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217 Cards in this Set
- Front
- Back
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Name the Dihydropyridines (DHP)
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one of the two classes of calcium channel blockers
Amlodipine Felodipine Isradipine Nicardipine Nifedipine Nisoldipine Nimodipine (Cereberal Artery Dilation) |
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Name the nonhydropyridines (non-DHP)
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one of the classes of CCB
Verapamil Diltiazem |
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Effects of CCB
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selectively dilate peripheral and coronary arterioles
Afterload= decreases Preload= no effect better in elderly and african-americans for hypertension can be combined with BB, ACEI, and alpha-1 antagonists not affected by high or low salt intake |
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Effect of CCB on:
1) Lipids, serum electrolytes, uric acid, or glucose insulin balance 2) renal dysfunction 3) diabetes mellitus 4) exercise 5) Long term treatment |
Effect of CCB on:
1) Lipids, serum electrolytes, uric acid, or glucose insulin balance- no adverse affect 2) renal dysfunction- good 3) diabetes mellitus- good 4) exercise- no effect 5) Long term treatment- reduces left ventricle hypertrophy more than diuretics but less than ACEI or alpha-methyldopa |
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Mechanism of action for CCB
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inhibit calcium entry through voltage dependent calium channels of the L-type channels that open when the membrane depolarizes
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CCB affect in Smooth Muscle
DHP vs non-DHP effect on renal blood flow? |
CCB induce arteriolar relaxation, a decrease in TPR, afterload, and in BP
CCB dilate large and small coronary arteries and arterioles DHP have stronger effect than non-DHP increases renal blood flow and GFR |
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CCB and patients with vasospastic angina
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CCB increase myocardial oxygen delivery in patients with vasospastic angina. Reduction in afterload with little associated with increases in cardiac work, may explain their use in effort-induced angina
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CCB with tissue selectivity
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Nimodipine- greater vasodilatory effect on cerebral arteries
Felodipine- negligible cardiace depressant action producing greater tachycardia and cardiac stimulation than most other DHPs Verapamil- greater effect on smooth muscle of GI tract producing constipation as a side effect |
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CCB and Cardiac Muscle
how are verapamil and diltiazem different |
entry of Ca is blocked during depolarization resulting in:
reduction of strength of myocardial contraction/ reduce myocardial contractility/ negative inotropic effect drop in blood pressure due to arteriolar vasodilation results in reflex sympathetic activity which increases NE release verapamil and diltiazem have greater cardiac depressant effects; they reduce cardiac work |
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main CCB used to treat cardiac arrhythmia
why? |
Verapamil
inhibition of pacemaker potentials by ccb produces bradycardia and slows down AV conduction. In addition they reduce automaticity. Verapamil is the best because it slows AV conduction and prolongs the effective refractory period within the AV node in a rate-related manner; reduces elevated ventricular rate associated to rapid arrhythmia originating in the atria allowing for normal sinus rhythm to be restored |
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CCB effect on Skeletal Muscle
drugs that drop BP with lesser cardiac depression and that has more reflex compensatory mechansisms |
DHP selective for vascular calcium channels
non-DHP selective for cardiac calcium channels DHP have lesser cardiac depression and more reflex compensatory mechansims |
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What is the best oral treatment of chronic hypertension?
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Verapamil formulations
Diltiazem formulations Nifedipine GITS (osmotic release) Amlodipine formulations b/c they have slow onset of action and long duration of action |
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What clinical indications are CCB used for?
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1. hypertension
2. Vasospastic angina, effort-induced angina, unstable angina 3. Arrhythmia 4. Subarachnoid hemorrhage 5. Esophageal spasm and gastro-esophageal reflux |
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What type of CCB increase heart rate, contractility, and work?
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DHP-CCB
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What drugs are contraindicated in congestive heart failure?
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Verapamil and Diltiazem (non-DHP) b/c they increase the heart rate, contractility, and work at a lesser extent compared to the DHP CCB.
CHF- heart is not able to pump enough blood out to the rest of the body |
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Drugs of choice for hypertensive patients with CHF or patients who have had a Myocardial Infartion?
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ACEI
ARB Beta-Blockers |
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Prefered drug for paitent with renal disease or diabetic with nephropathy
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ACEI
CCB can be added it not sufficient control is achieved with the ACEI or if ACE and ARB are contraindicated |
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CCB only act where?
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afferent arteriole vasodilaition and may increase intraglomerular pressure
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Side effects of CCB
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Headaches
Palpitations Flushing Peripheral Edema More common with DHP drugs slow release formulations have less side effects |
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Side effect of Verapamil
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constipation
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Anti-Hypertensive drugs compatible with breast feeding?
ACEI: CCB: BB: Diuretics: CNS: K channel activators: |
Anti-Hypertensive drugs compatible with breast feeding?
ACEI: Enalapril/Captopril CCB: Diltiazem, Verapamil, Nifedipine BB: Nadolol, Timolol, Propranolol, Labetolol Diuretics:HCTZ, spironolactone CNS: alpha-methyldopa K channel activators: hydralazine, minoxidil |
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Antihypertensive combinations
2 drugs 3 drugs polypill |
2 drugs:
CCB/ACEI CCB/ARB alpha blocker/diuretic beta blocker/ diuretic ACEI/ diuretic ARB/ diuretic 3 drugs: DHP-CCB/ ARB/ Diuretic Polypill: 3 antihypertensive/statin/aspirin |
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What are DARA compounds?
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Dual acting Receptor Antagonists: single compound (drug) is able to work at two different sites at the same time. single molecule that can block both angiotensin AT1 receptor and the endothelin 1 receptors
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Who does not benefit from DARA compounds?
