used,what is the half life of digoxin
Therapeutic uses: Digoxin therapy is indicated in patients with severe HFrEF after initiation of ACE inhibitor, β-blocker, and diuretic therapy. A low serum drug concentration of digoxin (0.5 to 0.8 ng/ mL) is beneficial in HFrEF. At this level, patients may see a reduction in HF admissions, along with improved survival. At higher serum drug concentrations, admissions are prevented, but mortality likely increases. Digoxin is not indicated in patients with diastolic or right- sided HF unless the patient has concomitant atrial fibrillation or flut- ter. Patients with mild to moderate HF often respond to treatment with ACE inhibitors, β-blockers, aldosterone antagonists, direct vaso- and venodilators, and diuretics and may not require digoxin.
3. Pharmacokinetics: Digoxin is available in oral and injectable for- mulations.
- Adverse effects: Anorexia, nausea, and vomiting may be ini- tial indicators of toxicity. Patients may also experience blurred vision, yellowish vision (xanthopsia), and various cardiac arrhythmias.[
It has a large volume of distribution, because it accumu- lates in muscle. The dosage is based on lean body weight. In acute situations such as symptomatic atrial fibrillation, a loading dose regimen is used. Digoxin has a long half-life of 30 to 40 hours. It is mainly eliminated intact by the kidney, requiring dose adjustment in renal dysfunction.
At low serum drug concentrations, digoxin is fairly well tolerated. However, it has a very narrow therapeutic index, and digoxin toxicity is one of the most common adverse drug reactions leading to hospitalization.
True or false
How is digoxin toxicity managed? What predisposes a patient to digoxin toxicity and why?
Patients receiving thiazide or loop diuretics may be prone to hypokalemia. True or false
True
Toxicity can often be managed by discontinuing digoxin, determin- ing serum potassium levels, and, if indicated, replenishing potassium. Decreased levels of serum potassium (hypokalemia) predispose a patient to digoxin toxicity, since digoxin normally competes with potassium for the same binding site on the Na+/K+-ATPase pump.
True
When there is severe digoxin toxicity resulting in ventricular tachycardia what kind of drugs are required to be administered
With the use of a lower serum drug concentration in HFrEF, toxic levels are infrequent. True or false
Digoxin is a substrate of what and name three drugs that inhibit the substrate of digoxin
Digoxin should be used with caution in what kinds of drugs?
Severe toxicity resulting in ventricular tachycardia may require administration of antiarrhythmic drugs and the use of antibod- ies to digoxin (digoxin immune Fab), which bind and inactivate the drug.
True
Digoxin is a substrate of P-gp, and inhibi- tors of P-gp, such as clarithromycin, verapamil, and amiodarone, can significantly increase digoxin levels, necessitating a reduced dose of digoxin.
Digoxin should also be used with caution with other drugs that slow AV conduction, such as β-blockers, verapamil, and diltiazem.
Name two beta adrenergic agonists used in HF,their route of administration ,how they work
Which inotropic agent other than digoxin is usually used?
β-Adrenergic agonists, such as dobutamine [doe-BYOO-ta-meen] and dopamine [DOH-puh-meen], improve cardiac performance by causing positive inotropic effects and vasodilation. β-Adrenergic agonists lead to an increase in intracellular cyclic adenosine monophosphate (cAMP), which results in the activation of protein kinase. Protein kinase then phosphorylates slow calcium channels, thereby increasing entry of calcium ions into the myocardial cells and enhancing contraction .
Dobutamine is the most commonly used inotropic agent other than digoxin.
Both drugs must be given by intravenous infusion and are primarily used in the short-term treat- ment of acute HF in the hospital setting.
How do phosphodiesterase inhibitors work?
Name one
Long-term, milrinone therapy may be associated with a substantial increased risk of mor- tality.true or false
Short term use of milrinone is associated with increased mortality in patients with a history of what kind of disease
Phosphodiesterase inhibitors
Milrinone [MIL-rih-nohn] is a phosphodiesterase inhibitor that increases the intracellular concentration of cAMP .Like β-adrenergic agonists, this results in an increase of intracellu- lar calcium and, therefore, cardiac contractility.
True
However, short-term use of intravenous milrinone is not associ- ated with increased mortality in patients without a history of coronary artery disease, and some symptomatic benefit may be obtained in patients with refractory HF.
Digoxin, aldosterone antagonists, and fixed-dose hydralazine and isosor- bide dinitrate are initiated in patients who continue to have HF symptoms despite optimal doses of an ACE inhibitor and β-blocker.
True or false
True
