Hypertension Treatments PDF

Hypertension treatments ACE inhibitors: Lisinopril, Catopril Mechanism of action: Blocks angiotensin converting enzyme in the renin angiotensin aldosterone system (prevents angiotensin 2 being formed) Side effects: Cough, diarrhoea, electrolyte imbalance, gastrointestinal discomfort, headache and d...

Hypertension treatments ACE inhibitors: Lisinopril, Catopril Mechanism of action: Blocks angiotensin converting enzyme in the renin angiotensin aldosterone system (prevents angiotensin 2 being formed) Side effects: Cough, diarrhoea, electrolyte imbalance, gastrointestinal discomfort, headache and dizziness, postural disorders can occur. All ACE inhibitors side-effects: angina, angioedema and alopecia (more common in African- Caribbean patients). Renal function needs to be checked before starting. Cautions – effectiveness in African-Caribbean patients, diabetes and atherosclerosis. Contradiction of all ACE inhibitors is that they are combined with renin inhibitors. It has been reported that cholestatic jaundice, hepatitis, hepatic necrosis and hepatic failure. If you have renal impairment, use ACEi’s use with caution, starting with low dose and adjust according to response. What is the pharmacokinetics of Lisinopril Oral administration --- 25% bioavailability Peak plasma concentration lasts around 4-6 hours and has a half-life of 12 hours Water soluble and not metabolised in the liver and undergoes renal excretion unchanged Furthermore, ACE inhibitors also inhibit Kininase 2 ,which blocks bradykinin from being inactive, allowing to decrease blood pressure in hypertension patients. Angiotensin-receptor blockers (ARBs): Losartan Mechanism of action: Selective competitive blockers of angiotensin 2 at the AT1 receptor It’s pharmacokinetics is that when given orally – 32% bioavailability, First- pass metabolism happens making 14% to active metabolite (more potent, non-competitive and longer acting), Half-life is 2hrs and 3-9hrs for metabolite, Binds to plasma proteins and excreted in the urine & bile Side-effects of all ARBs: Abdominal pain, headache, dizziness, diarrhoea, nausea, postural hypotension, hypotension and renal impairment Lorsartan: Anemia, hypoglycaemia and postural disorder. Cautions of using ARBs in hypertension paitents: Use in African-Caribbean paitents – particularly those with left-ventricle hypertrophy and elderly paitents Lorsartan’s cautions are severe cardiac failure, pregnancy and severe hepatic impairment Contraindications of all ARBs are: Combined with renin inhibitor with paitents with reduced eGFR and in paitents with diabetes mellitus Calcium channel blockers: Amlodipine Blocks calcium channels in the heart, act on myocardial muscle and inhibit contractibility. Side-effects of all calcium channel blockers: Dizziness, headache, nausea, palpitations, rash and vomiting. For amlodipine specifically: Diarrhoea, constipation, headache, dizziness, gastrointestinal disorders, vision disorders and dyspnoea (shortness of breath). Contraindications are Cardiogenic shock, significant aortic valve disease, unstable angina (chest pain), hepatic renal impairment and dose may be reduced- half-life prolonged. Pharmacokinetics of AMLODIPINE: It is given orally, and bioavailability is around 60%, half-life is 30-50 hours, has steady state plasma conc’s (7-8 days of dosing), metabolised slowly by the liver CYP450 and renal elimination. Poor renal function does not reduce renal elimination. What is the mechanism of action of Calcium channel blockers? Causes relaxation in the vascular smooth muscle cell As NO is broken-down by guanylyl cyclase, cGMP, and myosin-LC phosphatase to convert Myosin-LC- phosphate to Myosin-LC and cause relaxation.  Thiazide-like diuretics: Indapamide They inhibit the action of the Na+/Cl- symporter in the distal convoluted tubule, because they act on the reabsorptive process in the distal convoluted tubule, less potent and block only 3% of filtered Na+. Side-effects of all thiazide-like diuretics are Constipation, electrolyte imbalance, headache and postural disorders. Caution is hypokalaemia can occur and is dangerous in severe cardiovascular diseases and in patients also being treated by cardiac glycosides Indapamide’s side-effects are hypersensitivity and skin reactions. All elderly are susceptible to these side-effects Pharmacokinetics of Indapamide Indapamide is a low dose thiazide, sufficient for therapeutic effect, whereas high thiazide doses showed marked changes in Na+, K+, uric acid, glucose and lipids It is administered orally and earlier in the day, so diuresis does not interfere with sleep and duration of action is 12-24 hrs. When given orally, it acts within 1 to 2 hrs, administered earlier in the day so diuresis does not interfere with sleep Duration of action is 12-24 hrs 75% of the drug binds to plasma proteins Contraindications of all thiazide-like diuretics is Addison’s diseases and electrolyte imbalance. Cautious of gout, diabetes, hyperaldosteronism, malnourishment, nephrotic syndrome, history of hypersensitivity of sulphonamides. Avoid in severe liver disease, ineffective if renal function is low and Indapamide can cause acute polyphyrias. What drugs are used to treat paitents with resistant hypertension Spironolactone Alpha blockers Beta blockers Spironolacton e It is an anti-hypertensive patients with resistant hypertension It blocks aldosterone-induced Na reabsorption: as it inhibits aldosterone and causes Na+ & H2O loss, causing K+ retention. K-sparring diuretics inhibit the action of aldosterone on collecting ducts. By themselves they are weak diuretics and are important in sparring for K+. Often used in conjunction with other more potent diuretics. Alpha blockers: Doxazosin - Blocks arterial alpha 1 receptors - Postural hypotension - Mainly blocks sympathetic neurons and causes reduction of peripheral resistance and arterial pressure is lowered Beta blockers Not preferred for initial therapy for hypertension It is considered in younger patients as: They may have intolerance or contraindications to ACE inhibitors & ARBs, cannot be used in women with child-bearing potential and evidence of increased sympathetic drive It blocks NA into the heart and reduces heart rate and stroke volume decreases. It inhibits renin release and blocks renal sympathetic nerve activity – in RAAS – stops the production of angiotensin 2.