Debbie's Cardiac Meds Presentation Final Nn
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Cardiac med power point on January 12th

Cardiac med power point on January 12th

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Debbie's Cardiac Meds Presentation Final Nn Debbie's Cardiac Meds Presentation Final Nn Presentation Transcript

  • Cardiac Medications Michelle Mungcal, B.S. University of the Pacific Thomas J. Long School of Pharmacy Doctor of Pharmacy Candidate, Class of 2009 January 12, 2009
  • Overview
    • Inotropes
    • Chronotropes
    • Antianginal Agents
    • Antidysrhythmics
    • Sympathomimetics
    • Vasopressors
    • Diuretics
    • Anticoagulants
    • Fibrinolytic Enzymes
    • Beta Blockers
    • Ca Channel blockers
  • Inotropes
  • Inotropes
    • Agents that affect myocardial contraction
    • Positive Inotropes
      • Cardiac glycosides
      • Bypyridine derivatives (Milrinone)
      • PDE-I (Theophylline)
      • Catecholamines
    • Negative Inotropes
      • BB
      • CCB
      • Class IA & IC anti-arrhythmics
  • Class Participation Question #1
    • Which of the following is an example of a positive inotrope?
    • Docusate
    • Digoxin
    • HCTZ
    • Propranolol
    • Nitroglycerin
  • Class Participation Question #1
    • Which of the following is an example of a positive inotrope?
    • Docusate
    • Digoxin
    • HCTZ
    • Propranolol
    • Nitroglycerin
  • Cardiac Glycosides
    • Prototype: Digoxin (Lanoxin ® , Digitek ® , Lanoxicaps ® )
  • Digoxin MOA
  • Digoxin (cont’d)
    • Indications/dosage:
      • Afib & HF
        • LD : 10-15 mcg/kg IV or PO, given in 3 divided doses every 6-8 hrs, with the first dose equalling approximately 1/2 the total
        • MD : 125-350 mcg PO or IV per day, depending on CrCl, given in 1-2 divided doses
    • CrCL < 60 requires renal adjustment
    • Monitoring
      • ECG
      • serum Ca
      • Scr/BUN
      • serum Mg
      • serum K
  • Class Participation Question 2:
    • AJ is a 54 year old male weighing 50kg who has class III heart failure. AJ’s doctor will be starting him on Digoxin therapy. Calculate the Digoxin LOADING dose .
  • Class Participation Question 2:
    • AJ is a 54 year old male weighing 50kg who has class III heart failure. AJ’s doctor will be starting him on Digoxin therapy. Calculate the Digoxin LOADING dose .
    • Recall
      • LD: 10-15 mcg/kg IV or PO, given in 3 divided doses every 6-8 hrs, with the first dose equalling approximately 1/2 the total
  • Class Participation Question 2:
    • TOTAL dose
    • 100 kg x 10 mcg = 1000 mcg total
    • kg
    • 1 st dose is ½ the total dose
    • 1000 mcg / 2 = 500 mg
    • 2 nd & 3 rd dose
    • 500 mg / 2 = 250 mg
  • Class Participation Question 2:
    • Answer:
      • 500 mcg IV or PO initially
      • followed by 250 mcg IV or PO every 6 hours x 2 doses
  • Latest News on Digoxin
    • On April 28, 2008, Actavis Totowa LLC notified healthcare professionals of a Class I nationwide recall of all strengths of Digitek ™.
    • The products are distributed by Mylan Pharmaceuticals Inc. under a Bertek label and by UDL Laboratories, Inc. under a UDL label.
  • Digitalis Toxicity
    • Visual changes (unusual)
    • Confusion
    • Loss of appetite
    • Nausea, vomiting, diarrhea
    • Palpitations
    • Irregular pulse
    • Additional symptoms that may be associated with digitalis toxicity include:
    • Decreased urine output
    • Excessive nighttime urination
    • Overall swelling
    • Decreased consciousness
    • Difficulty breathing when lying down
  • Chronotropes
  • Chronotropes
    • Agents that change heart rate
      • affects the nerves controlling the heart
      • changes the rhythm produced by the SA node
  • Chronotropes (cont’d)
    • Positive Chronotropes
      • Atropine
      • Quinidine
      • Dopamine
      • Dobutamine
      • Epinephrine
      • Isuprel
    • Negative Chronotropes
      • Beta-blockers
      • Acetylcholine
      • Digoxin
      • Diltiazem
      • Verapamil
      • Ivabradine
      • Metoprolol
  • Positive Chronotrope
    • Prototype: Atropine
    • belladonna alkaloid
    • d,l -hyoscyamine
    • Anticholinergic
    • Uses
      • Symptomatic bradycardia
      • Aspiration prophylaxis
      • Produces mydriasis
      • IBS
      • Parkinson’s?
