PHARM EXAM 3- CARDIOVASCULAR

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what does Digoxin do?
increases cardiac contractibilty
How does Digoxin work?
cardiac glycoside (don't need to know)
↑ cardiac contractility (has a positive inotropic effect) by inhibiting Na-K ATPase (this ↑ Ca entry into cell) → ↑ CO (strength of contraction)
↓ HR
↓ AV nodal conduction
Pharmacokinetics of Digoxin, Dosage, and Therapeutic levels
-Pharmacokinetics: good PO absorption, but tablets< capsules
-Don't switch dosage forms!
-Dosage of Digoxin is based on lean body weight. It is 70% renally excreted, so good renal function is important or an adjustment in dosing needs to be made.
-Therapeutic digoxin levels = 0.5 - 0.8 ng/ml
ADR of Dig and toxicity
Adverse Drug Reactions:
*Anorexia, NVD
Confusion
Blurred vision (halos)
*Arrhythmias

Dig toxicity is made much worse by *hypokalemia (↓ K+) or anything that ↓ dig clearance
Treatment for Dig toxicity
Treatment for dig toxicity: d/c dig, correct K+, administer Digibind (antibodies to dig that pull it out of circulation).

in the acute patient Milrione may be used
Side effects of ACEI
Side effects of ACEI include: in some patients, a cough; an ↑ in serum K+, dizziness. Angioedema is a life-threatening SE
How does ACEI work?
does NOT work on the heart, but helps with BP, cardiac remodeling and fluid management overall in the body

decreased angiotensin II decreased TPR, BP, Blood volume

FIRST LINE TREATMENT FOR CHF
Captopril, Enalapril, Lisinopril, Fosinopril, Quinapril
ACEI
Lisinopril
Losartan
Valsartan
ACEI

Blocks angiotensin II; ARB. Decreases BP and salt and H2O load

Once-a-day dosing
Causes first-dose syncope, dizziness, GI SE
ARBS
ARBS- Angiotensin Receptor Blockers

Losartan, Valsartan - inhibit the pathway at the next step (angiotensin II)
Sacubitril/Valsartan
Just approves for Class II-IV HF
Improves QOL and reduces morbidity and mortality
Helps reduce Na and water and relives cardiac remodeling
Ivabradine
-Reduces hospitalization from worsening HF
-Indicated for patients with resting HR of at least 70 bpm taking beta blockers at the highest dose
-Decreases conductance through SA node
-Side effects include decreased HR, flashes of light, HTN, a-fib
Propranolol- HTN
B1 + B2 blocker

Good PO (all of these are)
Metoproplol
B1 blocker

Do NOT use in COPD + diabetes
Atenolol
B1 blocker

Long half life - dosed once a day DON'T NEED
Labetolol/Carvedilol
B1 + B2 blocker
alpha1 blocker

↓TPR WITHOUT a reflex ↑ HR; Post MI; CV history. Decrease work of heart and relax vessels
Beta Block ADR - (6)
Bronchoconstriction - better in cardioslective (B1 blocking) agents
Sleep disorders
Rebound HTN- do NOT d/c
Masks signs of hypoglycemia- some don't Rx in diabetics
Exercise intolerance- MOST IMPORTANT
Tiredness- MOST IMPORTANT
(due to decrease HR)
Contraindications In Beta Blockers
Contraindications:
CHF—depends on cause
Bradycardia
Asthma
*Caution in diabetes (may mask signs of hypoglycemia), COPD, PVD
Hydralazine- peripheral arterial vasodilaters
Directly relaxes arterioles via ↓
Ca ++ flux in smooth muscle cells. ↓ TPR (↓ afterload)

Causes reflex ↑ HR; ↓ Na, H20
Retention; may cause drug-induced SLE
May be used in pregnancy
Minoxidil
Directly relaxes arterioles via ↓ Ca ++ flux in smooth muscle cells.
↓ TPR (↓ afterload)

Used for refractory HTN only. Causes hypertrichosis
Prazosin
alpha 1 blocker causes vasodilation, ↓ TPR

Good for moderate HTN
Causes first dose syncope
Amlodipine- Ca blocker
Blocks Ca - flux in smooth muscle cells - vasodilation, ↓ TPR

May cause edema, hypotension, headache, dizziness, ↑ HR.- foot and ankle edema
Nifedipine- Ca Blocker
Blocks Ca - flux in smooth muscle cells - vasodilation, ↓ TPR

May cause edema, hypotension, headache, dizziness, ↑ HR
Verapamil- ca blocker
Blocks Ca - flux in smooth muscle cells - vasodilation, ↓ TPR

May cause AV node block, CHF, constipation, dizziness
Eplerenone
is an aldosterone antagonist used for HTN and HF

NONE of the ACEI, ARBs or the above 2 may be used in the 2nd or 3rd trimester of pregnancy. All may cause a cough, monitor for angioedema!
Clonidine
Stimulates alpha2 receptors in CNS → ↓ NE release

See vasodilation, ↓ HR, ↓ BP
*Do NOT d/c abruptly (causes rebound HTN). Causes sedation, dry mouth, constipation, edema
Available as a transdermal
Nitroprusside
- hospital use
Converted to nitric oxide which is a vasodilator (↓ BOTH preload + afterload)