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patients with CHF and/or diabetic nephropathy
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Chronotherapy for antihypertensive drugs
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optimizing time of day to take once daily oral medication
BP drops at night (dippers) BP rises at night (raisers) BP same at night (non-dippers) |
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Who has highest risk for CV events?
a. dippers b. non-dippers c. raisers |
Answer: non-dippers
nocturnal BP best predicts CV morbidity sleep apnea must be ruled out in patients with resistant hypertension |
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Drugs recommended at bedtime
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Nifedipine GITS, isradipine sustained release
Cilnidipine Verapamil and Diltiazem ER Valsartan, Telmisartan Irbesartan and olmesartan Lisinopril, quinapril, trandolapril, ramipril, perindopril, enalapril (less cough) Torsemide Carvedilol and propranolol ER |
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Drugs recommended in the morning
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Diuretics/ ACEI or ARB, or BB
Metoprolol SR Carvedilol ER Benazepril Candesartan cilexetil Amlodipine Nisoldipine ER |
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Top reasons for lack of BP control
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Poor compliance
excessive alcohol intake concomitant conditions sympathomimetics, NSAIDs, antidepressants Insufficient dose using drugs with same mechanism of action |
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Drug interactions with hypertensive medications
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NSAIDS
nasal decongestants amphetamines cocaine contraceptives erythropoietin cyclosporin glucocorticoids licorise low dose aspirin does NOT interfere with BP lowering affects of an ACEI |
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Primary symptom of Ischemic Heart Disease (IHD)
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Angina Pectoris- chest pain of cardiac origin
due to myocardial ischemia (inefficient blood flow and oxygen delivery to the heart) |
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Oxygen demand depends are what 3 things?
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1. Heart rate
2. Strength of contraction (contractility) 3. Ventricular wall tension concentration of hemoglobin in blood and flow rate are key factors |
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the diastolic pressure that distends the ventricle determines _________
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preload
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Angina Patterns:
1. Effort-Induced Angina 2. Rest Angina 3. Mixed Angina 4. Unstable Angina 5. Silent Angina |
Angina Patterns:
1. Effort-Induced Angina- obstruction; stable if predictable and unstable if inpredictable 2. Rest Angina- no pain during physical activity, usually due to coronary vasospasm (vasocontriction) 3. Mixed Angina- construction and vasospasm combined; both pains during effor-induced and resting 4. Unstable Angina- increased frequency and severity of angina; may lead to severe arrhythmia 5. Silent Angina- ischemic episodes not associated with pain |
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Chronic lack of oxygen to the heart may irreversible damage the tissues and lead to what?
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Congestive Heart Failure
Severe arrhythmia (atrial fibrillation, ventricular tachycardia, ventricular fibrillation , sudden death) |
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Level of Symptoms for Angina Severity
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class 1- normal activity fine
class 2- slight limitation on ordinary activity class 3- limitation on ordinary physical activity class 4- inability to carry out any physical activity without discomfort or angina at rest |
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Risk Factors and Recommendations for patients with Chronic Angina
Smoking BP control Lipid management Physical activity Weight management Diabetes management antiplatelet/anticoagulant ACEI ARBs Aldosterone blockade Influenza vaccination |
Risk Factors and Recommendations for patients with Chronic Angina
Smoking- complete cessation BP control- <140/90 or <130/80 if diabetic or chronic kidney disease Lipid management-LDL <100 mg/dl (ways to reduce non-HDL-C include niacin and fibrate) Physical activity-30-60 min/wk 7d/wk Weight management- BMI 18-25 Diabetes management- HbA1c<7% antiplatelet/anticoagulant- Aspirin use 75-162 mg/day ACEI-use if left ventricular ejection fraction= 40% ARBs- use in patients intolerant to ACEI Aldosterone blockade- use in post myocardial infarction without renal dysfunction or hyperkalemia Influenza vaccination- recommended for patients with cardiovascular disease |
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Pharmacological Treatment of IHD
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Beta Blockers
Organic Nitrates CCB Nicordanil Ivabradine Ranolazine |
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Antiplatelet drugs for IHD
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Heparin-for unstable angina
Aspirin- reduces incidence of myocardial infarction; decreases mortality Clopidogrel |
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Beta Blockers in IHD
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drug of choice for effort-induced angina; does not eliminate the obstruction or cause of the coronary obstruction
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Name some Organic Nitrates in IHD
aka Nitrosovasodilators |
Nitroglycerin
Isosorbide Dinitrate Isosorbide Mononitrate Erythrityl tetranitrate Pentaerythritol |
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Low dose organic nitrate
vs High dose organic nitrate |
Low- selective VENODILATORS, decrease preload, decrease myocardial oxygen consumption
High- arteriolar VASODILATION, decreases TPR, BP, Afterload, and myocardial oxygen consumption |
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Organic Nitrates are also CORONARY VASODILATORS
what is the major mechanism by which organic nitrates improve IHD |
decreasing myocardial oxygen consumption due to decreas in preload and by possible decrease in afterload
they also favor greater blood flow to ischemic areas |
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When is sublingual NTG more effective than intracoronary NTG in relieving pain?
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In paitents with stable, effort-induced angina
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compare mononitrate, dinitrate, and trinitrate metabolites
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mono- less metabolized, greater bioavailability, longer half life than di- and tri-
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Name some Organic Nitrates in IHD
aka Nitrosovasodilators |
Nitroglycerin
Isosorbide Dinitrate Isosorbide Mononitrate Erythrityl tetranitrate Pentaerythritol |
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Low dose organic nitrate
vs High dose organic nitrate |
Low- selective VENODILATORS, decrease preload, decrease myocardial oxygen consumption
High- arteriolar VASODILATION, decreases TPR, BP, Afterload, and myocardial oxygen consumption |
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Organic Nitrates are also CORONARY VASODILATORS
what is the major mechanism by which organic nitrates improve IHD |
decreasing myocardial oxygen consumption due to decreas in preload and by possible decrease in afterload
they also favor greater blood flow to ischemic areas |
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When is sublingual NTG more effective than intracoronary NTG in relieving pain?
