Pharmacology: Hypertension and Heart failure Flashcards
What are the physiological control mechanisms of BP?
RAAS system: decreased BP leads to decreased renal perfusion which activates RAAS. Aldosterone holds on to sodium causing BP to raise. (and visa versa)
Baroreceptors detect BP then raise and drop PNS and SNS activity accordingly to increase or decrease cardiac output.
Outline mechanism of the RAA system
Renin synthesised by the kidney cleaves angiotensinogen from the liver into angiotensin 1.
ACE then cleaves angiotensin 1 into angiotensin 2. Also cleaves vasodilating bradykinin.
Angiotensin 2 causes vasoconstriction and increases aldosterone which retains salt and water.
This all leads to an increase in BP.
How does hypertension result in morbidity and mortality?
High BP causes arterial thickening and smooth muscle hypertrophy. This leads to loss of arterial compliance leading to organ damage of the heart, kidneys, brain and eyes.
What is defined as hypertension?
140/90
How common is hypertension?
40% of the adult population have hypertension.
Lowering diastolic BP by just 10mmHg reduces risk of stroke by 60% and CHD by 35%.
What is primary and secondary hypertension?
What proportion of cases make up each?
Primary hypertension is high BP without an identifiable cause - 90% of cases
Secondary hypertension has an identifiable underlying causes - 10% of cases
What lifestyle advice should be given to patients with high BP?
- maintain healthy BMI
- reduce salt intake
- limit alcohol
- aerobic exercise for >30mins per day
- 5 a day
- reduce intake of sat fats
- smoking cessation - BP actually goes up but overall CVS risk goes down
- relaxation
List the 1st line pharmacological therapies
ACD
A - ACEI or angiotensin receptor blockers
C - calcium channel blockers
D - diuretics
Name some ACEIs and explain how they work.
What are the ADRs?
Lisinopril, rampiril
Prevents generation of angiotensin 2 and potentiates the action of bradykinin.
Dry cough is a common side effect Importants ADRs: - angio-oedema, rare but more common in black population so give ca channel blocker instead - renal failure - hyperkalaemia
Name some angiotensin receptor blockers and explain how they work.
What are the ADRs?
Lasartan, valsartan.
Inhibit the effects of angiotensin.
Well tolerated with v few side effects unlike ACEIs.
Important ADRs:
- renal failure
- hyperkalaemia
What are the main groups of calcium channel blockers?
Give an examples of each
Dihydropyridines eg amolodapine
Benzothiazepines eg diltiazem
Phenylalkylamines eg verapamil
What is the generic mechanism of calcium channel blockers?
Bind to the alpha subunit of L type calcium channels reducing calcium entry.
This causes vasodilation of peripheral, coronary and pulmonary arteries.
What are the pharmacological properties of dihydropyridine calcium channel blockers?
Well absorbed orally
Highly protein bound
Metabolised by liver so drug of choice in CKD.
Amilodapine has large Vd so long T1/2 so not to be used in critically high BP, instead use nifedipine.
What are some adverse effects of dihydropyridine calcium channel blockers?
- SNS activation so tachycardia and palpitations
- flushing ,sweating
- throbbing headache
- oedema
- gingival hyperplasia (rare)
What are the properties of phenylalkylamine calcium channel blockers?
Class 4 anti-arrhythmics so suppresses myocardial activity so dont use in heart failure.
Prolongs the cardiac AP, causes peripheral vasodilation.
