Theme 3: Lecture 11 - Drug treatments for CVD 2

Question 1

What are the 5 classes of anti-hypertensive drugs

Answer 1

• ACE inhibitors and Angiotensin receptor blockers.
• Calcium channel antagonists
• Diuretics
• Beta Blockers
• Vasodilators

Question 2

What is first line anti-hypertensive treatment to someone under 55

Answer 2

ACE inhibitors or angiotensin receptor blockers

Question 3

What is first line anti-hypertensive treatment to someone over 55 or a black person of African or Caribbean family origin of any age

Answer 3

Calcium channel blocker

Question 4

What is second line anti-hypertensive treatment

Answer 4

ACE inhibitors and Calcium channel blockers

Question 5

What is third line anti-hypertensive treatment

Answer 5

ACE inhibitors and calcium channel blockers and Thiazide like diuretics

Question 6

What is fourth line anti-hypertensive treatment

Answer 6

ACE inhibitor and calcium channel blockers and thiazide like diuretics and consider further diuretics or alpha blocker or beta blocker

Question 7

What are the side affects of ACE inhibitors

Answer 7

• 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

Question 8

Why can ACE inhibitors cause a dry cough

Answer 8

• 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

Question 9

Why do ACE inhibitors cause first dose hypotension

Answer 9

• 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

Question 10

What is hyperkalaemia

Answer 10

high blood K+ levels

Question 11

Give an example of an ACE inhibitor

Answer 11

Ramipril

Question 12

What is the suffix to all ACE inhibitors

Answer 12

-pril

Question 13

How do ACE inhibitors cause renal impairment

Answer 13

• 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

Question 14

Give an example of an angiotensin receptor blocker (ARB)

Answer 14

Losartan

Question 15

How do Angiotensin receptor blockers work (ARB)

Answer 15

Block the actions of angiotensin II on AT1 receptors

Question 16

What are the side affects of ARBs

Answer 16

minimal side effects

Question 17

Give an example of an aldosterone antagonist

Answer 17

Spironolactone

Question 18

How are aldosterone antagonists used

Answer 18

As an add on for resistant hypertension

Question 19

When do aldosterone antagonists become frontline treatment

Answer 19

For hypertension in patients with primary aldosteronism

Question 20

What is primary aldosteronism

Answer 20

a hormonal disorder that leads to high blood pressure. It occurs when your adrenal glands produce too much aldosterone

Question 21

What are the 3 main classes of Ca2+ channel blockers

Answer 21

• Dihydropyridines
• Phenylalkylamines
• Benzothiazepines

Question 22

What do dihydropyridine Ca2+ channel blockers target

Answer 22

L-type calcium channels on smooth muscle arterioles

Question 23

Which is the main type of Ca2+ channel blocker used to treat hypertension

Answer 23

dihydropyridines

Question 24

What do phenylalkylamines Ca2+ channel blockers do

Answer 24

Target L-type Ca2+ channels in the heart and decrease the frequency and force of contraction

Question 25

What do benzothiazepine Ca2+ channel blockers do

Answer 25

Target L-type Ca2+ channels in the heart and decrease the frequency and force of contraction

Question 26

Name a dihydropyridine calcium channel blocker

Answer 26

Amlodipine

Question 27

Name a phenylalkylamine calcium channel blocker

Answer 27

Verapamil

Question 28

Name a benzothiazepine calcium channel blocker

Answer 28

Diltiazem

Question 29

Describe the regulation of smooth muscle contraction in arterioles

Answer 29

- 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

Question 30

Side affects of calcium channel blockers

Answer 30

- Peripheral oedema | - Flushing and headaches

Question 31

Contraindications of calcium channel blockers

Answer 31

- Combinations of Ca2+ channel antagonists not recommended | - Grapefruit juice inhibits action (CYP3A4) - calcium channel blockers are broken down by this cytochrome P450 enzyme

Question 32

Why do you get peripheral oedema when taking calcium channel blockers

Answer 32

- 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.

Question 33

How do thiazide and thiazide like diuretics work

Answer 33

- 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

Question 34

How does Indapamide work

Answer 34

hyperpolarises smooth muscle cells causing a relaxation/dilation of the arteriole and a decrease in total peripheral resistance

Question 35

Name two thiazide or thiazide like diuretics

Answer 35

- Indapamide | - Bendroflumethiazide

Question 36

Side effects of thiazide and thiazide like diuretics

Answer 36

- Hypokalaemia - Increase in urate - Increase in glucose - Increase in blood lipids

Question 37

Contraindications of thiazide like diuretics

Answer 37

diabetes

Question 38

Why is diabetes a contraindication of thiazide like diuretics

Answer 38

- 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

Question 39

Side effects of beta blockers

Answer 39

- Fatigue - Vasoconstriction - Bronchoconstriction

Question 40

What do beta blockers do

Answer 40

Lower the heart rate and contractility

Question 41

Why do patients on beta blockers feel fatigued

Answer 41

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

Question 42

Why are beta blockers contraindicated in diabetics

Answer 42

- 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

Question 43

What are the types of beta blocker

Answer 43

- Non selective (beta 1 and beta 2) | - Selective beta 1 antagonist

Question 44

Name a non selective beta blocker

Answer 44

propranolol

Question 45

Name a selective beta 1 antagonist

Answer 45

bisoprolol

Question 46

What are vasodilators (which receptor do they bind to)

Answer 46

alpha 1 antagonists

Question 47

Name a vasodilator

Answer 47

Doxazosin

Question 48

What are vasodilators used to treat

Answer 48

Used to treat hypertension in patients with benign prostatic hypertrophy

Question 49

Name a vasodilator that will open K+ channels

Answer 49

Minoxidil