Pharmacology 2 - Lecture Notes For Exam 2

Pharm Exam 2 Study Guide 1. Mechanisms of action 2. Uses 3. Adverse Effects/side effects/issues Cardiovascular Drugs Anti-Anginals - - - - - Angina Pectoris - Severe chest pain - Usually short (5-10mins) - Brought on by exertion or emotional excitement - Related to the need for increased myocardial oxygen demand (myocardial ischemia) - Oxygen demand decreases with rest and relaxation - Steady intense pain sometimes with crushing pain that radiates to left shoulder and left arm. Can move to the jaw, epigastrium, and abdominal area - Considered classic or stable if predictable, does not progress - Frequency, intensity and duration S/S - Emotional distress - Feeling of doom, impending death - Pallor, dyspnea with cyanosis - Diaphoresis - Tachycardia - Elevated BP Vasospastic (Prinzmetal’s) Angina - Spasms of the coronary artery leads to decreased myocardial blood flow - Not specifically related to plaque build up - Pain related to vasoconstriction of artery - Generally occurs in periods of rest Silent Angina - No chest pain present (asymptomatic) - Myocardial ischemia is still occuring - High risk for acute MI and sudden death Unstable Angina (most severe form of angina) - Episodes occur suddenly, increasing intensity, and occur during periods of rest - Plaque within coronary artery ruptures - Medical emergency - Does not go away and leads to an MI Antianginal Drugs - Calcium Channel Blocker - Action: relax coronary artery spasm, causes negative inotropic effects, and reduces cardiac workload and oxygen demands - Relax arteriolar smooth muscle and reduces BP - SE: dizziness, flushing, headache, hypotension, reflex tachycardia, peripheral edema, fatigue - Nitrates (Nitroglycerin) - Action: forms nitric oxide in vascular smooth muscle, causes vasodilation - Reduces the amount of blood returning to the heart (preload) - Reduced cardiac output - Reduced workload - Reduced oxygen demands - Tolerance can occur, especially with long acting - Remove patch for 6+ hours per day at hs (night) - SE: headache (lets you know drug is working), decreased BP - Given sublingually - If it were given PO you would have the hepatic first pass and it would not be effective - Usually 0.4mg starting dose and takes about 30-40 mins before it works. - Beta-Adrenergic Blockers (Cardioprotective - reduces the incidence of MI) - Action: decreases the cardiac workload by lowering blood pressure, slowing heart rate and reducing contractility - This decreases frequency and severity of anginal episodes - Prefered selective beta blockers because non-selective can affect bronchodilation - Also effective for HTN Dysrhythmias - Occur in all age groups, in healthy and unhealthy people too. - Associated conditions/ diseases : HTN, cardiac valve disease, CAD, hyper/hypokalemia, MI, stroke, DM, HF - S/S: Dizziness, weakness, fatigue, decreased exercise tolerance, palpitations, dyspnea, syncope (temp. Loss of consciousness due to decrease in BP) - Cardiac Action Potential Phases - Phase 0 - Action potential begins when threshold potential is reached. - Sodium rushes in, producing rapid depolarization - Calcium enters at a slower rate - Phase 1 - - - - - - Brief transient phase - Inside of plasma membrane reverses charge, becomes positive - Phase 2 - Plateau reached in which depolarization is maintained - Contraction of cardiac muscle - Efflux of potassium from cells - Phase 3 - Calcium channels close - Additional potassium channels open - Repolarization returns negative resting membrane potential - Phase 4 - Refractory Period - Brief period where depolarization cannot occur - Ensures myocardial cell finishes contracting before another action potential begins Bradydysrhythmias - HR <60 bpm - Common among older adults - Major indication for pacemakers - Common bradydysrhythmias - Sinus bradycardia -life sustainable - Sinoatrial node dysfunction (HR in the 30s) - Atrioventricular (AV) conduction block - Arrhythmia - no rhythm (DEAD) Tachydysrhythmias - HR >100 bpm - Incidence increases in older adults and those with preexisting cardiac disease - Common tachydysrhythmias: - Atrial tachycardia - Paroxysmal supraventricular tachycardia (PSVT) >200 bpm - Atrial flutter - Atrial fibrillation - Ventricular tachycardia - Torsades de pointes - Ventricular fibrillation Asymptomatic dysrhythmias - No treatment - Little or no benefit to treatment with medications Acute dysrhythmias - In life-threatening cases, medications warranted Prophylaxis of dysrhythmias - - - Initiated for high-risk patients - Avoid drug combinations that increase QT interval Nonpharmacologic treatment of dysrhythmias - Cardioversion or defibrillation - Electrical stimulation of the heart for serious dysrhythmias - Identification and destruction of the cell responsible for abnormal conduction - Pacemakers - ICDs (implantable cardioverter defibrillators) Pharmacologic management of dysrhythmias - Sodium Channel Blockers (works in phase 0 of action potential) - Class 1A: procainamide - Uses: Ventricular tachycardia during CPR, Refractory ventricular fibrillation during CPR, Pulseless ventricular tachycardia during CPR, Premature atrial tachycardia, Atrial flutter, Atrial fibrillation - Action: - Blocks sodium ion channels in myocardial cells - Reduces automaticity and slows velocity of action potential - Adverse Effects: - N/V, headache, fever, anorexia, weakness, confusion, psychosis at high doses - Contraindications: AV block, Severe HF, Peripheral neuropathy, Myasthenia gravis, shock, severe hypotension - Precautions: Lupus, renal impairment, bone marrow suppression - Nursing Responsibilities for Class 1A - Check apical and radial pulses before dose - Continuous ECG and BP monitoring during IV administration - Assess for adverse effects - Monitor therapeutic blood levels - Class 1B: - Shorten repolarization - Little effect on conduction velocity - Primary indications are ventricular dysrhythmias - Drugs include: - Lidocaine (Xylocaine) - Mexiletine (Mexitil) - Phenytoin (Dilantin) - Class 1C: Antiarrhythmics - Decrease conduction velocity - PR, QRS, and QT intervals are often prolonged - Life-threatening atrial dysrhythmias - Beta Adrenergic Antagonist: Class II - - - - - - Reduce automaticity as well as slow conduction velocity in the heart - Treat: HTN, MI, HF and dysrhythmias - Action: block calcium channels in SA and AV nodes - Slows HR - Drugs: - Acebutolol (Sectral) - Esmolol (Brevibloc) - Propranolol (Inderal) Potassium Channel Blockers: Class III - Prolong the refractory period of the heart, delay repolarization - Block potassium ion channels in myocardial cells - Limited use due to serious AE such as: - N/V, anorexia, fatigue, dizziness, hypotension, visual disturbances, rashes, photosensitivity - Mechanism of action: - Exact mechanism unknown - Block potassium channels but also blocks sodium ion channels and inhibits sympathetic activity - Contraindications/precautions: severe bradycardia, cardiogenic shock, sick sinus syndrome, severe sinus node dysfunction, third-degree AV block, hypersensitivity to iodine, lactation, COPD, electrolyte imbalances - Drug interactions: Enhances actions of anticoagulants and potentiates dysrhythmias with other antidysrhythmic agents Nursing Responsibilities for Class III - Monitor BP during IV infusion - Assess for adverse effects - Baseline lab tests - Assess respiratory status - Supervise ambulation (could have hypotension) - Baseline ophthalmic exam Calcium Channel Blockers: Class IV - Effects similar to those of beta - adrenergic antagonists - Monitor for bradycardia and hypotension Other Management of Dysrhythmias: Adenosine (transient heart block) - Naturally occuring nucleoside - Activates potassium channels in SA and AV nodes - Terminates tachycardia - Primary indication is PSVT (very common) - 10-second half-life, so adverse effects are self-limiting Digoxin - Primarily for HF Can be prescribed for atrial flutter, fibrillation, or PSVT Not effective against ventricular dysrhythmias Patients must be carefully monitored for toxicity, drug interactions, and adverse effects - Loading dose needed Anticoagulants, Antiplatelets, and Thrombolytics - Anticoagulants - Action: Prevent formation of clots, but do not take care of current clots - Use: venous and arterial disorders at high risk for clot formation - DVT, PE, MI, artificial heart valves, strokes - HEPARIN - Action: binds with antithrombin iii, inhibits the action of thrombin, inhibits the conversion of fibrinogen to fibrin, therefore inhibiting clot formation - Use: prevent venous thrombosis - Issues: Must