Given IV in hypertensive crisis
when should Chlorthalidone or HCTZ be used
Chlorthalidone (Thalitone) or HCTZ should be considered first-line agents for patients with stage 1 hypertension
SE of Thiazide diuretics
Major side effects of the Thiazide diuretics include potassium loss, dehydration, dizziness, and hyperuricemia
What do Thiazides do to serum lipids?
Thiazides: ↑ LDL, ↑ TG note: thiazides are powerful antiHT drugs
Fursosemide, Amiloride, Spironolactone, mannitol
All diuretics cause sodium and water loss, with a resulting decrease in extracellular fluid. This lowers blood pressure. Examples of diuretics commonly used for hypertension include Hydrochlorothiazide (HCTZ), Chlorthalidone and Furosemide (Lasix). Diuretics may cause dizziness and electrolyte imbalances (e.g., potassium loss) as side effects.
With all diuretics what must be monitored?
electrolytes- exspeciall potassium
Most patients are advised to take their antihypertensives at night except for...
patients taking diuretics
Quinidine- antidysrhythmic
Blocks Na channels, ↓ automaticity of ectopic foci

Used for atrial + ventricular arrhythmias.
Can cause cinchonism (headache, blurred vision, tinnitus), slows HR

MONITOR HR and be ADHERENT
Lidocaine
Blocks Na channels, ↓ automaticity of ectopic foci

Used for vent. arr's following MI or surgery. ONLY given IV

MONITOR HR AND BE ADHERENT
Propranolol- beta-blocker for dysrhythmia
↓ AV nodal conductance by ↑ AV node refractory period

Good for digoxin induced arr's. atrial arr's. "A-fib"
AMIODARONE- dysrhythmia
↑ duration of the action potential; given IV
Given PO

Good for life-threatening vent arr's; Vent. Fibrillation

HIGH ALERT MEDICATION!!
Adenosine
Use of Adenosine for Supraventricular Tachycardia

Supraventricular arrhythmias—why do we care?? These patients MAY be patients who throw clots and have strokes
Heart feels like it is "beating out of the chest"

Adenosine may cardiovert; ablation is another therapy; beta blockers work for some

These patients often on an anticoagulant
Treatment for Angina
Drug therapy strives to ↑ O2 delivery to heart (vasodilators) or ↓ cardiac O2 consumption (B blockers).
Nitroglycerin
Vasodilator (↓ preload), dilates coronary
arteries; relaxes peripheral veins

Nitro is effective for all types of angina. Can be used just before exertion to prevent an attack. Short-acting sublingual preps - long acting patches. *Tolerance may develop.
Considerations for Nitrate use
Forms of Nitroglycerin and onset include: PO (20-30 min), patch (45 min), sl spray (2-3 min), sl tablet (1-3 min), IV (immediate), ointment (30-45 min), buccal tablet (1-3 min)
Patient MUST have a nitrate-free interval or tolerance to nitrates will develop!
Nitrates are effective for ALL types of angina
Nitrates may be used prophylactically to prevent an angina attack
Atenolol and Propranolol- beta blockers for chest pain
B blockers, ↓ work of heart NOT used for variant angina

DO NOT D/C ABRUPTLY
Verapamil, Nifedipine, Amlodipine
Ca++ channel blockers, dilate coronary arteries. Good for all 3 types of angina; good for patients with low ejection fraction

May cause a reflex ↑ HR (esp. nifedipine)
Summary of Angina Treatment
Nitroglycerine and CCBs used for all types of angina
Long-acting nitrates used for unstable, variant prophylaxis
B-blockers used for stable, unstable
Beta Blockers are good choices for
Good choices for hypertension, migraine, diabetes, vascular disease, CHF, valvular disease
CCBS are good for
Good to consider in cardiac conditions such as dysrhytmias, depression, asthma or COPD
Anticoagulants
These prevent thrombus formation or extension
Thrombolytics/Fibrinolytics
These dissolve clots
Antiplatelet drugs
These keep platelets from adhering to the fibrin meshwork of a clot
Heparin- antithrombin
Potentiates antithrombin III, blocking free thrombin

Prevents or retards formation of new thrombi; prevents clots from extending given IV or subQ
Used for anticoagulation in pregnancy, stroke, deep vein thrombosis, pulmonary embolism

Monitor for blood in stool, urine; do CBC and platelet count.
ADR: Hemorrhage! Antidote = protamine sulfate; thrombocytopenia
Epidural bleeds may cause paralysis!
Heparin given only IV or SC
Enoxaparin
MOA same as Heparin

Post-op DVT and PE prevention
DVT treatment, knee/hip surgery
Lab monitoring of APTT not necessary
Longer t ½--give every 12 h subQ
Used for prevention of DVT, clots during ischemia (MI); treatment of DVT

Enoxaparin may be given by IV bolus for acute STEMI

First-line therapy for DVT due to their decreased tendency to cause thrombocytopenia and due to no monitoring
Warfarin- antithrombitc (coumadin)
Antagonizes vitamin K's role in activating clotting factors