      • Organophosphate toxicity
      • Adjunct nerve agent & insecticide poisoning
  • Atropine (cont’d)
    • MOA
      • competitive inhibitor at autonomic postganglionic cholinergic receptors
    • Clinical effects
      • “ anti-SLUD”
      • ↓ in salivary bronchial, & sweat gland secretions; mydriasis; cycloplegia; changes in heart rate; contraction of the bladder detrusor muscle and of the GI smooth muscle; ↓ gastric secretion; and ↓ GI motility
  • Atropine Dosing
    • Bradycardia
      • 0.5-1 mg IV push; repeat if needed every 5 min up to 2 mg
    • Aspiration prophylaxis
      • po: 2 mg PO 30-60 min prior to anesthesia
      • parental: ≥ 20 kg: 0.2-1 mg (the usual dose is 0.4 mg) IV, IM or SC 30-60 min prior to anesthesia
    • IBS
      • po: 0.3-1.2 mg PO every 4-6 hours
    • Organophosphate insecticide toxicity
      • 1-2 mg IM or IV initially; repeat if needed every 20-30 min as needed until symptoms dissipate. Adjunct nerve agent & insecticide poisoning
    • Mydriasis
      • Opthalmic: drop of 1% solution instilled in eye 1 hour prior to procedure or, 0.3-0.5 cm of 1% ointment placed in conjunctival sac up to tid
    • Note: Lab monitoring not necessary
  • Anti-anginal Drugs
  • Antianginal Drugs
    • Prototype: Nitrites & Nitrates
    • BB
    • Calcium Channel Blockers (CCBs)
  • Symptoms of Angina
  • Nitrites/Nitrates
    • Previously known as “coronary dilators”
    • Main effect: to produce general vasodilation of systemic vein & arteries
      • ↓ preload & ↓afterload
      • ↓ cardiac work & oxygen consumption
    • 2 main uses
      • Angina attacks
      • Angina prophylaxis
  • Class Participation Question #3:
    • Which is the PREFERRED route for nitroglycerin during angina attacks?
      • Topical (ointment 2%)
      • IV infusion
      • Transdermal
      • SL
      • Extended release tablets/capsules
  • Class Participation Question #3:
    • Which is the PREFFERED route for nitroglycerin during angina attacks?
      • Topical (ointment 2%)
      • IV infusion
      • Transdermal
      • SL
      • Extended release tablets/capsules
  • 8 - 12 hr 30 min 1,2,3 mg XR tab ( Nitrogard ® ) 24 hr 30-60 min 2.5 - 15 mg/day Transdermal patch ( Transderm-Nitro ® ) 10 - 45 min 1-3 min 0.3 - 0.6 mg SL ( Nitrostat ® ) 4 - 8 hr 15 min 2% ointment ( Nitro-bid ® ) Nitroglycerin 2 - 4 hr 2-5 min 2.5 - 10 mg SL 5 - 30 mg po qid ISDN (Isordil ® ) 10 min 30-60 sec 0.3 ml inhalation Amyl nitrate (Vaporole ® ) Duration Onset Common Dosage Drug (Trade Name)
  •  
  • Nitroglycerin (NG)
    • Indications
      • Angina
      • Acute MI
      • HF
      • HTN
      • Hypertensive emergency
      • Hypotension induction
      • Peri/postoperative HTN
      • Pulmonary edema
      • Pulmonary HTN
  • NG (cont’d)
    • Dosing
      • 1 tablet (0.3 mg, 0.4 mg, or 0.6 mg strength) SL, dissolved under the tongue or in buccal pouch immediately following indication of anginal attack
      • During drug administration, the patient should rest, preferably in the sitting position
      • Symptoms typically improve within 5 minutes. If needed for immediate relief of stable angina symptoms, SL nitroglycerin may be repeated every 5 minutes as needed, up to 3 doses
  • NG (cont’d)
    • Adverse Effects
      • dizziness or fainting
      • flushing of the face or neck
      • headache, this is common after a dose, but usually only lasts for a short time
      • irregular heartbeat, palpitations
      • nausea, vomiting
    • Contraindication:
      • sildenafil (Viagra®)
      • tadalafil (Cialis®)
      • vardenafil (Levitra ®)
    • Lab monitoring not necessary
  • Antidysrhythmics/Antiarrhythmics
  • What are Arrhythmias?