be given IV or SubQ (Not PO because of first pass), monitor labs (PT/INR, aPTT), side effects of bleeding and bruising - Antidote: Protamine sulfate - Low Molecular weight heparin - Action: inactivates Xa factor - Use: prevent DVT, PE (high risk from abdominal and orthopedic surgeries) - Issues: ASA (aspirin), bleeding - Direct Thrombin Inhibitors - Action: directly inhibits thrombin, preventing fibrinogen converting to fibrin - Use: treatment and prevention of DVT/PE, and thrombus prophylaxis for unstable angina, a-fib, and stroke - Issues: IV, SubQ - WARFARIN - Action: inhibits synthesis of vitamin K, clotting factors II, VII, IX, and X are affected - Use: prevents thromboembolic conditions (thrombophlebitis, PE, DVT) - Issues: monitor labs (PT/INR) - Antidote: Vitamin K, takes 24-48 hours to be effective and may need to give frozen plasma or platelets in the meantime - Xa inhibitors - Newer, less lab monitoring - Action: reversible blocks the Xa factor so clots can be prevented without - impacting the fibrin cascade; it does not impact platelet aggregation Use: prevent stroke, treats a-fib, and venous thromboemboli Issues: hepatic function, certain disease processes, and food intake Remember that this is not commonly prescribed because “if it's not broke don’t fix it” Antiplatelets - Action: Prevent platelet aggregation, interrupts the cascade (the enzyme that helps them aggregate is no longer available) - Uses: prevent thrombosis of arteries, prevent MI and stroke (fam hx), prevent repeated MI or stroke, and prevent stroke with patients with TIAs - ASPIRIN - Action: Inhibits cyclooxygenase (needed for platelet aggregation) - Use: prevent MI and TE, prevent and treat a stroke - Issues: bleeding and GI upset - Thrombolytics - Action: bind to fibrin promoting conversion of plasminogen to plasmin - Uses: DVT, PE, MI (clots) - Issues: anaphylaxis, reperfusion dysrhythmias, hemorrhage - Only used for treatment and not prevention - 3-4 hours after the event occurs can you give this med Diuretics - Used for HTN, HF, renal failure, liver failure, and pulmonary edema - Common adverse effects: dehydration, hypotension, electrolyte imbalance - 5 types - Thiazide and Thiazide-Like Diuretics - Action: act on the distal convoluted renal tubule; promotes sodium, chloride, and water excretion (may also lose K and Mg) - Use: HTN and peripheral edema - Issues: must be used with normal renal function; electrolyte imbalance (biggest is hypokalemia) - Side effects: dizziness, headache, weakness, hypotension, GI distress, constipation, hyperglycemia, electrolyte imbalance, urticarial, hyperuricemia, blood dyscrasias, renal failure - Contradictions: renal failure - Loop Diuretics (lasix) - Action: act on the ascending loop of Henle; secretes Na, water, K, Ca, Mg - Side effects/adverse effects: dizziness, weakness, headache, hyperglycemia, blurred vision, photosensitivity, paresthesia, othro hypotension, hyperuricemia, electrolyte imbalance, blood dyscrasias, elevated BUN, creatinine, lipids, and renal failure - Must warrant immediate removal of body fluid - - - Osmotic Diuretics - Action: increase sodium reabsorption in the proximal tubule and loop of Henle. Increase osmolality which pulls in water to excrete Na, Cl, K and water - Use: prevent kidney failure, decrease ICP and IOP - Side effects/adverse reactions:Fluid and electrolyte imbalance, GI distress, acidosis, pulmonary edema, tachycardia - Contradictions:heart disease, HF, renal failure Carbonic Anhydrase Inhibitors - Action: block action of enzyme carbonic anhydrase. Excretes Na, K, and bicarb - Use: decrease IOP in patients with open-angle (chronic) glaucoma - Side effects/adverse reactions: confusion, ortho hypotension, GI distress, metabolic acidosis, fluid and electrolyte imbalance, crystalluria, renal calculi, hemolytic anemia. Potassium Sparing Diuretics - Action: block action of aldosterone. Promote Na/water excretion and K retention - Use: edema due to HF, cirrhosis of the liver - SE/adverse reactions: dizziness, headache, weakness, hyperkalemia, GI distress, paresthesia, muscle cramps, hyperuricemia, blood dyscrasias Pharmacology of Heart Failure - Patho - Location - Left sided HF: pulmonary edema - Right sided HF: Dependent edema - Systolic failure - Decrease contractility, and decreased