CV Hypertension notes PDF

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13.CV HYPERTENSION1. BLOOD PRESSUREi. Blood pressure is higher than normal atmospheric pressure; measured in mmHg (e. diastolic 80 mmHg is 80 + atmospheric pressure) ii. Measured as arterial pressure; venous pressure much lower iii. Varies by individual, and due to activity and circumstances2. SYSTO...

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13.12.18

CV HYPERTENSION 1. BLOOD PRESSURE i.

Blood pressure is higher than normal atmospheric pressure; measured in mmHg (e.g. diastolic 80 mmHg is 80 + atmospheric pressure)

ii.

Measured as arterial pressure; venous pressure much lower

iii.

Varies by individual, and due to activity and circumstances

2. SYSTOLE & DIASTOLE i.

Systolic: peak arterial pressure due to ventricular contraction

ii.

Diastolic: resting pressure whilst heart chambers fill

3. HYPERTENSION i.

High blood pressure is chronic arterial BP over 140/90 mmHg

ii.

Prehypertension over 120/80 mmHg)

iii.

Essential hypertension: high BP without identifiable cause (95% of cases)

iv.

Secondary hypertension: high BP due to known condition (usually heart, kidneys, etc.)

4. RISKS OF HYPERTENSION i.

Heart attack / stroke (atherosclerosis)

ii.

Aneurysm (“ballooning” of blood vessel)

iii.

Kidney failure (weakened blood vessels)

iv.

Others (vision loss, cognitive impairment, metabolic syndromes)

5. MAIN PHARMACOLOGICAL STRATEGIES I

6. MAIN PHARMACOLOGICAL STRATEGIES Blood pressure = cardiac output x peripheral vascular resistance BP = CO x PVR CO = HR x SV Cardiac output = heart rate x stroke volume A. Reduce PVR: dilate arteries B. Reduce cardiac output:

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i.

Decrease heart rate – negative chronotropes

ii.

Decrease contractile force – negative inotropes

iii.

Decrease blood volume

7. VASODILATORS A. Angiotensin converting enzyme (ACE) inhibitors B. Angiotensin receptor blockers C. Calcium channel blockers D. Diuretics (see Dr. Haylor lecture for MoA) E. Beta-blockers (Also see arrhythmias lecture) F.

Alpha blockers

G. Directly acting vasodilators: i.

Potassium channel blockers (niche use)

ii.

Phosphodiesterase inhibitors (niche use)

iii.

Cardiac nucleotide drugs (niche use)

8. VASODILATORS – SIDE EFFECTS A. Common side effects of CCBs, alpha blockers, directly acting vasodilators: i.

Oedema

ii.

Flushing

iii.

Postural hypotension (dizziness)

iv.

Fatigue

v.

Reflex tachycardia (baroreceptor response)

vi.

Headache

9. CALCIUM CHANNEL BLOCKERS A. L-type calcium channel blockers B. Reduce Ca2+ - dependent contraction in smooth muscle i.

Dihydropyridines selective for vascular muscle

ii.

Non-DHPs: verapamil is heart selective, diltiazem intermediate; reduce cardiac output leads to reduced BP

C. DHPs: (“dipine”) nifedipine, felodipine, lercanidipine, amlodipine

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10.

ALPHA-BLOCKERS

11.

i.

Doxazosin, Prazosin

ii.

a1 adrenoreceptor activation causes vasoconstriction (G q protein mediated calcium release) Therefore a1 blockers vasodilatory: ↓PVR

iii.

Effective at reducing BP and very well tolerated; side effects oedema, postural hypotension, dry mouth

iv.

Commonly used, but rarely as first line antihypertensives

v.

High blood pressure per se doesn’t kill anyone – it’s the secondary effects that do.

DIRECTLY ACTING VISODILATORS Drugs that directly affect contractility of vascular smooth muscle. A. Mostly drugs used when patient’s refractory to other treatments, or hypertensive crisis emergencies B. Usually prescribed with negative chronotrope (e.g. beta blockers) and diuretics. C. Two main classes:

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i.

Potassium channel blockers

ii.

Drugs that increase cytoplasmic cyclic nucleotides

POTASSIUM CHANNEL ACTIVAOTRS A. Open KATP channels and hyperpolarise cells; most commonly prescribed directly acting vasodilators B. Drugs of last resort C. Minoxidil, hydralazine D. Side effects: ankle oedema, weakness, nausea, headaches

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13.