    • Cardiac disorder of
      • Rate
      • Rhythm
      • Impulse generation
      • Conduction of electrical impulses in the heart
    • Causes
      • May develop from a diseased heart
      • Consequence of chronic drug therapy
    • Symptoms
      • Mild palpitations  cardiac arrest
    • Treatment goal
      • Covert arrhythmia to a normal rhythm
  • Antidysrhythmics/Antiarrhythmics
    • Uses
      • restore normal cardiac rhythm
      • Successful conversion of an arrhythmia depends on the type of arrhythmia present
  • Antidysrhythmics/Antiarrhythmics
    • 4 major classes
      • Class I
        • Class IA
        • Class IB
        • Class IC
      • Class II
      • Class III
      • Class IV
  • Cardiac Action Potential
    • 4: resting membrane potential; steady K+ flux
    • 0: Na+ influx into cell
    • 1: K+ efflux
    • 2: K+ efflux & Ca+ influx
    • 3: K+ efflux
  • Class Participation Question #4:
    • True or False?
    • Although antiarrthymics are used for treating arrhythmias, they can also PRODUCE arrhythmias.
  • Class Participation Question #4:
    • True or False?
    • Although antiarrthymics are used for treating arrhythmias, they can also PRODUCE arrhythmias.
    • Answer: TRUE
  • The Catch 22 with Antiarrhythmics
    • People with structural heart disease are at INCREASED risk for arrhythmias!
    • The problem…
      • Many antiarrhythmic drugs INCREASE sudden death in these patients compared to placebo
  • Antiarrthymics: Class I
    • Na channel blockers
    • Common features
      • Local anesthetic activity
      • Interferes with movement of Na ions
      • Slow conduction velocity
      • Prolong refractory period
      • Decreases automaticity of the heart
  • Class I A
    • Quinidine (Quinidine sulfate ® , Quinaglute ® , Quinidex ® , Cardioquin ® )
    • Disopyramide (Norpace ® )
    • Procainimide (Procainimide HCI ® , Procan ® , Procanabid ® , Pronestyl ® )
  • Class 1A – Quinidine
    • Derived from cinchona tree
    • Depresses both the myocardium & conduction system
    • Overall effect: slows heart rate
    • Pharmacokinetics
      • Well absorbed in GI tract after po administration
      • Metabolized to several active metabolites
      • Primarily excreted by urinary tract
      • Cardiac poison when large amounts are present in blood
  • Class 1A – Quinidine (cont’d)
    • Adverse Effects
      • N/V, diarrhea, weakness, fatigue, cinchonism
    • Drug Interactions
      • Hyperkalemia
      • Digitalis
      • propranolol
    • Monitoring
      • CBC
      • ECG
      • serum quinidine concentrations (target range 2-6 µg/ml or higher)
    • CI: AV block
  • Class I B
    • prototype: Lidocaine (Xylocaine®)
    • Tocainide (Tonocard®)
    • Mexiletene (Mexitel®)
    • Phenytoin (Dilantin®)
  • Lidocaine – Class IB
    • MOA: blocks influx of Na fast channels
        • What phase of the action potential does this affect?
    • Indication: ventricular arrhythmias
  • Dosage
    • Vfib, Vtach
      • IM 300 mg. May be repeated after 60 to 90 min
      • IV bolus 50 to 100 mg at rate of 25 to 50 mg/min; may repeat, but do not exceed 200 to 300 mg/h
      • Continuous infusion 1 to 4 mg/min
        • Lidocaine is prepared by mixing:
          • 2 Grams Lidocaine in 500 mL D5W
          • 1 Gram Lidocaine in 250 mL D5W
  • Lidocaine – Class IB (cont’d)
    • Common Adverse Effects
      • anxiety, nervousness
      • dizziness, drowsiness
      • feelings of coldness, heat, or numbness; or pain at the site of the injection
      • N/V
    • Monitoring
      • LFTs
      • Scr/BUN
      • serum lidocaine concentrations (target range 2-6 µg/ml): parenteral use
  • Lidocaine (cont’d)
    • CI
      • Hypersensitivity to amide local anesthetics
      • Stokes-Adams syndrome
      • Wolff-Parkinson-White syndrome
      • severe degrees of sinoatrial, AV or intraventricular block in absence of pacemaker
      • ophthalmic use
  • Class I C
    • prototype: Flecainide (Tambocor®)
    • Propafenone (Rhythmol®)
  • Flecainide – Class IC
    • MOA
      • Blocks fast Na channels depresses the upstroke of the action potential, which is manifested as a decrease in the maximal rate of phase 0 depolarization.
