Drug treatments for cardiovascular disease 1 & 2

Question 1

What is the definition of hypertension?

Answer 1

Persistently higher than normal blood pressure

Question 2

What is normal BP and what BP is treated?

Answer 2

Normal - 120/80

Treatment if mean BP>150/95mmHg

Question 3

What is the equation for blood pressure?

Answer 3

BP = CO x TPR

Total Peripheral Resistance a measure of the degree of constriction of the arterioles

Question 4

What is the equation for cardiac output?

Answer 4

Cardiac Output = Stroke Volume x Heart Rate

Stroke Volume regulated by Ventricles

Heart Rate by the SA-node

Question 5

Complete the diagram on sympathetic control of blood pressure

Answer 5

Question 6

Which nervous system controls extrinsic regulation?

Answer 6

Autonomic nervous system

Question 7

Does the sympathetic / parasympathetic nervous system increase / decrease heart rate?

Answer 7

Question 8

How does the sympathetic nervous sytem increase heart rate?

Answer 8

Sympathetic system increases frequency and force of contraction via

β1 receptors -> increase cAMP -> increase Ca2+ -> increase rate and force of contraction.

Question 9

How does parasympathetic nervous system decrease heart rate?

Answer 9

Parasympathetic system decreases frequency by decreasing cAMP via M2 receptors.

Question 10

Complete the diagram of the blood vessel

Answer 10

Question 11

Draw the renin-angiotensin-aldosterone system

Answer 11

Question 12

Complete the diagram on regulation of blood pressure by the renin-angiotensin-aldosterone system

Answer 12

Question 13

How does the RAAS system cause vasoconstriction?

Answer 13

Increases in Ang II -> increase IP3 -> increase intracellular [Ca2+]

Causes constriction of arterioles and an increase in total peripheral resistance and an increase in BP

Question 14

How does RAAS increase preload?

Answer 14

Constriction of venules via AT1-R

RAAS also facilitates Na+ and H2O retention

Question 15

What 3 things is the choice of anti-hypertensive drug reliant on?

Answer 15

a) Age (<55 years old ACE inhibitor/angiotensin receptor blocker (ARB); >55 years old or all Black African/Americans calcium channel blocker)
b) Race (ACE inhibitors/beta blockers may be less efficacious in black African/Amercians).
c) Co-existing diseases

Question 16

What are the 5 classes of hypertensives?

Answer 16

ACE inhibitors and Angiotensin receptor blockers.

Calcium channel antagonists

Diuretics

Beta Blockers

Vasodilators

Question 17

Draw the 4 steps in the national guidelines for anti-hypertenive drugs

Answer 17

Question 18

How do ACE inhibitors cause a dry cough?

Answer 18

Increase in bradykinin

Question 19

Which anti-hypertensive agents cause a dry cough as a side-effect?

Answer 19

ACE inhibitors

Question 20

What are the side-effects of ACE inhibitors?

Answer 20

Dry cough

First dose hypotension

Renal impairment

May cause hypokalaemia

Question 21

What 2 anti-hypertensives work via the renin-angiotensin-aldosterone system?

Answer 21

ACE inhibitors

ARB (angiotensin receptor blockers)

Question 22

ACE inhibitors are contraindicated in what condition?

Answer 22

Bilateral renal artery stenosis

Question 23

What tests are measured bedore ACE inhibitors are presribed?

Answer 23

Renal function

Creatinine levels in blood

Question 24

Which anti-hypertensive drug is the first line treatment for diabetics and why?

Answer 24

ACE inhibitors

No adverse effects on serum glucose or lipids

Question 25

What suffix do all ACE inhibitor drugs have and name an example

Answer 25

\_\_\_\_\_pril •Egs. RamiPRIL

Question 26

How do ARB work?

Answer 26

Block the actions of Ang II on AT1-R

Question 27

What does ARB stand for?

Answer 27

Angiotensin receptor blocker

Question 28

What is the suffix for ARBs and name an example

Answer 28

\_\_\_\_\_artan •E.g. Losartan

Question 29

What are the side effects for ARBs?

Answer 29

Minimal

Question 30

What is spironolactone?

Answer 30

Aldosterone antagonist.

Question 31

When is spironolactone used?

Answer 31

Can be used as an add on for resistant hypertension but FRONTLINE for hypertension in patients with primary aldosteronism (excess production of aldosterone from adrenal glands)

Question 32

What is the main type of calcium channel blockers?

Answer 32

Dihydropyridines

Question 33

What is the suffix for calcium channel blockers and name an example

Answer 33

\_\_\_\_\_\_\_dipine Amlodipine

Question 34

How do calcium channel blockers reduce hypertension?

Answer 34

* Target L-type Ca2+ channels on smooth muscle of arterioles. * Phenylalkylamines (e.g. verapamil) and benzothiazepines (e.g. diltiazem) target L-type channels in the heart and decrease the frequency and force of contraction, less used to treat hypertension.

Question 35

How do calcium channel blockers decrease smooth muscle contraction in arterioles?

