logging in or signing up Cardiac Drugs aSGuest1010 Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 3805 Category: News & Reports.. License: All Rights Reserved Like it (3) Dislike it (0) Added: October 15, 2008 This Presentation is Public Favorites: 4 Presentation Description No description available. Comments Posting comment... By: fmypa (22 month(s) ago) I am studying for my recertification exam and your presentation will be extremely valuable in assisting me in my studies. Thank you very much. fmypa@aol.com Saving..... Post Reply Close Saving..... Edit Comment Close By: shaikhussam (35 month(s) ago) how to download this presentation Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Pharmacology : Pharmacology Drugs that Affect the Cardiovascular System Topics : Topics Electrophysiology Vaughn-Williams classification Antihypertensives Hemostatic agents Cardiac Function : Cardiac Function Dependent upon Adequate amounts of ATP Adequate amounts of Ca++ Coordinated electrical stimulus Adequate Amounts of ATP : Adequate Amounts of ATP Needed to: Maintain electrochemical gradients Propagate action potentials Power muscle contraction Adequate Amounts of Calcium : Adequate Amounts of Calcium Calcium is ‘glue’ that links electrical and mechanical events. Coordinated Electrical Stimulation : Coordinated Electrical Stimulation Heart capable of automaticity Two types of myocardial tissue Contractile Conductive Impulses travel through ‘action potential superhighway’. A.P. SuperHighway : A.P. SuperHighway Sinoatrial node Atrioventricular node Bundle of His Bundle Branches Fascicles Purkinje Network Electrophysiology : Electrophysiology Two types of action potentials Fast potentials Found in contractile tissue Slow potentials Found in SA, AV node tissues Fast Potential : Fast Potential -80 -60 -40 -20 0 +20 RMP -80 to 90 mV Phase 1 Phase 2 Phase 3 Phase 4 controlled by Na+ channels = “fast channels” Fast Potential : Fast Potential Phase 0: Na+ influx “fast sodium channels” Phase 1: K + efflux Phase 2: (Plateau) K + efflux AND Ca + + influx Phase 3: K+ efflux Phase 4: Resting Membrane Potential Cardiac Conduction Cycle : Cardiac Conduction Cycle Slow Potential : Slow Potential -80 -60 -40 -20 0 Phase 4 Phase 3 dependent upon Ca++ channels = “slow channels” Slow Potential : Slow Potential Self-depolarizing Responsible for automaticity Phase 4 depolarization ‘slow sodium-calcium channels’ ‘leaky’ to sodium Phase 3 repolarization K+ efflux Cardiac Pacemaker Dominance : Cardiac Pacemaker Dominance Intrinsic firing rates: SA = 60 – 100 AV = 45 – 60 Purkinje = 15 - 45 Cardiac Pacemakers : Cardiac Pacemakers SA is primary Faster depolarization rate Faster Ca++ ‘leak’ Others are ‘backups’ Graduated depolarization rate Graduated Ca++ leak rate Potential Terms : Potential Terms APD ERP RRP relative refractory period effective refractory period action potential duration Dysrhythmia Generation : Dysrhythmia Generation Abnormal genesis Imbalance of ANS stimuli Pathologic phase 4 depolarization Ectopic foci Dysrhythmia Generation : Dysrhythmia Generation Abnormal conduction Analogies: One way valve Buggies stuck in muddy roads Reentrant Circuits : Reentrant Circuits Warning! : Warning! All antidysrhythmics have arrythmogenic properties In other words, they all can CAUSE dysrhythmias too! AHA Recommendation Classifications : AHA Recommendation Classifications Describes weight of supporting evidence NOT mechanism Class I Class IIa Class IIb Indeterminant Class III View AHA definitions Vaughn-Williams