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CDL301 Cardiovascular Pharmacology > Lecture 10 Hypertension II > Flashcards

Lecture 10 Hypertension II Flashcards

1
Q

What is the main therapeutic strategy in the treatment of hypertension

A

The main therapeutic strategy in the treatment of hypertension is to reduce the peripheral resistance

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2
Q

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

A

Ca2+ channel blockers

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3
Q

Which Ca2+ channels are targeted in hypertension

A

L-type Ca2+ channels

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4
Q

What are the clinical indications of Ca2+ channel blockers

A

Hypertension IHD/angina and arrhythmias such as tachycardia

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5
Q

Which cells do Ca2+ channel blockers act on

A

Ca2+ channel blockers act on peripheral resistance directly by blocking the Ca2+ channels in the membrane of vascular smooth muscle

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6
Q

What are the three classes of Ca2+ channel blocker

A

Dihydropyridines phenylalkylamines and benzothiazepines

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7
Q

Which are the main class of Ca2+ channel blockers used in hypertension because of their vasodilatory effects give examples

A

Dihydropyridines – amlodipine nifedipine and felodipine

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8
Q

Which classes of Ca2+ channel blockers are used in IHD and arrhythmias give examples

A

Phenylalkylamines – verapamil and benzothiazepines – diltiazem

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9
Q

Why are diltiazem and verapamil used in IHD and arrhythmia

A

They are rate-limiting mediations that reduce heart rate and oxygen demand

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10
Q

When are dihydropyridines used in IHD and arrhythmia

A

If patients already on β blockers (which is already reducing heart rate) then amlodipine can be a useful add on

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11
Q

What is the main effect of dihydropyridine CCBs

A

Dihydropyridines are peripheral vasodilators that preferentially affect vascular smooth muscle and cause peripheral arterial vasodilation

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12
Q

What is the main effect of phenylalkylamine CCBs

A

Verapamil mainly acts on the heart where it has a negative chronotropic and inotropic effect

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13
Q

When is verapamil contraindicated

A

In heart failure

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14
Q

Which drug belongs to the benzothiazepine class of CCBs

A

Diltiazem

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15
Q

What are the effects of benzothiazepines

A

They have an intermediate between heart and peripheral vascular affects

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16
Q

When are benzothiazepines used

A

They are used in hypertension and some arrhythmias

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17
Q

Which class of CCBs are primarily used in hypertension

A

Dihydropyridines

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18
Q

How does activity of dihydropyridines differ between the class

A

Nifedipine is relatively short acting and needs regular administration or controlled release. In contrast amlodipine is intrinsically longer acting

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19
Q

Which is the only CCB licenced in heart failure patients

A

Amlodipine

20
Q

What are the three categories of adverse effects due to CCB use in hypertension

A

Side effects due to peripheral vasodilation negative chronotropic effects and negative inotropic effects

21
Q

Which class of CCB side effects are mainly associated with the dihydropyridines

A

Peripheral vasodilation effects such as flushing headache oedema and palpitations

22
Q

Why do palpitations sometimes occur as a side effect of CCB use

A

Dihydropyridines cause palpitations as this is a natural reflex of the heart in order to restore blood pressure by raising heart rate

23
Q

Which side effects are mainly associated with verapamil and diltiazem CCBs

A

Negative chronotropic effects such as bradycardia and atrioventricular block

24
Q

What side effects are predominantly associated with verapamil

A

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

25
Q

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

A

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

26
Q

Where are the α1 receptors found and how can they be targeted therapeutically in hypertension

A

α1 receptors are postsynaptic receptors causing smooth muscle contraction. α1 blockers reduce vasoconstriction and cause vasodilation

27
Q

Give some examples of α1 blockers

A

Doxazosin prazosin indoramin and terazosin

28
Q

What is the main side effect with α1 blockers

A

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

29
Q

Why are α1 blockers also licenced in prostatic hypertrophy

A

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

30
Q

How can the α2 receptors be targeted in hypertension

A

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

31
Q

Moxonidine is another centrally acting anti-hypertensive what is its mechanism of action

A

Moxonidine acts as an imidazoline type 1 receptor (I1 receptor) agonist that reduces sympathetic nervous system outflow

32
Q

Methyldopa is another centrally acting anti-hypertensive what is its mechanism of action

A

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

33
Q

What is the benefit of methyldopa in hypertension

A

It can be used in patients who are pregnant. All other anti-hypertensives are contraindicated in pregnancy

34
Q

Clonidine is another centrally acting anti-hypertensive what is its mechanism of action

A

Clonidine is an agonist of the presynaptic α1 receptor decreasing noradrenaline release. It also agonises the I1 receptors causing the same effect

35
Q

What is sometimes seen when patients come off clonidine

A

A marked rebound hypertension

36
Q

What is the name of the renin inhibitor drug used in the treatment of hypertension

A

Aliskiren

37
Q

What are the side effects of renin inhibition

A

Hyperkalaemia dizziness due to postural hypertension arthralgia and diarrhoea

38
Q

What is the main contraindication for the use of renin inhibitors

A

They shouldn’t be used in combination with another RAAS inhibitor as this can cause a marked hyperkalaemia

39
Q

What is the first line treatment for patients with hypertension who are over 55 or Afro-Caribbean. Why is this treatment chosen

A

The first line treatment is to use Ca2+ channel blockers as these patients often have hypertension associated with low renin levels

40
Q

What is the first line treatment for patients with hypertension who are under 55. Why is this treatment chosen

A

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

41
Q

When are patients often switched from ACE inhibitors to angiotensin II receptor blockers

A

If they are intolerant to ACE inhibition and have a consistent dry cough

42
Q

What is the second line therapy for patients with hypertension

A

Dual therapy combining the ACE inhibitor/angiotensin II receptor blocker with the Ca2+ channel blockers

43
Q

What is the third line therapy for patients with hypertension

A

Add on therapies combining the ACE inhibitor/angiotensin II receptor blocker and Ca2+ channel blockers with a thiazide like diuretic

44
Q

What is the term given to patients whose hypertension persists after stage 3 treatment

A

Resistance hypertension

45
Q

What is step 4 in hypertension treatment

A

ACE-I/ARBs + CCB + Thiazide + Spironolactone and/or α blockers and/or β blockers

CDL301 Cardiovascular Pharmacology (17 decks)

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