Lecture 5: Pharmacology of the Medicines used in treating hypertnsion Flashcards
What is the goal of treating hypertension?
To achieve and maintain systolic blood pressure below 140 mmHg and diastolic blood pressure 90 mmHg
What is the first line of treatment for hypertension?
Lifestyle modifications
What are the lifestyle modifications required for the treatment of hypertension?
- Weight reduction
- Regular physical exercise
- DASH eating plan (lots of fruit and veg, little meat)
- Reduction of dietry sodium intake
- Moderation of alcohol intake
What are the pharmacological treatments for hypertension?
- Diuretics
- Sympatholytics
- Calcium channel blockers
- Direct acting vasodilators
How do diuretics work?
Indirectly prevent the reabsorption of water in the kidneys, most of them by preventing the reabsorption of sodium
What do ACE inhibitors lead to?
- less angiotensin II
- more bradykinin
What is first line treatment for hypertension?
ACE inhibitor
Where do diuretics have their effect?
Collecting duct
What are the different classes of diuretics?
- Loop diuretics
- Thiazides
- Potassium sparing diuretics
Name loop diuretics
Furosemide supplemented with spironolactone or amiloride
Where is the sight of action of furosemide?
Proximal convolated tubule
Where is the sight of action of thiazides?
Early distal convoluted tubule
Where is the sight of action of potassium sparing?
Tubule and collecting duct - distal nephron
What is the mechanism of action of diuretics?
Loop diuretics act principally by inhibiting the Na/K/2Cl co-transporter
What is a major problem with loop diurectics?
Hypokalaemia
What are the most commonly used diurects?
Thiazide
How do thiazide diuretics work?
Inhibit the sodium-chloride transporter in the distal tubule
What drugs act on RAAS?
Angiotensin converting enzyme:
- Captotril
- Enalapril
- Lisinopril
- Other ACE inhibitors
Angiotensin II receptors
- Losartan
- Valsartan
- Other ARBs
What inhibits renin production?
- B1 antagonists
- Aliskiren - not recommended for use
What do ACE inhibitors have thier effect on?
Lung
Give examples of ACE inhibitors (3)
- Catopril
- Lisinopril
- Enalapril
What does a decrease in angiotensin II result in?
- Vasodilation
- Decreased blood volume
- Decreased cardiac and vascular remodelling
- Potassium retention
- Fetal injury
What does an increase in bradykinin result in?
- Vasodilation
- Cough
- Angioedema (rare)
How do ACE inhibitors work?
Block the action of the ACE, to prevent the conversion of angiotensin I to angiotensin II
- Reduces peripheral vascular resistance (afterload), so lowers blood pressure
- Dilates the efferent glomerular arteriole, which reduces intra-glomerular pressure
- Reduces aldosterone levels which promotes sodium and water excretion, helps reduce preload
Name some angiotensin II receptor blockers (3)
- Losartan
- Valsartan
- Candesartan
How do ARBs work?
Block the action of angiotensin II on the angiotensin I receptor
Name aldosterone antagonist (3)
- Spironolactone
- Eplerenone
- Potassium sparing diuretics
How do aldosterone antagonists work?
- Competitively bind to aldosterone receptor
- Promote Na and H20 excretion in the collecting tubule and duct
What are the sympatholytics (Antiadrenergics)? (5)
- Beta blockers
- Alpha 1 blockers
- Centrally acting alpha 2 antagonists
- Adrenergic neuron blockers
- Ganglionic blockers
What are the actions of beta-adrenergic blockers in hypertension?
- Blockage of cardiac beta-1-receptors cause a decrease in heart rate and contractility, so a decrease in CO
- Improve efficiency
- Suppress reflex tachycardio caused by vasodilators
- Blockage of beta 1 receptors in JG in kidneys, decrease in renin release, decrease in RAAS mediated vasoconstriction ( angiotensin II) and volume expansion (aldosterone)
What does long term use of beta-adrenergic blockers cause?
A decrease in peripheral vascular resistance
What are non selective beta adrenergic blockers?
When the beta adrenergic blocker blocks both beta 1 and beta 2 receptors
What are cardioselective beta adrenergic blockers?
Beta adrenergic blockers that have greater affinity for beta 1 than beta 2
What do partial agnosists have?
Intrinsic sympathomimetic activity
Name calcium channel blockers - Dihydropyradines? (2)
- Nifedipine
- Amlodipine
How do calcium channel blockers work?
- Block calcium channels in arterioles
- Dilation of peripheral vessels, leading to a decreased blood pressure
- Dilation of coronary arteries, increase in coronary perfusion
Do calcium channel blockers block cardiac Ca channels at therapeutic doses?
No
How do nifedipine and amlodipine increase heart rate and contractility?
- Lowering blood pressure acts on the baroreceptor reflex, this stimulates the medulla to increase the firing of SNS to beta receptors in the heart
- Nifedipine lacks direct cardiosuppressant actions, cardiac suppression is unopposed, so an increase in heart rate and an increase in contractility.
Name non dihydropyradines calcium channel blockers
- Verapamil
- Diltiazem
How do non dihydropradine CCBs work?
Act on the heart to slow conduction and decrease contractility
Where do diuretics have their effect?
Collecting duct
What is first line treatment for hypertension?
ACE inhibitor
