Cardiovascular Pharmacology II (Angina)
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- What are the clinical features of the 4 stages of pathophysiology associated with Congestive Heart Failure?
- Reduced force of cardiac contraction, reduced cardiac output, reduced tissue perfusion, increased peripheral vascular resistance
- Because of low therapeutic index of cardiac glycosides, what should health professionals make sure is occurring for our patients?
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1. Dose should be kept low
2. regularly monitoring pt's plasma level is important
3. healthcare personnel should look for early signs of adverse effects associated with cardiac glycosides (i.e. GI probs) -
These drugs...
-increase cyclic AMP and activate protein kinase -->phosphorylates slow calcium channel to facilitate their opening
-Net effect is increase in calcium concentration to enhance contractility of myocardium
- Beta-adrenergic agonists
- Name three vasodilator drugs.
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1. Alpha-1 antagonists (prazocin)
2. Vasodilators (minoxidil and hydralazine)
3. Organic nitrates (nitroglycerin) - Implications for OT related to Calcium Channel Blockers
- CNS effects and GI effects
- What are examples of Calcium Channel Blockers?
- Nifedipine, Verapamil, Diltiazem, Nicardipine, Felopdipine
- What is the goal of pharmacotherapy for CHF?
-
To improve pumping ability (cardiac output) and load of heart
*done by creating a positive ionotropic effect (increase pumping ability/contractility) through the use of drugs - What are the drugs used to affect CHF?
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1.Cardiac glycosides, 2.Phosphodiesterase inhibitors (Amrinone and Milrinone)
3.Beta-adrenergic agonists (Dopamine & Dobutamine) - What types of drugs are used to decrease cardiac work on the heart or periphery?
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1.ACE inhibitors
2.Beta-blockers
3.Diuretics
4.Vasodilators - Name two Cardiac Glycosides.
- Digoxin & Digitoxin
- _______ increase mechanical pumping ability of heart by ______intracellular calcium concentration thereby facilitating interaction between ____ and ____ filaments in the myocardium cells.
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Cardiac Glycosides...increasing
...myosin... actin -
FACT:
Cardiac Glycosides increase calcium in a process involving 4 steps -
1. inhibition of na/k ATPase pump to increase na
2. increase na alters ca/na exchange in increase calcium
3. direct opening of membrane calcium channels
4. increase release of calcium from sarcoplasmic reticulum (for muscle contraction) -
1. Direct inhibitory effect on sympathetic nervous sys., thereby decreasing stress on failing heart
2. Stabilize heart rate and slow impulse conduction through the myocardium
3. Reflex stimulation of vagus nerve further slows heart - Autonomic and electrophysiological effects of Cardiac Glycosides
- What are the adverse effects of Cardiac Glycosides?
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Side effects are common and potentially fatal; low therapeutic index (easy to move from therapeutic to toxic dose):
1. GI effects-anorexia, nausea, vomiting and abdominal pain
2. Visual disturbances-halos, photophobia, color perception
3. CNS effects-headache, dizziness, psychosis, fatigue, weakness
4. Cardiac effects-rhythm abnormality, ventricular fibrillation, ventricular arrhythmias, atrioventricular block - Implications for OT related to Cardiac Glycosides
- Cardiac effects, CNS and visual side effects, GI side effects
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These drugs increase intracellular concentration of cyclic AMP to increase protein kinase enzyme thus increasing calcium and contractility of the heart.
SAME EFFECT AS DIGOXIN
What is the name of these drugs? - Phosphodiesterase inhibitors (have positive ionotropic effect)
- Name two examples of Phosphodiesterase inhibitors.
- Amrinone and Milrinone
- Name two beta-adrenergic agonists.
- Dobutamine and Dopamine
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True or False:
Other beta-1 agonists are not used because they increase both contractility AND heart rate (when compared to dobutamine) - True
- What type of drugs decrease cardiac work?
- Angiotensin-converting enzyme (ACE) inhibitors
-
What are examples of Angiotensin-converting enzyme (ACE) inhibitor drugs?
Hint: end with -pril - Benzapril, Captopril, Enalapril, Lisinopril, Fosinopril
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This type of drug act to:
1. inhibit formation of angiotensin II (a potent vasoconstrictor)by inhibiting ___ activity.
