CVD treatments

CVD treatments

1. hypertension

   • thiazide diuretics
     • bendroflumethiazide 2.5mg OM
     • inhibit Na reabsorption in the early diluting segment of the distal tubule
       • inhibit the Na/Cl co-transporter
     • side effects: hypokalemia, hyponatremia, hypomagnesaemia, hypercalcemia, hyperuricaemia, hyperglycemia,hyperlipidaemia, impotence(reversible)
   • beta blockers
     • cardioselective: bisoprolol, atenolol; nonselective: propranolol
     • decrease HR and contractile force thus decrease CO
     • vasodilation
     • decrease Na and water retention
     • SE:bradycardia, tiredness, fatigue, lipids, broncospasm, cold hands and feet, lipid soluble-nightmares, masking hypoglycaemia symp in insulin dep DM
   • ACE inhibitors
     • lisinopril 10mg od
     • inhibit the formation of A2 form A1
       • A2 is a potent vasoconstrictor and promotes aldosterone release
     • SE: hyperkalaemia(check U&E), acure renal failure(U&E), first dose hypotension, dry cough, skin rash and angioedema, alter sense of taste
   • angiotensin II receptor antagonists
     • losartan
     • SE: same as ACE inhibitors minus cough and angioedema
   • calcium channel blockers
     • dyhydropyridines: amlodipine&nifedipine
       • vasodilation of coronary and peripheral arteries
     • phenylalkamines: verapamil
       • slow AV nodal conduction
         • reduces HR & CO
       • causes constipation
     • benzothiazipine derivatives: diltiazem
   • alpha 1 antagonists
     • doxazosin up to 16mg od
     • dilate blood vessels and reduce PVR

2. dyslipidaemia

   • HMG Co A Reductase Inhibitors (statins)
     • simvastatin max 80mg od
     • partially block HMG Co A reductase
     • inhibit biosynthesis in liver
     • metabolised by CYP3A4
     • rhabdomylosis
     • SE: skin reactions, headaches, GI, myalgia
   • fibrates
     • CI in gallbladder disease
     • benzafibrate 400mg/day
     • bind to PPAR alpha on hepatocytes
       • increases VLDL clearance
     • also decrease hepatic TG secretion
     • SE: gi, headache, skin reactions, fatigue
     • increace warfarin conc by binding to albumin
   • bile acid binding agents
     • ionic exchange resins insoluble in water mix with water and take with meal take other meds 1hr before or 4-6hrs after the resin
     • cholestyramine 4-36g/day
     • not absorbed! bind to bile acid in intestine
       • increase bile excretion
     • reduced absorption of fat sol vit & many drugs eg digoxin
     • SE: significant GI
   • cholesterol binding agents
     • ezetimibe 10mg od
     • inhibits absorption of endogenous and biliary cholesterol in the GI
       • this is done using transporter protein NPC1L1
     • SE: headache, abdo pain, diarrhoea
   • nicotinic acid and derivatives
     • poor side effects profile
     • inhibits hepatic TG production and VLDL secretion

