Lecture 10 Hypertension II Flashcards
What is the main therapeutic strategy in the treatment of hypertension
The main therapeutic strategy in the treatment of hypertension is to reduce the peripheral resistance
What is the first line choice of therapy in patients with hypertension these tend to be patients who are over 55 and/or Afro-Caribbean
Ca2+ channel blockers
Which Ca2+ channels are targeted in hypertension
L-type Ca2+ channels
What are the clinical indications of Ca2+ channel blockers
Hypertension IHD/angina and arrhythmias such as tachycardia
Which cells do Ca2+ channel blockers act on
Ca2+ channel blockers act on peripheral resistance directly by blocking the Ca2+ channels in the membrane of vascular smooth muscle
What are the three classes of Ca2+ channel blocker
Dihydropyridines phenylalkylamines and benzothiazepines
Which are the main class of Ca2+ channel blockers used in hypertension because of their vasodilatory effects give examples
Dihydropyridines – amlodipine nifedipine and felodipine
Which classes of Ca2+ channel blockers are used in IHD and arrhythmias give examples
Phenylalkylamines – verapamil and benzothiazepines – diltiazem
Why are diltiazem and verapamil used in IHD and arrhythmia
They are rate-limiting mediations that reduce heart rate and oxygen demand
When are dihydropyridines used in IHD and arrhythmia
If patients already on β blockers (which is already reducing heart rate) then amlodipine can be a useful add on
What is the main effect of dihydropyridine CCBs
Dihydropyridines are peripheral vasodilators that preferentially affect vascular smooth muscle and cause peripheral arterial vasodilation
What is the main effect of phenylalkylamine CCBs
Verapamil mainly acts on the heart where it has a negative chronotropic and inotropic effect
When is verapamil contraindicated
In heart failure
Which drug belongs to the benzothiazepine class of CCBs
Diltiazem
What are the effects of benzothiazepines
They have an intermediate between heart and peripheral vascular affects
When are benzothiazepines used
They are used in hypertension and some arrhythmias
Which class of CCBs are primarily used in hypertension
Dihydropyridines
How does activity of dihydropyridines differ between the class
Nifedipine is relatively short acting and needs regular administration or controlled release. In contrast amlodipine is intrinsically longer acting
Which is the only CCB licenced in heart failure patients
Amlodipine
What are the three categories of adverse effects due to CCB use in hypertension
Side effects due to peripheral vasodilation negative chronotropic effects and negative inotropic effects
Which class of CCB side effects are mainly associated with the dihydropyridines
Peripheral vasodilation effects such as flushing headache oedema and palpitations
Why do palpitations sometimes occur as a side effect of CCB use
Dihydropyridines cause palpitations as this is a natural reflex of the heart in order to restore blood pressure by raising heart rate
Which side effects are mainly associated with verapamil and diltiazem CCBs
Negative chronotropic effects such as bradycardia and atrioventricular block
What side effects are predominantly associated with verapamil
Worsening of heart failure due to negative inotropic effects. Also constipation is often seen most likely due to an inhibition of smooth muscle contraction in the colon
Diltiazem verapamil and β blockers are contraindicated in patients with heart block due to the negative chronotropic effects. When is the only time that these drugs may be used and why
The only time that diltiazem verapamil and β blockers may be used in patients with conduction defects is when they’ve had a pacemaker fitted. In these patients if the drug stops occasional electrical activity then the pacemaker can stimulate atria or ventricles only if needed
Where are the α1 receptors found and how can they be targeted therapeutically in hypertension
α1 receptors are postsynaptic receptors causing smooth muscle contraction. α1 blockers reduce vasoconstriction and cause vasodilation
Give some examples of α1 blockers
Doxazosin prazosin indoramin and terazosin
What is the main side effect with α1 blockers
Upon standing up the bodies response is to trigger vasoconstriction via stimulating the α1 receptors. One key issue with α1 blockers is that they cause postural hypotension which can lead to syncope
Why are α1 blockers also licenced in prostatic hypertrophy
Hypertrophy of the prostate blocks outflow of urine through the urethra. However the bladder neck and prostate itself contains smooth muscle that contract via α1 receptors. Blocking these receptors with indoramin alfuzosin and Tamsulosin alleviates some of the restricted flow
How can the α2 receptors be targeted in hypertension
The α2 adrenoceptors are found on the presynaptic membrane in the brainstem. Stimulation of these α2 receptors decreases noradrenaline release and hence the effects of sympathetic nervous system stimulation
Moxonidine is another centrally acting anti-hypertensive what is its mechanism of action
Moxonidine acts as an imidazoline type 1 receptor (I1 receptor) agonist that reduces sympathetic nervous system outflow
Methyldopa is another centrally acting anti-hypertensive what is its mechanism of action
Methyldopa has a dual mechanism of action in hypertension. It activates pre-synaptic α2 receptors leading to a decrease in noradrenaline release but is also a competitive inhibitor of DOPA decarboxylase the enzyme that converts L-Dopa to dopamine. Dopamine is a precursor to noradrenaline and so an inhibition of DOPA decarboxylase means that less dopamine and less noradrenaline is produced
What is the benefit of methyldopa in hypertension
It can be used in patients who are pregnant. All other anti-hypertensives are contraindicated in pregnancy
Clonidine is another centrally acting anti-hypertensive what is its mechanism of action
Clonidine is an agonist of the presynaptic α1 receptor decreasing noradrenaline release. It also agonises the I1 receptors causing the same effect
What is sometimes seen when patients come off clonidine
A marked rebound hypertension
What is the name of the renin inhibitor drug used in the treatment of hypertension
Aliskiren
What are the side effects of renin inhibition
Hyperkalaemia dizziness due to postural hypertension arthralgia and diarrhoea
What is the main contraindication for the use of renin inhibitors
They shouldn’t be used in combination with another RAAS inhibitor as this can cause a marked hyperkalaemia
What is the first line treatment for patients with hypertension who are over 55 or Afro-Caribbean. Why is this treatment chosen
The first line treatment is to use Ca2+ channel blockers as these patients often have hypertension associated with low renin levels
What is the first line treatment for patients with hypertension who are under 55. Why is this treatment chosen
The first line treatment is to use an ACE inhibitor or an angiotensin II receptor blocker as these patients often have hypertension associated with high renin levels
When are patients often switched from ACE inhibitors to angiotensin II receptor blockers
If they are intolerant to ACE inhibition and have a consistent dry cough
What is the second line therapy for patients with hypertension
Dual therapy combining the ACE inhibitor/angiotensin II receptor blocker with the Ca2+ channel blockers
What is the third line therapy for patients with hypertension
Add on therapies combining the ACE inhibitor/angiotensin II receptor blocker and Ca2+ channel blockers with a thiazide like diuretic
What is the term given to patients whose hypertension persists after stage 3 treatment
Resistance hypertension
What is step 4 in hypertension treatment
ACE-I/ARBs + CCB + Thiazide + Spironolactone and/or α blockers and/or β blockers
