Pharmacokinetics I Flashcards
Why is a particular dose given to a particular animal?
Depends upon the target therapeutical effect and what dose is needed for that effect as well as the dose needed to reach the target site for therapeutic effect
What is Pharmacokinetics?
Movement of drugs when they are in the body -
Encompasses:
Absorption of a drug - from the site of administration (preceded by disintergratin (of a tablet) or dissolution (into ECF) at the site of administration)
Distrubution - around the body
Elimnation - removal from the body by - Metabolism and/or excretion
What is water solubility in terms of drugs?
Drugs need to be in aqueous solution:
- At the site of administration to achieve absroption
- For distrubution around the body
- At the site of action to interact with its target
- To enable passage to organs of excretion and metabolism
What is lipid solubility in terms of drugs?
Specific drugs have some lipid solubility meaning:
- They can cross cell membranes easily (passive diffusion)
- Distribute into fatty tissue
- Will easily get to sites of action within cells
- Will easily reabsrob from the kidney, therefore needs to be meatabolised before excretion
What is the importance of drug presence within the blood plasma?
Of primary significance except when the site of administration = site of action
Only when a drug is in solution in the plasma is the activated drug available for distrubution around the body to sites of action and for elimination
How do drugs pass into and out of the circulation?
Primarily cross vascular endothelium via gaps between the cells, these gaps are packed with a matrix of proteins that act to retain molecules of high molecular weight (most drugs are small molecules with a molecular weight of <1000.
They pass across cell membranes via passive diffusion or active or facilated transport.
They may also pass via pinocytosis or aqueous pores
What factors effect drug movement?
- Molecular weight - high molecular weight molecules will reamin at administration site
- Lipid solubility - lipid solubility means the drugs can readily cross cell membranes
- Chemical Nature - Drugs can be neutral, acidic or basic, polar or non-polar and the degree of ionisation therefore varies
Weak Acidic/Basic, Neutral, Very Weakly Acidic/Basic, Strongly Acidic/Ba
What is the significance of drug ionisation on a drugs ability to cross cell membranes?
Influences the ability of a drug to cross cell membranes -
* Weakly acidic or basic drugs (most drugs) are partially ionised at physiological pH, only the unionised fraction easily crosses cell membranes
* Neutral drugs are completley unioinised as well as very weakly acidic or basic drugs meaning they readily cross cell membranes
* Strongly acidic or basic drugs are very ionised and do not readily cross cell membranes
What is Diffusion/Ion trapping of weak acids and bases?
Occurs when two sides of amembrane differ in pH:
- Weak acids get trapped in an ionised form in alkaline fluids
- Weak bases are trapped in an ionsed form in acidic fluids
What are the different routes of drug administration?
- Intravenous - faster acting and can be done at site of action
- Orally (tablet, bolus etc.) - act on GIT, less invasive
- Intramuscular - can be done at site of action, absorbed over a longer period of time
- Rectal - avoids portal circulation
- Subcutaneous - quick/rapid acting
- Topical - site of action
- Inhalation/ Intranasal - site of action
- Vaginal - site of action
etc.
How is the rate and extent of drug absorption affected?
Not all drugs are absorbed at the same rate and to the same extent
- The properties of the drug
- Physiological variables
- The drug formulation into a drug product (particularly orally administered drugs)
What factors affect drug absorption?
- pH at site of absorption
- Area of the absorbing surface (decrease in surface area = less drug absorbed)
- Local blood flow (less perfusion = less diffusion (slower rate) at administration site)
What is the affect of pH at the site of absorption?
In plasma, a weakly basic drug will be present in an unionised form (move readily across cell membranes)
In acidic conditions a weakly basic drug will pick up H+ ions becoming ionised in the plasma and move across cell membranes less readily
In acidic conditions a weakly acidic drug will be unioinsed and in plasma will be ionised
What is first pass metabolism?
A drug is extensively metabolised in the wall of the GIT, portal blood or in the liver before it is able to reach sytemic circulation
What is the Cmax and Tmax of a drug?
Cmax = The max plasma concentration of a drug
Tmax = The time taken to reach Cmax
