Lec 7 Flashcards
The process by which a drug reversibly leaves the bloodstream and enters the interstitium (extracellular fluid) and the tissues know as ?
Drug distribution
For drugs administered IV, absorption is not a factor, and the initial phase (from immediately after administration through the rapid fall in concentration) represents the distribution phase . (T/F) ?
True
during distribution phase , the drug slowly leaves the circulation and enters the tissues . (T/F) ?
F—>(rapidly) ?
Mention the factors that affecting distribution :
1- Blood flow
2- Capillary permeability
3- Binding of drugs to plasma proteins and tissues
4- Lipophilicity
Give me the descending order of the organelles in terms of the availability of blood and blood vessels in them :
(brain, liver, and kidney) > skeletal muscles > Adipose tissue, skin and viscera
Capillary permeability is determined by ?
- Capillary Structure
- Chemical nature of the drug .
Capillary structure varies in terms of the …………… exposed by …………. between endothelial cells.
- fraction of the basement membrane
- slit junctions
significant portion of the basement membrane is exposed due to ……….. through which ( large / small ) plasma proteins can pass .
A. large discontinuous capillaries
B. Large
In the brain, the capillary structure is discontinuous , and there are slit junctions . (T/F) ?
F —> ( The capillary structure is continuous, and there are no slit junctions )
The capillary structure is continuous, and there are no slit junctions .
So how drugs will passes ?
Drugs must pass through the endothelial cells of the CNS capillaries or be actively transported .
Give me example about drug can pass into the brain by specific transporter carries :
Levodopa
Reversible binding to ………….. sequesters drugs in a non-diffusible form and slows their transfer out of the vascular compartment
Plasma proteins
——————————
sequesters—> (يعزل)
The major drug-binding protein and may act as a drug reservoir is called ?
Albumin
lipid-soluble drugs readily penetrate the CNS because they dissolve in the endothelial cell membrane.
(T/F) ?
True
Ionized or polar drugs generally success to enter the CNS because they can pass through the endothelial cells that have no slit junctions . (T/F) ?
F—> (Ionized or polar drugs generally fail to enter the CNS because they cannot pass through the endothelial cells that have no slit junctions)
The albumin act as ?
drug reservoir
How the albumin act as drug reservoir ?
As the concentration of free drug decreases due to elimination, the bound drug dissociates from the protein .
When albumin act as a drug reservoir it lead to ?
maintains the free drug concentration as a constant fraction of the total drug in the plasma
All drugs accumulate in tissues , leading to higher concentrations in tissues than in the extracellular fluid and blood . (T/F) ?
F—> ( many not all )
Many drugs accumulate in tissues, leading to ?
Higher concentrations in tissues than in the extracellular fluid and blood .
Drugs may accumulate as a result of binding to ?
lipids, proteins, or nucleic acids .
Drugs may also be actively transported into tissues. (T/F) .
True
Tissue reservoirs may serve at two function, mention them
- As a major source of the drug .
- prolong its actions or cause local drug toxicity .
Acrolein, the metabolite of cyclophosphamide , can cause ?
hemorrhagic cystitis
Acrolein, the metabolite of cyclophosphamide, can cause hemorrhagic cystitis because ?
It accumulates in the bladder.
The metabolite of cyclophosphamide is called ?
Acrolein
The chemical nature of a drug weakly influences its ability to cross cell membranes ? (T/F)
F—>[The chemical nature of a drug strongly
influences its ability to cross cell membranes]
Lipophilic drugs can’t move across most biologic membranes ? (T/F) ?
F—> (Lipophilic drugs “ readily “ move across most
biologic membranes)
The features of Lipophilic drugs are ?
A. These drugs dissolve in the lipid membranes
B. It penetrate the entire cell surface.
The major factor influencing the distribution of lipophilic drugs is ?
blood flow
hydrophilic drugs do not readily penetrate cell membranes and must pass through slit junctions . (T/F) ?
True
The fluid volume that is required to contain the entire drug in the body at the same concentration measured in the plasma.
This statement describe ?
The apparent volume of distribution
How we can calculated the apparent volume of distribution ( Vd ) ?
It is calculated by dividing the dose that ultimately gets into the systemic circulation by the plasma concentration at time zero (C0).
Slides from 18 - 22 are ?
Examples about the apparent volume of distribution (Vd) .
Vd has physiologic and physical basis . (T/F) ?
F —[Vd has no physiologic or physical basis]
Although Vd has no physiologic or physical basis, it can be useful to ?
Compare the distribution of a drug with the volumes of the water compartments in the body .
The pecture in slide num.24 is ?
Ktheeeer Mohm 🥳
The drug effectively trapped within the plasma (vascular) compartment. This case happen if the drug ?
• Has a high molecular weight
• Extensively protein bound,
• Too large to pass through the slit junctions of the capillaries
The result from the previous case is ?
The drug has a low Vd that approximates the plasma volume (4 L in a 70-kg individual) .
Give me example about drug trapped within the plasma .
Heparin
The drug can pass through the endothelial slit junctions of the capillaries into the interstitial fluid if it ?
• Has a low molecular weight
• Hydrophilic
Hydrophilic drugs cannot move across the lipid membranes of cells to enter the intracellular fluid. (T/F) ?
True
In the previous case ,the drugs distribute into a volume that is the sum of the ?
plasma volume and the interstitial fluid
plasma volume and the interstitial fluid together constitute the ?
extracellular fluid (about 20% of body weight or 14 L in a 70- kg individual).
The drug can move into the interstitium through the slit junctions and also pass through the cell membranes into the intracellular fluid if it ?
• Has a low molecular weight
• Lipophilic
The drug in the previous case distribute into a volume of about ……….
and the example about it is ………..
A. 60% of body weight or about 42 L in a 70-kg individual.
B. Ethanol
A drug commonly associates exclusively with only one of the water compartments of the body.(T/F) ?
F—> ( rarely)
the vast majority of drugs distribute into several compartments, often avidly binding cellular components, such as:
- Lipids : (abundant in adipocytes and cell membranes)
- Proteins : (abundant in plasma and cells)
- Nucleic acids : (abundant in cell nuclei)
The volume into which drugs distribute is called ?
The apparent volume of distribution, Vd .
Vd is useful pharmacokinetic parameter for ?
Calculating the loading dose of a drug .
This process can be most easily analyzed by plotting the ……. of the plasma drug concentration (Cp) versus time
Log
The concentration of drug in the plasma can be extrapolated back to time zero (the time of IV bolus) on the Y axis to determine C0. (T/F) ?
T
The concentration of drug that would have been achieved if the distribution phase had occurred instantly . This statement describe ?
C0
Why Vd has an important influence on the half-life of a drug ?
Because drug elimination depends on the amount of drug delivered to the liver or kidney (or other organs where metabolism occurs) per unit of time.
Delivery of drug to the organs of elimination depends only on blood flow . (T/F) ?
F—(Delivery of drug to the organs of elimination depends not only on blood flow but also on the fraction of the drug in the plasma) .
a drug has a large Vd, most of the drug is in the ?
extravascular space and is unavailable to the excretory organs.
Any factor that increases Vd can decrease the half-life and extend the duration of action of the drug .(T/F) ?
F—(increase)
