PBL 5.1

Question 2

What type of drug is Ramipril? In basic terms, what does it do?

Answer 2

Ramipril is an ACE inhibitor. It lowers blood pressure by inhibiting Angiotensin Converting Enzyme

Question 3

What type of drug is Atenolol? What does it do?

Answer 3

Atenolol is a selective beta1 receptor antogonist - a beta blocker. This makes the heart resistant to sympathetic stimulation, thereby avoiding a high heart rate that could cause a cardiovascular event.

Question 4

What type of drug is Atorvastatin? What does it do?

Answer 4

Atorvastatin is a Statin. It is used for lowering cholesterol. Atorvastatin in a competitive inhibitor of HMG Co-A reductase, the rate-determining enzyme in cholesterol biosynthesis.

Question 5

What types of food and drink should you have/not have with Atorvastatin?

Answer 5

• Avoid alcohol
• Avoid taking grapefruit/grapefruit juice throughout the treatment. Grapefruit can significantly increase serum levels of this product.
• Take with a low fat meal
• Avoid drastic changes in dietary habit

Question 6

What is automaticity?

Answer 6

Automaticity: this describes the property of cardiac muscle, which can contract on its own in the absence of neural or hormonal stimulation.

Question 7

What is the electrical system of the heart called?

Answer 7

The conducting system: aka cardiac conduction system or nodal system: a network of specialised cardiac muschle cells that initiate and distribute electrical impulses.

Question 8

What elements does the conducting system of the heart contain? (7)

Answer 8

• The sinoatrial node (SA node) located in the wall of the right atrium
• The atrioventricular node (AV node) located at the junction between the atria and the ventricles
• Conducting cells, which interconnect the two nodes and distribute the contractile stimulus through the myocardium
• Internodal pathways: distribute the contractile stimulus to atrial muscle cells as the impulse travels from the SA to the AV node
• The AV bundle, the bundle branches and the Purkinje fibres are the ventricular conducting cells which distribute the stimulus to the ventricular myocardium.

Question 9

What special characteristic do cells of the AV node and cells of the SA node share?

Answer 9

Conduciting cells of the SA and AV node: their excitable membranes cannot maintain a stable resting potential. After each repolarisation, their membranes gradually depolarise. This is called prepotential or pacemaker potential.

Question 10

How does the heart beat if the SA node is damaged? How does the heart beat if both the SA node and the AV node are damaged?

Answer 10

If any of the atrial pathways or the SA node become damaged, the heart will continue to beat, but at a slower rate, usually 40-60bpm, as dictated by the AV node.

Certain cells in the Purkinje fibre network depolarise spontaneously at an even slower rate, and if the rest of the conducting system is damaged, they can stimulate the heart rate if 20-40bpm.

Question 11

At what point does the rate of an electrical impulse slow down in a healthy heart?

Answer 11

The rate of propagation of the impulse slows as it leaves the internodal pathway and enters the AV node, becasue the nodal cells are smaller in diameter than the conducting cells.

Question 12

After the AV node, which structures does the electrical impulse of the heart move through?

Answer 12

After the AV node, the impulse is conducted along the interventricular bundle and bundle branches to the Purkinje fibres and the papillary muscles. The Purkinje fibres then distribute the impulse to the ventricular myocardium, and ventricular contraction begins.

Question 13

What is the maximum heart rate and why? Why is this limitation important?

Answer 13

230bpm. This is the maximum rate that cells of the AV node can conduct impulses. Because each impulse in a ventricular contraction, this value is the maximum normal heart rate. Even if the SA node generates impulses at a faster rate, the ventricles will still contract at 230bpm. This limitation is important, becasue mecanical factors begin to decrease the pumping efficiency of the heart at rates above approx 180bpm.

Question 14

What is the difference between the two bundle branches?

Answer 14

The left bundle branch, which supplies the massive left ventricle, is much larger than the right bundle branch.

Question 15

What is the ST segment?

Answer 15

The ST segment represents the period when the ventricles are depolarized.

Question 16

What can ST elevation indicate?

Answer 16

ST elevation may indicate myocaridal infarction.

Question 17

On an ECG which are the anterior leads?

Answer 17

V1-V4, which are pre-cordial leads, electrodes directly attached to the chest.

Question 18

What is the guideline for diagnosing ST elevation type MI by ECG?

Answer 18

The current guidelines for the ECG diagnosis of the ST segment elevation type of acute MI require at least 1mm (0.1mV) of ST segment elevation in the limb leads, and at least 2mm elevation in the precordial leads.

Question 19

What is Clopidogrel?

Answer 19

Clopidogrel is an antiplatelet agent and is used to reduce aterosclerotic events

Question 20

What is the very basic MOA of a tissue plasminogen activator?

Answer 20

It activates plasminogen and converts it into Plasmin, which is a serine protease that acts to dissolve fibrin blood clots.

Question 21

What ratio of blood lipids is a good predictor of coronary artery disease?

Answer 21

The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk

Question 22

What blood lipid measurements are associated with increased risk of atherosclerosis and cardiovascular disease?

Answer 22

High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease

Question 23

Where does atorvastatin primarily work? What happens here?

Answer 23

Atorvastatin acts primarily in the liver.
Decreased hepatic cholesterol levels increases uptake of cholesterol by the liver and reduces plasma cholesterol levels.