      • significantly slow His-Purkinje conduction and cause QRS widening
      • shorten the action potential of Purkinje fibers without affecting the surrounding myocardial tissue.
    • Indications
      • Afib
      • Atrial flutter
      • Paroxysmal supraventricular tachycardias
      • Ventricular tachycardia prophylaxis
      • Wolff-Parkinson-White Syndrome
  • Flecainide – Class IC
    • Adverse Reactions
      • visual impairment, dizziness, asthenia, edema, abdominal pain, constipation, headache, fatigue, and tremor, N/V, arrhea, dyspepsia, anorexia, rash, diplopia, hypoesthesia, paresthesia, paresis, ataxia, flushing, increased sweating, vertigo, syncope, somnolence, tinnitus, anxiety, insomnia, and depression.
    • Avoid in
      • CHF
      • Acute MI
      • Hx of MI (LVEF < 30%)
    • Monitoring
      • ECG
      • serum creatinine/BUN: baseline
  • Class II – Beta Blockers
    • Propranolol (Inderal®)
    • Acebutolol (Sectral®)
    • Atenolol (Tenormin®)
    • Betaxolol (Kerlone®)
    • Bisoprolol (Zebeta®)
    • Carvedilol (Coreg®)
    • Esmolol ( Brevibloc®)
    • Metoprolol(Toprol®, Lopressor®)
    • Nadolol (Corgard®)
    • Timolol (Blocadron®)
  • Propranolol Warning
    • 2 situations in which propranolol requires extreme caution
      • AV block
      • CHF
      • Asthma or emphysema
  • Class III
    • K+ channel blockers
    • Drugs:
      • Prototype: Amiodarone (Cordarone)
      • Bretylium (Bretylol)
      • Sotalol (Betapace)
  • Amiodarone – Class III
    • MOA
      • noncompetitively inhibits alpha- and beta-receptors,
      • possesses both vagolytic and calcium-channel blocking properties
      • relaxes both smooth and cardiac muscle
    • Indications
      • Vfib
      • Vtach
  • Vfib Amiodarone Dosage
    • po
      • Initially, 800-1600 mg/day PO in single or divided doses for a minimum of 1-3 weeks in a monitored setting until an initial therapeutic response is achieved
      • followed by 600-800 mg/day PO in one or divided doses for about one month.
      • Then reduce dosage again to the lowest effective maintenance dose, usually 400 mg/day PO in one or divided doses
    • iv
      • initial IV rapid infusion of 150 mg over the first 10 minutes. Then begin a slow IV infusion of 1 mg/min for the next 6 hours (total dose infused = 360 mg). Then, the infusion rate is lowered to 0.5 mg/min for the next 18 hours (total dose infused = 540 mg). After the first 24 hours, a maintenance IV infusion of 0.5 mg/minute (720 mg/day) is recommended.
  • Amiodarone – Adverse Reactions
    • Cardiovascular: exacerbation of the arrhythmias, CHF (3%) and bradycardia. Cardiac arrhythmias, CHF, sinoatrial node dysfunction (1% to 3%); cardiac conduction abnormalities, hypotension (less than 1%)
    • CNS: 20% to 40% of patients and including malaise and fatigue, peripheral neuropathy, poor coordination & gait, & tremor and involuntary movements; they are rarely a reason to stop therapy and may respond to dose reductions or discontinuation; Abnormal gait/ataxia, dizziness, lack of coordination, malaise and fatigue, paresthesias, tremor/abnormal involuntary movements (4% to 9%); decreased libido, headache, insomnia, sleep disturbances (1% to 3%).
    • Dermatologic: ~ 15% of patients, with photosensitivity being most common (approximately 10%). Sunscreen and protection from sun exposure may be helpful, and drug discontinuation is not usually necessary. Prolonged exposure to amiodarone occasionally results in a blue-gray pigmentation; Solar dermatitis/photosensitivity (4% to 9%); alopecia, blue skin discoloration, rash, spontaneous ecchymosis (less than 1%).
    • Endocrine: Hyperthyroidism, hypothyroidism (1% to 3%).