Classification : Vaughn-Williams Classification Class 1 Ia Ib Ic Class II Class III Class IV Misc Description of mechanism NOT evidence Class I: Sodium Channel Blockers : Class I: Sodium Channel Blockers Decrease Na+ movement in phases 0 and 4 Decreases rate of propagation (conduction) via tissue with fast potential (Purkinje) Ignores those with slow potential (SA/AV) Indications: ventricular dysrhythmias Class Ia Agents : Class Ia Agents Slow conduction through ventricles Decrease repolarization rate Widen QRS and QT intervals May promote Torsades des Pointes! PDQ: procainamide (Pronestyl®) disopyramide (Norpace®) qunidine (Quinidex®) Class Ib Agents : Class Ib Agents Slow conduction through ventricles Increase rate of repolarization Reduce automaticity Effective for ectopic foci May have other uses LTMD: lidocaine (Xylocaine®) tocainide (Tonocard®) mexiletine (Mexitil®) phenytoin (Dilantin®) Class Ic Agents : Class Ic Agents Slow conduction through ventricles, atria & conduction system Decrease repolarization rate Decrease contractility Rare last chance drug flecainide (Tambocor®) propafenone (Rythmol®) Class II: Beta Blockers : Class II: Beta Blockers Beta1 receptors in heart attached to Ca++ channels Gradual Ca++ influx responsible for automaticity Beta1 blockade decreases Ca++ influx Effects similar to Class IV (Ca++ channel blockers) Limited # approved for tachycardias Class II: Beta Blockers : Class II: Beta Blockers propranolol (Inderal®) acebutolol (Sectral®) esmolol (Brevibloc®) Class III: Potassium Channel Blockers : Class III: Potassium Channel Blockers Decreases K+ efflux during repolarization Prolongs repolarization Extends effective refractory period Prototype: bretyllium tosylate (Bretylol®) Initial norepi discharge may cause temporary hypertension/tachycardia Subsequent norepi depletion may cause hypotension Class IV: Calcium Channel Blockers : Class IV: Calcium Channel Blockers Similar effect as ß blockers Decrease SA/AV automaticity Decrease AV conductivity Useful in breaking reentrant circuit Prime side effect: hypotension & bradycardia verapamil (Calan®) diltiazem (Cardizem®) Note: nifedipine doesn’t work on heart Misc. Agents : Misc. Agents adenosine (Adenocard®) Decreases Ca++ influx & increases K+ efflux via 2nd messenger pathway Hyperpolarization of membrane Decreased conduction velocity via slow potentials No effect on fast potentials Profound side effects possible (but short-lived) Misc. Agents : Misc. Agents Cardiac Glycocides digoxin (Lanoxin®) Inhibits NaKATP pump Increases intracellular Ca++ via Na+-Ca++ exchange pump Increases contractility Decreases AV conduction velocity Pharmacology : Pharmacology Antihypertensives Antihypertensive Classes : Antihypertensive Classes diuretics beta blockers angiotensin-converting enzyme (ACE) inhibitors calcium channel blockers vasodilators Blood Pressure = CO X PVR : Blood Pressure = CO X PVR Cardiac Output = SV x HR PVR = Afterload BP = CO x PVR : BP = CO x PVR Key: CCB = calcium channel blockers CA Adrenergics = central-acting adrenergics ACEi’s = angiotensin-converting enzyme inhibitors Slide 37: BP = CO x PVR Peripheral Sympathetic Receptors alpha beta 1. alpha blockers 2. beta blockers Local Acting 1. Peripheral-Acting Adrenergics Alpha1 Blockers : Alpha1 Blockers Stimulate alpha1 receptors -> hypertension Block alpha1 receptors -> hypotension doxazosin (Cardura®) prazosin (Minipress®) terazosin (Hytrin®) Central Acting Adrenergics : Central Acting Adrenergics Stimulate alpha2 receptors inhibit