2. inhibits angiotensin-induced vascular hypertrophy
3. inhibits angiotensin-induced release of aldosterone (a hormone t -
ACE...
Drug is: Angiotensin-converting enzyme (ACE) inhibitors - aldosterone is...
- a hormone that increases na and water absorption
- ACE Inhibitors have been shown to do what?
- increase the lifespan of CHF patients
- _______ are usually administered in combo with cardiac glycosides and diurectics in severe cases of CHF.
- ACE Inhibitors
- Beta-Adrenergic Blockers are used to have what effect on the heart?
-
...used to decrease cardiac work by
1. decreasing heart rate (neg. chronotropic) and contractility (neg. ionotropic)
2. attenuate excessive sympathetic activity assoc. with CHF
3. prevent angina by stabilizing cardiac workload
4. prevent certain arrythmias by stabilizing heart
5. is superior to cardioselective drugs - Drug examples of Beta-Adrenergic Blockers
- Atenolol, Acebutol, Metoprolol, Nadolol (is non-selective not beta-1 selective like the rest)
- What type of drug was previously thought to be dangerous, yet has been shown to be beneficial because it attenuates excessive sympathetic activity assoc. with CHF?
- Beta-Adrenergic Blockers
-
Diuretics________ reabsorption of na and _____ to reduce cardiac work.
They are useful in CHF due to ability to reduce ______ in lungs and peripheral tissue -
inhibit...chloride;
congestion - What are three examples of diuretics?
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1. Thiazide diuretics (hydrochorthiazide)
2. Loop diuretics (furosemide)
3. Potassium sparing diuretics (spironolactone) - Vasodilators provide what function?
- Cause vasodilation to reduce peripheral resistance and decrease cardiac work (thereby reducing stress on failing heart)
- Left congestive heart failure is when the...
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left atrium and ventricle are unable to handle blood returning from the LUNGS
AND
pressure builds up in pulmonary veins and fluid accumulates in LUNGS - Right congestive heart failure is when the...
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Right atrium and ventricle are unable to handle blood returning from SYSTEMIC CIRCULATION
AND
Fluid accumulates in PERIPHERAL TISSUES, ankle edema, organ congestion (liver, spleen) occurs - Calcium Channel Blockers are used for:
- Variant Angina
- The purpose of Calcium channel blockers is to:
- Cause vasodilation and decrease the work of the heart
- _____________ reduce entry of calcium into vascular smooth muscle cells to cause relaxation and vasodilation of coronary blood vessels. The net effect is an increase of O2 to the myocardium
- Calcium channel blockers
- Prophylactic administration to prevent onset of anginal attack
- Therapeutic use of Beta-adrenergic blockers
- Implications for OT related to use of Beta-adrenergic blockers
- -Orthostatic hypotenstion, CNS side effects, respiratory side effects (i.e. endurance), impotence can all influence performance areas
- Nifedipine is the _________ of calcium channel blocker drugs
- prototype (of calc. chann. blocker drugs)
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GI disturbance, CNS effects (dizziness, headache, fatigue)
*in older people=diabetic pts with unstable angina, short acting nifedipine may increase risk of myocardial infarction
*May increase risk for cancer - Adverse effects of Calcium Channel Blockers
- Therapeutic Uses of Calcium Channel Blockers
- Useful in tx of hypertensives with asthma, diabetes, angina and/or peripheral vascular disease
- What is Congestive Heart Failure?
- A chronic condition in which the heart is unable to pump a sufficient quantity of blood to meet the needs of peripheral tissues
- What is the condition in which fluid accumulates in the lungs and peripheral tissues(lungs and legs in particular), leading to congestion?
- Congestive Heart Failure
- Edema, decreased tolerance of physical activity, dyspnea(=labored breathing), shortness of breath
- Symptoms of Congestive Heart Failure
- What is dyspnea
- It is labored breathing and an associated symptom of Congestive Heart Failure
- Risk factors of Congestive Heart Failure include:
- Cardiomyopathy, Myocardial ischemia & infarction, hypertension, cardiac valve disease, congenital heart disease, coronary artery disease
- 5 steps of pathophysiology of Congestive Heart Failure.
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1. Decrease in cardiac performance
2. Neurohormonal compensation (Renin & sympathetic discharge)
3. Increase cardiac WORK
4. Myocardial changes
5. Decrease cardiac PERFORMANCE -
True or False?