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In paitents with stable, effort-induced angina
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compare mononitrate, dinitrate, and trinitrate metabolites
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mono- less metabolized, greater bioavailability, longer half life than di- and tri-
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Drugs to be used for acute angina attacks
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sublingual NTG or isosorbide dinitrate
SL 0.3mg NTG can be repeated after 15 min if pain still present max 3 tablets |
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Does tolerance and dependence occur with organic nitrates?
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YES
Intermittent therapy should be used (interrupted treatment) |
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Side effects of NTG
If dose is too high or absorbed too fast what will happen? |
headache
dizziness postural hypotension flush SL drug should be taken when sitting or lying down ethanol worsens side effects of organic nitrates possibly by enhancing vasodilation Reflex tachycardia and myocardial oxygen consumption |
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increase in heart rate with DHP-CCB can be prevented by doing what?
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adding a Beta blocker
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Effects of CCB
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slows heart rate at SA node and AV node, reduce Ca intry into muscle cells, induce coronary artery vasodilation, induce dilation of the systemic arterioles with the consequent reduction in total peripheral resistance and in BP
non-DHP-CCB do not have reflex tachycardia (mostly bradycardia) |
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_________ are effective in effort-induced angina because they reduce myocardial oxygen consumption
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CCB
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DHP-CCB are safe to use when?
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when the patient has uncomplicated hypertension
may needed to be combined with beta blocker |
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Similar to organic nitrates, the __________ also dilate the coronary arteries and prevent relief coronary vasospasm
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CCB
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distal coronary arterioles are _______ responsive to vasodilators such as NTG than the proximal, larger, coronary arteries
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less responsive
the smaller, more distal coronary arterioles are effected by CCB |
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drugs that can be used for spasms on the small coronary vessels
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Intracoronary adenosine and sodium nitroprusside
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DHPs are (preferred or not preferred) as monotherapy for stable angina
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NOT prefered
monotherapy with Verapamil or diltiazem would be a better choice unless contraindicated (presence of AV block) |
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Specificities of DHP-CCB
Felodipine Isradipine Amlodipine |
Specificities of DHP-CCB
Felodipine- great vascular specificity and little negative inotropic action Isradipine- decreases TPR but inhibits SA node; lowers BP without reflex tachycardia Amlodipine- slow absorption and prolonged effect; therefore, lowers BP with less reflex stimulation to the heart |
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Side effects of CCB
AV block with: Constipation with: |
AV block: Verapamil and Diltiazem
Constipation: Verapamil |
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What is contraindicated with patients with CHF?
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anything that that is a cardiac depressant agent such as verapamil, diltiazem, even DHPs
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What drug is approved in the U.S. to treat angina?
Which are approved outside the U.S.? |
Ranalazine
Nicorandil Ivabradine |
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Can Ranolazine be in combination with other drugs?
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Yes. It should be used in combination with other antianginal agents
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Can Ranolazine be used to treat an acute attack of angina?
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No. It is indicated for the treatment of chronic angina
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How does Ranolazine work?
What is the typical dosing? |
inhibits the late phase of sodium current therefore reducing intracellular sodium and calcium overload which improves diastolic function
started at 500 mg BID increased to 1000mg BID if needed |
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What is the effect of Ranolazine on the electrocardiogram?
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Increases the QT interval
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Side effects and Contraindications for Ranolazine
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Side effects: dizziness, headache, constipation, and nausea
Contraindications: avoid use with other drugs that also increase the QT interval |
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What are some combined therapies for IHD?
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Beta Blockers with Organic Nitrates prescribed prn
Verapamil or diltiazem with SL organic nitrates for acute attacks beta blocker, organic nitrates, and SL nitrates for acute attacks beta blocker, organic nitrates, CCB (ex: atenolol, isosorbide monitrate, and amlodipine, plus SL NTG) Ranolazine can also be added |
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How to treat unstable angina?
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aggressively
Triple therapy (Beta Blockers, nitrates, CCB) combined with heparin and aspirin for prevention of MI |
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What actions should be taken during acute period of myocardial Infarction?
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bed rest, oxygen, general support measures (analgesics) and hemodynamic monitoring, thrombolytic therapy, aspirin, nitroglycerine, prophylactic antiarrhythmic drugs (lidocaine), beta blockers, and ACEI
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What should be prescribed during post MI period?
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aspirin
beta blockers ACEI |
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Can taking Aspirin daily help prevent the occurance of a MI?
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yes. even if it would be the first MI, it reduces their chances by 30%
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What results from a decreased ejection of blood by the left ventricle leading to a decrease in oxygentation of tissue?
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Congestive Heart Failure
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What is the main problem with CHF?
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decreased stroke volume
and tissue perfusion (reduced renal blood flow) heart muscle is also undergoing abnormal cardiac growth and remodeling (spherical instead of elliptical shape) |
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Acute CHF may be characterized by what?
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acute dyspnea
pulmonary edema fluid retention |
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What are the common denominators for all forms of CHF?
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1. decreased stroke volume (cardiac output)
2. Tissue perfusion (reduced renal blood flow) compared to a healthy heart, the CHF heart ventricle ejects a smaller amount of blood |
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What are the three possible types of CHF?
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1. systolic dysfunction (decreased contractility)
2. diastolic dysfunction (ventricle stiffness) 3. Combination of both |
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Characteristics of systolic dysfunction?
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reduced ejection fraction
smaller volume of blood in the ventricle at end of diastole low ejection fraction due to decrease in myocardial contractility (weak muscle) cardiac hypertrophy and/or cardiac dilation associated withan enlarged heart commonly due to ischemic heart disease and hypertension decreased ejection fraction leads to a reduced cardiac output |
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Characteristics of diastolic dysfunction?
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more than half have normal ejection fraction
elderly and female left ventricle fails to fill during relaxed "diastolic" phase left ventricle is thickened and stiff left side pumps too little blood while the right side pumps normally, filling the lungs with blood occurs due to restriction in ventricular filling produced by ventricular stiffness cardiac output is reduced |
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Combination of diastolic and systolic dysfunction is characterized by what?
