Pharma 9Antihypertension Flashcards
Thiazide/Thiazide Like Diuretics (Bendroflumethiazide)
- Reduce distal tubular sodium reabsorption inhibit cl/Na symport
- Sustained action
- Blood pressure reduction – complex
- Several mechanisms
- Initial blood volume decrease
- Later - total peripheral resistance falls
• 💋💋💋Dose-blood pressure response curve flat
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يقل الظغط
Bendro-flu-methiazide: Adverse Effects
And of the thiazides
- Hypokalaemia
- Increased urea and uric acid levels may cause goat
- Impaired glucose tolerance (especially with beta-blockers)
- Cholesterol and triglyceride levels increased
- Actives renin angiotensin system
1 st
Line Pharmacological Therapy of HT
§ Angiotensin Converting Enzyme (ACE)
inhibitors/ Angiotensin Receptor Blockers (ARB)
§ Calcium channel blockers
§ Diuretics
And commonly ACEI and Ca blocker
ACE Inhibitors
- E.g. lisinopril, ramipril
- Inhibit Angiotensin Converting Enzyme activity
- Prevents generation of Angiotensin II
- Potentiates the action of bradykinin
- Main side effect – dry cough (10-15%)
- Important side effects
- Angio-oedema (rare, but more common in black pop.)
- Renal failure (incl. renal artery stenosis)
- Hyperkalaemia
Angiotensin Receptor Blockers
- Eg. Losartan, Valsartan
- Bind to angiotensin AT 1 receptor
💋💋• Inhbit vasoconstriction and aldosterone stimulation caused by angiotensin II
- Well tolerated few side effects
- 🤮🤮Important side effects
- Renal failure
- Hyperkalaemia
Dihydropyridine Calcium Channel Blockers
Properties:
- Good oral absorption
- 👋👋Protein bound > 90%
- Metabolised by the liver
- Few have active metabolite
🤮🤮Adverse effects:
- Sympathetic nervous system activation – tachycardia and palpitations
- Flushing, sweating, throbbing headache
- Oedema
- Gingival hyperplasia (rare)
Phenylalkylamines - Verapamil
Properties:
👾👾• Impedes calcium transport across the myocardial and vascular smooth muscle cell membrane
- Class IV anti-arrhythmic agent/prolongs the action potential/effective refractory period
- 👾👾Peripheral vasodilatation and a reduction in cardiac preload and myocardial contractility
🤮🤮🤮Adverse effects:
- Constipation
- Risk of bradycardia
- Reduce myocardial contractility (negative inotrope) can worsen heart failure
Benzothiazepines - Diltiazem
Properties:
- 👾👾Impedes calcium transport across the myocardial and vascular smooth muscle cell membrane
- 👾👾Prolongs the action potential/effective refractory period
- 👾👾Peripheral vasodilatation and a reduction in cardiac preload and myocardial contractility
🤮🤮Adverse effects:
- Risk of bradycardia
- Less negative inotropic effect than verapamil – can worsen heart failure
Alpha Blockers (Doxazosin)
Properties:
- Selective antagonism at post-synaptic a-1 adrenoceptors and antagonise the contractile effects of noradrenaline on vascular smooth muscle
- 👾👾Reduce peripheral vascular resistance
- 👾👾More effect in upright position
- 👾👾Benign effect on plasma lipids / glucose
- 👋👋Safe in renal disease
🤮🤮Adverse effects:
- Postural hypotension
- Dizziness
- Headache and fatigue
- Oedema (especially if combined with dihydropyridines)
Beta Blockers
- E.g. Atenolol, bisoprolol, nebivolol
- Developed for angina but found to lower blood pressure
- Reduce heart rate and cardiac output
- Inhibit renin release
- Initially TPR increases later falls to normal
b
-Blockers Adverse Effects
- Lethargy, impaired concentration
- Reduced exercise tolerance
- Bradycardia
- Cold hands – Raynaud’s
- Impaired glucose tolerance
- Contraindication - asthma
Ali-skiren (Direct Renin Inhibitor)
علي سكايرن
Aliskiren binds to a pocket in the renin molecule, blocking cleavage of angiotensinogen to angiotensin I
Aliskiren Pharmacokinetics
- Bioavailability ~2.6%
- t 1/2 ~ 40 hours (range 25-45) - supports once-daily dosing
- Steady state takes 5-8 days
- Main elimination route:
o Mainly eliminated as unchanged compound in faeces (78%) o Less than 1% is renal excreted o NOT metabolised via cytochrome P450 o Caution in patients at risk of hyperkalaemia, sodium and volume-depleted patients, patients with HF, severe renal impairment and renal stenosis
- No initial dosage adjustment required in elderly patients
- Contra-indicated in pregnancy
- 👋Only significant drug interaction: furosemide
Methydopa
converted to a-methyl-noradrenaline a potent a2-adrenoceptor agonist
Can by used in pregnancy 🤰🏻
Clonidine
direct pre-synaptic a2-adrenoceptor agonist
Central effect
