PK1 Flashcards
(19 cards)
What is the ADME principles?
Absorption
Distribution
Metabolism
Excretion/Elimination
Why do drugs need to be in aqueous solution?
At the site of administation to achieve absorption
To bbe distributed within the body
At the site of action to be able to interact with target molecule e.g. receptor
To enable transport to organs of excretion and metabolism.
Drug that is water soluble will move well within the plasma
Why do drugs need to be some what lipid soluble?
To cross the cell membrane
Distribute into fatty acids
will easily get to sites of actions within cells
Will easily reabsorb from the kidney and therefore will need to be metabolised prior to excretion
Presence of drugs in plasma is primary significance EXCEPT….
The drug acts locally at the site of application or injection
BECAUSE
the active drug is only available for distribution to the site of action and for passage to organs of excretion and metabolism when it is in solution in plasma
What are teh 2 ways drug moves across cell membranes?
Passive diffusion along the conc gradient
Active/facilitated transport
What is pinocytosis and how is it related to drug absorption?
Small amounts of drug can be enveloped by the plasma membrane and moved through
Pinocytosis (“pino” means “to drink”) is a process by which the cell takes in the fluids along with dissolved small molecules
What are the 3 main factors affecting drug movement?
Molecular weight: High molecular weight compounds will remain at the site of administration
Lipid solubility: Lipid soluble drugs pass readily across cell membrane
Chemical nature: Drugs can be neutral, acidic or basic, polat or non-polar and the degree of ionisation therefore varies
—>Larger molecules need transporters Gas+small molecules do not
Drug ionisation: Whats their movement like? WEAKILY OR BASIC DRUGS
Weakly acidic or basic drugs (MOST): partially ionised at physiological pH. The unionised fraction readily crosses cell memebrane—>How strong thier charge depends on whether they are in neutral, alkaline or acidic pH environment.
Drug ionisation: Whats their movement across the membrane like? NEUTRAL DRUGS 100% UNIONISED & VERY WEAKILY ACIDIC OR BASIC DRUGS :100%UNIONISED
Readily cross cell membrane
Drug ionisation: Whats their movement across the membrane like? STRONGLY ACIDIC OR BASIC DRUGS:100% IONISED
Polar moleucles that do not readily cross cell membrane
What is the effect of pH in an acidic environement e.g. Stomach? What happens to acidic drugs?
In acidic environments, pH < pKa, so the drug remains in its unionized (HA) form.
Unionized drugs are more lipophilic, allowing them to be better absorbed through membranes (e.g., in the stomach).
What is the effect of pH in an acidic environement e.g. Stomach? What happens to basic drugs?
In acidic environments, pH < pKa, so the drug exists mostly in its ionized (BH⁺) form.
Ionized drugs are more hydrophilic, making them less likely to cross lipid membranes and poorly absorbed in the stomach.
So they are better absorbed in the intestines.
Give a short summary of lipid permeability of unionised and ionsied molecules
Unionised molecules readily pass across lipid membranes
Ionised molecules do not easily pass across lipid membranes
When the drug is ionised and therefore rate and extent of its absorption and distribution is influced by what?
The pKa of the drug and the local pH
What is drug absorption influenced by?
Route of administration
What are teh physiological variables affecting drug absorption?
pH at site of absorption
Area of absorbing surface
Local blood flow–>decreaed drug perfusion will reduce the rate of diffusion of a drug fromits site of administration
What is bioavailability?
The fraction of administered dose that reaches the systemic cirulation in an active form.
It is expressed as a percentage of the total administration.
How to calculate bioavailablity?
Area under the curve of oral dose / Area under the curve of IV dose
Bioavailabilty takes no account of the rate of drug absorption therefore:
2 drugs may have the same bioavailability but the peak plasma conc will be higher if one is absorbed more rapidly.
A difference in the peak conc achieved may affect the therapeutic effect