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this is the most common situation
CHF results from reduced ventricular filling and reduced myocardial contractility HF with preserved EF is associated with a higher mortality rate compared to that of patients with reduced EF |
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what is responsible for ventricular hypertrophy, myocyte dysfunction, and changes in chamber architecture?
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local production of AII and of cytokines together with high local levels of NE
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low molecular weight proteins which are secreted by several different cell types and have a variety of immune and/or inflammatory actions
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cytokines
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Examples of cytokines involved with CHF?
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tumor necrosis factor alpha
and interleukin-6 |
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what is released by the atria end ventricles in response to elevated filling pressures and that are venous and arterial dilators, which promote sodium and water excretion
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B-type Natriuretic peptide (BNP)
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What are the goals of treating CHF?
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improve myocardial performance
reduce myocardial oxygen consumption prevent local changes in NE, AII, TNFalpha and aldosterone responsible for the deterioration of the muscle |
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Characteristic symptoms associated with CHF with left ventricular failure
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Dyspnea on exertion (shortness of breath)
Orthopnea (shortness of breath when laying flat) Paroxysmal Nocturnal (shortness of breath at night)Dyspnea (shortness of breath) Dyspnea at rest Pulmonary Edema |
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What are some characteristic symptoms of CHF when there is right ventricular failure
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Peripheral Edema
Ascitis (fluid in the peritoneal cavity) Jugular Venous Distension Hepato-Jugular Reflux |
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NYHA functional classifications
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class 1- well compensated, no physical limitation, no symptoms on ordinary physical activity
class IV- symptomatic at rest, no activity without symptoms |
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Drug therapy for CHF
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-Vasodilators (ACEI, AII-AT1 antagonists/ ARB, hydralazine, organic nitrates, sodium nitroprusside)
-Diuretics and sodium restriction -Digitalis (digoxin) -Beta Blockers -Aldosterone antagonists -Miscellaneous (PDE III inhibitors, adenosine antagonists, anti-cytokine therapy) |
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Positive inotropic drugs for CHF
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digoxin
PDEIII inhibitors |
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Afterload reducers for CHF
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arterial vasodilators increase SV and CO in patients with CHF.
ACEI ARB Hydralazine reduces afterload, increases cardiac output, improves signs and symptoms of CHF |
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Preload reducers for CHF
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organic nitrates
ACEI ARB diuretics decreases the over-stretching of the ventricles, improves symptoms of congestion, reduces myocardial oxygen consumption and improves myocardial blood flow |
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Anti-remodeling and anti-fibrotic drugs
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beta blockers
spironolactone anti-cytokines |
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Drug of choice for symptomatic CHF?
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ACEI> ARB> hydrolazine with organic nitrates> add diuretic> digoxin> add another vasodilator or trial with beta blocker
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monotherapy for treatment of systolic dysfunction wiht CHF associated with atrial fibrillation
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digoxin
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The combination of which drugs are indicated for preventing the progression of disease, reducing mortality, and inducing regression of myocardial abnormalities
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ACEI
Beta blockers Aldosterone antagonist |
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which is the only class of drugs shown to reduce CHF mortality
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Vasodilators
Ex: ACEI or a combination of hydralazine and isosorbide dinitrate |
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Drugs recommended for patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated
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ACEI
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What are the benefits of ACEI in CHF?
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delay progression of CHF
reduce incidence of sudden death and of MI; patients with combined treatment of diuretic and digitalis with enalapril added reduces mortality by 40% decreases hospitalization time and improve the quality of life |
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What stimulates fibroblast and collagen production, induces hypertrophy and changes the shape of the ventricle to a less efficient shape (spherical instead of elliptical)
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AII
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What must be monitored closely during treatment with ACEI?
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serum creatinine levels
ACEI should not decrease renal function (GFR), but in some cases it does ACEI must be started at low doses |
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ACEIs that are used for HF
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captopril
lisinopril enalapril ramipril quinapril fosinopril benazepril trandolapril |
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Which ACEIs are approved for CHF after a myocardial infarction?
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Ramipril and Trandolapril
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which ARBs are approved for HF if patient is intolerant to ACEI?
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valsartan
candesartan losartan irbesartan telmisartan eprosartan olmesartan |
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What do Organic Nitrates do for people with CHF?
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Reduce preload
decrease pulmonary and systemic vascular resistance Induce coronary vasodilation and redistribution of blood flow to subendocardial regions improves systolic and diastolic function due to increased coronary flow in patients with myocardial ischemia |
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What medications are used in patients with venous congestion with dyspnea, edema, pulmonary edema, neck vein distention, etc?
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Organic Nitrates
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Course of treatment for paitents with CHF?
patients with moderate CHF treated with: |
ACEI> ARBs> hydralazine with organic nitrates
digoxin and diuretics with isosorbide nitrate + hydralazine |
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What can be done to prevent/ limit the tolerance developed with organic nitrates?
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- let blood levels drop for at least 6-8 hours each day
-skip a dose of isosorbide dinitrate or remove patch at night (if no symptoms at night) -N-Acetylcysteine may decrease tolerance |
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Drug that increases NO bioavailability
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Hydralazine
should not be used for treatment of CHF if patient has not tried ACEI yet |
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Can diuretics be prescribed as monotherapy for patients with HF?
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No.
Intravenous diuretics are the first drugs given to treat acute pulmonary edema Loop diuretics can be combined with a thiazide to promote diuresis |
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most common diuretics employed in CHF
give examples Side effects |
Loop diuretics
furosemide bumetanide torsemide electrolyte and volume depletion, arrhythmias, insuline resistance, increased lipids and uric acid development |
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What causes resistance to the effects of diuretics?
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non compliance
high sodium diet decreased renal blood flow and GFR worsening of arrhythmias reduced GFR due to ACEI |
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the main indication for using Digoxin is what?