A person can have both right and left CHF. - TRUE!!!
- What is the non-selective Beta-Adrenergic drug?
- Nadolol
- What are the adverse effects of Beta-adrenergic blockers?
- CNS EFFECTS (fatigue, lethargy, hallucinations, insomnia); Non-selective beta-blockers may antagonize ß2 receptors in the bronchioles=BRONCHOCONSTRICTION; Orthostatic hypotension and dizziness; Drug withdrawal may result in REBOUND HYPOTENSION; Sexual dysfunction (cause impotence)
- ___________ is pain in the chest that results from an imbalance between coronary blood supply and myocardial oxygen demand.
- Angina Pectoris
- What does oxygen imbalance cause? What does that problem lead to?
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cardiac ischemia
This problem leads to metabolic, electrophysiological and contractile changes in the heart. - What are the pharmacokinetics (method of administration) of Nitroglycerin?
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Administered sublingually, via transdermal patch or inhalation
Quick onset-in minutes (in approx. 2 min. acts on heart) -
-Headache, dizziness, orthostatic hypotension
-Tolerance occurs on continuous use (especially with patch use) - Adverse effects of Nitroglycerin
- How can you decrease risk for tolerance of Nitroglycerin?
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Provide daily nitrite-free intervals
*BUT increases risk for attack -
1. Sublingual _______ is used therapeutically to treat acute attack.
2. ______ ______used to prevent anginal attacks. -
1. Nitroglycerin
2. Long-acting...nitrites - Implications for OT related to Nitroglycerin
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-Orthostatic Hypotension
-CNS (headache and dizziness) can affect performance areas (i.e. mobility, leisure, etc.) - What are the Metabolic changes that occur with Angina Pectoris? (Flow chart)
- Decreased blood flow-->decreased oxygen-->heart muscle uses alternative fuel-->INCREASE lactic acid-->Pain
-
_______that is associated with ______
of blood vessels *____________* may lead to acute myocardial infarction - Angina...narrowing...ATHEROSCLEROSIS
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Define:
Myocardial ischemia - lack of oxygen in myocardium
- Pain from Angina is caused by________.
- =lactic acid
- As therapists, what should we be aware of with patients who have a history of Angina?
- Be observant! They could have an attack while in therapy
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There are three types of Angina.
Name them! -
1. Stable angina
2. Variant angina(Prinzmetal's angina)
3. Unstable angina -
Myocardial oxygen demand exceeds supply
example: Over-exercise - Stable angina=exertional angina
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Decreased oxygen due to coronary artery vasospasm; occurs at rest
cause is unknown - Variant angina (Prinzmetal's angina)
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Associated with thrombosis; most serious type; may progress to heart attack
Combination of two other types - Unstable angina
- Drugs used in tx of angina act to...
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restore or maintain balance between myocardial oxygen demand and supply.
(increase O2 supply to heart) - Beta-Adrenergic Blockers serve to:
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-decrease heart rate (negative chronotropic), decrease contractility of heart (neg. ionotropic), decrease blood pressure
*Net effect: prevent angina by reducing myocardial O2 demand; reduce workload of the heart - What are the 3 main classes of drugs used to tx angina?
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1. Organic Nitrates (nitroglycerin)
2. Beta-Adrenergic Blockers (propranolol)
3. Calcium Channel Blockers (nifedipine) - Name the Organic Nitrate prototype.
- Nitroglycerin
- Mechanism of Action for Nitroglycerin
- Causes relaxation of vascular smooth muscle
- Pharmacological actions of Nitroglycerin.
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-Cause dilation of large veins to pool blood in veins;reduce the work of the heart
-Vasodilate coronary blood vessels, thereby increasing the blood supply to the heart -
Propranolol (prototype)
Atenolol
Acebutol
Metoprolol
Nadolol - Beta-Adrenergic Blocker drugs
- Which of the method of administration of Nitroglycerin is slower acting, transdermal patch or inhalation?
- Inhalation
- What is the Beta-Adrenergic Prototype?
- Propranolol
- What are the beta-1 selective drugs?
-
Atenolol
Acebutol
Metoprolol
*All are Beta-Adrenergic Blockers