    • GI: GI complaints, most commonly anorexia, constipation, N/V (10% to 33%); anorexia, constipation (4% to 9%); abdominal pain (1% to 3%)
    • Hepatic: Abnormal liver function tests (4% to 9%); nonspecific hepatic disorders (1% to 3%)
    • Ophthalmic: optic neuropathy and/or optic neuritis, in some cases progressing to corneal degeneration, eye discomfort, lens opacities, macular degeneration, papilledema, permanent blindness, photosensitivity, and scotoma, have been reported . Asymptomatic corneal microdeposits are present in virtually all adult patients who have been on the drug for more than 6 months. Some patients develop eye symptoms of dry eyes, halos, and photophobia. Vision is rarely affected and drug discontinuation is rarely needed. Visual disturbances (4% to 9%)
    • Respiratory: Fibrosis, pulmonary inflammation (4% to 9%)
    • Miscellaneous: Abnormal salivation, abnormal taste and smell, coagulation abnormalities, edema, flushing (1% to 3%).
  • Amiodarone – Class III (cont’d)
    • Monitoring
      • CBC
      • chest x-ray
      • ECG
      • LFTs
      • ophthalmologic exam
      • PFTs: baseline
      • thyroid function tests (TFTs)
  • Class IV
    • Ca channel blockers
    • Drugs
      • Adenosine (Adenocard ® )
      • Diltiazim (Cardizem®, Tiazac®)
      • Verapamil (Dovera®, Isoptin®, Calan®)
    • Clinical Effects
      • widen the blood vessels
      • may decrease the heart’s pumping strength
  • Sympathomimetics
  • Sympathomimetics
    • 2 classes:
      • α - agonist
        • Phenylephrine
        • Clonidine
        • Oxymetazoline
        • Tetrahydralazine
        • Xylometazoline
      • β -agonist
        • Prototype: Epinephrine
        • Norepinephrine
        • Dopamine
        • Dobutamine
        • Isoproterenol
    • SE:
      • hypertension,
      • excessive cardiac stimulation
      • cardiac arrhythmias
      • Long-term use increases mortality in heart failure patients.
    • CI
      • CAD  
  • Epinephrine
    • “ fight or flight “hormone
    • Aka “adrenaline”
    • increases heart rate and stroke volume
    • dilates the pupils
    • constricts arterioles in the skin and gastrointestinal tract while dilating arterioles in skeletal muscles
  • Epinephrine MOA
  • Epinephrine (cont’d)
    • Indications
      • Vfib
      • Ventricular asystole
      • Cardiac arrest
      • Pulseless electrical activity
    • IV Dosage
      • IV: 1 mg (10 ml of a 1:10,000 solution) IV; may repeat every 3-5 minutes
      • Each dose may be given by peripheral injection followed by a 20 ml flush of IV fluid.
  • Epinephrine
    • Common Adverse Effects
      • anxiety or nervousness
      • dry mouth
      • drowsiness or dizziness
      • headache
      • increased sweating
      • nausea
      • weakness or tiredness
    • Monitoring
      • ECG: in patients receiving IV therapy
      • PFTs
  • Vasopressors
  • Vasopressors
    • Vasoconstrictors vs. Vasodilators
    • 2 Vasoconstrictor Classes
      • Sympathomimetics
      • Vasopressin Analogs
    • Vasodilators
        • Alpha-adrenoceptor antagonists (alpha-blockers)
        • Angiotensin converting enzyme (ACE) inhibitors
        • Angiotensin receptor blockers (ARBs)
        • Beta2-adrenoceptor agonists (b2-agonists)
        • Calcium-channel blockers (CCBs)
        • Centrally acting sympatholytics
        • Direct acting vasodilators
        • Endothelin receptor antagonists
        • Ganglionic blockers
        • Nitrodilators
        • Phosphodiesterase inhibitors
        • Potassium-channel openers
        • Renin inhibitors
  • Vasoconstrictor
    • any agent that produces vasoconstriction and a rise in blood pressure (usually understood as increased arterial pressure)
    • Drugs
      • Prototype: Vasopressin
      • Epinephrine
      • Dobutamine
      • Dopamine
      • Norepinephrine
  • Vasopressin
    • aka : “AVP” or “ADH”
    • MOA
      • ↑ the resorption of water at the renal collecting ducts
      • Vasoconstrictive property: stimulates the contraction of vascular smooth muscle in coronary, splanchnic, GI, pancreatic, skin, and muscular vascular beds
  • Vasopressin (cont’d)
    • FDA indication: Diabetes Insipidus
    • Non-FDA indications
      • Cardiac arrest
      • Cardiogenic shock
      • Cardiopulmonary resuscitation
      • Hypotension
      • Septic shock
      • And many more….