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CHF associated with supraventricular arrhythmias (atrial fibrillation, atrial flutter)
treats both CHF and arrhythmia |
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What factors predict a good response from Digitalis?
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enlarged heart, low ejection fraction presence of a S3 sound
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Mechanism of action for Digoxin in patients with CHF
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1. increase in myocardial contractility (inhibits Na/K ATPase)
2. Reduction in SNS activity (increases baroreceptor responsiveness and decreases the reflex compensatory mechanism) |
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What are the three typical cardiac glycosides?
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1. Ouabain
2. Diogoxin 3. Digitoxin |
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When should Digoxin doses be reduced?
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1. renal dysfunction
2. patient is on amiodarone |
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What enhances the effects of Digoxin?
What dose does it become toxic? |
enhanced by antibiotics and elimination of gut bacteria
Toxic when >2 ng/ml |
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What is Digoxin mainly eliminated by?
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Kidney
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What is special regarding Dixogin's Vd?
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accumulates in tissues (skeletal muscle) dosing must be based on lean body weight
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Drugs that can displace digoxin causing an increase in plasma digoxin levels
Drugs that increase digoxin levels by affecting renal and/or non-renal clearance of digoxin |
Quinidine
Amiodarone Verapamil Spironolactone Propafenone |
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Can all Beta Blockers be used to treat CHF?
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No.only
Carvedilol Metoprolol SR Bisoprolol |
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What effect do Beta Blockers have on CHF paitens?
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improve ejection fraction
improve quality of life improve exercise capacity reduce BP, ischemia, and arrithymias |
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What indications are Metoprolol approved for?
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hypertension
angina pectoris Arrhythmias myocardial infarction migraine hyperthyroidism |
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What is the importance of Aldosterone in CHF?
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Aldosterone is increased in CHF patients
Aldoserone causes Na and H20 retension, and K and Mg depletion Aldosterone produces myocardial fibrosis and vascular remodeling ACEI cannot completely suppress aldosterone levels Spironolactone antagonizes aldosterone actions at the heart |
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Why is Spironolactone okay with Digoxin even though it may increase digoxin levels?
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Spironolactone prevents hypokalemia therefore reduces digoxin toxicity
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What are the acceptable ranges for creatine and potassium levels when using aldosterone antagonists in HF patients?
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Creatine: <2.5mg/dl in men
Creatine: < 2.0mg/dl in women Potassium: <5.0 mEq/l |
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What is Nesiritide?
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new B-type natriuretic peptide that dilates both veins and arterioles; length of infusion is 1-2 days
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What is the response to low and high doses of Intravenous nitroglycerin?
most common side effect? |
low= venodilator
high= arteriolar dilator Headaches It reduces ventrcular preload and reduces myocardial ischemia |
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Effects of Sodium Nitroprusside in CHF
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venodilation and arteriolar dilation
relaxes pulmonary arterioles decreaces preload and afterload increases aortic wall distensibility (compliance) |
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Name some Positive Inotropic Agents
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Dopamine
Dobutamine (beta 1 selective) Milrinone may induce arrhythmias and ischemia |
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What are the effects of Phophodiesterase III inhibitors
Give an example |
icnrease inotropism
induce bronchodilation inhibit platelet aggregation stimulate lipolysis dilates pulmonary arteries increases mortility by 53% only use short term Milrinone |
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Drugs and Conditions that may worsen CHF
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Cardiac depressants(beta blockers, CCB, doxorubicin, and antiarrythmics)
Volume explansion (NSAIDS, steroids) Increased sodium intake (canned soups, potato chips, fleet enema, ticarcillin) Artrial fibrillation or other arrhythmicas Diabetic TXD drugs (pioglytazone, rosiglytazone) |
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Potassium levels in CHF should be between what values?
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4-5 mEq/l
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What are the two most common arrhythmias in patients with HF?
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1. Atrial Fibrillation
2. Ventricular Tachycardia |
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most antiarrhythmis drugs have what effect?
examples |
negative inotropic effects which worse HF
quinidine procainamide propafenone d-sotalol exception: Amidoranone- class III drug but it has a sympatholytic action |
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What happens during Atrial Fibrillation?
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atria do not contract
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Adverse effects of supraventricular arrhythmias
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1. reduce cardiac output
2. increased oxygen demand and decrease coronary perfusion 3. reduced cardiac output because rapid ventricular rate 4. blood predisposing to pulmonary and systemic emboli |
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Drugs that slow down AV conduction
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Verapamil
Diltiazem Digoxin Beta Blockers |
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Most common employed drugs to attempt RYTHYM control?
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amiodaron
Sotalol Dofetilite |
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drugs that reduce afterload
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ACEI
hydralazine Diuretic |
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increases renal blood flow and GFR
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hydralazine
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Drugs that increase natriuresis by hemodynamic improvement
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ACEI
Hydralazine Organic Nitrates Digitalis Diuretics |
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Drugs that decrease central volume
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diuresis
venodilation |
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decreases SNS activity
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ACEI
ARB Digitalis indirectly: hydralazine organic nitrates diuretics ACEI ARB |
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Drugs that decrease local heart production of AII
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ACEI and ARB
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Drug that decreases mortality due to sudden death and arrhythmias associated to less hypokalemia
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ACEI
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New drug and treatment for CHF
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Etomoxir
inhibits carnitine palmitoyl-tranferase 1 (CPT1) a key enzyme of mitochondrial fatty acid oxidation shifts from fatty acid oxidation to glucose oxidation |
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Type IC Drugs.
Flecainide |
Binds and blocks the sodium channel in the open state and has a very long recovery time
from block · Indications: Because of the excessive mortality or non-fatal cardiac arrest rate seen in patients treated with flecainide, it is unacceptable its use in patients whose ventricular arrhythmias are non-life threatening. The drug is not recommended for chronic atrial fibrillation, because of reports of VT, VF and death during its use. So, it should be used only for life-threatening refractory arrhythmias. Concomitant use of digoxin or beta blockers is required if flecainide is used for atrial flutter or fibrillation. |
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Type IC Drugs.