alpha1 stimulation hypotension clonidine (Catapress®) methyldopa (Aldomet®) Peripheral Acting Adrenergics : Peripheral Acting Adrenergics reserpine (Serpalan®) inhibits the release of NE diminishes NE stores leads to hypotension Prominent side effect of depression also diminishes seratonin Adrenergic Side Effects : Adrenergic Side Effects Common dry mouth, drowsiness, sedation & constipation orthostatic hypotension Less common headache, sleep disturbances, nausea, rash & palpitations ACE Inhibitors : Angiotensin I ACE Angiotensin II 1. potent vasoconstrictor - increases BP 2. stimulates Aldosterone - Na+ & H2O reabsorbtion ACE Inhibitors . RAAS Renin-Angiotensin Aldosterone System : Renin-Angiotensin Aldosterone System Angiotensin II = vasoconstrictor Constricts blood vessels & increases BP Increases SVR or afterload ACE-I blocks these effects decreasing SVR & afterload ACE Inhibitors : ACE Inhibitors Aldosterone secreted from adrenal glands cause sodium & water reabsorption Increase blood volume Increase preload ACE-I blocks this and decreases preload Angiotensin Converting Enzyme Inhibitors : Angiotensin Converting Enzyme Inhibitors captopril (Capoten®) enalapril (Vasotec®) lisinopril (Prinivil® & Zestril®) quinapril (Accupril®) ramipril (Altace®) benazepril (Lotensin®) fosinopril (Monopril®) Calcium Channel Blockers : Calcium Channel Blockers Used for: Angina Tachycardias Hypertension CCB Site of Action : CCB Site of Action diltiazem & verapamil nifedipine (and other dihydropyridines) CCB Action : CCB Action diltiazem & verapamil decrease automaticity & conduction in SA & AV nodes decrease myocardial contractility decreased smooth muscle tone decreased PVR nifedipine decreased smooth muscle tone decreased PVR Side Effects of CCBs : Side Effects of CCBs Cardiovascular hypotension, palpitations & tachycardia Gastrointestinal constipation & nausea Other rash, flushing & peripheral edema Calcium Channel Blockers : Calcium Channel Blockers diltiazem (Cardizem®) verapamil (Calan®, Isoptin®) nifedipine (Procardia®, Adalat®) Diuretic Site of Action : Diuretic Site of Action . loop of Henle proximal tubule Distal tubule Collecting duct Mechanism : Mechanism Water follows Na+ 20-25% of all Na+ is reabsorbed into the blood stream in the loop of Henle 5-10% in distal tubule & 3% in collecting ducts If it can not be absorbed it is excreted with the urine Blood volume = preload ! Side Effects of Diuretics : Side Effects of Diuretics electrolyte losses [Na+ & K+ ] fluid losses [dehydration] myalgia N/V/D dizziness hyperglycemia Diuretics : Diuretics Thiazides: chlorothiazide (Diuril®) & hydrochlorothiazide (HCTZ®, HydroDIURIL®) Loop Diuretics furosemide (Lasix®), bumetanide (Bumex®) Potassium Sparing Diuretics spironolactone (Aldactone®) Mechanism of Vasodilators : Mechanism of Vasodilators Directly relaxes arteriole smooth muscle Decrease SVR = decrease afterload Side Effects of Vasodilators : Side Effects of Vasodilators hydralazine (Apresoline®) Reflex tachycardia sodium nitroprusside (Nipride®) Cyanide toxicity in renal failure CNS toxicity = agitation, hallucinations, etc. Vasodilators : Vasodilators diazoxide [Hyperstat®] hydralazine [Apresoline®] minoxidil [Loniten®] sodium Nitroprusside [Nipride®] Pharmacology : Pharmacology Drugs Affecting Hemostasis Hemostasis : Hemostasis Reproduce figure 11-9, page 359 Sherwood Platelet Adhesion : Platelet Adhesion Coagulation Cascade : Coagulation Cascade Reproduce following components of cascade: Prothrombin -> thrombin Fibrinogen -> fibrin