Flashcards in Session 10 Deck (37):
Describe the phases of the cardiac action potential.
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.
When is the absolute refractory period?
From the beginning of phase 0, until part way through phase 3.
What are the two causes of arrhythmias?
Abnormal automaticity (at sites other than the SA node).
Abnormalities in impulse conduction (e.g. re-entry)
Many random electrical impulses fire off from different parts of the atria. The atria fibrillate very rapidly, and only some pass to the ventricles.
Describe ventricular arrythmias.
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.
Describe supraventricular tachycardia.
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.
What are class 1a anti-arrhythmics?
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.
What are class 1b anti-arrhythmics?
E.g. Lidocaine. Block sodium channels and shorten phase 3 repolarisation. Also decreases the duration of the AP. Used to treat VF. Given IV.
What are class 1c anti-arrhythmics?
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.
What are class 2 anti-arrhythmics?
Beta-adrenoceptor antagonists. E.g. propanolol, metoprolol. Dimish phase 4 depolarisation. Depress automaticity and decrease HR and contractility.
What are class 3 anti-arrhythmics?
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.
What are class 4 anti-arrhythmics?
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.
How does adenosine act as an anti-arrhythmic?
Acts on A1-receptor of the AV node, and on potassium channels to hyperpolarise the AVN. Used in SVT.
How does digoxin act as an anti-arrhythmic?
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.
Which drugs would you use in AF?
Which IV drug would you use for VT?
Lidocaine, flecainide, lignocaine.
Should flecainide be used alone in atrial flutter?
Should be prescribed with a ventricular rate controlling drug such as a beta-blocker, or verapamil.
What is the best drug for Wolff-Parkinson-White syndrome?
Which drugs are used for ectopic atrial tachycardia?
Stop automaticity, use verapamil or visoprolol.
Which drugs are used for sinus tachycardia?
Beta-blockers or calcium channel blockers.
Give three characteristics of cancer cells.
-loss of cell growth control
-loss of specific function
-often produce their own angiogenesis factors
-metastasis and invasiveness
Name the three compartments of cells within a tumour.
a) dividing cells with adequate nutrient and vascular supply
b) resting cells in G0
c) cells no longer able to divide
What is the log kill ratio?
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.
What is chemotherapy?
Administration of cytotoxic drugs used in cancer treatment.
How can tumours be classified according to their sensitivity to chemo?
Highly sensitive = lymphomas, germ cell tumours, small cell lung.
Modest = breast, colorectal, bladder, ovary.
Low sensitivity = prostate, renal cell, brain tumour and endometrial.
What are alkylating agents?
Interfere with DNA processes. E.g. cisplatin. Covalent bonds form between DNA strands, so replication cannot occur.
What are anti-metabolites?
Affect DNA synthesis. 5-fluorouracil and methotrexate. Inhibit formation of DNA by interfering with purine/pyrimidine nucleotide production.
How does 5-FU work?
Inhibits thymidylate synthase, preventing pyrimidines incorporating into DNA.
What are spindle poisons?
Interfere with mitosis. Affect metaphase, preventing excessive growth.
Give two examples of spindle poisons.
Vinca alkaloids and taxanes.
Why is chemo usually given in stages?
To prevent any excess loss of bone marrow cells whilst still allowing tumour cell to levels to reduce to necessary levels.
How can cells become resistance to chemo?
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.
How do clinicians offset chemo drug resistance?
Use a high dose, short term intermittent repeated therapy, with drugs in optimal combination.
Give two reasons why predicted response can differ within the same cancer.
Performance score, clinical stage of the tumour, prognostic factors, molecular or cytogenetic markers.
Give three common ADRs of chemotherapy drugs.
Nausea, vomiting, diarrhoea.
Acute renal failure
Disseminated intravascular coagulopathy
Give two drugs that may increase plasma levels of chemotherapy drugs.
Vincristidine, capecitabine, methotrexate, St John's wort.