Propafenonegs. |
In addition to its IC antyarrhythmic profile (see flecainide), it has beta adrenergic
blocking activity. · In most subjects propafenone undergoes extensive first pass metabolism. Zero-order kinetics. · Indication: life-threatening ventricular arrhythmias (sustained VT). Chronic treatment is used to maintain sinus rhythm in patients with supraventricular tachycardias, including atrial fibrillation. It has strong proarrhythmic action. · Elevations of ANA have been reported (check ANA titers).s |
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Effects of Type II Anti-arrhythmics. Beta Blockers
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Propranolol, sotalol, acetobutolol, esmolol, metoprolol, nadolol, atenolol.
· Beta receptor antagonists inhibit effects of SNS stimulation on the heart, reducing automaticity, prolonging AV conduction time and decreasing myocardial contractility. Non-selective beta blockers prevent epinephrine-induced hypokalemia. · An important action of these drugs is to increase the threshold to reach ventricular fibrillation. This effect could explain the reduction in mortality observed after myocardial infarction. · These drugs control ventricular responses in atrial fibrillation and flutter. However, should be used with caution if myocardial function is depressed. 11 · Side effects are those expected for beta blockers. Remember that abrupt discontinuation of chronic treatment with beta blockers, may produce “rebound symptoms” including increase in blood pressure, increased angina pectoris and arrhythmias. Most beta blockers may have some “membrane stabilizing effects”, perhaps due to some inhibition of sodium channels.utton(" |
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__________ is a non-selective beta receptor antagonist, with additional inhibitory effects
on potassium currents. Therefore, it prolongs action potential duration and QT interval on the ECG. By blocking Beta receptors and potassium currents, the drug decreases automaticity, slows AV nodal conduction and prolong refractoriness. It is approved for the management of ventricular arrhythmias. |
Sotalol is a non-selective beta receptor antagonist, with additional inhibitory effects
on potassium currents. Therefore, it prolongs action potential duration and QT interval on the ECG. By blocking Beta receptors and potassium currents, the drug decreases automaticity, slows AV nodal conduction and prolong refractoriness. It is approved for the management of ventricular arrhythmias. Sotalol increases incidence of Torsades de pointes, especially if hypokalemia is present. |
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cardioselective drug, with a very short half life (9 minutes), is metabolized within
the central compartment by esterases present in the red blood cellstmb=139 |
Esmolol
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Affects of Bretylium
(Type III) |
prolongs action potentials, and reduces heterogeneity of repolarization times. May
induce transient hypertension due to norepinephrine release. Chronic treatment causes decrease norepinephrine release and hypotension. It does not get to the brain since it is a quaternary ammonium compound. |
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Affects of Amiodarone
(Type III) |
Although classified as a Type III anti-arrhythmic, it exerts multiple effects:
· blocks inactivated sodium channels and the recovery from block is rapid (Type IB); · decreases calcium current (Type IV); · decreases potassium currents (Type III); · non-competitive beta blockade (type II?); · anti-thyroid action. Prolongs PR, QRS and QT intervals, and may produce bradycardia. Its major action is to prolong refractoriness in all cardiac tissues mainly due to its Type I and III effects. |
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Current indications for Amiodarone
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Current indications:
· IV: treatment and prophylaxis of recurring ventricular fibrillation or unstable ventricular tachycardia in patients refractory to other therapy. · Oral therapy of VT or VF resistant to other drugs. · Also effective in maintaining sinus rhythm in Atrial Fibrillation.b=13979 |
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Amiodarone is highly____________ (lipid to plasma ratio: 300)
· Highly concentrated in tissues, it slowly accumulates (requires loading regimen), and is slowly eliminated. · It is metabolized to____________ , which retains the pharmacological activity of the parent drug. · Amiodarone is a potent inhibitor of hepatic metabolism and of renal elimination of many drugs. · It may _________ the effects of digoxin, quinidine, procainamide, fentanyl, warfarin, dextromethorphan and cyclosporin. · Note: cholestiramine and phenytoin may _______ amiodarone levels. · Beta-blockers should be used with care in combination with amiodarome (both have beta-blocking activity). · _____________ effects with verapamil and diltiazem may occur, resulting in AV block, bradycardia and depressed myocardial contractility. |
Amiodarone is highly lipophilic (lipid to plasma ratio: 300)
· Highly concentrated in tissues, it slowly accumulates (requires loading regimen), and is slowly eliminated. · It is metabolized to desethyl-amiodarone, which retains the pharmacological activity of the parent drug. · Amiodarone is a potent inhibitor of hepatic metabolism and of renal elimination of many drugs. · It may increase the effects of digoxin, quinidine, procainamide, fentanyl, warfarin, dextromethorphan and cyclosporin. · Note: cholestiramine and phenytoin may decrease amiodarone levels. · Beta-blockers should be used with care in combination with amiodarome (both have beta-blocking activity). · Additive effects with verapamil and diltiazem may occur, resulting in AV block, bradycardia and depressed myocardial contractility. |
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Serious adverse events have been reported during chronic treatment using Amiodarone
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· pulmonary fibrosis: often with doses equal to or greater than 400 mg/day.
· hepatic dysfunction, hypo or hyperthyroidism , neuromuscular symptoms. · corneal microdeposits. |
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amiodarone is contraindicated with what?