Plasminogen -> plasmin Platelet Inhibitors : Platelet Inhibitors Inhibit the aggregation of platelets Indicated in progressing MI, TIA/CVA Side Effects: uncontrolled bleeding No effect on existing thrombi Aspirin : Aspirin Inhibits COX Arachidonic acid (COX) -> TXA2 ( aggregation) GP IIB/IIIA Inhibitors : GP IIB/IIIA Inhibitors GP IIb/IIIa Inhibitors Fibrinogen GP IIb/IIIa Receptor GP IIB/IIIA Inhibitors : GP IIB/IIIA Inhibitors abciximab (ReoPro®) eptifibitide (Integrilin®) tirofiban (Aggrastat®) Anticoagulants : Anticoagulants Interrupt clotting cascade at various points No effect on platelets Heparin & LMW Heparin (Lovenox®) warfarin (Coumadin®) Heparin : Heparin Endogenous Released from mast cells/basophils Binds with antithrombin III Antithrombin III binds with and inactivates excess thrombin to regionalize clotting activity. Most thrombin (80-95%) captured in fibrin mesh. Antithrombin-heparin complex 1000X as effective as antithrombin III alone Heparin : Heparin Measured in Units, not milligrams Indications: MI, PE, DVT, ischemic CVA Antidote for heparin OD: protamine. MOA: heparin is strongly negatively charged. Protamine is strongly positively charged. warfarin (Coumadin®) : warfarin (Coumadin®) Factors II, VII, IX and X all vitamin K dependent enzymes Warfarin competes with vitamin K in the synthesis of these enzymes. Depletes the reserves of clotting factors. Delayed onset (~12 hours) due to existing factors Thrombolytics : Thrombolytics Directly break up clots Promote natural thrombolysis Enhance activation of plasminogen ‘Time is Muscle’ streptokinase (Streptase®) alteplase (tPA®, Activase®) anistreplase (Eminase®) reteplase (Retevase®) tenecteplase (TNKase®) Occlusion Mechanism : Occlusion Mechanism tPA Mechanism : tPA Mechanism Cholesterol Metabolism : Cholesterol Metabolism Cholesterol important component in membranes and as hormone precursor Synthesized in liver Hydroxymethylglutaryl coenzyme A reductase (HMG CoA reductase) dependant Stored in tissues for latter use Insoluble in plasma (a type of lipid) Must have transport mechanism Lipoproteins : Lipoproteins Lipids are surrounded by protein coat to ‘hide’ hydrophobic fatty core. Lipoproteins described by density VLDL, LDL, IDL, HDL, VHDL LDL contain most cholesterol in body Transport cholesterol from liver to tissues for use (“Bad”) HDL move cholesterol back to liver “Good” b/c remove cholesterol from circulation Why We Fear Cholesterol : Why We Fear Cholesterol Risk of CAD linked to LDL levels LDLs are deposited under endothelial surface and oxidized where they: Attracts monocytes -> macrophages Macrophages engulf oxidized LDL Vacuolation into ‘foam cells’ Foam cells protrude against intimal lining Eventually a tough cap is formed Vascular diameter & blood flow decreased Why We Fear Cholesterol : Why We Fear Cholesterol Plaque cap can rupture Collagen exposed Clotting cascade activated Platelet adhesion Thrombus formation Embolus formation possible Occlusion causes ischemia Lipid Deposition : Lipid Deposition Thrombus Formation : Thrombus Formation Platelet Adhesion : Platelet Adhesion Embolus Formation : Embolus Formation Occlusion Causes Infarction : Occlusion Causes Infarction Antihyperlipidemic Agents : Antihyperlipidemic Agents Goal: Decrease LDL Inhibition of LDL synthesis Increase LDL receptors in liver Target: < 200 mg/dl Statins are HMG CoA reductase inhibitors lovastatin (Mevacor®) pravastatin (Pravachol®) simvastatin (Zocor®) atorvastatin (Lipitor®) You do not have the permission to view this presentation. 