Hypertension and HF Flashcards
What are the ranges for the different grades of hypertension?
Grade I: 140-159/90-99
Grade II: 160-179/100-109
Grade III: >180/>110
What are some drugs that can cause hypertension?
OCP
Corticosteroids
NSAIDs
Problems and complications of hypertension?
Increased arterial thickening Smooth muscle cell hypertrophy Accumulation of vascular matrix Loss of arterial compliance Target organ damage such as heart, kidneys, brain, eyes
Endocrine causes of secondary hypertension?
Conn's syndrome Congenital adrenal hyperplasia Cushing's Phaeochromocytoma Thyroid disease Acromegaly Hyperparathyroidism Carcinoid
Renal causes of hypertension?
Renovascular hypertension Chronic pyelonephritis Diabetic renal disease Renal parenchymal disease Liddle's syndrome Gordon's syndrome
What is phaeochromocytoma?
Adrenal catecholamine-secreting tumour - produces large amounts of adrenaline and NA
How is phaeochromocytoma treated?
Non-selective alpha-adrenoreceptor antagonists
What is Conn’s syndrome?
An aldosterone-secreting adenoma causing fluid reabsorption
How is Conn’s syndrome treated?
Aldosterone antagonists eg spironolactone
How is mild (grade I) hypertension treated?
Normally a non-pharmacological therapy (lifestyle changes)
What is isolated systolic hypertension and what is it due to?
A low diastolic BP and a high systolic BP (>140mmHg)
Common with increasing age due to loss of compliance of arteries
What are some non-pharmacological interventions?
Maintain normal body weight
Reduce salt intake
Consume 5+ portions of fruit and veg a day
Limit alcohol
Regular exercise
Reduce total and saturated fat
Stop smoking (just reduces CV risk, not BP)
When is blood pressure treated pharmacologically?
When it is above 160/100mmHg
Above 140/90mmHg in diabetics
What is someone under 55 initially treated for hypertension with?
ACE inhibitors
What is someone over 55 or black of any age initially treated with?
Calcium channel blockers
If there is no response in someone with hypertension with initial treatment, what is done?
Combine ACE inhibitors and Ca channel blockers
Then add diuretics
Then add alpha-blockers, beta-blockers, centrally acting drugs or vasodilators
Name some ACE-i
Lisinopril
Ramipril
What is the mechanism of action of ACE-i?
Competitively inhibits ACE activity
- reducing formation of angiotensin II
- preventing degradation of bradykinin
- minimising production of aldosterone
What are the overall effects of ACE-i?
Reduce effect of RAAS
- reduce Na and water reabsorption
- reduce peripheral vasoconstriction
- some venodilation action
ADRs of ACE-i?
HARD Hyperkalaemia Angioedema Renal problems/failure Dry cough
Name some angiotensin-II receptor blockers (ARBs)
Losartan
Valsartan
ADRs of ARBs?
Renal failure
Hyperkalaemia
Indications for ARBs?
For individuals who cannot tolerate adverse effects of ACE-i
Mechanism of action of calcium-channel blockers?
Bind to the alpha-subunit of L-type calcium channels, reducing calcium entry
Causes vasodilation of peripheral, coronary and pulmonary arteries by smooth muscle relaxation
What are the main groups of calcium channel blockers? Name a drug in each group
Dihydropyridines - nifedipine, amlodipine
Phenylalkylamines - verapamil
Benzothiazepines - dilitiazem
Absorption, distribution and metabolism of dihydropyridines?
Good oral absorption
90% protein bound
Metabolised by liver
ADRs of dihydropyridines?
Baroreflex-mediated tachycardia SNS activation - tachycardia and papitations Flushing and sweating Ankle oedema Throbbing headache
However normally well-tolerated
Mechanism of action of phenylalkylamines eg verapamil and overall effects?
Act on myocardial and smooth muscle cell membrane calcium transport - leads to vasodilation, reducing cardiac preload and myocardial contractility
Class IV anti-arrhythmic - prolongs action potential/effective refractory period
ADRs of phenylalkylamines?