Prevents extension of a thrombus; prevents formation of new thrombi
COnsiderations with Warfarin
Indications: DVT, PE, lifelong in pts with heart valves, recurrent MI, strokes, atrial fibrillation
Dosage: Monitor Prothrombin Time (PT), or International Normalized Ratio (INR). Want an INR of 2.0-3.0. Or a PT Ratio of 1.3-1.5
Dosing is q day, and may be started with heparin. Overlap warfarin and heparin days before d/c heparin.
ADR:Hemorrhage! Antidote = phytonadione (Vitamin K)
Also, many drug interactions w/ warfarin (aspirin, vit K, DIET—keep vitamin K constant)
PATIENT TEACHING
International Normalized Ratio
. For most patients, an INR of 2-3 is used. When you monitor patients using the INR, it will "look" like they take about twice as long to clot while taking warfarin. This is a good thing!
Your patient will have to be monitored daily during the first 5 days of treatment; 2x/week for the next 1-2 weeks; once a week for next 1-2 mos; every 2-4 mos thereafter.
Dabigatran Extilate (Pradaxa)
Dabigatran Extilate (Pradaxa)—Thrombin inhibitor. No monitoring, rapid onset, few drug-food interactions, lower risk of bleeds, same dose works for all patients. Only approved for prevention of stroke in patients with afibrillation
Apixaban
Apixaban (Eliquis)—Used to prevent stroke in afib patients; thrombin inhibitor; no monitoring
Rivaroxaban (Xarelto)
Rivaroxaban (Xarelto)—Factor Xa inhibitor. No monitoring, rapid onset, fixed dose, lower bleeds risk, few drug or food interactions. Same use as above and for patients with hip/knee replacements
Tenecteplase- clot buster
Binds to fibrin then activates plasminogen-plasmin
May be given by bolus injection--faster

Used for MI, stroke, massive PE. Few SE, few allergic reactions, but VERY expensive ($2750/dose)

They are given after an acute MI or stroke
Asprirn- antiplatelet
Inhibits cyclooxygenase blocks formation of TXA2 which aggregates platelets

Dose: 80-325 mg/day
Can be used for unstable angina, MI, stroke
Clopidogrel
Ticlopidine
Inhibits platelet
Phosphodiesterase; ↓ platelet aggregation
"Super aspirins" given IV

Used w/ warfarin post-op, MI.

Used with heparin. Decreases CV mortality from MI (Acute Coronary Syndrome)
Simvastin, Rosuvastatin, Atorvastatin
Inhibit cholesterol synthesis in liver → ↓ LDL-C in the serum. Up regulates LDL receptors leading to ↑ catabolic clearance of serum LDL-C

Overall effect:
1. Significant ↓ serum LDL-C.
2. Modest ↑ HDL-C,
↓ triglycerides
3. May also ↓ C-reactive protein (↓ inflammatory process associated with atherosclerosis).
Statin SE
Statins may cause the following side effects:
Hepatotoxicity--monitor
Myopathy—monitor??
DO NOT USE IN PREGNANCY
Confusion?
Increased risk of diabetes
Gemmfibrozil/Fenofibrate- fibric acid
↑ lipoprotein lipase activity.
↓ lipolysis in adipose tissue and ↓ hepatic uptake of fatty acids.

Effectively ↓ triglycerides and VLDL-C; ↑ HDL-C.
Concurrent use with "statins" may ↑ risk of myositis and rhabdomyolysis; also ↑ risk of hepatotxicity
*Monitor LFTs
Colesevelam/Ezetemibe- Bile Acid
Block cholesterol
absorption

Indicated for lowering LDL-C, will decrease triglycerides and VLDL-C a little.

Interferes with absorption of other drugs: (take 1 hr before or 4 hrs after)
Niacin
Inhibits lipolysis in adipose tissue; ↓ hepatic production of VLDL → ↓ serum triglycerides and LDL-C

Least expensive of all antihyperlipidemics
*Most effective at ↓ triglycerides and ↑ HDL-C
Main limitation: Cutaneous flushing (↓ with continued use; take aspirin to reduce)
*Monitor LFTs as with statins.
Use with caution in diabetics (impaired glucose tolerance) and in those with gout (hyperuricemia)
How to give iron Oral
Oral iron - give thru straw (stains teeth) in elixir form. Constipating; may ↓ tetracycline absorption.
Iron Z-track technique
Parenteral iron - Iron dextran given by Z track technique (IM, pull skin back, may get staining).
Give a test dose first to make sure patient is not allergic
B-12 Anemia
B12-deficiency Anemia - due to ↓ intrinsic factor, gastrectomy, or vegetarian diet
Folic Acid Anemia
Folic acid-deficiency Anemia - seen in alcoholics, malnourished
Epoietin- Hematopoietic Drugs
Stimulates RBC production. Used in renal disease, HIV, Infection, and patients receiving chemotherapy.
Filgrastim- Hematopoieitc Drug
↑neutrophil production. Used for neutropenia (severe cyclic, chronic), especially that seen in chemo patients. SE of note is bone pain.
Thrombopoietin- Hematopoietic Drug
Stimulates platelet production.