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Cardiac Drugs aSGuest1010 Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 3805 Category: News & Reports.. License: All Rights Reserved Like it (3) Dislike it (0) Added: October 15, 2008 This Presentation is Public Favorites: 4 Presentation Description No description available. Comments Posting comment... By: fmypa (22 month(s) ago) I am studying for my recertification exam and your presentation will be extremely valuable in assisting me in my studies. Thank you very much. fmypa@aol.com Saving..... Post Reply Close Saving..... Edit Comment Close By: shaikhussam (35 month(s) ago) how to download this presentation Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Pharmacology : Pharmacology Drugs that Affect the Cardiovascular System Topics : Topics Electrophysiology Vaughn-Williams classification Antihypertensives Hemostatic agents Cardiac Function : Cardiac Function Dependent upon Adequate amounts of ATP Adequate amounts of Ca++ Coordinated electrical stimulus Adequate Amounts of ATP : Adequate Amounts of ATP Needed to: Maintain electrochemical gradients Propagate action potentials Power muscle contraction Adequate Amounts of Calcium : Adequate Amounts of Calcium Calcium is ‘glue’ that links electrical and mechanical events. Coordinated Electrical Stimulation : Coordinated Electrical Stimulation Heart capable of automaticity Two types of myocardial tissue Contractile Conductive Impulses travel through ‘action potential superhighway’. A.P. SuperHighway : A.P. SuperHighway Sinoatrial node Atrioventricular node Bundle of His Bundle Branches Fascicles Purkinje Network Electrophysiology : Electrophysiology Two types of action potentials Fast potentials Found in contractile tissue Slow potentials Found in SA, AV node tissues Fast Potential : Fast Potential -80 -60 -40 -20 0 +20 RMP -80 to 90 mV Phase 1 Phase 2 Phase 3 Phase 4 controlled by Na+ channels = “fast channels” Fast Potential : Fast Potential Phase 0: Na+ influx “fast sodium channels” Phase 1: K + efflux Phase 2: (Plateau) K + efflux AND Ca + + influx Phase 3: K+ efflux Phase 4: Resting Membrane Potential Cardiac Conduction Cycle : Cardiac Conduction Cycle Slow Potential : Slow Potential -80 -60 -40 -20 0 Phase 4 Phase 3 dependent upon Ca++ channels = “slow channels” Slow Potential : Slow Potential Self-depolarizing Responsible for automaticity Phase 4 depolarization ‘slow sodium-calcium channels’ ‘leaky’ to sodium Phase 3 repolarization K+ efflux Cardiac Pacemaker Dominance : Cardiac Pacemaker Dominance Intrinsic firing rates: SA = 60 – 100 AV = 45 – 60 Purkinje = 15 - 45 Cardiac Pacemakers : Cardiac Pacemakers SA is primary Faster depolarization rate Faster Ca++ ‘leak’ Others are ‘backups’ Graduated depolarization rate Graduated Ca++ leak rate Potential Terms : Potential Terms APD ERP RRP relative refractory period effective refractory period action potential duration Dysrhythmia Generation : Dysrhythmia Generation Abnormal genesis Imbalance of ANS stimuli Pathologic phase 4 depolarization Ectopic foci Dysrhythmia Generation : Dysrhythmia Generation Abnormal conduction Analogies: One way valve Buggies stuck in muddy roads Reentrant Circuits : Reentrant Circuits Warning! : Warning! All antidysrhythmics have arrythmogenic properties In other words, they all can CAUSE dysrhythmias too! AHA Recommendation Classifications : AHA Recommendation Classifications Describes weight of supporting evidence NOT mechanism Class I Class IIa Class IIb Indeterminant