Answer 35

1. Block L-type channels 2. Reduce intracellular Ca2+ 3. Reduce activation of myosin light chain kinase (MLCK) 4. Reduce phosphorylation of myosin light chain 5. Muscles relax more

Question 36

What does this diagram show? Which anti-hypertensive targets this?

Answer 36

Regulation of smooth muscle contraction in arterioles Calcium channel blockers

Question 37

What are the side-effects of calcium channel blockers?

Answer 37

Peripheral oedema Flushing and headaches

Question 38

How do calcium channel blockers cause peripheral oedema?

Answer 38

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 39

What happens when this goes wrong? What anti-hypertensive causes this to go wrong as a side effect?

Answer 39

Peripheral oedema Calcium channel blockers

Question 40

Combination of which class of anti-hypertensives is not recommened?

Answer 40

Calcium channel antagonists

Question 41

What are calcium channel blockers also known as?

Answer 41

Calcium channel antagonists

Question 42

What affect does grapefruit juice have on calcium channel blockers?

Answer 42

Enhances action (CYP3A4)

Question 43

How do thiazide and thiazide-like diuretics decrease hypertension?

Answer 43

Some diuretic action but also acts via activation of KATP in smooth muscle of blood vessel to dilate arterioles and decrease BP

Question 44

How does indapamide work?

Answer 44

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

Question 45

What are the side-effects of thiazide and thiazide-like diuretics?

Answer 45

* Hypokalaemia * Increase in urate * Increase in glucose * Increase in blood lipids

Question 46

What is the suffix for thiazide diuretics and name an example

Answer 46

•E.g. bendroflumethiazide

Question 47

Name a thiazide-like diuretic

Answer 47

Indapamide

Question 48

How does indapamide cause relaxation of artereoles?

Answer 48

* Diuretic causes more K+ to leave cell - cell more negative * Inhibits Ca2+ channel which normally opens up when cell depolarises * Less intracellular Ca2+ * Smooth muscle cell relaxes

Question 49

Thiazide-like diuretics are contraindicated in which patients and why?

Answer 49

Diabetics * Less Ca2+ in cell * Less insulin * Increase in blood glucose levels

Question 50

What do beta blockers do?

Answer 50

Block B1 receptors B1 receptors increase frequency and force of contraction.

Question 51

What are the side effects of beta blockers?

Answer 51

Fatigue Vasocontriction Bronchoconstriction Hypoglycaemia

Question 52

What effects do beta blockers have on the SA node?

Answer 52

Decrease heart rate Decrease O2 demand

Question 53

What effects do beta blockers have on vetricular myocardium?

Answer 53

Decrease contractility Decrease O2 demand

Question 54

What effects do beta blockers have on arterioles?

Answer 54

Decrease in blood pressure (decreased afterload) Decrease in myocardial 02 demand

Question 55

How do beta blockers cause fatigue?

Answer 55

* Excerisise increases O2 demand * Patients on beta blockers can't beat harder or faster - tissues lacking nutrients and O2

Question 56

How does adrenaline cause vaso/bronchodilation?

Answer 56

* Stimulates B2 receptors on smooth muscle cell in the airways or peripheral arterioles perfusing skeletal muscle * Increase in cAMP * Increae in protein kinase A * PKA phosphorylises myosin light chain kinase * MLCK cannot phosphorylate mysoin light chain * Smooth muscle relaxation

Question 57

How do beta blockers cause vasoconstricton and bronchoconstriction?

Answer 57

Beta blockers are selective for B1 receptors but can also block B2 receptors Adrenaline cannot cause vaso/bronchodilation on smooth muscle cell in the airways or peripheral arterioles perfusing skeletal muscle

Question 58

How can beta blockers cause hypoglycaemia?

Answer 58

* Low blood glucose activates the release of adrenaline, mobilises glucose release from liver. * Leads to tremor, palpitations and sweats * Action of adrenaline is blocked by Beta Blockers

Question 59

Which anti-hypertensives are contraindicated in diabetes?

Answer 59

Combinations of beta blockers and thiazides

Question 60

What is the suffix for beta blockers?

Answer 60

\_\_\_\_\_olol

Question 61

What are the 2 types of beta blockers and name an example for each

Answer 61

Non-selective (b1 and b2) e.g. propranolol Selective b1 antagonist e.g. bisoprolol

Question 62

How do vasodilatators work?

Answer 62

a1-antagonists Noradrenaline -\> a1 -\> IP3 -\> Ca2+ -\> constriction

Question 63

What is a powerful vasoconstricter found in the body?

Answer 63

Noradrenaline

Question 64

What are vasodilatators used for?

Answer 64

Used to treat hypertension in patients with benign prostatic hypertrophy (Doxazosin)

Question 65

What is the suffix for vasodilatators and name an example

Answer 65

\_\_\_\_\_\_azosin Doxazosin

Question 66

What is minoxidil?

Answer 66

Other vasodilators such as minoxidil open K+ channels