Drugs Affecting Blood pressure Flashcards
what are some non-specific symptoms of hypertension?
dizziness
headache
what is hypertension?
isolated systolic blood pressure may be due to stiffness ion arteries as you age, unable to accomodate for the sudden increase in BP at systole
what are some of the main causes of hypertension?
primary hypertension
-smoking
-obbesity
-diet
-exercise
-genetic
secondary hypertension
-renal hypertension ro pheochromocytoma
what are the effects of chronic hypertension?
further cardiovascular disease
-atherosclerosis
-stroke
-myocardial infarction
-heartfailure
-renal failure
-retinopathy
what are the clinical benefits of reducing BP?
40% reduction of stroke
25% red in myocardial infarction
>50% red in heart failure
how do we calculate BP?
total peripheral resistance x cardiac output
What are the different pathways that can be affected to reduce blood pressure and the drug classes associated?
-block of sympathetic NS
-kidneys (reduce blood volume)
-hormones
-vasodilation of peripheral resistance arterioles (Ca2 channel blockers)
how can we block the sympathetic NS to reduce BP?
- reduce effects on heart (b1-blockers)
- reduce effects on blood vessels (a1-blockers)
- reduce renin release from kidney (b1-blockers)
how can we use hormones to reduce the BP?
inhibit renin-angiotensin-aldosterone system (angiotensin converting enzyme [ACE] inhibitors and angiotensin receptor blockers)
what is the mechanism of action of B-adrenoceptor blockers?
comeptitive reversible antagonists
-reduction in blood pressure via blockade of b1 sympathetic tone on heart and reduction in renin release from kidney
-reduction in heart rate and stroke volume (speeds up relaxation, changes in conduction velocity and reduction in ionotropy)
-reduction in cardiac output
what are some B-adrenoceptor blockers?
propranolol (b1 and b2)
atenolol (b1 selective)
what are some of the adverse effects of B-adrenoceptor blockers?
-exacerbate asthma (block of b2 absolute contraindication)
-even with b-1 selective drugs you wouldn’t prescribe because there is always a bit of a crossover
-intolerant to exercise
-hypoglycaemia
-vivid dreams
what are some examples of A-adrenoceptor blockers?
-phentolamine (a1 and a2)
-doxazosin, prazosin (a1 selective)
what are the mechanism of action of A-adrenoceptor blockers?
-competitve reversible antagonists
-reduction in blood pressure via reduction in sympathetic tone in arterioles (a1)
-reduction in peripheral resistance
what are some adverse effects of A-adrenoceptor blockers?
-postural hypertension (loss of sympathetic venoconstriction)
-reflex tachycardia (via baroreceptors)
-impotence
what are some other uses of alpha 1 receptors?
-increased closure of internal sphincter of the bladder
-mydriasis
-vasoconstriction
-increased peripheral resistance
-increased blood pressure
what are examples of ACE inhibitors?
captopril and enalapril
what is the mechanism of action of ace inhibitors?
-angiotensin converting enzyme on vascular endothelial surface converts angiotensin I to the active angiotensin II (very small peptide)
how do ACE inhibitors lower blood pressure?
- Reduced formation of the vasoconstrictor angiotensin II (reduction in peripheral resistance)
- Reduced blood volume (loss of angiotensin II-stimulated release of aldosterone, thus reduction of renal reabsorption of Na+ and water)
what are some adverse effects of ACE inhibitors?
Generally very well tolerated but:
- Sudden fall in BP on 1st dose - given with supervision
- Persistent irritant cough – due to reduced breakdown of bradykinin, a peptide that activates sensory nerves in lung tissue
what are angiotensin II receptor blockers?
-two receptor subtypes: AT1 and AT2
useful antihypertensive agents
-side effect profile appears good - no irritant cough as seen with ACE inhibitors
what do AT1 receptors mediate?
vasoconstriction anf aldosterone releasing actions of angiotensin II
what kind of drugs are losartan and candesartan?
AT1 blockers
what is the mechanism of action of diuretics?
- Lower blood pressure by reducing blood volume
- Mechanism is through reduced renal reabsorption of Na+ and water
- (additional vasodilator action may also contribute: reduced peripheral resistance)
what is an example of a diuretic?
bendroflumethiazide (a thiazide)
what are some adverse effects of diuretics?
Reduction in plasma K+ - hypokalaemia
Potassium-sparing may be favoursed
Hypokalaemia may also affect effectiveness of digoxin
what are some examples of calcium channel blockers?
verapamil, diltiazem and nifedipine
what is the mechanism of action of calcium channel blockers?
L-Type Voltage Operated Calcium Channels
- open upon membrane depolarisation
- calcium entry into cardiac and vascular smooth muscle (therefore TPR effect)
Some have more of an effect on cardiac muscle:
Reduce Ca2+ entry into vascular smooth muscle and cardiac muscle by blocking L-type voltage-operated calcium channels
what is the different mechanisms of action of calcium channel blockers?
- Open channel block (cork in a bottle!)
- verapamil and diltiazem work this way
- Allosteric modulation - bind at allosteric site and reduce channel opening
- nifedipine works this way
what is the tissue selectivity of calcium channel blockers?
smooth muscle: nifedipine > diltiazem > verapamil
cardiac muscle: verapamil > diltiazem > nifedipine
how do calcium channel blockers reduce bloop pressure?
- Reducing peripheral resistance (block of Ca2+ entry into vascular smooth muscle 4 vasodilatation)
- Reducing cardiac output (block of Ca2+ entry into cardiac muscle - heart rate and stroke volume both reduced)
what are non rate limiting agents?
Dihydropyridines examples include amlodipine and lercanidipine
what are Dihydropyridines?
They are more effective vasodilators and more vascular-selective because they exhibit voltage-dependent blockade
Cardiac conducting cells are relatively hyperpolarised whereas vascular smooth muscle is relatively depolarised.
So Dihydropyridines do not reduce heart rate and may cause an indirect tachycardia
A new agent called cilnidipine combines L/N blockade and causes less reflex tachycardia.
what are rate limiting channel modulators?
examples include verapamil and diltiazem
They have more marked effects directly on the cardiac conduction pathways and cardiac muscle.
They slow the heart rate and reduce conduction and contractility; this is more noticeable with verapamil than diltiazem
what are some adverse effects of calcium channel blockers?
headache- dilation of cerebral blood vessels
constipation - relaxation of GI smooth muscle
heart block due to reduced calcium and therefor cardiac failure
gingival hyperplasia
what is step one of NICE treatment for hypertension (under age 56)?
ACE inhibitor or low cost angiotensin II receptor blocker
what is step one of NICE treatment for hypertension (over 65 or ethnic origin of any age)?
calcium channel blocker
what is step 2 of NICE treatment for hypertension?
ACE inhibitor or angiotensin II receiptor blocker + calcium channel blocker
what is step 3 of NICE treatment for hypertension?
ACE inhibitor or angiotensin II receptor blocker + calcium - channel blocker +thiazide like diuretic
what is step 4 of NICE treatment for hypertension?
ACE inhibitor or angiotensin II receptor blocker + calcium- channel blocker + thiazide like diuretic + consider further diuretic or alpha blocker or beta blocker
Which hypertensive drug reduces BP without affecting vascular remodelling?
Atenolol (beta blocker) no effect on angiotensin system
Which neurotransmitters cause vasoconstriction?
ATP