Class III View AHA definitions Vaughn-Williams Classification : Vaughn-Williams Classification Class 1 Ia Ib Ic Class II Class III Class IV Misc Description of mechanism NOT evidence Class I: Sodium Channel Blockers : Class I: Sodium Channel Blockers Decrease Na+ movement in phases 0 and 4 Decreases rate of propagation (conduction) via tissue with fast potential (Purkinje) Ignores those with slow potential (SA/AV) Indications: ventricular dysrhythmias Class Ia Agents : Class Ia Agents Slow conduction through ventricles Decrease repolarization rate Widen QRS and QT intervals May promote Torsades des Pointes! PDQ: procainamide (Pronestyl®) disopyramide (Norpace®) qunidine (Quinidex®) Class Ib Agents : Class Ib Agents Slow conduction through ventricles Increase rate of repolarization Reduce automaticity Effective for ectopic foci May have other uses LTMD: lidocaine (Xylocaine®) tocainide (Tonocard®) mexiletine (Mexitil®) phenytoin (Dilantin®) Class Ic Agents : Class Ic Agents Slow conduction through ventricles, atria & conduction system Decrease repolarization rate Decrease contractility Rare last chance drug flecainide (Tambocor®) propafenone (Rythmol®) Class II: Beta Blockers : Class II: Beta Blockers Beta1 receptors in heart attached to Ca++ channels Gradual Ca++ influx responsible for automaticity Beta1 blockade decreases Ca++ influx Effects similar to Class IV (Ca++ channel blockers) Limited # approved for tachycardias Class II: Beta Blockers : Class II: Beta Blockers propranolol (Inderal®) acebutolol (Sectral®) esmolol (Brevibloc®) Class III: Potassium Channel Blockers : Class III: Potassium Channel Blockers Decreases K+ efflux during repolarization Prolongs repolarization Extends effective refractory period Prototype: bretyllium tosylate (Bretylol®) Initial norepi discharge may cause temporary hypertension/tachycardia Subsequent norepi depletion may cause hypotension Class IV: Calcium Channel Blockers : Class IV: Calcium Channel Blockers Similar effect as ß blockers Decrease SA/AV automaticity Decrease AV conductivity Useful in breaking reentrant circuit Prime side effect: hypotension & bradycardia verapamil (Calan®) diltiazem (Cardizem®) Note: nifedipine doesn’t work on heart Misc. Agents : Misc. Agents adenosine (Adenocard®) Decreases Ca++ influx & increases K+ efflux via 2nd messenger pathway Hyperpolarization of membrane Decreased conduction velocity via slow potentials No effect on fast potentials Profound side effects possible (but short-lived) Misc. Agents : Misc. Agents Cardiac Glycocides digoxin (Lanoxin®) Inhibits NaKATP pump Increases intracellular Ca++ via Na+-Ca++ exchange pump Increases contractility Decreases AV conduction velocity Pharmacology : Pharmacology Antihypertensives Antihypertensive Classes : Antihypertensive Classes diuretics beta blockers angiotensin-converting enzyme (ACE) inhibitors calcium channel blockers vasodilators Blood Pressure = CO X PVR : Blood Pressure = CO X PVR Cardiac Output = SV x HR PVR = Afterload BP = CO x PVR : BP = CO x PVR Key: CCB = calcium channel blockers CA Adrenergics = central-acting adrenergics ACEi’s = angiotensin-converting enzyme inhibitors Slide 37: BP = CO x PVR Peripheral Sympathetic Receptors alpha beta 1. alpha blockers 2. beta blockers Local Acting 1. Peripheral-Acting Adrenergics Alpha1 Blockers : Alpha1 Blockers Stimulate alpha1 receptors -> hypertension Block alpha1 receptors -> hypotension doxazosin (Cardura®) prazosin (Minipress®) terazosin (Hytrin®) Central Acting Adrenergics : Central Acting