Constipation
Bradycardia
Negative inotropy
DDIs of phenylalkylamines?
Cannot be given with beta-blockers as they cause bradycardia
Effects of benzothiazepines?
Peripheral vasodilation and reduced myocardial contractility
Prolongs action potential/effective refractory period
ADRs of benzothiazepines?
Bradycardia
Negative inotropy
What are benzothizaepines mostly used for?
Angina rather than hypertension
Overall effects of thiazide diuretics?
Act on Na-Cl symport in DCT
Reduced sodium and water absorption, reduced blood volume
Long-term, reduces TPR
ADRs of thiazides?
Hypokalaemia
Increased urea and uric acid
Impaired glucose tolerance
Raised cholesterol and triglyceride levels
Name an alpha blocker
Doxazosin
Mechanism of action of alpha blockers?
Antagonise alpha-1 adrenoreceptors and antagonises contractile effects of NA, reducing TPR
ADRs of alpha-blockers?
Postural hypotension
Dizziness
Headache and fatigue
Oedema
Mechanism of action of beta blockers?
Antagonise beta-1 adrenoceptors on ventricular myocardium, reducing HR and CO
Inhibit renin release
Rarely used as anti-hypertensive as have little significant effect
Why are beta-blockers good for angina?
Slow heart rate, increasing diastolic filling of coronary arteries
ADRs of beta-blockers?
Lethargy Impaired concentration Reduced exercise tolerance Bradycardia Raynaud's Impaired glucose tolerance
Contra-indications of beta-blockers?
Asthma
How do direct renin inhibitors work?
Bind to the renin molecule, preventing cleavage of angiotensinogen to angiotensin I
Name a renin inhibitor
Aliskiren
Bioavailability and excretion of aliskiren?
Low bioavailability
Eliminated unchanged in faeces
1% renally excreted
In which patients must care be taken in prescribing renin inhibitors?
Patients at risk of hyperkalaemia, sodium and volume-depleted patients, patients with HF, severe renal impairment, renal stenosis
Examples of centrally acting agents?
Methyldopa - alpha-2 adrenoceptor agonist
Clonidine - pre-synaptic alpha-2 agonist
Monoxidine - alpha-2 agonist
Effects of centrally acting agents?
Reduce sympathetic outflow which reduces blood pressure
Benefits of centrally acting agents?
Good response
Safe in pregnancy
ADRs of centrally acting agents?
Tiredness and lethargy
Depression
What can happen in withdrawal of clonidine?
Rebound hypertension - due to NA release leading to desensitisation of alpha 2 receptors and super-sensitivity of post-synaptic alpha-1 receptors
What is a hypertensive emergency?
Very high BP of >220/120
What can happen in a hypertensive emergency if BP is not reduced by around 20% within 1-2 hours?
Pulmonary oedema
Renal failure
Aortic dissection
Treatment of hypertensive emergencies?
Sodium nitroprusside - acts as an endogenous nitrous oxude causing vasodilation and rapid onset of reduction of BP
What are the goals in HF treatment?
Symptomatic improvement
Delay progression
Reduce mortality
Treat complications/associated conditions/CVS risk factors
What are the drugs used in HF?
ACE inhibitors and ARBs
Aldosterone antagonists
Diuretics (loop and thiazide)
What can aldosterone do/cause in HF?
Can return to normal even with ACE-i/ARB therapy
Endothelial dysfunction leading to myocardiac fibrosis and acute coronary events
Potassium and magnesium leading to arrhytmias
Myocardiac fibrosis leading to arrhythmias
All of these increase risk of sudden cardiac death
Why are beta-blockers good in HF?
Reduce myocardial oxygen demand
- reduce heart rate via beta receptors
- reduce BP, reducing CO
Reduce metabolism of glycogen
Negate unwanted effects of catecholamines
Why do beta-blockers need to be prescribed with care in HF?
A failing myocardium is dependent on HR
