Cardiovascular Pharmacology PDF

"Don'tlike fake people" Drugs for Tachycardia Class 1a drugs Nat blockers: s l ows down myocyte depolarization phase, and time Drug Br...

"Don'tlike fake people" Drugs for Tachycardia Class 1a drugs Nat blockers: s l ows down myocyte depolarization phase, and time Drug Brief mechanism of Used for: Contraindication Adverse Effects action Quinidine - High risk of Torsades de (discontinued) poire (TdP) - Risk of heart attack - Anticholinergic side effect - Urinary hypertension Procainamide - Anticholinergic - Urinary (discontinued) retention Disopyramide Also anticholinergic Atrial / ventricular Avoid w. people who - Anticholinergic tachycardia have - Urinary Negative inotropic - Hypotension retention effect (contractionS - Low - Negative force ventricular inotropic effect output (reduces contractibility) Class 1b drugs Tend to be effective at very fast heart rates Lidocaine Administered: IV Local anaesthetics - Low effect: for atrial ventricular tachycardia fibrillation + tachycardia ofventricle  - Rapid - Ventricular dissociation tachycardia Mexiletine Administered: Orally - Ventricular Low effect: for atrial tachycardia / tachycardia (Rarely used) - Rapid fibrillation dissociation - Effective with fast heart rate Tocainide - Rapid - Ventricular Low effect: for atrial dissociation tachycardia / tachycardia (discontinued) fibrilllation Class 1c drugs Flecainide - Atrial - Myocardial - Potent fibrillation & infarction (if negative ventricular used after inotropes tachycardias causes death) - Risk of heart - failure Propafenone - Beta-blocker - Atrial effects fibrillation & ventricular tachycardias Class ll drugs Blocks Ca2+ channels ‘ol’ ending  Prolong phase in 4 Nodal Ap Solatol Beta-blocker Reduce arrythmias - Asthma - Hypotension contradiction - Fatigue / Class lll activity Given post MI dizziness (unique) - Peripheral vasoconstriction Others: Beta-blocker only - Atenolol - Metoprolol - Propranolol Class lll MOA Block K+ channels · effect S on both nodal myocyte t Ap /phase 3- ventricle repolarisations extends effective refractory period a slows hear tr a t e Brief mechanism of contraindications action Amiodarone Effective: slow heart Bradycardia + Block K channels rate Reverse use dependency - More effective the slower the heart rate Amiodarone Extremely lipophilic - Extremely toxic = acculates in fatty - Thyroid Has class 1a, class ll & tissues dysfuntion class lV activity - TdP - Skin discouration  - Photosensitivity Downside: Easy to overdose due to it being extremely lipophilic Class lV drugs Blocks Ca2+ channels & I type cat D repolarisation ↑ Drugs Brief mechanism of action Used for Contraindications Adverse effects Verapamil Blocks Ca2+ (L-type) - Atrial fibrillation Ventricular - Hypotension - paroxysmal tachycardia - dizziness, [a-blocker and Na+ channel superventricular D DUT to: - oedema, blocker] tachycardia Shortens - constipation Myocyte Ap - dilate blood Therapeutic effect nodal AP: vessels Decreases amplitude of AP also antihypertensive Increases length of & antianginal nodal AP (ERP) medication Effects myocytes AP: Negative inotrope Decreases length of myocyte AP – risk with ventricular tachycardias. Diltiazem Blocks Ca2+ (L-type) -  Therapeutic effect nodal AP: Decreases amplitude of AP Increases length of nodal AP (ERP) Effects myocytes AP: Negative inotrope Decreases length of myocyte AP – risk with ventricular tachycardias. Others Drugs Brief mechanism of Used for Contraindications Adverse Effects action Digoxin Na+/K+ pump inhibitor - Increases heart - Ventricular - Very low TI [pumps out 3 Na ions / rate tachycardias - Dizziness Properties pumps in 3 K ions after [due to increase - Confusion - Water- AP] Ca in myocytes] - Symptomatic - Fatigue solable relieve of - Nausea Vagus nerve - Heart failure heart failure - Vomiting depolarisation treatment - Increases ACh 2x dose - M2 receptor - Risk of death action Myocytes AP - Keeps more Ca in cells = more AP  Nodal AP - K ion efflux = hyperpolarisation Adenosine Short-acting (short - acute - Chest pains duration) superventriculsr - Shortness of Administered tachycardia breath - IV Activates A1 receptors - Dizziness Gi receptors in AV - vasodilator - Nausea node K+ permeability increases = hyperpolarisation - Slows down heart rate Drugs for Bradycardia Typically for short term treatment Drugs Brief mechanism of action IV Atropine Non-specific muscarininc antagonist IV Adrenaline - Non-specific adrenergic agonist B1 in hearts IV Dopamine Activates beta 1 receptors IV Dobutamine Slightly selective of beta 1 over beta 2  chronotrope $ - = AR + chronotrope=I AR Cardiac Drugs - inotrope:↓su Angina Imbalance in supply/demand oxygen by heart inotrope:4Su A Key - Glyceryn Trinitrate - Beta-cloker - Calcium Channel blocker Drug Brief mechanism of Used for Contraindications Adverse Effects action Glyceryl Prodrug Relieve May gain tolerance Trinitrate for acute (GTN) 1. Reduces O2 via angina vesodilation attack Admin: 2. Peripheral Avoid liver Sublingual / arteriolar dilation metabolism tablet Positive Inotrope (weak) Beta Inhibit action of Reduce Patients who take - Cold hands & feet Adrenorecptor adrenaline & sympathetic angina Salbutamol - Peripheral vasoconstriction Antagonist nervous system on heart attacks (won’t be - Bronchoconstriction effective) - Peripheral Vasoconstriction ‘Beta Blockers’ Action by b-1 receptor Most Bt - Hypoglycaemia blocking effective - Diarrhoea Propranolol - improves left w. ventricular end atheroma Prevents diastolic volume angina - Salbutamol from providing - decreases therapeutic effect ventricular mass  - remodeling fibrosis - preventing cellular hypertrophy Reduces O2 demand - Negative inotrope - Reduce afterload (antihypertensive) - Negative chronotropic (reduce heart rate) Effect - Reduce heart rate - Reduce cAMP & Ca2+ Other beta- - blockers Atenolol - 30 fold selectivity - Water soluble Bisoprolol - 75-fold selectivity  - B1 selective antagonist Carvedilol B-bloCKer Gi UpSOES -used for heart failure Bradycardia. nightmares Nitrate Alternatives Isosorbide mononitrate - Oral nitrate - Taken daily Nicorandil - Doesn’t induce tolerance - May activate guanylate cyclase directly - Causes hyperpolarisation Calcium Channel Blockers Calcium Channel Decrease O2 Effective for: Variant Blocker demand angina - Inhibit myocardial contractility  - Reduce afterload Dihydropyridines Long duration of - Vasospasm action angina Include - Used when B- - Amlodipine Inhibits blockers are - L-form calcium ineffective channels inhibited - all channel states inhibited Negative inotrope Nifedipine Short duration - Sustained-release (1x daily) Negative inotrope Diltiazem Decreases heart rate - & BP Negative inotrope Heart Failure Inotropic Agents – increase heart rate Drug Brief mechanism of Used for Contraindication Adverse Effects action Sympathomimetic Beta-1 adrenoreceptor Increase heart rate - Build up lactic Amines agonist acid Agent: noadrenaline Action - Activates adenylate cyclase = elevates cardiac cAMP - Produces - Positive chronotropic - Positive inotropic Effects - Increase heart rate - Increase heart contraction - vasoconstriction Dobutamine Selective Beta-1 Increase heart rate - adrenoreceptor agonist Developed from Treats - Isoprenaline Action - Heart failure Administered - Increases cAMP - Shock  - IV - Enhances Ca