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amiodarone is contraindicated in cardiogenic shock, marked sinus bradycardia, second or
third degree of AV block. Most important side effects are: hypotension, bradycardia, arrhythmia. >o |
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Affects of Type IV Anti-arrhythmics. Calcium channel Blockers
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Their major effect is in SA and AV nodes. AV conduction velocity decreases and
refractoriness increases. These effects explain their clinical efficacy in supra-ventricular tachycardia, in particular reentrant arrhythmias whose circuit involves the AV node. May also reduce ventricular rate in atrial flutter and fibrillation. CCB can induce bradycardia. Reductions in cardiac contractility and in BP are additional effects of these drugs. |
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________ in addition to CCB, increases action potential duration (type III effect), leading to
additional antiarrythmic and pro-arrhythmic effects. |
Bepridil, in addition to CCB, increases action potential duration (type III effect), leading to
additional antiarrythmic and pro-arrhythmic effects. |
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Activates potassium currents in the atrium, SA and AV nodes. The increase in potassium
current hyperpolarizes, inhibits automaticity, and shortens AP duration. ·___________ slows conduction time in the AV node (AV node block). It may produce a transient asystole (less than 5 secs). · Used as a rapid IV bolus for acute termination of reentrant supraventricular arrhythmias. · In large doses, induces hypotension and flushing due to peripheral vasodilation. · Is taken immediately by carrier-mediated uptake in most cells, where is subsequently metabolized. Has a half life of seconds. Must be given in a rapid IV bolus through a large central IV line. |
Adenosine.
· Acts on specific adenosine receptors. · Activates potassium currents in the atrium, SA and AV nodes. The increase in potassium current hyperpolarizes, inhibits automaticity, and shortens AP duration. · Adenosine slows conduction time in the AV node (AV node block). It may produce a transient asystole (less than 5 secs). · Used as a rapid IV bolus for acute termination of reentrant supraventricular arrhythmias. · In large doses, induces hypotension and flushing due to peripheral vasodilation. · Is taken immediately by carrier-mediated uptake in most cells, where is subsequently metabolized. Has a half life of seconds. Must be given in a rapid IV bolus through a large central IV line. |
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Inhibition of the ATPase by ______________, increases intracellular sodium levels and
modestly depolarizes the membrane, closing the gap between threshold and resting potential. At higher doses (toxicity), oscillatory afterpotentials appear following normally evoked action potentials. If an afterpotential reaches threshold, an ectopic beat is elicited, which is coupled with a preceding normal one (bigeminy). These arrhythmias are associated with excess intracellular calcium. |
Inhibition of the ATPase by digitalis glycosides, increases intracellular sodium levels and
modestly depolarizes the membrane, closing the gap between threshold and resting potential. At higher doses (toxicity), oscillatory afterpotentials appear following normally evoked action potentials. If an afterpotential reaches threshold, an ectopic beat is elicited, which is coupled with a preceding normal one (bigeminy). These arrhythmias are associated with excess intracellular calcium. |
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_________ induce central
vagal stimulation, which leads to greater Ach release in the heart>o |
digitalis induce central
vagal stimulation, which leads to greater Ach release in the heart>o |
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parasympathetic innervation is richer in the atria than in the
ventricles, this is why digitalis exert greater effects on the atria and the SA and AV node cells.nd.ms |
FYI
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____________ is given to prevent development of
14 rapid ventricular rhythms which could be associated to rapid atrial arrhythmias) |
Digoxin is given to prevent development of
14 rapid ventricular rhythms which could be associated to rapid atrial arrhythmias. Digoxin is favored over other AV nodal blocking drugs in patients with ventricular dysfunction; since other antiarrhythmic drugs depress cardiac function (verapamil, quinidine, etc).mc=1397 |
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what is Bigeminism?
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two coupled beats
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common causes of hypokalemia
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diuretics and diarrhea
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___________ work better than digoxin in reducing ventricular rate during exercise, and are preferred because they decrease disease progression and mortality
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Beta blockers work better than digoxin in reducing ventricular rate during exercise, and are preferred because they decrease disease progression and mortality
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most commonly employed drugs to attempt
RHYTHM control |
Amiodarone, sotalol, or dofetilite are the most commonly employed drugs to attempt
RHYTHM control |
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treatment goal of Antiarrhythmic drugs
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the treatment goal is to reduce the ventricular rate to less than 80-90 beats/min ate
rest and less than 110-130 beats/min during moderate exercise. |
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_________ should be
maintained in all patients with HF and a history of AFib, even if at present are at a sinus rhythm |
Anticoagulation should be
maintained in all patients with HF and a history of AFib, even if at present are at a sinus rhythm |
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Drugs that interfere with the renin-angiotensin aldosterone system
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beta-blockers and inhibitors of SNS activity
Angiotensin converting enzyme inhibitors (ACEI) Antagonists of AT1-angiotensin II receptors (ARB) Renin Inhibitors Aldosterone antagonists Neutral Endopeptidase Inhibitors |
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peptidyldipeptidase that catalyzes the conversion of angiotensin I to AII
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ACE
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Substances that exert protective actions on blood vessels, decreasing platelet and oxidized LDL cholesterol adhesion to the endothelium; vasodilators
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NO and prostacyclin
their production is stimulated by bradykinin |
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Long term administration of ACEI may do what?
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BP reduction
regression of left ventricular hypertrophy prevention of ventricular remodeling following a myocardial infarction do not induce hypokalemia/ reduce diuretic-induced hypokalemia no adverse metabolic effects on lipids and glucose inhibition of AII-mediated vascular cellular migration, proliferation, and hypertrophy |
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drug of choice for treatment of diabetic nephropathy
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ACEI
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what is agustia?
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loss of taste
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decreased amount of amniotic fluid
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Oligohydramnios
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ACE inhibitors (ACEI)
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• Captopril
• Enalapril • Lisinopril • Quinapril • Ramipril • Benazepril • Fosinopril • Perindopril • Moexipril • Trandolapril |
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reduces the formation of AII; decrease preload and afterload; BP lowers due to decrease in TPR and CO; compensatory reflex effects are seen less than expected; decreasing AII resets the baroreceptors to a lower point reducing reflex-increases in SNS activity- reduces stimulating effects of AII on SNS activity; causes high levels of renin; increases Bradykinin levels which acts on receptors present in the vascular endothelium to stimulate the production of nitric oxide and of prostacyclin level
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ACE inhibitors (ACEI)
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1st-line treatment for mild to moderate essential hypertension, HT in patients with type 1 diabetes, proteinuria, heart failure, myocardial infarction with systolic dysfunction and congestive heart failure (CHF)
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ACE inhibitors (ACEI)
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Side Effects of ACEI
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Side Effects: dry cough, skin itching, rashes
Captopril→ presence of SH group may be reason for side effects such as loss of taste (agustia), renal toxicity, and decreased granulocytes (neutropenia). |
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Side effects of Captopril
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Captopril→ presence of SH group may be reason for side effects such as loss of taste (agustia), renal toxicity, and decreased granulocytes (neutropenia).