  • Vasopressin (cont’d)
    • Dosage for cardiac arrest including ventricular asystole and pulseless electrical activity (PEA) during cardiopulmonary resuscitation (CPR)
      • IV or intraosseous dosage:
        • Adults: A single dose of 40 units IV (or intraosseous) may be given one time to replace the first or second dose of epinephrine during cardiac arrest
        • Do not interrupt cardiopulmonary resuscitation to administer drug therapy.
  • Vasopressin (cont’d)
    • Adverse Effects
      • Cardiovascular: Cardiac arrest; circumoral pallor; arrhythmias; decreased cardiac output; angina; myocardial ischemia; peripheral vasoconstriction; and gangrene
      • CNS: Tremor; vertigo; “pounding” in head
      • Dermatologic: Sweating; urticaria; cutaneous gangrene
      • GI: Abdominal cramps; nausea; vomiting; passage of gas
      • Hypersensitivity: Anaphylaxis (cardiac arrest and/or shock) has been observed shortly after injection
      • Respiratory: Bronchial constriction.
    • Monitoring
      • serum osmolality
      • serum Na
  • Diuretics
  • Diuretics
    • “water pill”
    • Promotes formation of urine by the kidney  forced diuresis
    • Uses
      • HTN
      • Edema
      • Glaucoma
      • Anuria
  •  
  • Diuretic Properties Diuretic agent Site of Action & Misc. Chlorothiazide PO/IV Distal Tubule Calcium Reabsorption Increased May transiently increase Lipids, BG and UA Hypomagnesemia (may complicate K+ correction) Severe Potassium Depletion – Creation of Combos ??? Pregnancy categories: B and C Hydrochlorothiazide Indapamide Metolazone (Mykrox) Furosemide Ascending Limb of Henle Ototoxocity (reversible and irreversible) Hypokalemia (supplement with K+) Pregnancy categories: B Torsemide Bumetanide Ethacrynic acid Amiloride Distal and Proximal tubule Impact Hyperkalemia and serum creatinine elevations Avoidance: BUN > 30 mg/dl or SCr > 1.5 mg/dl Triamterene Eplerenone Distal and Aldosterone receptor Impact Same as amiloride and triamterene – avoid K spare combos Spironolactone
  • Diuretics
    • Prototype: Furosemide (Lasix ® )
    • MOA
      • inhibits the reabsorption of sodium and chloride in the ascending limb of the loop of Henle
    • Indications
      • Edema
      • HF
      • HTN
      • Nephrotic syndrome
      • Pulmonary edema
      • Renal impairment
  • Furosemide – Edema Dosage
    • po : Initially, 20-80 mg as a single dose; may repeat dose in 6-8 hr. Titrate upward in 20-40 mg increments. The usual dosage is 40-120 mg/day. Max dosage is 600 mg/day.
    • IV or IM : Initially, 20-40 mg, increasing by 20 mg every 2 hours prn to attain clinical response. Administer IV doses slowly. A max infusion rate of 4 mg/min has been recommended when administering doses >120 mg or for patients with cardiac or renal failure
  • Furosemide
    • Common Adverse Reactions
      • Cardiovascular: Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates or narcotics.
      • CNS: Tinnitus and hearing loss, paresthesias, vertigo, dizziness, headache, blurred vision, xanthopsia. Dermatologic: Exfoliative dermatitis, erythema multiforme, purpura, photosensitivity, urticaria, rash, pruritus. GI: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), anorexia, oral and gastric irritation, cramping, diarrhea, constipation, nausea, vomiting. Hematologic: Aplastic anemia (rare), thrombocytopenia, agranulocytosis (rare), hemolytic anemia, leukopenia, anemia. Hypersensitivity: Systemic vasculitis, interstitial nephritis, necrotizing angiitis. Miscellaneous: Hyperglycemia, glycosuria, hyperuricemia, muscle spasm, weakness, restlessness, urinary bladder spasm, thrombophlebitis, fever.
