Hypertension: Pharmacology Flashcards
How do diuretics reduce BP?
By reducing intravascular volume
What thiazide and thiazide-like diuretics are used to treat HTN?
How do they work?
Thiazide:
- Bendroflumethiazide
- Hydrochlorothiazide
Thiazide-like:
- Chlortalidone
- Indapamide
Act at the DCT, inhibiting Na+/Cl- co transporter from the lumen, increasing water, Na+ and therefore K+ loss also.
What are the side effects of thiazide and thiazide-like diuretics?
- High uric acid = gout
- Hypokalaemia
- Hyponatraemia
- High glucose
- High cholesterol
What are thiazide and thiazide-like diuretics used to prevent?
Used to prevent MI and stroke
What potassium-sparing diuretics are used to treat HTN?
What are the side effects?
Aldosterone antagonists:
- Spironolactone
- Eplerenone
Epithelial Na+ channel blockers:
- Amiloride
Side effects:
- Hyperkalaemia
- Hyponatraemia
- Gyanaecomastia (spironolactone)
How are B1 and B2 adrenoceptor blockers used in HTN?
Which drugs are used? Which receptors do they work on?
- Negative inotropic and chronotropic effects
- Reduced AV node conduction
- Prevention of MI and stroke
Drugs:
- Atenolol (B1 cardioselective)
- Bisoprolol (B1 and B2)
- Propranolol (B1 and B2)
What are the side effects of Beta blockers?
- Broncospasm
- Lethargy
- Heart failure
- Reynaud’s
- Reduced HDL cholesterol
- Diarrhoea
What do calcium channel blockers act on?
What effect is caused?
- Vascular smooth muscle- relaxation
- Cardiomyocytes - reduced contractility & HR
- AV and SA nodes - reduced contracility & HR
- Renal tubules - natriuresis and diuresis
Which calcium channel blockers are used in HTN?
- Verapamil
- Diltiazem
- Dihydropyridines: nifedipine, amlodipine
How does verapamil work for HTN?
What are its effects on the CVS?
Mostly works on cardiac muscle. Slow Ca entry during phases 2 and 3 of cardiac action potential. Useful for tachyarrythmia esp. re-entry and atrial origin. Slow AV node conduction and therefore useful for atrial flutter. Little effect on vasomotor tone.
- Reduces SVR from peripheral vasodilation
- Coronary vasodilation
- Decreased cardiac contractility
- Reduces heart rate
- Mild reduction in stroke volume
(Mild decrease in BP)
What are the side effects of verapamil?
- Heart failure
- Heart block
- Peripheral oedema
- Facial flush
- Headaches
- Constipation
How does diltiazem work for HTN?
Affects cardiac smooth muscle
- Mild reduction in SVR through peripheral vasodilation
- Moderate coronary vasodilation (useful for angina)
- Moderate slowing of AV node- antiarrhythmic
- Mild reduction in HR and SV
Mild decrease in BP
What are the side effects of diltiazem?
- Facial flush
- Heart failure
- Heart block
- Peripheral oedema
- Headaches
- Constipation
(Same as verapamil)
What is diltiazem used for?
HTN
Angina
How do dihydropyridines work in HTN?
- Peripheral vasodilation (reduced SVR)
- Cardiac vasodilation
- Mild decreased cardiac contractility
- Reflex increase in sympathetic tone
- Mild slowing of AV node conduction
- Increase in HR (compensatory from drop in BP)
- Natriuresis and diuresis
Which dihydropyridines are used in HTN?
- Nifedipine
- Amlodipine
- Lercanidipine
How do dihydropyridines increase HR?
Lowering BP causes compensatory increase in HR
Name some circumstances in which the RAAS system is activated
- Hypotension
- HF
- Septicaemia
How do ACE inhibitors work in HTN?
Inhibit all formation in the RAAS system preventing increased BP.
Inhibit bradykinin breakdown
What are the side effects of ACE inhibitors?
- Cough
- Angio oedema
- Hyperkalaemia
- Caution in renal artery stenosis
Why do ACE inhibitors cause a dry cough?
Prevent the breakdown of bradykinin resulting in more active bradykinin in the lungs = cough
Which Angiotensin II receptor blockers are used for HTN?
How do they work to treat HTN?
- Losartan
- Valsartan
- Candesartan
Blocking angiotensin II receptors preventing their effects on blood pressure and the production of aldosterone.
What are the side effects of angiotensin receptor blockers?
- Generally well tolerated
- Caution in renal artery stenosis
- Hyperkalaemia
- Myalgia
- Raised CPK
Which alpha receptor blockers are used in HTN?
How do they work to reduce BP?
What are their side effects?
- Doxazosin
- Phenoxybenzamine for phaeochromocytoma- in emergencies
Used in combination with other therapies
Side effects:
- Hypotension with first dose
- Postural hypotension
What are alpha1 receptor blockers also used for?
BPH
What are the BP targets for under 80s?
<140/90 in clinic
<135/85 AMBP/HMBP
What are the BP targets for those 80 years and over?
<150/90 in clinic
<145/85 AMBP/HMBP
What is the first line pharmacological treatment for a person with HTN and T2DM or who is <55 and not from black Afro-Caribbean origin?
What is the second line?
1st line: ACE inhibitor or ARB
2nd line: ACE-inhibitor or ARB + CCB or thiazide-like diuretic
What is the first line pharmacological treatment for a person with HTN without diabetes or who is >55 or of black Afro-Caribbean origin?
What is the second line?
1st line: CCB
2nd line: CCB + ARB or ACE-i
What is the third line pharmacological treatment for HTN regardless of diabetes, ethnicity or age?
CCB + ACE-i or ARB + thiazide-like diuretic
What is the 4th line treatment for HTN regardless of diabetes, ethnicity or age?
Confirm resistant HTN with ABPM or HBPM and discuss adherence.
Seek expert advice or add:
- Low dose spironolactone if serum K+ 4.5mmol/L or less
- Alpha blocker or beta blocker if serum K+ >4.5mmol/L
Seek expert advice if BP remains uncontrolled on optimal tolerated doses of 4 drugs
