Session 10

Question 1

Describe the phases of the cardiac action potential.

Answer 1

4: resting membrane potential, between -85 to -95mV.
0: rapid depolarisation due to sodium influx.
1: inactivation of sodium channels, some outward flow of potassium.
2: plateau phase, L-type calcium channels open, hence inward flow. Potassium leaks out via rectifier channels.
3: Calcium channels gradually inactivated, rectifier potassium channels remain open. Resting potential brought back to -90mV.

Question 2

When is the absolute refractory period?

Answer 2

From the beginning of phase 0, until part way through phase 3.

Question 3

What are the two causes of arrhythmias?

Answer 3

Abnormal automaticity (at sites other than the SA node). 
Abnormalities in impulse conduction (e.g. re-entry)

Question 4

Describe AF.

Answer 4

Many random electrical impulses fire off from different parts of the atria. The atria fibrillate very rapidly, and only some pass to the ventricles.

Question 5

Describe ventricular arrythmias.

Answer 5

Many random electrical impulses fire off from different parts of the ventricles. Hence the heart only weakly contracts, not enough to push blood out of the heart.

Question 6

Describe supraventricular tachycardia.

Answer 6

Heartbeat is not controlled by the SA node. The source of the impulse is somewhere above the ventricles. Heart contracts faster than normal, but the heartbeat is regular.

Question 7

What are class 1a anti-arrhythmics?

Answer 7

E.g. Quinidine. Binds to open and inactivated sodium channels and prevents sodium influx. Slows the rapid upstroke during phase 0 depolarisation. Used to treat AF and VF.

Question 8

What are class 1b anti-arrhythmics?

Answer 8

E.g. Lidocaine. Block sodium channels and shorten phase 3 repolarisation. Also decreases the duration of the AP. Used to treat VF. Given IV.

Question 9

What are class 1c anti-arrhythmics?

Answer 9

E.g. Flecainide. Decrease phase 0 upstroke and reduces speed of conduction. Automaticity is reduced due to an increase in the threshold potential. Used in Af or atrial flutter. Can aggrevate chronic heart failure.

Question 10

What are class 2 anti-arrhythmics?

Answer 10

Beta-adrenoceptor antagonists. E.g. propanolol, metoprolol. Dimish phase 4 depolarisation. Depress automaticity and decrease HR and contractility.

Question 11

What are class 3 anti-arrhythmics?

Answer 11

Potassium channel blockers. E.g. amiodarone. Diminish outward potassium current during repolarisation of cardiac cells. Prolong AP without altering phase 0. Prolong the effective refractory period. Can induce arrhythmias. Used for SVT and VT.

Question 12

What are class 4 anti-arrhythmics?

Answer 12

Calcium channel blockers, e.g. Verapamil. Decrease the inward current carried by calcium. Prevents repolarisation until the drug dissociates, hence decreased rate of phase 4 spontaneous depolarisation.

Question 13

How does adenosine act as an anti-arrhythmic?

Answer 13

Acts on A1-receptor of the AV node, and on potassium channels to hyperpolarise the AVN. Used in SVT.

Question 14

How does digoxin act as an anti-arrhythmic?

Answer 14

Decreases conduction of electrical impulses through the AV node and increases vagal activity, leads to an increase in acetylcholine production, stimulating M2 receptors on AV node leading to an overall decrease in speed of conduction.

Question 15

Which drugs would you use in AF?

Answer 15

Flecainide, vernakalant.

Question 16

Which IV drug would you use for VT?

Answer 16

Lidocaine, flecainide, lignocaine.

Question 17

Should flecainide be used alone in atrial flutter?

Answer 17

Should be prescribed with a ventricular rate controlling drug such as a beta-blocker, or verapamil.

Question 18

What is the best drug for Wolff-Parkinson-White syndrome?

Answer 18

Flecainide

Question 19

Which drugs are used for ectopic atrial tachycardia?

Answer 19

Stop automaticity, use verapamil or visoprolol.

Question 20

Which drugs are used for sinus tachycardia?

Answer 20

Beta-blockers or calcium channel blockers.

Question 21

Give three characteristics of cancer cells.

Answer 21

• loss of cell growth control
• loss of specific function
• often produce their own angiogenesis factors
• metastasis and invasiveness
• tumour compartmentation

Question 22

Name the three compartments of cells within a tumour.

Answer 22

a) dividing cells with adequate nutrient and vascular supply
b) resting cells in G0
c) cells no longer able to divide

Question 23

What is the log kill ratio?

Answer 23

If a treatment kills 10^4 or 99.99% of cancer cells, then for a population of 10^9 cells, this would mean a reduction to 10^5 or 0.01% of the original population. This would be a four log kill ration and further treatment would be warranted.

Question 24

What is chemotherapy?

Answer 24

Administration of cytotoxic drugs used in cancer treatment.

Question 25

How can tumours be classified according to their sensitivity to chemo?

Answer 25

Highly sensitive = lymphomas, germ cell tumours, small cell lung.
Modest = breast, colorectal, bladder, ovary.
Low sensitivity = prostate, renal cell, brain tumour and endometrial.

Question 26

What are alkylating agents?

Answer 26

Interfere with DNA processes. E.g. cisplatin. Covalent bonds form between DNA strands, so replication cannot occur.

Question 27

What are anti-metabolites?

Answer 27

Affect DNA synthesis. 5-fluorouracil and methotrexate. Inhibit formation of DNA by interfering with purine/pyrimidine nucleotide production.

Question 28

How does 5-FU work?

Answer 28

Inhibits thymidylate synthase, preventing pyrimidines incorporating into DNA.

Question 29

What are spindle poisons?

Answer 29

Interfere with mitosis. Affect metaphase, preventing excessive growth.

Question 30

Give two examples of spindle poisons.

Answer 30

Vinca alkaloids and taxanes.

Question 31

Why is chemo usually given in stages?

Answer 31

To prevent any excess loss of bone marrow cells whilst still allowing tumour cell to levels to reduce to necessary levels.

Question 32

How can cells become resistance to chemo?

Answer 32

1) decreased entry or increased exit of the agent
2) inactivation of the agent in the cell
3) enhanced repair of DNA lesions produced by alkylation.

Question 33

How do clinicians offset chemo drug resistance?

Answer 33

Use a high dose, short term intermittent repeated therapy, with drugs in optimal combination.

Question 34

Give two reasons why predicted response can differ within the same cancer.

Answer 34

Performance score, clinical stage of the tumour, prognostic factors, molecular or cytogenetic markers.

Question 35

Give three common ADRs of chemotherapy drugs.

Answer 35

Nausea, vomiting, diarrhoea. 
Acute renal failure
GI perforation
Disseminated intravascular coagulopathy
Alopecia
Mucositis
Cardio-toxicity.

Question 36

Give two drugs that may increase plasma levels of chemotherapy drugs.

Answer 36

Vincristidine, capecitabine, methotrexate, St John’s wort.

Question 37

How can responses of the cancer to chemo drugs be monitored?

Answer 37

Radiological imagine, tumour marker blood tests, bone marrow testing.