Question 24

When is atorvastatin a primary measure, when a secondary measure?

Answer 24

Atorvastatin may be used as

• primary prevention in individuals with multiple risk factors for coronary heart disease (CHD) and
• secondary prevention in individuals with CHD to reduce the risk of myocardial infarction (MI), stroke, angina, and the need for revascularization procedures (bypass, angioplasty)

Question 25

How does atorvastatin interact with HMG-coA Reductase?

Answer 25

Atorvastatin selectively and competitively inhibits the hepatic enzyme HMG-CoA reductase

Question 26

Other than CHD, what illnesses can you use atorvastatin for? (4)

Answer 26

May be used in the treatment of

• primary hypercholesterolemia and mixed dyslipidemia,
• homozygous familial hypercholesterolemia,
• primary dysbetalipoproteinemia,
• and/or hypertriglyeridemia as an adjunct to dietary therapy

Question 27

What is the Mode of Action of Clopidogrel?

Answer 27

Clopidogrel prevents binding of ADP to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex.
As the glycoprotein GPIIb/IIIa complex is the major receptor for fibrinogen, its impaired activation prevents fibrinogen binding to platelets and inhibits platelet aggregation.

Question 28

What does HMG-CoA reductase actually do - what reaction does it catalyse?

Answer 28

HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate in the cholesterol biosynthesis pathway.

Question 29

How does decreased hepatic cholesterol levels reduce serum LDL-C concentrations?

Answer 29

Decreased hepatic cholesterol levels stimulates:
upregulation of hepatic LDL-C receptors
which increases hepatic uptake of LDL-C.

Question 30

Other than HMGcoA Reductase, what else does atorvastatin target? (1) What is this involved in?

Answer 30

HMG CoA Reductase inhibits Dipeptidyl peptidase 4 which plays a role in T-cell activation.

Question 31

How is Atorvastatin excreted from the body?

Answer 31

Eliminated primarily in bile after hepatic and/or extrahepatic metabolism. Does not appear to undergo significant enterohepatic recirculation. Less than 2% of the orally administered dose is recovered in urine.

Question 32

What are the side effects of atorvastatin?(5) Who might need a lower dose? (1)

Answer 32

Generally well-tolerated. Side effects may include myalgia (muscle pain), constipation, asthenia (weakness/tiredness), abdominal pain, and nausea. To avoid toxicity in Asian patients, lower doses should be considered.

Question 33

What is the mode of action of Glyceryl trinitrate?

Answer 33

Ultimately causes vasodilation;

• nitroglycerin is converted to nitric oxide (NO, nitrogen monoxide), which activates the enzyme guanylate cyclase.
• This stimulates the synthesis of cyclic guanosine 3’,5’-monophosphate (cGMP)
• which eventually causes the dephosphorylation of the myosin light chain of the smooth muscle fibre, a release of calcium ions and the relaxation of the smooth muscle cells and vasodilation.

Question 34

What is the target receptor of glyceryl trinitrate?

Answer 34

Atrial natriuretic peptide receptor A

Question 35

What type of drug is aspirin? What does it do? (4)

Answer 35

Acetylsalicylic acid, also known aspirin, belongs to a class of drugs known as non-steroidal anti-inflammatory drugs (NSAIDs).

• analgesic - used in the treatment of mild to moderate pain.
• anti-inflammatory
• antipyretic
• anticoagulant - inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis.

Question 36

How does aspirin produce its anti inflammatory, analgesic (2), antipyretic and anticoagulant properties?

Answer 36

• antiinflammatory and antirheumatic agent: due to inhibition of synthesis and release of prostaglandins.
• analgesia: both a peripheral and CNS effect. Peripherally, acetylsalicylic acid acts by inhibiting the synthesis and release of prostaglandins. Acting centrally, it would appear to produce analgesia at a hypothalamic site in the brain, although the mode of action is not known.
• antipyresis: also acts on the hypothalamus to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow. Acetylsalicylic acid’s antipyretic activity may also be related to inhibition of synthesis and release of prostaglandins.
• anticoagulant: inhibits the production of thromboxane A2 (TXA2), which is a potent inducer of platelet aggregation

Question 37

What is the specific chemical that aspirin inhibits? How is this different from other NSAIDS?

Answer 37

• Directly and irreversibly inhibits the activity of both types of cyclooxygenase (COX-1 and COX-2) (aka prostaglandin G/H synthase 1 and 2.)
• Acetylsalicylic acid is different from other NSAIDS (such as diclofenac and ibuprofen) which are reversible inhibitors of COX 1 and 2.

Question 38

Aspirin and other NSAIDS inhibit COX-1 and 2. What are COX-1 and 2 normally responsible for?

Answer 38

• COX-1 and -2 normally catalyze the conversion of arachidonic acid to prostaglandin G2 and prostaglandin G2 to prostaglandin H2.
• Prostaglandin H2 is the precursor to a number of other prostaglandins involved in pain, fever and inflammation.

Question 39

The inhibition of which prostaglandin gives aspirin its antipyretic properties?

Answer 39

The antipyretic properties of aspirin arise from inhibition of prostaglandin E2 synthesis in the preoptic region of the hypothalamus.