Cardio L26 Drug therapy 3

Question 1

Angina definition

Answer 1

A condition marked by severe chest pain, often also spreading to the shoulders, arms and neck, caused by an inadequate blood supply to the heart.

Question 2

Clinical definition of angina

Answer 2

Angina is chest pain or discomfort that occurs when an area of your heart muscle doesn’t get enough oxygen-rich blood.

Question 3

Angina pectoris

Answer 3

Pain localized to the chest that can be abrupt (acute) or persistent (chromic)

Question 4

Causes of angina pectoris

Answer 4

Decreasing o2 supply
Increase Cardiac work = o2 consumptions increased
→ Lack of supply and build up of metabolites leads to ischemic pain.

Question 5

Common Causes of Angina Pectoris

Answer 5

1. Restriction (usually incomplete) in blood supply to working heart muscle.

→ Partial occlusion of blood vessels
Atheroma
Thrombus
→Vasopasm in coronary arteries
Overly reactive vessels
Drugs e.g. cocaine, smoking
→ Severe anaemia

Question 6

Types pf angina pectoris

Answer 6

1. Chromic stable angina (exercise induced)
2. Unstable angina (sudden rupture of atherosclerotic plaque)
3. Prinzmetals (angina inversa)
   • Vasospasm due to oversensitivity to vasoconstrictors

Question 7

Atheroma process

Answer 7

→Damage to endothelium
→ Cholesterol accumulation
→ Monocyte invasion
→ Foam cell degeneration

Question 8

Foam cell degeneration

Answer 8

• Fibrous tissue, calcium salts
• Artery narrows
• Increasing stiffness at margin

Question 9

Monocyte invasion

Answer 9

• Convert to macrophages

* Convert to foam cells

Question 10

Cholesterol accumulation

Answer 10

• Oxidation

* Inflammatory response

Question 11

Damage to endothelium

Answer 11

• Exposes intima matrix above smooth muscle layer

Question 12

Prevent atherosclerosis

Answer 12

1. Statins
2. Fibrates
3. Bile acid binding resins

Question 13

Angina control

Answer 13

Nitrates
Beta-blockers
Ca2+ channel blockers
(Aspirin)

Question 14

Treatment – possibly after first

MI

Answer 14

1. Ranolazine, aspirin

2. Bypass surgery, stents, angioplasty, clot disrupting drugs (enzymes)

Question 15

Process of cholesterol formation

Answer 15

3-Hydroxy-3- methyl-glutaryl-CoA reductase is the rate-controlling enzyme of the mevalonate pathway, which produces cholesterol and other isoprenoids.

Question 16

Lovastin and Atorvastatin action

Answer 16

Inhibit 3-Hydroxy-3- methyl-glutaryl-CoA reductase leading to:

a. Decreased liver cholesterol synthesis
b. Increased VLDL and LDL receptor expression, and decreasing LDL in blood

Question 17

Side effects: HMG CoA reductase inhibitors:

Answer 17

a. Myalgias
b. Muscle cramps
c. Rhabdomyolysis (leading to kidney failure)
d. GI tract disturbances
e. Malabsorption of lipid soluble vitamins (A,D,E,K) and lipid soluble drug

Question 18

Fibrates: definition

Answer 18

Fibrates are amphiphatic carboxylic acids.

Question 19

Fibrates: Example drugs

Answer 19

Bezafibrate

Ciprofibrate

Question 20

Agonists of the peroxisome proliferator-activated receptor alpha (PPAR – alpha) receptor leads to:

Answer 20

1. Increased Beta-pxidation in the liver
2. Decreased hepatic triglyceride secretion
3. Increased lipoprotein lipase activity → increased VLDL clearance
4. Increased HDL

Question 21

Main use of fibrates

Answer 21

Hypercholesterolemia

Question 22

Side effects of fibrates

Answer 22

1. Mild stomach upset and myopathy (muscle pain with CPK elevations)
2. Increased risk for gallstones due to increased cholesterol in bile.
3. Increased risk of rhabdomyolysis – especially if added to statins.

Question 23

Bile acid recycling

Answer 23

Between intestine and liver

Question 24

What binds bile acid

Answer 24

Cholestipol and Cholestyramine in gut leading to increased loss.

