Theme 3: Lecture 11 - Drug treatments for CVD 2 Flashcards
What are the 5 classes of anti-hypertensive drugs
- ACE inhibitors and Angiotensin receptor blockers.
- Calcium channel antagonists
- Diuretics
- Beta Blockers
- Vasodilators
What is first line anti-hypertensive treatment to someone under 55
ACE inhibitors or angiotensin receptor blockers
What is first line anti-hypertensive treatment to someone over 55 or a black person of African or Caribbean family origin of any age
Calcium channel blocker
What is second line anti-hypertensive treatment
ACE inhibitors and Calcium channel blockers
What is third line anti-hypertensive treatment
ACE inhibitors and calcium channel blockers and Thiazide like diuretics
What is fourth line anti-hypertensive treatment
ACE inhibitor and calcium channel blockers and thiazide like diuretics and consider further diuretics or alpha blocker or beta blocker
What are the side affects of ACE inhibitors
- Dry cough (number 1 reason why these drugs aren’t tolerated)
- 1st dose hypotension
- Renal impairment (therefore contraindicated in bilateral renal artery stenosis)
- May cause hyperkalaemia
- No effect on serum glucose or lipids
Why can ACE inhibitors cause a dry cough
- ACE inhibitors also inhibit the breakdown of Substance P and Bradykinin into inactive peptides
- Substance P and Bradykinin are irritants that cause respiratory tract sensitivity leading to this dry cough
Why do ACE inhibitors cause first dose hypotension
- Angiotensin is meant to keep BP high, if we suddenly reduce the amount of it, BP is going to plummet quite dramatically
- Over time body will adapt to ACE inhibitors and hypotension stops becoming a problem
What is hyperkalaemia
high blood K+ levels
Give an example of an ACE inhibitor
Ramipril
What is the suffix to all ACE inhibitors
-pril
How do ACE inhibitors cause renal impairment
- Normally if blood flow is reduced going into Bowman’s capsule, this is sensed by the kidneys
- Renin is produced which eventually produces angiotensin II
- This acts on AT1 receptors present in the blood vessel leaving Bowman’s capsule causing it to constrict
- The pressure in the glomerulus will build up improving filtration
- This doesn’t happen if the patient is on ACE inhibitors
Give an example of an angiotensin receptor blocker (ARB)
Losartan
How do Angiotensin receptor blockers work (ARB)
Block the actions of angiotensin II on AT1 receptors
What are the side affects of ARBs
minimal side effects
Give an example of an aldosterone antagonist
Spironolactone
How are aldosterone antagonists used
As an add on for resistant hypertension
When do aldosterone antagonists become frontline treatment
For hypertension in patients with primary aldosteronism
What is primary aldosteronism
a hormonal disorder that leads to high blood pressure. It occurs when your adrenal glands produce too much aldosterone
What are the 3 main classes of Ca2+ channel blockers
- Dihydropyridines
- Phenylalkylamines
- Benzothiazepines
What do dihydropyridine Ca2+ channel blockers target
L-type calcium channels on smooth muscle arterioles
Which is the main type of Ca2+ channel blocker used to treat hypertension
dihydropyridines
What do phenylalkylamines Ca2+ channel blockers do
Target L-type Ca2+ channels in the heart and decrease the frequency and force of contraction
What do benzothiazepine Ca2+ channel blockers do
Target L-type Ca2+ channels in the heart and decrease the frequency and force of contraction
Name a dihydropyridine calcium channel blocker
Amlodipine
Name a phenylalkylamine calcium channel blocker
Verapamil
Name a benzothiazepine calcium channel blocker
Diltiazem
Describe the regulation of smooth muscle contraction in arterioles
- Calcium enters the cell and combines with the protein calmodulin
- Calcium and calmodulin will stimulate MLCK
- MLCK is inhibited by cAMP
- MLCK uses ATP to phosphorylate the myosin light chain of a protein, this allows actin and myosin to interact and muscle to contract
- Phosphatase dephosphorylates the myosin light chain
Side affects of calcium channel blockers
- Peripheral oedema
- Flushing and headaches
Contraindications of calcium channel blockers
- Combinations of Ca2+ channel antagonists not recommended
- Grapefruit juice inhibits action (CYP3A4) - calcium channel blockers are broken down by this cytochrome P450 enzyme
Why do you get peripheral oedema when taking calcium channel blockers
- Pre capillary sphincters have L type calcium channels on them
- Preferential dilation of precapillary arteriole and impairment of the function of the pre-capillary sphincter increases hydrostatic pressure across the capillary and reducing fluid reabsorption.
How do thiazide and thiazide like diuretics work
- Some diuretic action. Work on the distal convoluted tubule to block the Na+,Cl- cotransporter
- also acts via activation of ATP K+ channel in smooth muscle of blood vessel to dilate arterioles and decrease BP
How does Indapamide work
hyperpolarises smooth muscle cells causing a relaxation/dilation of the arteriole and a decrease in total peripheral resistance
Name two thiazide or thiazide like diuretics
- Indapamide
- Bendroflumethiazide
Side effects of thiazide and thiazide like diuretics
- Hypokalaemia
- Increase in urate
- Increase in glucose
- Increase in blood lipids
Contraindications of thiazide like diuretics
diabetes
Why is diabetes a contraindication of thiazide like diuretics
- After a meal, glucose levels are elevated and will enter beta cells of the pancreas
- They become metabolised, generate ATP and ADP, which would close the ATP K+ channel
- This acts to depolarise the cell which leads to Ca2+ being able to enter the cell through voltage dependant calcium channels (VDCC)
- The Ca2+ causes release of insulin into the bloodstream
- Thiazide like diuretics will open the ATP K+ channel which inhibits Ca2+ coming into the cell so insulin isn’t released leading to a rise in blood glucose
Side effects of beta blockers
- Fatigue
- Vasoconstriction
- Bronchoconstriction
What do beta blockers do
Lower the heart rate and contractility
Why do patients on beta blockers feel fatigued
Patient’s can’t get the oxygen and nutrients that they need when exerting themselves because the heart rate and contractility won’t increase as the receptors are blocked
Why are beta blockers contraindicated in diabetics
- Low blood glucose activates the release of adrenaline, mobilises glucose release from liver.
- Leads to tremor, palpitations and sweats
- Blocked by Beta Blockers i.e the symptoms are removed so patients won’t know that their blood sugar is low
What are the types of beta blocker
- Non selective (beta 1 and beta 2)
- Selective beta 1 antagonist
Name a non selective beta blocker
propranolol
Name a selective beta 1 antagonist
bisoprolol
What are vasodilators (which receptor do they bind to)
alpha 1 antagonists
Name a vasodilator
Doxazosin
What are vasodilators used to treat
Used to treat hypertension in patients with benign prostatic hypertrophy
Name a vasodilator that will open K+ channels
Minoxidil
