PK2 Flashcards
(21 cards)
Once absorbed from the site of administration drugs can distribute into…?
PLamsa and from plasma it can move into the ECF and ICF
What is volume of distribution?
Its a measure of volume of fluid required to contain the totatl amount of drug at its plasma conc
Vd: the body has many different compartments, it’s possible for insoluble drugs which can move outside the body water
We need the drugs to travel to the area of interest we know this through the concentration and properties of the drug
What can we predict from the conc of drug in plasma?
The lower the concentration in the plasma we can predict if the drug moved or can move to ECF and ICF
Whats the calculation of Vd?
Vd= Q Dose (total amount of drug in the body; mg/kg) / Cp Plasma conc (usually ug or ng/ml)
the lower the value the higher the volume of distribution
How do interpret Vd?
Vd very low: 0.05 to 0;1 L/kg, drug confined to the plasma compartment (large molecules)
Vd low: 0.2 L/kg drug confined to the plasma and interstitial space (highly polar molecules which penetrate membrances poorly)
Vd intermediate 0.6 L/kg: drug enters total body water (crosses membranes)
Vd very high >1l/kg: drug concentrated in fat or binds to a site within a tissue or cell
What is the Vd value of total body water?
approx. 0.6L/kg
Why is it important to know the Vd of a drug?
- It enables you to predict whether the drug selected for administration is likely to reach the target site at effective concentrations.
- The Vd can be used to determine the loading dose necessary to achieve a target plasma conc
We need a certain concentration at the target for it to work and if the drug distribution is high maybe we need to add more so more of the drug goes to the target
The ability of a drug to leave the circulation and enter ICF and then cross cell membranes can be influenced by?
- size
- plasma protein binding
- endothelial cell barrier function
- ion trapping
5.lipid solubility
What is plasma protein binding?
Once a drug has entered the vasculat compartment it may circulate bound to plasma albumin & glubulin
The plasma protein bound and free drug in the circulation are in equilibrium.
Normally only the free drug crosses the endothelial cell barrier
What are the consequences of drug plasma binding?
Pharmacodynamics: the protein bound fraction is pharmocologically inactive
PK: only the free portion of the protein bound drug will readily leave the circulation/be ultra-filtered in the kidney
Toxicity: Few individuals the drug protein complex may be recognised as foreign, i.e behaves as an antige, causing an hypersensitivity reaction on second exposure.
Interaction: competition between drugs or endogenous compounds for protein binding can occur which may lead to unwanted effects
Why is drug metabolism important?
Most drugs require this prior to elimination from the body as they are converted into more water soluble compounds and aids their elimination
Some drug metabolites are biologically active
Some drugs are administered as inactive, pro drugs and must be metabolised to an active form.
What are the main enzymes involved in drug metabolism in the liver?
Mitochondrial mixed function oxidase enzymes or otherwise known as cytochrome P-450 or CYP enzymes
What are the different phases of metabolism?
Phase I: converts lipophilic molecules into more polar molecules
Phase II: add a conjugating group to the molecule to increase polarity, decrease lipophilicity and therefore aid drug excretion
DRUG—>METABOLITE—>CONJUGATE
What process happen in Phase I matabolism?
Oxidation, reduction, hydrolysis
What process happens in Phase II metabolism?
Conjufation, addition of e.g. acetyl, sulphate, glucuronic acid and/or glycine
What is first pass metabolism?
Some drugs are extensively metabolised
> in the wall of the GIT
or
>In the portal blood or in the liver
before they reach the systemic circulation
This affectst he absorption of orally administered drugs
What is enterohepatic (re)cycling?
Liver cells transfer drugs or drug conjugatesto bile
They are delivered to the intestines where: conjugates are hydrolysed, the parent drug can be reabsorbed
What kind of molecules tend to be excreted most efficiently as they are not reabsorbed?
Water soluble molecules
What molecules in terms of pharmacology are filtered/reabsorbed in renal excretion?
No filtration…
Partial filtration…
Filtered then completely reabsorbed…
Filtered then partially reabsorbed fromt he tubules, partially excreted…
Filtered then no reabsorption from the tubules…
Filtered then actively secreted into the tubules…
No filtration—> proteins>70,000 kD)
Partial filtration—>Drugs bound to plasma proteins; free drug is filtered
Filtered then completely reabsorbed—>Glucose etc.
Filtered then partially reabsorbed fromt he tubules, partially excreted—>Most drugs
Filtered then no reabsorption from the tubules—>Ionised,water soluble drugs; many drug metabolites
Filtered then actively secreted into the tubules—>some drugs and drug metabolites
What is the effect of pH on rate of excretion give examples?
The rate of excretion in the urine of drugs that are weak acids or weak bases depends on urine pH because this inluences the proportion of unionied and ionised drug.
In animals producing acidic urine e.g carnivores, concentrate fed herbivores. weak bases will be eliminated most efficiently
In animals producing alkaline urine so herbivores on forage, weak acids will be eliminated most efficiently
There is and example of species difference in metabolism and excretion go see and rewatch the lecture to see explanation!!
