drugs affecting blood pressure Flashcards
(21 cards)
definition of hypertension
: a higher than normal BP which if left untreated increases the risk of CV disease
hypertension systolic and diastolic
Risk increases with rises in both systolic and diastolic BP, although more emphasis given to systolic BP
Isolated systolic hypertension (i.e. without major increases in diastolic pressure) is common in the elderly and particularly deleterious
Absolute boundaries depend on method of measurement. These are in-clinic measurements where the phenomenon of “whitecoat hypertension” is recognised.
The boundary for at home measurements is slightly lower at 135mmHg
causes of hypertension
Primary (Essential) hypertension (~90%)
No obvious cause; Multifactorial risk factors
Lifestyle: smoking, obesity, high salt, excessive alcohol, lack of exercise
Genetic (40% of variability)
Ageing ( vascular stiffness)
Anxiety and emotional stress
Secondary hypertension (<10 %)
e.g. due to renal disease or endocrine disorders (hyperaldosteronism)
chronic hypertension
leads to vascular remodelling and end-organ damage
Damaged endothelium
Impaired endothelial function
↓ blood flow to organs
SMC hypertrophy
vessel stiffness
↑ vessel leakiness
↑ thrombosis risk
↑ total peripheral resistance
↑ afterload => workload => cardiac hypertrophy
= hypertensive heart failure
correlated adverse cardiovascular events
Increased risk of: -
Coronary artery disease
Chronic kidney disease
Peripheral arterial disease
Vascular dementia
High blood glucose: since hypertension a risk factor for insulin resistance and therefore glucose uptake (increased risk of diabetes)
control of blood pressure
- Mean arterial Blood Pressure = CO x TPR
Cardiac Output = Heart Rate x Stroke Volume - Regulation of blood volume (i.e. Na+ and H2O control)
interventions of blood pressure
Lifestyle (↓ dietary Na+, weight loss, exercise, quit smoking etc.)
Block of sympathetic nervous system
- reduce cardiac output (b1-blockers)
- reduce effects on blood vessels (a1-blockers)
- reduce renin release from kidney (b1-blockers)
Kidney - ↑ Na+ and water excretion to reduce blood volume (diuretics)
Kidney hormones - inhibit renin-angiotensin-aldosterone system
(ACE inhibitors and angiotensin receptor blockers)
Vasodilatation to ↓peripheral resistance (Ca2+ channel blockers)
The renin-angiotensin-aldosterone system (RAAS)
ACE = Angiotensin converting enzyme; ADH = anti-diuretic hormone
Release of Renin by specialist cells in the juxtaglomerular apparatus is stimulated by low BP or reduced blood volume; low [Na+] levels and by increased sympathetic activation
Renin cleaves angiotensinogen to form Angiotensin I
Angiotensin converting enzyme (ACE) cleaves-off 2 amino acids to form the active Angiotensin II
This acts on angiotensin II type 1 receptors to (i) promote release of the hormone aldosterone from the adrenal cortex; (ii) increase Na+ reabsorption by the proximal tubule and thereby increase blood volume; (iii) act centrally on the hypothalamus to stimulate aldosterone release; iv) mediate vasoconstriction
Aldosterone increases Na+ reabsorption at the distal tubule
hyperaldosteronism
Hyperaldosteronism is a major cause of secondary hypertension as well as being a downstream consequence in primary hypertension
ACE inhibitor mechanisms
Angiotensin Converting Enzyme on vascular endothelial surface converts angiotensin I to the active angiotensin II
Captopril – active compound + active metabolites
Enalapril, ramipril, trandolapril – longer half-life; prodrugs converted to active metabolite by liver
Lower blood pressure by:
Reduced formation of the vasoconstrictor angiotensin II (i in peripheral resistance)
Reduced blood volume (loss of angiotensin II-stimulated release of aldosterone, thus reduction of renal reabsorption of Na+ and water)
Minor: inhibit breakdown of vasodilatory peptide bradykinin
ACE side effects
Sudden fall in BP on 1st dose – introduce gradually
Persistent irritant cough (~10%) – due to reduced breakdown of bradykinin which activates sensory nerves in lung tissue
Hyperkalaemia – monitor electrolytes
Contraindicated in:
Pregnancy – retard foetal growth
Renovascular disease – can precipitate renal failure
angiotensin II receptor blockers
Two receptor subtypes: AT1 and AT2
AT1 receptor mediates vasoconstrictor and aldosterone-releasing actions of angiotensin II
Losartan, valsartan and candesartan – AT1 blockers
Similar adverse effects and contraindications as ACEi
Except… do not affect bradykinin levels, hence no irritant cough as seen with ACE inhibitors
mineralocorticoid receptor antagonist
Add Spironolactone for resistant hypertension
Blocks effects of aldosterone, so may cause hyperkalaemia
calcium channel blockers
Bind to and block L-type voltage-operated Ca2+ channels
↓ Ca2+ entry in response to membrane depolarisation
Resting membrane potential (Em) determines tissue selectivity
vascular smooth muscle- vasodilation, decrease in blood pressure
cardiac muscle= decrease in force of contraction + HR = reduced cardiac output
dihydropyridines
Allosteric modulators which reduce probability of pore opening
Highest affinity for channels when they are in an inactivated state
Smooth muscle is more sensitive due to less negative Em
Relatively selective for vascular smooth muscle
Small effect on cardiac muscle is counteracted by baroreceptor reflex to maintain inotropy
First line treatment for hypertension
eg. nifedipine, amlodipine, felodipine
Non- dihydropyridines
Interacts directly with the channel pore to prevent Ca2+ entry
Highest affinity when channel is in active ‘open’ state (like a cork!)
Both vascular and cardiac channels are blocked
Vasodilation + ↓ inotropy + ↓ HR
AV node particularly sensitive since depolarisation dependent on Ca2+ entry
Uses: supraventricular arrhythmias, angina, hypertension
eg. verapamil, diltiazem
side effects calcium channel blockers
Headache & dizziness (dilation of cerebral blood vessels)
Flushing
Peripheral oedema
Abdominal pain & constipation
Gingival hyperplasia (less common)
For non-DHPs:
Atrioventricular block
thiazide diuretics
eg, bendroflumetheziade
Lower blood pressure by reducing blood volume
Mechanism: reduced renal reabsorption of Na+ and water in the distal tubule
(additional vasodilator action may also contribute: i peripheral resistance)
Side-effects: i in plasma K+
Generally well tolerated: GI disturbances, fatigue, dizziness, headache
beta- adrenoceptors blockers
e.g. propranolol (b1 and b2); atenolol, metoprolol, bisoprolol (relatively b1 selective)
Competitive reversible antagonists
Block b1 sympathetic tone in heart:
heart rate and stroke volume = cardiac output In kidney: renin release = blood volume
Reduces blood pressure & unloads heart
beta- adrenoceptor blockers- side effects
Bronchospasm and exacerbation of asthma due to block of b2 receptors in lungs (avoid in asthma even if ‘cardioselective’ )
Intolerance to exercise; fatigue
Bradycardia and dizziness
Depression and confusion
Sleep disturbances & nightmares
alpha- adrenoceptor blockers
e.g. Doxazosin, prazosin (a1 selective)
Competitive reversible antagonists
Block a1 adrenoceptors in arterioles to reduce effect of sympathetic tone
Peripheral resistance is reduced and therefore BP
Side-effects:
Postural hypotension (loss of sympathetic venoconstriction)
Reflex tachycardia (via baroreceptor reflex)
