What is the physiological control of blood pressure?
Autonomic Nervous system
Renin-Angiotensin system
Others:
- Bradykinin
- Endothelin
- Nitric Oxide
- Atrial Natriuretic Peptide
What happens when blood pressure goes down to increase it?
Decrease in Renal perfusion:
- Decrease in Urinary output
- Increase in Blood volume
- RAS system increases (Increase in blood volume)
- Increase in vasoconstriction
- Increase in peripheral resistance
Change sensed by baroreceptors:
- Decrease parasympathetic nervous system
- Increase in Sympathetic nervous system (Activates RAS)
- Increase in cardiac output
All lead to an increase in BP
What happens when blood pressure goes up to reduce it?
Increase renal perfusion:
- Increase in urinary output
- Decrease in blood volume
- Decrease in RAS system (decreases blood volume)
- Decrease in vasoconstriction
- Decrease in peripheral resistance
Change sensed by baroreceptors:
- Increase parasympathetic nervous system
- Decreases sympathetic nervous system
- Decrease cardiac output
Decrease in blood pressure
Describe the Renin-Angiotensin-Aldosterone system.
Angiotensinogen is created in the liver Renin from the kidney Converts it into Angiotensin I ACE (angiotensin II then converts that into Angiotensin II
Angiotensin II The has 3 major effects:
- Increase in Aldosterone production
- Retention of salt and water (Aldosterone also promotes this)
- Vasoconstriction
All this leads towards an increase in blood pressure
ACE also converts Bradykinin into inactive kinins
How can a higher blood pressure lead to morbidity and mortality?
Higher blood pressure \/ Increased arterial thickening \/ Smooth muscle cell hypertrophy Accumulation of vascular matrix Loss of arterial compliance \/ Target Organ Damage \/ Heart - Kidneys - Brain - Eyes
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CV morbidity and mortality
Does hypertension treatment improve mortality and morbidity?
Yes
In a study Done it showed that against a placebo hypertensive treatment improves mortality and morbidity
What is defined as hypertension?
Defined 140/90mmHg
What are causes of hypertension?
Primary (essential) hypertension
- High BP without any single evident cause
- 90% hypertensive population
Secondary hypertension
- High BP with a discrete, identifiable underlying cause
- 10% hypertensive population
How do we treat hypertension?
Identify and treat underlying cause if present
Identify and treat other cardiovascular risk factors or co-morbidities
Lifestyle advice/non-pharmacological therapy
Pharmacological therapy
What are some lifestyle therapies to reduce hypertension?
Patient education Maintain normal body weight (BMI 20-25) Reduce salt intake to 30 min/day consume >5 portions of fresh fruit/vegetables daily Reduce intake of total and saturated fat (Smoking cessation) (Relaxation therapies)
What is the 1st line pharmacological therapy of hypertension?
A - Angiotensin Converting Enzyme (ACE) inhibitors
- Angiotensin Receptor Blockers (ARB)
C - Calcium channel blockers
D - Diuretics (thiazide)
What do ACE Inhibitors do?
Competitive inhibitors of Angiotensin Converting Enzyme (ACE)
Reduction in formation of angiotensin II
Mainly arteriolar vasodilators
Some venodilation
Circulating aldosterone reduced
Tell me about ACE inhibitors.
Lisinopril, ramipril
Inhibit ACE activity
Prevents generation of Angiotensin II
Potentiates the action of bradykinin
Main side effect - dry cough (10-15%)
Important side effects:
- Angio-oedema (rare, more common in black pop.)
- Renal failure (incl. renal artery stenosis)
- Hyperkalaemia
Tell me about Angiotensin Receptor Blockers.
Losartan, Valsartan Bind to angiotensin AT1 receptor Inhibit vasoconstriction and aldosterone stimulation caused by angiotensin II Well tolerated few side effects Important side effects: - Renal failure - Hyperkalaemia
Tell me about calcium channel blockers.
Bind to specific alpha subunit of L-type calcium channel, reducing cellular calcium entry
Vasodilates peripheral, coronary and pulmonary arteries
No significant effect on veins
Short acting dihydropyridines - baroreflex mediated tachycardia
Verapamil depresses SA node and slows A-V conduction
3 main groups:
- Dihydropyridines (Nifedipine, Amlodipine)
- Benzothiazepines (Diltiazem)
- Phenylalkylamines (Verapamil)
Tell me about dihydropyridine calcium channel blockers
Amlodipine, Nifedipine
Properties: Good oral absorption Protein bound >90% Metabolised by the liver Few have active metabolite
Adverse effects: Sympathetic nervous system activation - tachycardia and palpitations Flushing, sweating, throbbing headache Oedema Gingival hyperplasia (rare Amlodipine - gynaecomastia
Tell me about Phenylalkylamines.