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Contraindications of ACEI
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NSAIDs; patients with history of angioedema
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Kinetics of ACEI
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converted to active metabolites in the body (except for captopril and lisinopril); mainly eliminated by kidney (should be used with care in renal insufficiency); ACEI may increase serum K levels due to inhibition of aldosterone production; serum creatine levels must be monitored to evaluate renal function; AII has greater vasoconstrictive effect on the efferent than on the afferent arterioles
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can ACEI be used in pregnancy?
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Should NOT be used in pregnancy. Associated with fetal hypotension, neonatal skull hypoplasia, pulmonary hypoplasia, growth retardation, reversible or irreversible renal failure and death. Oligohydramnios- decreased amount of amniotic fluid
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Salt depleted patients have _____ levels of renin, AII, and aldosterone and are thus very sensitive to the BP-lowering action of ACEI
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Salt depleted patients have HIGH levels of renin, AII, and aldosterone and are thus very sensitive to the BP-lowering action of ACEI
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Angiotensin receptor antagonist (ARB)
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• Losartan
• Valsartan • Candesartan • Telmisartan • Eprosartan • Irbesartan |
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Renin Inhibitors
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• Aliskiren
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Neutral endopeptidase inhibitors
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• Omaprilat
• Sampatrilat • Fasidotril |
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selective antagonists of the AT1 subtype of AII receptors; blocks AII-AT1 receptors
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Angiotensin receptor antagonist (ARB)
prevents vasoconstrictor and aldosterone-secreting effects of AII; decrease preload and afterload |
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low incidence of side effects; bradykinin does not accumulate during treatment; lower incidence of cough and of angioedema than in ACEI; no adverse effects on renal prostaglandins, serum lipids or fasting glucose levels; may induce hyperkalemia in patients with renal impairment, in those receiving potassium-sparing diuretics, oral potassium supplements, or salt substitutes; potassium and creatinine levels must be monitored in renal failure patients
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Angiotensin receptor antagonist (ARB)
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ARB that increases urinary excretion of uric acid
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Losartan
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Angiotensin receptor antagonist (ARB) that undergoes extensive first pass metabolism by cytochrome P450 enzymes and is converted to an active metabolite
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Losartan
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renin and AII levels increase 2-3 times during treatment
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Angiotensin receptor antagonist (ARB)
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ARB vs ACEI
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ARB→ produce greater anti-AII effects than ACEI; AII is formed via other pathways; ARBS block just AT1 receptor leaving beneficial AT2 receptors available for stimulation by AII
ACEI→ longer history and research; increases bradykinin and vasodilatory prostaglandin levels which add to long-term beneficial effects of ACEI; ACEI generally used most, unless patient is intolerant to ACEI then they prefer ARBS |
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side effects of Renin Inhibitors
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diarrhea, headaches, and angioedema
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orally-active, non-peptide, specific inhibitor of human renin, indicated for the treatment of hypertension; inhibits renin and reduces formation of angiotensin II; metabolized by CYP 3A4
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Renin Inhibitors
• Aliskiren |
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What are the contraindications of Renin Inhibitors
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when combined with atorvastatin, Cmax and AUC of Aliskiren increases by 50%; ketoconazole increases Aliskiren plasma concentrations by 80%
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mediates the cnoversion of AI to AII and inactivates bradykinins
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ACE
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inactivates bradykinin and inactivates the natriuretic peptides
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neutral endopeptidase
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inhibits the ACE and the neutral endopeptidase enzymes; act as ACEI but in addition further increases the levels of Bradykinin and leads to an increase in the level of Natriuretic peptides (ANP, BNP, CNP, DNP)
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Neutral endopeptidase inhibitors
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Have NOT been approved for clinical use yet
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Neutral endopeptidase inhibitors
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Very effective for treating hypertension in patients with CHF
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Neutral endopeptidase inhibitors
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Natriuretic and vasodilator actions; inhibit effects of AII and on sodium and water reabsorption, decrease renin secretion and inhibit aldosterone secretion
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ANP and BNP
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direct acting vasodilator
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Activators of K-channels
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barareceptor mechanisms and the renin-angiotensin system
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are reflex compensatory mechanisms that reduce the BP lowering actions of drugs
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direct acting , selective arteriolar dilators that lower TPR; interfere with the contraction of the arteriolar smooth muscle; no venodilating effects; increases potassium efflux and induces hyperpolarization causing Ca2+ influx to be inhibited and arteriolar smooth muscle relaxes
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K-CHANNEL ACTIVATORS
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K-channel activator that may be given intravenously for the treatment of hypertensive emergencies
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Diazoxide
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Side effects of K-channel blockers
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Tachycardia, palpitations, increased myocardial contractility with increase in cardiac work, myocardial oxygen consumption and cardiac output; reflex venoconstriction due to higher levels of AII and increases sympathetic stimulation; increases venous return=increases preload; fluid retention and weight gain
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side effects of Minoxidil
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should be given with loop-diuretic due to weight gain and fluid accumulation; pericardial effusions have been reported with this drug; also can cause hypertrichosis or hirsutism (hair growth)
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side effects of hydralazine
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metabolized by acetylation; therefore, slow acetylators may get lupus- joint pain, muscle aches, pleuritic chest pain , and rash
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Contraindications of K-channel activators
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Not used as monotherapy in patients with ischemic heart disease; may trigger anginal attacks
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