  • Furosemide (cont’d)
    • Monitoring
      • audiometry
      • blood glucose
      • serum creatinine/BUN
      • serum electrolytes
      • serum uric acid
    • CI/Precautions
      • Sulfa allergy
      • Kidney failure
      • Anuria
  • Anticoagulants
  • Antiplatelets/Anticoagulants
    • Prevents/interferes with coagulation
    • Uses
      • deep vein thrombosis (DVTs), pulmonary embolism, myocardial infarctions & strokes in those who are predisposed
  • Types of Antiplatelets/Anticoagulants
    • Antiplatelets
      • Aspirin
      • Dipyridamole
      • Thienopyridines
        • Clopidogrel (Plavix)
        • Ticlopidine (Ticlid)
      • Glycoprotein IIb/IIIa antagonists
        • Abciximab (ReoPro)
        • Eptifibatide (Integrelin)
        • Tirofiban (Aggrastat )
  • Antiplatelets/Anticoagulants
    • Anticoagulants
      • Heparin
      • LMWH
        • Enoxaparin (Lovenox ® )
        • Dalteparin (Fragmin ® )
        • Tinzaarin (Innohep ® )
      • Factor Xa inhibitors
        • Fondaparinux (Arixtra ® )
      • Direct Thrombin Inhibitors
        • Argatroban
        • Lepirudin (Refludan ® )
      • Oral Anticoagulants
        • Prototype: Warfarin
  • Heparin Recall in 2008
    • In February 2008 , the FDA issued a MedWatch in response to an increase in the number of serious adverse events including allergic or hypersensitivity-type reactions with the administration of higher bolus doses of heparin. The reports have mainly involved the use of Baxter multiple-dose vials ; however, there have been reports of these reactions occurring when the combination of multiple- and single-dose vials have been used to administer a bolus dose. In February 2008, Baxter International announced expanding their voluntary recall to include all lots and doses of its Heparin Sodium UPS multi-dose, single-dose vials, and HEP-LOCK heparin flush products . The company initially recalled nine lots of heparin sodium injection multi-dose vials as a precautionary measure due to a higher than usual number of reports of adverse patient reactions involving the product. In March 2008, the FDA announced that the contaminant found in samples of Baxter's heparin was oversulfated chondroitin sulfate, a substance derived from animal cartilage. The FDA also stated that it does not know whether this contaminant caused the adverse events, only that a contaminant has been identified . Investigations continue as to whether this contaminant was added to heparin by accident or intentionally. Customers with questions regarding the Baxter recall may contact the Center for One Baxter at 1-800-422-9837.
  • Coagulation Cascade
  • Warfarin – Oral Anticoagulant
    • MOA: Warfarin inhibits the synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S
  • Warfarin (cont’d)
    • Indications
      • Stroke
      • DVT
      • Post MI
      • Afib
      • Cardiomyopathy….and many more!
    • Dosage
      • Initially, 2-5 mg PO or IV once daily, with dosage adjustments made according to INR result
  • Warfarin Warnings
    • Bleeding Risk!
    • Warfarin can cause major or fatal bleeding . Bleeding is more likely to occur during the starting period and with a higher dose (resulting in a higher international normalized ratio [INR]). Risk factors for bleeding include high intensity of anticoagulation (INR of more than 4), 65 years of age and older, highly variable INRs, history of GI bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, malignancy, trauma, renal function impairment, concomitant drugs, and long duration of warfarin therapy. Regular monitoring of INR should be performed on all treated patients . Those at high risk of bleeding may benefit from more frequent INR monitoring, careful dose adjustment to desired INR, and a shorter duration of therapy. Patients should be instructed about prevention measures to minimize risk of bleeding and to report immediately to health care provider signs and symptoms of bleeding
    • Pregnancy Category X
  • Warfarin (cont’d)
    • SE
      • Hemorrhage: Signs of severe bleeding resulting in the loss of large amounts of blood depend upon the location and extent of bleeding. Symptoms include: chest, abdomen, joint, muscle, or other pain; difficult breathing or swallowing; dizziness; headache; low blood pressure; numbness and tingling; paralysis; shortness of breath; unexplained shock; unexplained swelling; weakness
    • Monitoring
      • INR
      • prothrombin time (PT)
      • stool guaiac
      • bleeding
      • DDIs
        • NSAIDs
        • 3 G’s
          • Garlic
          • Ginger
          • Ginsing
      • Vitamin K intake
    • Class Participation Question #5:
    • Which foods are high in vitamin K?
    • Class Participation Question #5:
    • Which foods are high in vitamin K?