entry - Sepsis o Onset: 1- - Stimulates force of 2 min muscle o Steady: contraction 10-12 min Effects - Increase heart rate - Vasodilator Milrinone Action - - Inhibits enzyme phosphodiesterase = elevates cAMP Digoxin - Check info above No longer used commonly Beta-blockers - Carvedilol Check info above Blood Coagulation Antithrombosis drugs - Anticoagulants - Anti-platelets drugs - Fibrinolytics Anticoagulation Inhibits initiation by limiting small scale production of thrombin Drug Brief mechanism of Used for Contraindication Adverse Effects action Warfarin Inhibits VKORC1 Removing blood clots - Teratogen, enzyme - hepatotoxicity, “Vitamin K - Blocks Antidote - soft tissue antagonist” production of - Vitamin K necrosis active form of - Prothrombin - Requires initial Vit K administration of heparin - Low therapeutic index: requires heavy monitoring. - Gene polymorphisms – variations in effectiveness - Numerous CYP450 drug interactions  - Synergistic bleeding (e.g. aspirin, heparin) Warfarin Alternatives Xaban Direct inhibitors of Rapid onset Factor X Administered -Atrial fibrillation Antidote - Oral -DVT - Andexanet alfa -Pulmonary embolism - Post-surgical venous thromboembolisms Dabigatran Direct thrombin Antidote inhibitor - Idarucizumab IV Anticoagulation Heparins Bind paradoxical Removes clotting clotting for warfarin treatment Activates antithrombin lll High molecular weight Hirudins Thrombin inhibitor Alternative for patient intolerant to heparin Antiplatelet drugs Inhibits amplification by restricting platelet activation P2Y12 Antagonist “grel” Clopidogrel Prodrug Irreversible drug Ineffective in poor metabolisers Prasugrel Irreversible drug Ticagrelor Reversible PAR Antagonist – new, not available in UK Alternatives to P2Y12 / PAR antagonist Dipyridamole Phosphodiesterase Treats - Hypotension inhibitor - Stroke - MI Not popular prevention - Migraine - Prescribes w. Effect - Post transient asprin - Decrease cAMP ischaemic & cGMP attack (TIA) - Vasodilator Other Aspirin Cyclooxygenase Irreversible inhibitor - Low side effects risks inhibitor (COX-1 platelets) in children May gain tolerance Low dose - Avoid eyes syndrome - ¼ of analgesic May be administered w. other drugs GPllb/lla receptor inhibitor Abciximab Prevents binding of During/post cardiac fibrinogen to surgery Monoclonal antibody GPllb/lla receptors Eptifibatide / Prevents binding of During/post cardiac Tirofiban / Peptides fibrinogen to surgery GPllb/lla receptors Administered: IV Fibrinolytics / Thrombolytics Promotes degradation of fibrin stands, “clot buster” Drugs Mechanism of action Used for Contraindications Adverse Effects Alteplase Recombinant tPA Stroke - Most recommened Acute throbotic/emboluc events Post MI Streptokinase Bacterial plasminogen- Acute activating enzyme throbotic/emboluc events Post MI Antifibrinolytic / proagulants Drug Mechanism of action Used for Contraindication Adverse Effects Tranexamic acid Procoagulant Creation of clots Administered Blocks fibrin - Heavy - Orally degradation menstrual cycle Vitamin K Formation of clotting factors “phytomenadione” Desmopressin Stimulates vWF - Heamophillia release Atherosclerosis Prevention Drugs Drug Brief mechanism of Used for Contraindication Adverse Effects action Statins HMG-CoA reductase Decreasing ↑ regnancy Rare inhibitor cholesterol - Liver damage - Reduces rate - Increase of cholesterol Perform liver test bleeding synthesis - Increase diabetes - Mellitus risk Ezetimibe Enterocyte Decreasing cholesterol transport cholesterol inhibitor Co-administered w. statin Nicotinic acid / Niacin receptors Decreasing Acipimox mediate cholesterol - Reduce triglyceride production - Increase HDL