Drugs Used In Hypertension Flashcards
What is the single biggest cause of death worldwide?
Hypertension
What is the first line treatment for hypertension in patients below the age of 55? 2
- Angiotensin converting enzyme (ACE) inhibitors
2. Angiotensin receptor blockers (ARBs)
Where is renin produced?
Juxtaglomerular cells
What does renin do?
Renin convert angiotensinogen into angiotensin I
Where is ACE found?
On the surface of the epithelial cells in the capillaries
What ACE do?
Converts angiotensin I into angiotensin II
Describe the functions of angiotensin II 5
- Causes vasoconstriction in blood vessels; increases resistance
- Stimulates the pituitary gland to release ADH (increasing water reabsorption); increased SV
- Stimulates the adrenal gland to release aldosterone (increasing Na reabsorption; increased SV
- Increases Na/H2O reabsorption in the kidneys; increased stroke volumes
- Increased resistance and increased SV increases BP
Why don’t we use ACE inhibitors and ARBs in patients over the age of 55?
Over the age of 55 the renin-angiotensin system isn’t as functional. We therefore use calcium channel blockers.
Describe the MOA of thiazide and other diuretics? 4
Diuretics cause a decrease in 1. Blood volume 2. Venous return 3. Cardiac output Which leads to a decrease in blood pressure
Explain a possible theory for diuretics causing vasodilation 3
- Diuretics result in the reduction in smooth muscle Na
- This may result in a secondary reduction of intracellular Ca
- Muscle may therefore be less responsive to vasoconstriction
What are the side effects of diuretics? 3
Diuretics may result in :
- Hypokalaemia
- Diabetes mellitus
- Gout
Who is thiazide diuretics useful in?
Thiazide diuretics is particularly useful in older patients (>55 )
Give two examples of thiazide like diuretics 2
- Hydrochlorothiazide
2. Indapamide
Give an example of a potassium sparing diuretic
Amiloride
Explain the effects of β adrenoceptor antagonist 2
- β blockers initially reduce BP by decreasing CO.
- It is also suggested that β blockers, antagonize β1 receptors in the juxtaglomerular cells, inhibiting the release of renin
What are the disadvantages of β blockers?7
- Cold hands
- Fatigue
- Provocation of asthma
- Heart failure
- Conductance block
- Raise serum triglyceride levels
- Decrease high density lipoprotein levels
How can some of the side effects of β blockers be prevented?
We can use cardio-selective hydrophillic drugs (drugs without liver metabolism or brain penetration) such as atenolol.
How does the body increase BP? 3
- Stimulation of β1 receptors increases CO
- Stimulation of α1 receptors causes vasoconstriction in smooth muscle of blood vessels increasing resistance
- Increased renin -> increased angiotensin II -> increased aldosterone
How do α1 blockers reduce BP?3
- α1 receptors cause vasoconstriction in vascular smooth muscle
- Inhibition results in vasodilation
- Decreased SVR -> decreased BP
Give 2 examples of α1 blockers
- Doxazosin
2. Prazosin
Hoe do selective β blockers decrease BP?
- β1 receptors in the heart stimulate an increase in heart rate and increase strength of contraction
- β1 antagonists would result in decreased CO
- Decreased CO -> BP
Give 2 examples of selective β blockers
- Atenolol
2. Bisoprolol
Describe how non selective β blockers decrease BP 2
- Antagonize both β and α receptors
2. Therefore, decrease CO (β) and SVR (kidneys β1; VSM α1)
Name a non-selective β adrenoceptor antagonist
Propanolol
Name a non selective α & β blocker
Carvedilol
Name an α2 adrenoceptor agonist
Methyldopa
What is the MOA of methyldopa? 4
- Methyldopa is converted into methyl epinephrine
- Methylepinephrine stimulates α2 receptors in the medulla
- Result in decreased sympathetic outflow decreased SVR
- Decreased CO and SVR decreases BP
What are the 2 classes of calcium channel blockers?
- Dihydropyridines
2. Non-dihydropyridines
What do dihydropyridine calcium channel blocks inhibit?
L type calcium channels
Discuss how dihydropyridines work 4
- L type caclium channels allow calcium to enter the cell
- When calcium enters the cell, muscle contracts causing vasoconstriction-> increasedSVR
- Dihydropyridines selectively block calcium channels on VSM
- Blocking the channel results in vasodilation-> decreasing BP
Name 2 dihydropyridines
- Amlodipine
2. Nifedipine
What are the side effects of dihydropyridines? 5
All side effects are related to systemic vasodilation and include:
- Dizziness
- Headaches
- Flushing
- Peripheral oedema
- Swelling of gums (gingival hyperplasia)
How do non-dihydropyridines work 5
- No dihydropyridines are non-selective calcium channel blockers
- Block calcium channels in VSM and cardiac cells
- Decreased AV node and SA node
- Decreased contractility, HR and conduction
- Anti-arrhythmic properties
List 2 non-dihydropyridines
- Dilitiazem
2. Verapamil
What are the side effects of non-dihydropyridines
- Excessive bradycardia
- Cardiac conduction abnormalities
- Verapimil can inhibit the calcium channels in the gut leading to constipation
Describe the 3 classes of diuretics
- Loop diuretics
- Thiazide diuretics
- Potassium sparing diuretics
Explain loop diuretics
- Reduces the reabsorption of sodium chloride in the kidneys
- Increased diuresis
- Decreased volume is the vascular system results in decreased volume returning to the heart
- Decreased BP -> decreased CO
Give an example of a loop diuretic
Furosemide
Explain how thiazide diuretics work 3
- Reduce sodium reabsorption in the kidneys to a lesser extent than loop diuretics. Decreased sodium reabsorption-> increased diuresis -> decreased CO. Short term effect
- Long term effects are thought to be produced by thiazide induced vasodilation
Give an example of thiazide diuretics 1
Hydrochlorothiazide
Explain how potassium sparing diuretics work
- Interrupts the actions of aldosterone (Na reabsorption and K excretion)
- Used in conjunction with loop or thiazide diuretics
What do ACE inhibitors do? 3
- Angiotensin converting enzyme converts angiotensin I into its active form angiotensin II
- Inhibition of ACE results in decreased angiotensin II
- ACE inhibitors up-regulate bradykinin -> vasodilation
Name 2 ACE inibitors
- Captopril
2. Ramipril
How do angiotensin receptors blockers function? 2
- Angiotensin II binds to angiotensin type I receptors (AT1) which results in vasoconstriction and activation of aldosterone release
- ARBs antagonistically bind to AT1 resulting in vasodilation and inhibition of aldosterone release
List 2 ARBs
- Losartan
2. Valsartan
List side effects of ACE inhibitors and ARBs
- Inhibition of aldosterone-> hyperkalaemia
- Dry couch
- Angiooedema (increased levels of bradykinin and substance P)