  • Fibrinolytic Enzymes
  • Fibrinolytic Enzymes
    • “clotbusters”
    • MOA: stimulate the synthesis of fibrinolysin which breaks the clot into soluble products
    • Drugs
      • Urokinase (Abbokinase ® )
      • Anistreplase (Eminase ® )
      • Alteplase (Activase ® )
      • Reteplase (Retevase ® )
      • Prototype: Streptokinase (Strepase ® )
  • Streptokinase (cont’d)
    • Indications
      • Acute MI
      • Acute ischemic stroke
      • Pulmonary embolism
      • Lysis of DVT
    • Dose Administration
      • Parental infusion (usually IV)
      • Deep vein or arterial thrombosis
        • IV: 250,000 IU over 30 min followed by 100,000 IU per hour up to 72 hours
  • Streptokinase (cont’d)
    • Adverse Effects
      • Hemorrhage
      • Concomitant use of heparin, oral anticoagulants, NSAIDs is NOT recommended because of the increased risk of bleeding
      • Allergic reactions
  • Streptokinase (cont’d)
  • Beta Blockers
  • Beta Blockers
    • MOA : bind to beta-adrenergic receptors & block the effects of EPI & NE
    • Indications
      • Angina
      • HTN
      • Arrhythmias
      • Glaucoma
      • Migraine prophylaxis
      • Post MI
  • Beta Blockers (cont’d)
    • Non-Selective BB
      • carvedilol (Coreg ® )
      • labetalol (Normodyne ® )
      • nadolol (Corgard ® )
      • pindolol (Visken ® )
      • propranolol (Inderal ® )
      • timolol (Blocadren ® )
    • Selective B-1 Blockers
      • acebutolol (Sectral ® )
      • altenolol (Tenormin ® )
      • bisoprolol (Zebeta ® )
      • esmolol (Brevibloc ® )
      • metoprolol tartrate (Lopressor ® )
      • metoprolol succinate (Toprol XL)
  • Propranolol
    • HTN Dosage
      • po: initially, 40 mg PO twice daily, then increase at 3-7 day intervals up to 160-480 mg/day, given in 2-3 divided doses. Maximum dosage is 640 mg/day
    • Main Effects
      • ↓ in rate, force of contraction, & conduction velocity of the heart
      • Blocks carbohydrate & lipid metabolism
  • Propranolol (cont’d)
    • Adverse Reactions
      • changes in blood sugar
      • cold hands or feet
      • difficulty breathing, wheezing
      • difficulty sleeping, nightmares
      • dizziness or fainting spells
      • hallucinations (seeing and hearing things that are not really there)
      • muscle cramps or weakness
      • skin rash, itching, dry peeling skin
      • slow heart rate (less than 50 beats per minute)
      • swelling of the legs and ankles
      • vomiting
      • dark coloration of skin
      • diarrhea
      • dry sore eyes
      • hair loss
      • nausea
      • sexual difficulties (impotence or decreased sexual urges)
      • weakness or tiredness
  • Propranolol (cont’d)
    • Lab monitoring NOT necessary
    • Check vital signs frequently with parenteral drug administration
    • Observe patient for signs of cardiac depression & hypotension
  • Calcium Channel Blockers
  • Calcium Channel Blockers (CCBs)
    • MOA
      • prevent calcium from entering cells of the heart and blood vessel walls
      • relax and widen blood vessels by affecting the muscle cells in the arterial walls
    • Indications:
      • HTN
      • Angina
      • Migraine prophylaxis
      • Brain aneurysm complications
      • Arrhythmia
      • Reynaud's disease
      • Pulmonary HTN
  • CCBs (cont’d)
    • Drugs:
    • Amlodipine (Norvasc ® )
    • Diltiazem (Cardizem LA ® , Dilacor XR ® , Tiazac ® )
    • Felodipine (Plendil ® )
    • Isradipine (DynaCirc CR ® )
    • Nicardipine (Cardene ® , Cardene SR ® )
    • Nifedipine (Procardia ® , Procardia XL ® , Adalat CC ® )
    • Nisoldipine (Sular ® )
    • Verapamil (Calan ®, Verelan ® , Covera-HS ® )
  • Amlodipine
    • Indications
      • hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina
    • Dosage
      • Initially, 5 mg PO qd
      • Maximum dosage is 10 mg qd
  • Amlodipine http://online.factsandcomparisons.com/MonoDisp.aspx?monoID=fandc-hcp10122&inProdGen=true&quick=Amlodipine&search=Amlodipine
  • Amlodipine
    • Monitoring
      • No lab monitoring needed
    • CI
      • Known sensitivity to amlodipine
    • Questions?