EF - Diastolic failure - Decreased ventricular filling, normal EF - Ventricular Hypertrophy - Left wall thickens to compensate for increase workload allowing heart or maintain stroke volume and cardiac output - Cardiac remodeling: changes to myocyte structure and function - Sympathetic Nervous System - CO=SV x HR - Constricts arteries and activates RAAS (adds to myocardium workload, destructive cycle can lead to or worsen HF) - ANP (secreted by atria) BNP (secreted by ventricles, less than 100 is normal), CNP (secreted by the brain) - - - - - Symptoms: dyspnea on exertion, fatigue, pulmonary congestion, peripheral edema Nonpharm - Exercise, diet (limit salt and saturated fat), tobacco cessation, EToH intake, treatment of CAD, HTN, and DM Goals of pharm management of HF - Reduce preload (end diastolic volume) - Reduce afterload (systemic vascular resistance) - Inhibition of RAAS and vasoconstrictor mechanism of sympathetic nervous system Cardiac Glycosides - DIGOXIN (prototype) - Positive Inotropic: increases myocardial contractility - Negative chronotropic: decreases heart rate - Negative dromotropic: decreases conduction of the electric system within the heart - Increase stroke volume -> increase in cardiac output - Sympathetics stimulation of the heart goes down - Increase the force of contraction - Improves symptoms, does not improve mortality - Stabilizes cardiac conduction issues (negative dromotropic) - Digitalization: taper dose up to decrease HF symptoms - Need to give loading dose in order to get a minimum effective concentration - Side effects: bradycardia (negative chronotropic) **hold at 60 bpm, cardiac dysrhythmias (PVCs abnormal beat in the ventricles), anorexia, N/V/D, headache, blurred vision, “yellow vision” - Toxicity effects: same as side effects and premature ventricular contractions - Need to watch levels closely - Antidote - Digibind: binds and inactivates Digoxin - Interactions: Diuretics (related to hypokalemia), Cortisone (related to sodium retention), Antacids (decrease the absorption of Digoxin) - Nurse Responsibilities: - Take apical pulse 1 minute before admin (withhold if below parameters) - Monitor labs, monitor for toxicity, and monitor I&O ACE Inhibitors ARBs (angiotensin receptor blockers) Vasodilators - Reduce failure by reducing preload and afterload Diuretics - Reduce blood volume, lower BP, reduce workload, increase CO - - - - Used only for fluid overload (loop diuretics are best with thiazide added) Phosphodiesterase Inhibitor: Primicor (other positive inotropic agents) - Action: inhibits Phosphodiesterase III in cardiac and vascular smooth muscle. Rise in cAMP increases intracellular calcium, resulting in greater contractility - Increases contractility, decreased pulmonary vascular resistance - Vasodilator, so afterload is decreased and increased effectiveness of the contraction - AE: headache, N/V, ventricular dysrhythmias - Contractions/precautions: valvular heart disease, pre existing dysrhythmias, hypovolemia, electrolyte imbalances, renal impairment - Cascade: related to increased calcium reflux=increased contractility - Multiple toxicities with other drugs - Additive cardiac effects with inotropic drugs - Additive hypotension with antihypertensive drugs - Nursing responsibilities: - Monitor cardiac status before and following infusion, monitor BP, Monitor fluid/ electrolyte balance - For patients with HF who do not respond to ACE inhibitors, digoxin, or others. - Made for resistant HF (HF we cannot get a hold of) Spironolactone (Aldactone) - Aldosterone antagonist (not a diuretic) - Prevents cardiac remodeling Beta Adrenergic Antagonists - Blocks the catecholamines, slows HR, reduces contractility - prevents tachydysrhythmias, prevents MI damage - May produce remodeling of the heart - May worsen failure, taper dose up Antihypertensives - Regulators of BP - kidneys via RAAS - Baroreceptors in the aorta and carotid (feel the pressure and the need for pressure change) - Vasomotor center in the medulla - Hormones: ADH, ANP, BNP - Physiologic Risk Factors - Excess saturated fat and simple carbs, alcohol increases renin secretions, obesity increase CO, SV, and left ventricular filling - Race factors - African Americans have lower renin levels - Asian Americans tend to be more responsive to drugs