Cardiovascular Drugs

This is a summary of most of the drugs discussed in 210 with brief notes on actions, effects and mechanisms. Courtesy of Heath.

Beta Blockers
Have one heart and two lungs so have mostly β1 in the heart and β2 in the lungs.
β1 selective: Metoprolol (lipid soluble, hepatic), atenolol (polar, renal), celiprolol, esmolol
β1 and β2: Propranolol (lipid soluble, hepatic), nadolol
β1 and β2 and α1: Carvedilol (vasodilator as well)

ACE Inhibitors/antagonists
Cilazapril (ACEi) 5mg/once day
Captopril (ACEi) 50mg/3 times a day

Candesartan (angiotensin II receptor antagonist)
Note suffix ‘artan’ = ATII antagonist.

Diuretics
Loop diuretics: Inhibit NaKCl Symporter in ascending loop.
Frusemide –, also vasodilatory, steep dose response curve, most effective diuretic.

Thiazide diuretics: inhibits sodium absorption at NaCl symporter at the beginning of the DCT. Not potassium sparing. Mild effects. Also vasodilators (open K+ channels). Side effects = Erectile dysfunction, kaliuresis and naturesis, reduction in glucose tolerance.
Bendrofluazide
Chlorthalidone
Hydrochlorothiazide

Potassium-sparing diuretics: Block the epithelial sodium channel (ENaC) in principal cells thereby inhibiting sodium reabsorption in the distal convoluted tubules
Amiloride
Triamterene

Calcium Channel Blockers
Three categories: Dihydropyridines, Benzothiazepines, Phenylalkylamines.

Dihydropyridines: Suffix ‘dipine’, Vasodilatory (Works on cardiac and smooth muscle cells). Side effects = flushing, headache, oedema.
Nifedipine
Felodipine
Amlodipine

Benzothiazepines: Intermediate between Dihydropyridines and Phenylalkylamines
Diltiazem- calcium channel blocker, used in Tx of hypertension, angina pectoris, atrial fib, atrial flutter. –ve inotrope, -ve chronotrope via slowing of AV conduction.

Phenylalkylamines: Myocardium selective, non vasodilatory. Side effects = heart block, constipation.
Verapamil

Anti Arrythmics
Amiodarone - beta blocker-like and potassium channel blocker-like actions on the SA and AV nodes, increases the refractory period via sodium- and potassium-channel effects, and slows intra-cardiac conduction of the cardiac action potential, via sodium-channel effects. Tx of VT, AF and cardioversion in VF.

Beta Agonists (bronchodilators)
Adrenaline – Non selective for all adrenergic receptors
Isoprenaline - β1 and β2 agonist
Salbutamol (ventolin) and terbutaline (Bricanyl) - β2 selective agonists. Are resistant to COMT which would break them down > last for 5-6 hrs.
Salmeterol (Severent) and eformoterol (Oxis) – long acting beta agonists. Last 12 hrs. Long hydrocarbon tail to make lipid soluble > sequesterd in membrane. Tail also binds to exosite. Good for regular dosing as opposed to prn.

Anticholinergics
Ipratropium – Blockade of all muscarinic receptors, but is poorly absorbed across epithelial membranes. 6-8 hr duration but lower peak than beta agonists.

Tiotropium – Also blocks all muscarinic receptors, but has more affinity for M3 (in airways). Used for COPD Tx. Lasts for 24hrs.

Steroids
Hydrocortisone – Artificial cortisol
Prednisone – 4 times as potent as hydrocortisone, longer half life and less minaralocorticoid activity. Iactive pro-drug which is activated in liver
Dexamethasone – 25 times as potent, almost no mineralocorticoid activity

Inhaled steroids: 80% is swallowed, 20% makes it to lungs.
Beclomethasone - 80% first pass hepatic metabolism
Butesonide – 90% first pass hepatic metabolism
Fluticasone – 99% first pass hepatic metabolism – 2 times as potent as the other two so need half the dose.

Side effects of steroids can be remembered by the mnemonic BECLOMETHASONE
Buffalo hump
Easy bruising
Cataracts
Large appetite
Obese
Moon face
Euphoric
Thin arms and legs
Hypertension
Avascular necrosis of the femoral head
Skin thinning
Osteoporosis
Negative nitrogen balance
Emotional liability

Anti-thrombic
Low molecular weight heparin (Enoxaparin) – activates antithrombin which in turn deactivates thrombin and factor Xa. Clotting cascade inhibited. Contraindications – AVM, haemophiliacs, recent surgery, etc.

Warfarin – inhibits epoxide reductase, limiting available Vit K. Clotting factor formation reduced, slower acting and longer term effects (7 days for full effect).

Anti-platelet
Aspirin – Irreversible cyclooxygenase 1 blockade, inhibits thromboxane A2 formation.
Clopidogrel – inhibits purine platelet receptor, platelet aggregation inhibited. Give if allergic to aspirin or with aspirin if stented.

Thrombolytic
Streptokinase – Bacterial agent, activates plasmin > plasminogen, can only give once because immunity develops.
Reteplase – recombinant tissue plasminogen activator
Tenecteplase - recombinant tissue plasminogen activator

Lipid lowering
Statins: Simvastatin (HMGCoA reductase inhibitor). Is eliminated by CYP3A4, Erythromycin, grapefruit juice, verapamil, amiodarone and diltiazem all inhibit, therefore cannot give at same time.

Less freq used Lipid lowering drugs:
Fibrates eg Bezafibrate (increased beta oxidation in liver, increased LDL clearance, increased HDL production). Side effects = GI upset, deranged LFTs, myositis (muscle inflammation), rhabdomyolysis.

Cholesterol absorption inhibitors eg ezetimibe (increases expression of LDL receptors on liver and reduces cholesterol absorption), not good for use on own – use with statin.

Nicotinic acid.

Other
Theophylline, phosphodiesterase inhibitor. Blocks degradation of cAMP, [cAMP] rises and see relaxation of bronchial smooth muscle. Non selective for all 12 isoforms of phosphodiesterase. Narrow therapeutic index. Clearance increased by smoking, phenytoin and rifampicin. Clearance decreased by heart failure, erythromysin. Min side effects: nausea, vomiting, headache, tremor, insomnia. Maj effects: VT, AF, seizures.

Gentamycin – AB. Interrupts protein synth in bacterium. IV, IM or topically administered. Nephotoxic to cells in PCT. Can also be ototoxic. Won’t affect streptococcus.

Digoxin – NaKATPase blockade (competes with K for same binding site). Will increase conctractility of heart at appropriate doses due to higher intracellular Na > lower Ca extrusion. Also slows HR by increasing length of Phase 4 and 0. Also increases vagal activity via effects on CNS > HR slows. Use for Tx of atrial fibrillation or flutter and possibly heart failure. 1-2.6 nmol/l effective range. ECG changes: ST depression or T wave inversion, which do not indicate toxicity. PR interval prolongation, however, may be a sign of digoxin toxicity.

Spironolactone - competitive aldosterone antagonist. Used in heart failure to prevent effects of high aldosterone induced by Angiotensin and Angiotensin 1.

Glyceryl trinitrate (GTN) – spray, take sublingually, NO release causes vasodialtion.

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