M and R Flashcards
What is the length of a nerve axon AP?
0.5-1.0ms
Why is the equlibrium potential of sodium not reached during a nerve axon AP?
K+ is also being effluxed at the same time as Na+ is moving into the cell, so it’s because of the permeability of the membrane to K+.
Why does the membrane potential become driven towards the equlibrium potential for potassium during the downstroke of a nerve axon AP?
Na+ channels inactivate, and more K+ channels open, so the cell becomes repolarised.
When is the absolute refractory period?
Directly after the onset of an AP.
What is happening during the absolute refractory period?
Nearly all Na+ channels are in the inactivated state, and so the membrane cannot be further excited, so another AP cannot be produced during this time, limiting the rate of firing of APs.
What is happening during the relative refractory period?
Na+ channels are recovering, with the no. in their inactivated state decreasing, so an AP can be produced if stronger than normal stimulus as higher threshold. K+ channels maintained in open state.
Why do slowly increasing currents fail to fire nerve APs?
Adaptation occurs, as if membrane slowly depolarised, some Na+ channels open but not many, and one open, they inactivate, and an insufficient no. are open to cause an AP, so as depolarisation continues, the threshold for AP will never be reached as all sodium channels will end up in their inactivated state.
What is the equation for conduction velocity?
Distance/time
What happens if acute complete demyelination occurs?
Conduction fails as increased capacitance, so current leakage, which means that the nodes are not raised to threshold.
What happens if chronic complete demyelination occurs?
Slower than normal conduction can occur as new Na+ and K+ channels are synthesised, and inserted not just at the nodes.
What is the relationship between conduction velocity and fibre diameter in a myelinated nerve?
CV is proportional to FD
What is the relationship between conduction velocity and fibre diameter in an unmyelinated nerve?
CV is proportional to the square root of FD
Would an AP be easier or harder to fire in acute hyperkalaemia?
Easier as a lesser change in ion conductance is required for depolarisation.
Why might chronic hyperkalaemia cause arrhythmias?
The less -ve Vm due to less efflux of K+ ions will prevent the repriming of Na+ channels that have been inactivated, so electrically silent or ‘accomodated’ membrane, which can lead to arrhythmias.
Name 2 inhibitors of warfarin action and describe how they produce their inhibitory effect.
Barbiturates and rifampicin. These induce liver metabolising enzymes.
How does alchol potentiate the action of warfarin?
It inhibits the metabolism of warfarin.
Name some drugs which displace warfarin from plasma proteins
Aspirin, Sulphonamides, Phenytoin
Why do broad spectrum antibiotics potentiate warfarin action?
They reduce Vit K synthesis by bacteria in gut.
Give an example of a drug that potentiates the action of warfarin by reducing platelet function.
Aspirin-cyclooxygenase inhibitor, the enzyme is required for the synthesis of thromboxane A2 which is involved in platelet aggregation.
Define oral bioavailability
Proportion of a drug given orally, or by any other route that IV, that reaches the systemic circulation in an unchanged form.
What is the 1st pass effect?
It refers to the inactivation of a fraction of a drug by liver enzymes before the drug has exerted its effect in the body, e.g. if a drug is given orally.
How can the 1st pass effect be avoided?
By giving a drug parenterally e.g. IV, IM, SC.
What is oral bioavailability affected by?
Administration route, chemical form of drug and patient-specific factors e.g. GI and hepatic disorders, and enzymes.
How is oral bioavailability measured?
Amount- dependent on 1st pass met. and gut absorption, and Rate of availability- dependent on form and administration.
What is the therapeutic ratio?
LD50/ED50, so the dose of drug causing a toxic response in 50% of pop./ dose of drug that is therapeutically effective in 50% of pop.
What would a large therapeutic ratio indicate?
A large difference between therapeutic and toxic doses, so large therapeutic window.
Other than parenterally, how can a drug be administered to avoid the 1st pass effect?
Rectal- drains into both portal and systemic circulations, and sublingual e.g. use of GTN in angina.
What is the volume of distribution?
The theoretical vol. into which a drug has distributed assuming that this occurred instantaneously.
When are protein binding drug interactions important?
When the object drug (Class I):- is highly bound to albumin
- has a small vol. of distribution
- has a low therapeutic ratio