Verapamil
Properties:
Impedes calcium transport across the myocardial and vascular smooth muscle cell membrane
Class IV anti-arrhythmic agent/prolongs the action potential/effective refractory period
Peripheral vasodilation and a reduction in cardiac preload and myocardial contractility
Adverse effects:
Constipation
Risk of bradycardia
Reduce myocardial contractility (negative inotrope) - can worsen heart failure
Tell me about benzothiazepines.
Diltiazem (not really used in hypertension)
Properties:
Impedes calcium transport across the myocardial and vascular smooth muscle membrane
Prolongs the action potential/effective refractory period
Peripheral vasodilation and a reduction in cardiac preload and myocardial contractility
Adverse effects:
Risk of bradycardia
Less negative inotropic effect than verapamil - can worsen heart failure
Tell me how thiazide/thiazide like diuretics work.
E.g. Bendroflumethiazide
Reduce distal tubular sodium reabsorption
Sustained action
Blood pressure reduction - complex
Several mechanisms
- Initial blood volume decrease
- Later - total peripheral resistance falls
Dose-blood pressure response curve flat
What are the adverse effects of Bendroflumethiazide?
Hypokalaemia
Increased urea and uric acid levels
Impaired glucose tolerance (especially with beta-blockers)
Cholesterol and triglyceride levels increased
Activates renin angiotensin system
What is the BHS and NICE pharmacological treatment guideline?
Step 1:
Younger than 55 years - A
55 years or older/black patients - C or D
Step 2:
A + C or A + D
Step 3:
A + C + D
Step 4 Add further diuretic therapy or Alpha-blocker or Beta-blocker Consider seeking specialist advice
Give an indication, caution, contraindication of thiazide/diuretics.
Elderly, ISH (Isolated systolic hypertension), Heart failure
No caution
Gout
Give an indication, caution, contraindication of Beta-blockers
MI/Angina
Heart failure, PVD, diabetes (except with CHD)
Asthma, COPD, heart block
Give an indication, caution, contraindication of CCB (dihydropyridines
Elderly, ISH
Give an indication, caution, contraindication of CCB (rate limiting)
Angina
Combination with beta-blockade
Heart block, heart failure
Give an indication, caution, contraindication of ACE inhibitors.
Heart failure, LV dysfunction, MI, Diabetes (Type 1), nephropathy
Renal impairment, PVD
Pregnancy, renovascular hypertension
Give an indication, caution, contraindication of ARBs
ACE inhibitor intolerance, hypertension with LVH, type 2 DM
Renal impairment, PVD
Pregnancy, renovascular hypertension
Give an indication, caution, contraindication of alpha blockers.
Benign prostatic hyperplasia
Postural hypotension, heart failure
Urinary incontinence
What are some other anti-hypertensive drugs?
Alpha adrenoceptors blockers
Beta adrenoceptors blockers
Direct renin inhibitors (new class) - Aliskirin
Centrally acting agents
- Methyl Dopa
- Clonidine
- Moxonidine
Vasodilators
- Hydralazine
- Minoxidil
- Sodium nitroprusside
Tell me about alpha blockers.
Properties: -Selective antagonism at post-synaptic alpha-1 adrenoceptors and antagonise the contractile effects of noradrenaline on vascular smooth muscle Reduce peripheral vascular resistance More effect in upright position Benign effect on plasma lipids/glucose Safe in renal disease
Adverse effects: Postural hypotension Dizziness Headache and fatigue Oedema (especially if combined with dihydropyridines)
Tell me about beta blockers.
E.g. Atenolol, bisoprolol, nebivolol
Developed for angina but found to lower blood pressure
Reduce heart rate and cardiac output
Inhibit renin release
Inhibit renin release
Initially TPR increases later falls to normal
Adverse effects: Lethargy, impaired concentration Reduced exercise tolerance bradycardia Cold hands - Raynaud's Impaired glucose tolerance Contraindication - asthma
What are some of the treatments for heart failure?
Prognosis may be improved by:
RAS antagonism:
- ACE inhibitors/ARB
- Aldosterone blockade
Beta blocker
What are the physiological effects of beta-blockers?
Reduce heart rate (cardiac beta receptor) Reduce BP (Reduced CO)
Reduced myocardial oxygen demand
Reduce mobilisation of glycogen
Negate unwanted effects of catecholamines