Pharm 2 Flashcards
What is first passage of medication and where does this happen
First passage is the loss of medication due to metabolism or transport before it arrives in systemic circulation
This leads to a decrease in medication concentration and effect
This of course occurs during absorption in the intestine as well as during its transportation to the Vina Cava for example in the liver
How can you reduce first passage in terms of administration
You can choose to administer a medication in other ways than per us orally
For example intravenously by inhalation sublingually or by injection and even rectally
What is bioavailability
It is the percentage of medication that reaches the systemic circulation after its administration
Can be calculated as the (SSC oral/SSC injected) the fraction that is left over what it could be (max)
Explain what could happen for a medication in terms of bioavailability if we double the dose in an environment with limited number of Enzymes
He could have a saturation of Enzymes that do the first passage
Which reduces the amount of medication that is eliminated and thus increases bioavailability
We could potentially enter a kinetics of order zero which makes it very difficult to predict what will happen
What is the volume of distribution depended on
What type of medication will have a large volume of distribution and what type of medication will have a small volume of distribution
Study this until it becomes a spinal reflex
Vd = D/Cp
D: dose administered
Cp: Plasmatic Concentration (amount of medication that is in the blood; can be bound to proteins or not)
A medication that has a higher albumin affinity will likely have a larger plasmatic concentration which means a smaller volume of distribution which means less drug in tissue
Similarly a medication that is very large that has a hard time passing inside of tissues will have a large plasma concentration and a small volume of distribution
Describe the difference between a drug with a small volume of distribution and a drug with the very large volume of distribution
Insulin has a volume of distribution of 0.05
This means that very little of the medication enters tissue and the majority of it is found in the blood
On the other hand morphine has a volume of distribution of 5
This means that we have very little medication that is in the bloodstream and most of it is in the tissues
What are the proteins that bind medication and what type of medication do they bind
Albumine
– Lie les médicaments acides
Alpha1-glycoprotéines
– Lie les médicaments basiques
exam exam exam
We have a patient that has been taking medication X for the past three weeks
Because the medication wasn’t doing much the patient has decided to take twice as much
Knowing that the medication is one that could saturate plasma albumin what could explain a possible intoxication of the patient
At lower concentrations most of the medication is bound to albumin thus it does not enter the cells
But as the patient has increased the dose she has gotten more medication that is freely circulating which means more medication that can enter the tissues
The fraction of bound and free would have stayed the same if this medication was a first order relationship but since it has a possibility of saturating plasma albumin we have moved to order zero kinetics
This explains the toxicity that the patient is suffering from
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You have a patient that has been taking medication X for the past 4 weeks
In general the medication works very well and sometimes the patient is recommended to take larger doses and this is not problematic as the medication has a order 1 kinetic
But recently she’s been getting intoxicated from the medication and she says that she’s been also taking a medication that potentially has an order zero kinetic
What could have happened here?
The increase in dose of the prescribed medication doesn’t lead to intoxication because in order one the fraction of bound and free medication stays about the same
It seems that the second medication that she has taken has saturated the albumin it might have a higher affinity for albumin for example
This means that the initial medication is now causing toxicity
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What type of medication are medications that have a large volume of distribution versus small volume of distribution in terms of their ph and what they’re bound to
Acidic medication has a higher affinity for plasma proteins and thus has a small volume distribution as it cannot get to the cells
Basic medication has a large affinity for tissue proteins and thus has a large volume of distribution
What are the two cellular profusion territories
We have V-1 as well as V2
**V1 **are territories that have a fast equilibrium such as the brain the liver the kidneys the lungs intestines and receive less the most amount of blood
**V2 **are territories with a slow equilibrium which is also 90% of our body
These are stuff like muscles skin and fatty deposits
Describe how the elimination curve changes following an intravenous administration of a certain medication
Talk about the V-1 and V2
- Administration of medication intravenously leads to maximum concentration in blood at time 0.
- At this point, all of the drug is in the blood (V-1).
- High blood concentration results in maximum elimination rate, causing a steep initial elimination slope.
- Due to absence of medication in V2, the law of equal concentrations drives drug movement from V-1 to V2 until both have equal concentration.
- Equilibrium is reached when concentration in blood matches that in both V-1 and V2.
- Decrease in concentration thereafter is solely due to medication elimination via kidneys.
- Elimination removes medication from blood (V-1), not tissues.
- Decrease in V-1 concentration prompts movement of medication from V2 to V-1 to equalize concentrations.
- This cycle continues until no medication remains.
In terms of elimination we say that this is dependent on distribution and elimination constant
Explain why this is dependent on distribution
- In short this is dependent on distribution because the more medication in the tissues the slower the elimination will be as it is harder for the medication to go from the tissues into the blood
- Tissue-mediated elimination: The presence of medication in tissues slows elimination, as it’s more challenging for medication to transition from tissues to the bloodstream.
- Impact of patient weight: Patients with higher body weight tend to have more medication stored in their tissues. Consequently, when the kidneys eliminate medication from the bloodstream, it takes longer for medication to transfer from tissues to the bloodstream, leading to a reduction in the elimination rate.
- Effect of weight gain: Increased adipose tissue in overweight patients results in greater medication accumulation in tissues. This accumulation prolongs the process of medication transferring from tissues to the bloodstream during elimination, thereby reducing the elimination rate and flattening the elimination slope.
- Contrast with weight loss: Conversely, patients undergoing significant weight loss experience a decrease in adipose tissue, leading to less medication stored in tissues. As a result, during medication elimination, there’s a quicker transfer of medication from the reduced tissue reservoir to the bloodstream, which accelerates elimination and steepens the elimination slope.
True or false
A patient with a larger V2 will have a smaller area under the curve that a patient with the smaller V2
False the area under the curve does not change
A patient with a larger V2 will have a smaller cmax a larger tmax in a smaller elimination slope but the area under the curve does not change
True or false a
A patient with a larger V2 will have a bigger therapeutic effect when taking a medication than a patient with a smaller V2
False but could be true
The therapeutic effect of a drug depends on its side of action
For example if a medication targets the heart well a patient with a larger V2 will have less therapeutic effect
But if a patient takes medication that targets tissues then the inverse would happen