CARDIAC NUCLEOTIDES Drugs that increase concentrations of cytoplasmic cyclic nucleotides in vascular tissue and promote vasodilation. Rarely used in hypertension.

14.

INDIRECTLY ACTING VASODILATORS Reduce smooth muscle contraction indirectly A. Central system (sympathetic; usually a2) antagonists B. Renin-angiotensin system antagonists C. Vascular NO stimulators D. Endothelin antagonists

15.

RENIN – ANGIOTENSIN SYSTEM

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16.

ACE INHIBITORS (ACEI) A. Inhibit Angiotensin Converting Enzyme (ACE) B. Non-peptide, orally active drugs C. Reduce arterial pressure & cardiac load D. Act preferentially on angiotensin-sensitive vascular beds – kidney, heart & brain. E. pril: captopril (first in class), enalapril, ramipril, etc. F.

Newer ACEIs tend to have longer half-life; one dose per day

G. Side effects: i.

17.

Relatively mild for antihypertensives: dry cough / bronchospasm, hyperkalaemia, angioedema, teratogenic.

ANGIOTENSIN RECEPTOR BLOCKERS (ARBS) A. Sartan, e.g. losartan, valsartan, candesartan B. Target Angiotensin II type 1 receptors; similar clinical effects to ACEIs. C. Lesser side effects than ACEI (no dry cough), but weaker evidence base. Teratogenic. D. Generally used when patients resistant to ACEIs.

18.

ALDOSTERONE RECEPTOR ANTAGONISTS A. Form of potassium sparing diuretics B. Aldosterone acts on intracellular mineralocorticoid receptors to upregulate Na+/K+ pumps; ↑ plasma Na+ C. ↑ plasma Na+ → ↑ water retention D. e.g. Eplerenone, Spironolactone E. Side effects: i.

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Hyperkalaemia, vomiting, dry mouth, headaches, breast pain & enlargement (spironolactone)

19.

(OTHER) DIURETICS A. Good second line treatments for high BP B. Thiazide diuretics (powerful; most popular diuretics for high BP) C. Loop diuretics (intermediate; infrequent for high BP) D. Other potassium sparing diuretics (weak; e.g. sodium channel blockers like amiloride)

20.

ANGIOTENSIN/ALDOSTERONE

21.

BETA-BLOCKERS A. β1 & β2 antagonists B. Second line hypertension treatment in UK, although commonly used C. Contraindicated in hypertensive individuals with asthma / COPD, diabetes (suppression of insulin release), some arrhythmias

22.

Β-BLOCKERS IN HYPERTENSION To get started right away, just tap any placeholder text (such as this) and start typing. A. b1 receptor antagonism negative chronotropic and inotropic in heart B. b2 receptor antagonism smooth muscle constriction C. b1 receptor agonism also increases renin release ( ↑ angiotensin) D. BP = CO x PVR 7

23.

CENTRALLY ACTING ANTIHYPERTENSIVES To get started right away, just tap any placeholder text (such as this) and start typing. A. Mostly obsolete for hypertension; last resort drugs B. Inhibit sympathetic activity by reducing noradrenaline release C. e.g. α2 agonists: clonidine Other: methyldopa (α2 hypothesised)

24.

NICE GUIDELINES Black people and over 55s have less responsiveness to renin; ACEIs less effective A. ACEI or ARB (low cost preferred) B. Calcium channel blocker C. Diuretic (usually thiazide)

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25.

CONSIDER CIRCUMSTANCES A. Lifestyle changes should be first route for treatment B.

Comorbidities: i.

Arrhythmias (B-blockers, CCBs)

ii.

Decreased renal function (diuretics)

iii.

Diabetes (B-blockers)

iv.

Heart failure (complex)

v.

Benign prostatic hyperplasia (a-blockers)

vi.

Etc.

C.

Pregnancy i.

26.

Avoid ACEIs/ARBs

SUMMARY A. First line pharmacological treatments are ACEIs, ARBs and CCBs B. Then diuretics (usually thiazide first, then aldosterone antagonist), beta-blockers, alpha blockers C. Finally, others depending on refractoriness or circumstances D. Combination therapy extremely common in hypertension; many patients on steps 2-4

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