Question 25

Cholestipol and Cholestyramine binding leads to:

Answer 25

1. Decreased enterohepatic recirculation of bile salts 2. Increased synthesis of new bile salts by the liver 3. Decreased liver cholesterol 4. Increased LDL receptor expression, and decreasing LDL in blood

Question 26

Side effects of bile acid binding agents

Answer 26

1. Increased in VDLD and triaylglycerides synthesis 2. GIT disturbances 3. Malabsorption of lipid soluble vitamins (A,D,E,K) and lipid soluble drugs

Question 27

Nitric oxide is

Answer 27

Endothelium-derived relaxing factor

Question 28

What increases NO production

Answer 28

Organic nitrates

Question 29

Function of nirtrates

Answer 29

``` Venous vasodilation/pre-load reduction Arterial dilation/ after-load reduction Coronary artery vasodilation Prevention of coronary vasoconstriction Enhancement of coronary collateral flow Antiplatelet and antithrombotic effects ```

Question 30

Nitrates action

Answer 30

All increase NO (EDRF)

Question 31

Types of nitrates

Answer 31

1. Nitroglycerin sI (fast acting) 2. Isosorbide mononitrate 3. Isosorbide dinitrate 4. Transdermal patches (long acting) 5. Alkyl Nitrates (Poppers)

Question 32

nitrates Side effects

Answer 32

``` Headaches Flushing Palpitations Tolerance Major interaction with drugs for impotence (Viagra etc.) leading to hypotensive crisis ```

Question 33

Nitrates are metabolites to

Answer 33

To increase NO

Question 34

NO is

Answer 34

EDRF

Question 35

NO stimulates

Answer 35

Guanylate cyclase

Question 36

Gaunylate cyclase synthesizes

Answer 36

cyclic guanosine monophosphate (cGMP)

Question 37

cGMP activates

Answer 37

cCGMP – dependent protein kinase

Question 38

cGMPdK activates

Answer 38

Myosin light chain phosphate (s) (MLCP)

Question 39

Myosin light chains in smooth muscle cells are

Answer 39

Dephosphorylated

Question 40

The contractile state of smooth muscle depends

Answer 40

On phosphorylation if the myosin light chains (calmodulin – dependent kinase phosphorylate)

Question 41

Beta-Blockers: Function

Answer 41

Reduce myocardial Oxygen demand

Question 42

Beta-Blockers: Used for

Answer 42

First line therapy in the treatment of chronic stable angina (esp, effort-induced angina)

Question 43

Beta-Blockers: Examples

Answer 43

1. Propanolol → non-selective Beta1, Beta2 (not in asthma) 2. Atenolol →metroprolo more Beta1 – selective 3. Carvedilol → also block alpha-receptors improving coronary perfusion

Question 44

Beta-Blockers: Side effects

Answer 44

``` Constipation, indigestion Hypotension Sleep disturbance, hallucinations (rare) Reduce aqueous humour secretion →glaucoma Skin reactions e.g. hives, psorias ```

Question 45

Calcium channel blockers: Calcium entry

Answer 45

Entry into SM depends on activity of voltage dependent Ca2+ channels (mainly L-type VDCC)

Question 46

Main classes of L-type VDCC antagonists are:

Answer 46

1. Dihyropyridines e.g. Nifedipine (all dipines) 2. Phenylakyllamines e.g. verapamil 3. Benzothiazepines e.g. Diltiazem (also non-selective VDCC blockers e.g. Fluspiriline)

Question 47

Side effects calcium channel blockers

Answer 47

1. Peripheral vasodilation: Dizziness, headache, erythema 2. Constipation 3. Heart rate changes 4. Gingival overgrowth

Question 48

calcium channel blockers Reason for use

Answer 48

To reduce myocardial oxygen demand and reverse coronary vasospasm.

Question 49

calcium channel blockers Don’t want

Answer 49

Reflex sympathetic activation due to peripheral effects.

Question 50

Verapamil

Answer 50

Selective for myocardium | → Hence minimal peripheral vasodilatory effects (compared with dihydropyridines

Question 51

Benzothiazepine calcium channel blocker are

Answer 51

Intermediate between phenylalkylamine and dihydropyridines in their selectivity for vascular calcium channels. → Cardiac depressant and vasodilator actions → Reduce arterial pressure without producing as much reflex cardiac stimulation cause by dihydropyridines

Question 52

Clopidegrel

Answer 52

A prodrug, and blocks an ADP receptor on platelet cell membranes.

Question 53

Antiplatelet drugs: Action

Answer 53

* Blockage of this receptor inhibits platelet aggregation by blocking activation of the glycoprotein IIb/IIIa pathway and formation of IIb/IIIa complex. * The Iib/ IIIa complex is a receptor mainly for fibrinogen and vitronectin but also for fibronectin and von Willebrand factor. * By blocking croos-linking of platelets by fibrin help prevent clot formation

Question 54

Antiplatelet drugs: Side effects

Answer 54

Haemorrhage Severe neutropenia Thrombotic thrombocytopenic purpura (paradoxical)

Question 55

Ranolazine blocks

Answer 55

Late Na+- entry reducing cardiac dysfunction following ischemia. 1. Increases QT interval 2. Decreases angina episodes in individuals with coronary artery disease on maximal doses of amlodipine and exercise tolerance in those taking atenolol, amlodipine or diltiazem.

Question 56

Ranolazine side effects

Answer 56

Worsen electrical dysfunction in long QT syndrome → risk of sudden cardiac death