Lecture notes, lecture 7 - An introduction to cardiovascular and hypertensive pharmacology PDF

Preview

Summary

An introduction to cardiovascular and hypertensive pharmacology ...

Description

Lecture Seven: Cardiovascular and Hypertensive Pharmacology CCF 





L vs. R side failure. LEFT is termed ‘CCF’. Pulmonary congestion and fluid in lungs. CO is diminished = decreased BP and tissue perfusion – when less blood to kidneys = more peripheral oedema and fluid retention. Also, significant amount of blood is left in ventricle – increases ventricular filling pressure and wall stress (preload). To compensate for decreased CO – sympathetic and renin-angiotensin system incr. Sympathetic: increases HR and causes vasoconstriction, higher possibility of dysrhythmias. Renin-angiotensin: increases CO – better tissue perfusion, however causes more congestion/oedema. Also vasoconstricts – increasing BP – heart struggles to pump blood. All of this causes cardiac hypertrophy.

Diuretics:    



Anti-hypertensive. ECF loss = decreased blood vol. = decreased BP = lower end diastolic volume (amount of blood in ventricles at relaxation) = decreased afterload = decreased work. ‘Loop’ diuretics eg. Frusemide most effective and common. Causes electrolyte loss. Potassium sparing diuretics: Aldosterone antagonists (spironolactone) – inhibits hormone at distal tubule and collecting duct = sodium loss only. Independent actions (amiloride) – directly causes sodium loss and potassium retention at same sites. BOTH these diuretics must be matched w/ another diuretic such as thiazide family. Thiazide and related drugs: act on cortical segments of loop of Henle. Not as potent as Frusemide.

ACE Inhibitors:  

 

Anti-hypertensive. Decreases angiotensin II = decreased peripheral resistance = decreased BP. Decreased aldosterone = sodium/water loss and potassium retention = decreased blood vol. = decreased BP. A reduced BP = reduced cardiac afterload, increasing efficacy of pumping. Side effects: postural hypotension/hypotension, persistent cough as stimulates chemicals (pulmonary bradykinins) in lungs, increased pulse pressure as systolic remains same and diastolic lowers, causing headache.

Cardiac Glycosides:   

Act on ion channels of heart (Ca, Na+ and K+) = positive inotropic and decreased chronotropic effect. Allows Ca into heart = longer duration of action potential. Can alter electrical properties of heart and cause dysrhythmias. Only prescribe if definite cardiac failure. Digitization (stabilisation) takes a long time, and patients must always be observed because of v. low Ti, and T1/2 is 40 hours.

Beta Blockers   

  

Anti-hypertensive. Negative inotropic effects – more time for heart to fill – beneficial for CCF. Carvedilol: non-selective beta blocker (alpha antagonist). Acts on smooth muscle/blood vessels as well = vasodilation = decreased BP = reduction in cardiac afterload. Vasodilation also reduces EDV and ESV (preload and afterload). Blocks B1 receptors: decrease in Renin-Angiotensin system – reducing TPR (reducing BP) and reducing fluid accumulation. Also decreases HR. Paradox: negative inotropic effects. May protect heart against long term effects of adrenaline/noradrenaline (cardiac hypertrophy). Long term strategy.

Vasodilators 

 

Peripheral vasodilators: Glyceryl trinitrate, Isosorbide mono/dinitrates. Converted into Nitric Oxide – increases cGMP (2nd messenger) altering availability of Ca ions within muscle cell and myosin = vasodilation, primarily venodilation. Instant effect. Coronary vasodilators: Dipyridamole – prophylactic. Anti-platelet, minimizing risk of clots, and causes dilation. Huge drop in diastole = increased PP = headache! Both of these useful for patients who can’t take ACE inhibitors.

Anti-Dysrhythmic Drugs      

Reduces ion influx across cardiac cell membrane (blocks ion channels), inducing stability and minimizing chance of ectopic (extra) beats. Dysrhythmia may be caused by an AV block – partial or full. If full, atrials take over as they are controlled by SA node. Class 1: Quinidine and Lignocaine. Blocks Na+ channels and have local anaesthetic properties. Short acting. Class 2: Atenolol and Acebutolol. Beta blockers. Stops sympathetic stimulation – stabilizes SA node. Class 3: Sotalol and Amiodarone. Prolong cardiac action potential. Class 4: Verapamil and Adenosine. Ca channel blockers – suppress activity of AV and SA nodes.

Tissue Perfusion Drugs  

Beta blockers – peripheral vasodilation. Better to use than GTN – less side effects. Ca channel blockers (Nifedipine and Verapamil) – act on vascular smooth muscle = vaso and venodilation.

Anti-hypertensives  

ABCD: ACE Inhibitors (as above) and Alpha 1 Antagonists: Prazoin and Doxazosin (specific). Phentolamine (non-specific).

 



Beta blockers Ca channel antagonists: Nifedipine (selective for vascular smooth muscle) – most commonly prescribed. Verapamil (depresses vascular smooth muscle, myocardium and AV node) – used as an anti-dysrhythmic as well. Diltiazem (depresses vascular smooth muscle and myocardium). Diuretics

HYPERLIPIDAEMIA  

 

HDL/LDL ratio should be high. LDL’s/VLDL’s: transport triglycerides and cholesterol to body cells for deposition. Have same fat and protein composition as cell membrane, which is useful when depositing cholesterol into cells however can merge into blood vessels and cause an inflammatory response, subsequently causing plaque formation. HDL’s: transport cholesterol to liver for metabolism. Cholesterol: essential lipid. Can be synthesized by the body from carbohydrates and lipids. Needed for cell membranes, steroid hormones and vitamin D. Found in excess in modern diets – saturated fats stimulate synthetic metabolism and elevate plasma levels.

NON-pharmaceutical Strategies:    

Red wine: increases HDL levels and reduces likelihood of plaque deposition – due to histamine and other organic ‘essences’ from skin of red grape. Linoleic acid: major ingredient of olive oil – monounsaturated fat. Fish oil: eicosa pentaoic acid – highly unsaturated fat. All of the above assist in increasing HDL and lowering LDL’s.

Anti-Hyperlipidaemia Drugs Fibrates (Bezafibrinate): 

Increases conversion of VLDL to LDL. A parallel increase in HDL’s as well. VLDL’s are associated with triglycerides (trigs) and therefore plasma trig levels drop, reducing risk of plaque.

Nicotinic acid/Niacin/B3:  

Reduces VLDL – only suitable for some forms of hyperlipidaemia (genetic causes). Must be given in high doses: 1000 – 3000mg daily. Potentially dangerous as increases liver enzymes.

Gemfibrozil:   

Similar to Bezafibrinate. Less likelihood of gallstones and less toxicity (no halogen binding). Raises HDL levels in preference to reducing LDL’s.

HMG-CoA Reductase Inhibitors    

The STATINS: Pravastatin, Simvastatin. Reduces endogenous cholesterol synthesis – blocks biosynthetic pathway. Liver expresses more LDL receptors as cholesterol levels in bile drop. More LDL is ‘trapped’. Not effective on patients with genetically low levels of LDL receptors. No effect on HDL’s.

Neomycin: cationic aminoglycoside binds with cholesterol and reduces absorption: rarely prescribed. Cholestryamine/Colestipol: polymers bind bile salts, removing them from enterohepatic cycle (prevents the bile from being reabsorbed and therefore fat can’t be reabsorbed) and increasing LDL receptors. However, also get an increase in HMG-CoA Reductase which synthesizes cholesterol!...