1. Introduction to drugs in the management of hypertension Katy Harries

2. How can we achieve this? What is hypertension? What are our goals for blood pressure control? Why is it important? What are the problems? How to overcome these?

3. Hypertension  BP above normal (on 3 occasions min 2 days apart) Systolic BP ≥ 140mmHg and/orSystolic BP ≥ 140mmHg and/or Diastolic BP ≥ 90mmHgDiastolic BP ≥ 90mmHg  Hypertension is a major risk factor for CV disease and stroke Goal: most cases BP < 140/90mmHg special cases e.g. diabetic, cardiac or renal impairment BP 130/80mmHg more severe renal disease < 120/75mmHg

4. Blood pressure Arterial BP = CO (cardiac output) x PVR (peripheral vascular resistance) Arterial BP = CO (cardiac output) x PVR (peripheral vascular resistance) CO and PVR controlled by 2 systems:  Baroreceptors & SNS (sympathetic nervous system) these are pressure sensitive neurons in the circulatory system they respond to a fall in BP by sending fewer impulses to the spinal cord. This causes a reflex response ↑ SNS &↓PNS output to heart and vasculature→vasoconstriction & ↑CO→↑BP  RAS (Renin-angiotensin-aldosterone system) kidney controls BP by altering blood volume baroreceptors in kidney respond to ↓arterial BP (& sympathetic stim of β receptors) → renin angiotensinogen→ angiotensin I → angiotensin II (vasoconstrictor) →↑aldosterone→↑BP renin angiotensin converting enzyme

5. Blood pressure

6. Treatment steps   1:lifestyle modification   2: +hydrochlorothiazide (HCT) 12.5mg daily   3: +ACE inhibitor e.g. enalapril or Ca channel blocker e.g.amlodipine daily   4: + ACE inhibitor e.g. enalapril and Ca channel blocker e.g.amlodipine daily   5: + beta-blocker e.g. atenolol daily Compelling indications for specific drugs (see table in EDL Evidence see http://www.nice.org.uk/nicemedia/live/13561/56007/56007.pdf

7. Non-drug treatment All patients with hypertension require lifestyle modification  weight loss if overweight  regular physical exercise (150 minutes/week)  stop smoking  moderate or no alcohol intake  restrict salt intake  restrict fat intake  adequate daily fibre intake (fruit, veg, unrefined carbs) Step 1 treatment for ↑BP no major risk factors →goal BP control in 3 months

9. Lifestyle modification Adherence to lifestyle interventions by the healthcare workers themselves is probably the best starting point when attempting to motivate and convince patients

10. Step 1  Mild hypertension (Diastolic 90-99mmHg and/or Systolic 140/159mmHg) and/or Systolic 140/159mmHg)  No existing disease  No major risk factors

11. Step 2 –Initiate drug therapy  If mild hypertension, no major risk factors and failure with lifestyle modification for 3 months  If moderate hypertension at diagnosis  If mild hypertension with major risk factors or existing disease: -diabetes mellitus -obesity, smoking, physical inactivity -target organ damage (heart Dx, stroke, TIA, renal, retinopathy, peripheral arterial dx) -dyslipidaemia -family history ↑BP or prem CV Dx in men < 50 & women < 55

12. Compelling indications for specific drugs IndicationDrug class AnginaBeta blocker or long-acting calcium channel blocker Prior MIBeta blocker and ACE inhibitor Heart failureACE inhibitor and carvedilol For volume overload: loop diuretic (furosemide) Left ventricular hypertrophyACE inhibitor Stroke: secondary preventionHCT and ACE inhibitor Diabetes type I or IIACE inhibitor (usually +diuretic) Chronic kidney diseaseACE inhibitor (usually +diuretic) Isolated systolic hypertensionHCT or long-acting Ca channel blocker Pregnancymethyldopa

13. Diuretics  Thiazide diuretics e.g. hydrochlorothiazide (HCT) ↓ sodium, water retention ↓ ↓ blood volume ↓ ↓ peripheral resistance ↓ cardiac output ↓ decrease in bp

14. Hydrochlorothiazide ADR & CI  CI in gout (causes hyperuricaemia)  CI in pregnancy (use methyldopa)  CI in renal failure (not effective in patients with inadequate kidney function)→ need loop diuretics (e.g. furosemide) for these patients  CI in liver failure  Causes ↓K + (hypokalaemia) ↓Mg ++ but ↑Ca ++  Causes hyperglycaemia in 10% of patients

15. β Blockers

16. β Blockers CI and ADR  Absolute CI asthma  Absolute CI COAD (chronic obstructive airways disease)  Relative CI heart failure (carvedilol ok)  Relative CI diabetes mellitus  Relative CI peripheral vascular dx  Relative CI bradycardia  ADR fatigue, insomnia  ADR hypotension  ↓ libido  Disturb lipid metabolism ↓HDL↑TG

17. Renin-Angiotensin System

18. ACE inhibitors ↓ PVR without reflexly ↑ CO, rate or contractility block ACE so AGI not converted to AGII ↓ breakdown of vasodilator bradykinin ↓ AGII (vasoconstrictor) & ↑bradykinin (vasodilator) →↑vasodilation  Use for HTN with DM – if HCT alone does not control BP  Take 1 tab immediately to treat hypertensive emergency diastolic BP↑30mmHg and associated symptoms (angina, retinopathy, neirological signs e.g. severe headache, pulmonary oedema, renal failure)

19. ACE inhibitors ADR & CI  Pregnancy  Bilateral artery stenosis  Aortic valve stenosis

20. Angiotensin II Antagonists  E.g. losartan  Similar to ACE I  Vasodilation blocks aldosterone secretion

21. Ca ++ Channel Blockers  Intracellular Ca ++ concentration NB in maintaining smooth muscle tone and contraction of myocardium.  Ca ++ enters muscle cells through calcium channels.  Ca ++ Channel blockers block inward movement of calcium causing smooth muscle to relax, dilating mainly arterioles  Verapamil and diltiazem ↓HR useful in some anginas arrhythmias  Nifedipine, isradipine, amlopidine, felodipine greater affinity for vascular channels than channels in heart

22. Αlpha Blockers  E.g. prazosin  Block α 1 receptors  ↓PVR & ↓BP by causing the relaxation of both arterial and venous smooth muscle  Long term reflex tachycardia and renin release do not occur  Get reflex tachycardia at first so often given with a beta blocker to prevent this  Can get postural hypotension  Reserve as a last choice/add-on drug associated with twice the risk of heart failure

23. Centrally acting adrenergic drugs  e.g. methyldopa:pregnancy-induced hypertension  α 2 agonist ↓ adrenergic outflow from CNS →↓PVR & ↓ BP  recommended for HTN of pregnancy  ADRs e.g. depression impair quality of life

24. Problems  Motivating patients to implement lifestyle changes  Patients often asymptomatic and expected to change daily habits for no immediate tangible benefits →NB to build trusting relationship

25. Clinical inertia  Failure to titrate or combine medications and to reinforce lifestyle modifications despite knowing that the patient is not at goal blood pressure

26. Consider Drug-related reasons for non-adherence  Side-effects  Long duration of therapy  Compicated regiments  Expensive  Ask patients what they use for pain relief → simplify regimen →incorporate treatment into patient’s lifestyle → include patient in decision making process