Adrenergics Stimulate alpha2 receptors inhibit alpha1 stimulation hypotension clonidine (Catapress®) methyldopa (Aldomet®) Peripheral Acting Adrenergics : Peripheral Acting Adrenergics reserpine (Serpalan®) inhibits the release of NE diminishes NE stores leads to hypotension Prominent side effect of depression also diminishes seratonin Adrenergic Side Effects : Adrenergic Side Effects Common dry mouth, drowsiness, sedation & constipation orthostatic hypotension Less common headache, sleep disturbances, nausea, rash & palpitations ACE Inhibitors : Angiotensin I ACE Angiotensin II 1. potent vasoconstrictor - increases BP 2. stimulates Aldosterone - Na+ & H2O reabsorbtion ACE Inhibitors . RAAS Renin-Angiotensin Aldosterone System : Renin-Angiotensin Aldosterone System Angiotensin II = vasoconstrictor Constricts blood vessels & increases BP Increases SVR or afterload ACE-I blocks these effects decreasing SVR & afterload ACE Inhibitors : ACE Inhibitors Aldosterone secreted from adrenal glands cause sodium & water reabsorption Increase blood volume Increase preload ACE-I blocks this and decreases preload Angiotensin Converting Enzyme Inhibitors : Angiotensin Converting Enzyme Inhibitors captopril (Capoten®) enalapril (Vasotec®) lisinopril (Prinivil® & Zestril®) quinapril (Accupril®) ramipril (Altace®) benazepril (Lotensin®) fosinopril (Monopril®) Calcium Channel Blockers : Calcium Channel Blockers Used for: Angina Tachycardias Hypertension CCB Site of Action : CCB Site of Action diltiazem & verapamil nifedipine (and other dihydropyridines) CCB Action : CCB Action diltiazem & verapamil decrease automaticity & conduction in SA & AV nodes decrease myocardial contractility decreased smooth muscle tone decreased PVR nifedipine decreased smooth muscle tone decreased PVR Side Effects of CCBs : Side Effects of CCBs Cardiovascular hypotension, palpitations & tachycardia Gastrointestinal constipation & nausea Other rash, flushing & peripheral edema Calcium Channel Blockers : Calcium Channel Blockers diltiazem (Cardizem®) verapamil (Calan®, Isoptin®) nifedipine (Procardia®, Adalat®) Diuretic Site of Action : Diuretic Site of Action . loop of Henle proximal tubule Distal tubule Collecting duct Mechanism : Mechanism Water follows Na+ 20-25% of all Na+ is reabsorbed into the blood stream in the loop of Henle 5-10% in distal tubule & 3% in collecting ducts If it can not be absorbed it is excreted with the urine Blood volume = preload ! Side Effects of Diuretics : Side Effects of Diuretics electrolyte losses [Na+ & K+ ] fluid losses [dehydration] myalgia N/V/D dizziness hyperglycemia Diuretics : Diuretics Thiazides: chlorothiazide (Diuril®) & hydrochlorothiazide (HCTZ®, HydroDIURIL®) Loop Diuretics furosemide (Lasix®), bumetanide (Bumex®) Potassium Sparing Diuretics spironolactone (Aldactone®) Mechanism of Vasodilators : Mechanism of Vasodilators Directly relaxes arteriole smooth muscle Decrease SVR = decrease afterload Side Effects of Vasodilators : Side Effects of Vasodilators hydralazine (Apresoline®) Reflex tachycardia sodium nitroprusside (Nipride®) Cyanide toxicity in renal failure CNS toxicity = agitation, hallucinations, etc. Vasodilators : Vasodilators diazoxide [Hyperstat®] hydralazine [Apresoline®] minoxidil [Loniten®] sodium Nitroprusside [Nipride®] Pharmacology : Pharmacology Drugs Affecting Hemostasis Hemostasis : Hemostasis Reproduce figure 11-9, page 359 Sherwood Platelet Adhesion : Platelet Adhesion Coagulation Cascade : Coagulation Cascade Reproduce following components of cascade: Prothrombin -> thrombin Fibrinogen -> fibrin Plasminogen -> plasmin Platelet Inhibitors : Platelet Inhibitors Inhibit the aggregation of platelets Indicated in progressing MI, TIA/CVA Side Effects: uncontrolled bleeding No effect on existing thrombi Aspirin : Aspirin Inhibits COX Arachidonic acid (COX) -> TXA2 ( aggregation) GP IIB/IIIA Inhibitors : GP IIB/IIIA Inhibitors GP IIb/IIIa Inhibitors Fibrinogen GP IIb/IIIa Receptor GP IIB/IIIA Inhibitors : GP IIB/IIIA Inhibitors abciximab (ReoPro®) eptifibitide (Integrilin®) tirofiban (Aggrastat®) Anticoagulants : Anticoagulants Interrupt clotting cascade at various points No effect on platelets Heparin & LMW Heparin (Lovenox®) warfarin (Coumadin®) Heparin : Heparin Endogenous Released from mast cells/basophils Binds with antithrombin III Antithrombin III binds with and inactivates excess thrombin to regionalize clotting activity. Most thrombin (80-95%) captured in fibrin mesh. Antithrombin-heparin complex 1000X as effective as antithrombin III alone Heparin : Heparin Measured in Units, not milligrams Indications: MI, PE, DVT, ischemic CVA Antidote for heparin OD: protamine. MOA: heparin is strongly negatively charged. Protamine is strongly positively charged. warfarin (Coumadin®) : warfarin (Coumadin®) Factors II, VII, IX and X all vitamin K dependent enzymes Warfarin competes with vitamin K in the synthesis of these enzymes. Depletes the reserves of clotting factors. Delayed onset (~12 hours) due to existing factors Thrombolytics : Thrombolytics Directly break up clots Promote natural thrombolysis Enhance activation of plasminogen ‘Time is Muscle’ streptokinase (Streptase®) alteplase (tPA®, Activase®) anistreplase (Eminase®) reteplase (Retevase®) tenecteplase (TNKase®) Occlusion Mechanism : Occlusion Mechanism tPA Mechanism : tPA Mechanism Cholesterol Metabolism : Cholesterol Metabolism Cholesterol important component in membranes and as hormone precursor Synthesized in liver Hydroxymethylglutaryl coenzyme A reductase (HMG CoA reductase) dependant Stored in tissues for latter use Insoluble in plasma (a type of lipid) Must have transport mechanism Lipoproteins : Lipoproteins Lipids are surrounded by protein coat to ‘hide’ hydrophobic fatty core. Lipoproteins described by density VLDL, LDL, IDL, HDL, VHDL LDL contain most cholesterol in body Transport cholesterol from liver to tissues for use (“Bad”) HDL move cholesterol back to liver “Good” b/c remove cholesterol from circulation Why We Fear Cholesterol : Why We Fear Cholesterol Risk of CAD linked to LDL levels LDLs are deposited under endothelial surface and oxidized where they: Attracts monocytes -> macrophages Macrophages engulf oxidized LDL Vacuolation into ‘foam cells’ Foam cells protrude against intimal lining Eventually a tough cap is formed Vascular diameter & blood flow decreased Why We Fear Cholesterol : Why We Fear Cholesterol Plaque cap can rupture Collagen exposed Clotting cascade activated Platelet adhesion Thrombus formation Embolus formation possible Occlusion causes ischemia Lipid Deposition : Lipid Deposition Thrombus Formation : Thrombus Formation Platelet Adhesion : Platelet Adhesion Embolus Formation : Embolus Formation Occlusion Causes Infarction : Occlusion Causes Infarction Antihyperlipidemic Agents : Antihyperlipidemic Agents Goal: Decrease LDL Inhibition of LDL synthesis Increase LDL receptors in liver Target: < 200 mg/dl Statins are HMG CoA reductase inhibitors lovastatin (Mevacor®) pravastatin (Pravachol®) simvastatin (Zocor®) atorvastatin (Lipitor®)