3. IHD

   • stable angina
     • -symptoms usually precipitate by exercise, cold environment and relieved by rest -burning sensation over the sternum, often radiates to the left jaw, shoulder and arm -chest tightness & shortness of breath -30s to 30min
     • modification of disease
       • Antiplatelets
       • ACE inhibitors
       • Statins
     • symptomatic therapy
       • nitrates
         • -dilate veins more then arteries -they reduce cardiac workload (angina) -low oral bioavailability need nitrate free period - 8-12 hours
         • orally: *isosorbide dinitrate 30-120mg daily in 2-3 doses *isosorbide mononitrate 20-120mg daily in 1-2 doses
         • GTN - sublingual glyceryl trinitrate
           • every 5 mins, up to 3 doses in total, if chest pain persists
       • beta blockers
         • reduce myocardial O2 demand and prevent symptoms
       • calcium channel blockers
         • dyhydropyridines - vasodilation & improve coronary blood flow - prevent symptoms verapamil & diltiazem - decrease AV node conduction - reduce cardiac workload
       • potassium channel blockers
         • nicorandil
           • -ATP dependent K channel activation & nitrate like activity -arterial and venous vasodilation may be used as monotherapy or with beta blockers or calcium channel blockers
       • ivabradine
         • HR lowering drug use if beta blockers CI
       • ranolazine
         • adjunctive therapy in patients who are inadequately controlled or intolerant of beta-blockers or calcium channel blockers -reduces calcium overload in ischaemic myocytes through inhibition of the late sodium current
     • surgical procedures
       • Percutaneous transluminal coronary angioplasty (PTCA)
       • coronary artery bypass grafting (CABG)
   • STEMI
     • -burning or chest discomfort even at rest, severe new onset angina or increasing angina that lasts >20 min -pain may radiate to jaw, shoulder and down left arm -may also present with nausea, vomiting, shortness of breath
     • immediate care
       • to remove pain, prevent deterioration, prevent complications and improve cardiac function
       • ECG monitoring
       • oxygen
       • slow IV diamorphine
         • reduce pain and anxiety
       • metoclopramide 10mg IV
         • antiemetic
       • SL or IV nitrate
         • for ischaemic pain
       • clopidogrel 300mg & aspirin 300mg
         • antiplatelet to limit further extension of thrombus
       • restoring patency of the occluded artery
         • percutaneous coronary intervension
         • thrombolytic agent
           • lyse thrombus and restore blood flow + anticoagulant
     • secondary prophylaxis
       • prevent further infraction/death; modification of risk factors
       • antiplatelets
         • eg aspirin, clopidogrel, prasugrel, ticagrelor
         • aspirin inhibits COX enzyme irreversibly by acetylation
           • reduces thromboxane, prostaglandins, and prostaglandins synthesis
         • clopidogrel inhibits platelet aggregation by irreversibly blocking ADP pathway
           • SE: thrombotic thrombocytopenia purpura
         • if patients can't tolerate antiplatelets give warfarin INR 2-3 for up to 4 years
       • Beta-blockers
       • race limiting calcium channel blockers
       • ACE inhibitors
       • Aldosterone antaginists - Eplerenone
       • nitrates
       • lipid lowering treatment
     • initial management - drug therapy
       • glycoprotein IIb/IIIa
       • antiplatelets
       • anticoagulant
       • thrombolytic drugs
         • to break up thrombus and restore blood flow

4. HF

   • diuretics
     • loop
     • thiazide
     • K sparing
   • ACE inhibitors
   • Angiotensin II antagonists
   • Aldosterone antagonists
   • Beta-blockers
   • Cardiac glycosides
   • other vasodilators

5. thrombosis

   • Heparin
     • ADR: haemorrage - most common Major bleeding is less common in LMWH thank UFH
     • UFH
       • mixtures of sulfated mucopolysaccharides of variable lengths
       • MOA: prevents the growth and propagation of a formed thrombus
         • -binds to antithrombin: causes conformational change. activation of heparin-antithrombin complex accelerates certain activated clotting factors (9a.10a,11a,12a,thromnin(2a)) -also binds directly to thrombin
     • LMWH
       • more expensive then UFH show similar efficacy
       • MOA: enhance and accelerate the activity of antithrombin on factor Xa. Prevents growth and propagation of formed thrombi.
       • eg enoxaparin, deltaparin, tinzaparin
   • Heparinoids
     • a mixture of low molecular weight sulfated glycosaminoglycans
     • MOA: promotes inhibition of factor Xa by antithrombin but it does not prolong the APTT
     • danaparoid
   • Hirudins
     • eg lepirudin
     • MOA: they bind to the active site on thrombin
   • Fondaparinux
     • MOA: bind to antithrombin and accelerates antithrombin activity factror Xa
   • Vit K antagonists
     • warfarin
     • MOA: bind to the hepatic reductase enzyme that converts vit K to the active form. Inhibits hepatic synthesis of vit K dependent clotting factors
   • Thromobolitycs
     • only indicated in life-thretening acute massive pulmonary embolus
     • MOA: activate plasminogen, thus promote the breakdown of fibrin to fibrinogen

6. AF

   • Proxymal AF
     • Recurrent, self terminating episodes of AF. Episode <7 days (most resolve within 24h)
     • rhythm control
       • rate control (if rhythm fails)
   • Persistent AF
     • Sustained AF that terminates with cardioversion
     • rate or rhythm control
       • try other if previous fails
   • Permanent AF
     • AF that is long standing, cardioversion failed of not attempted
     • rate control
       • rhythm control (if rate fails)