Drug Absorption Flashcards
What is the pharmaceutical process
Getting the drug into the patient
What is the pharmacokinetic process
Getting the drug to the site of action
What is the pharmacodynamic process
Producing the correct pharmacological effect
What is the therapeutic process
Producing the correct therapeutic effect
What factors determine drug pharmacokinetics
Absorption Distribution Metabolism Elimination (ADME)
What do the factors of pharmaknetics enable us to understand
Dosage Drug administration Drug handling Patient variability Potential for harm
What is absorption in relation to pharmakinetics
The process of movement of unchanged drug from the site of administration to the systemic circulation
How can drugs be absorbed into the system
Oral Intravenous Subcutaneous Intramuscular Other GI - Sublingual, rectal Inhalation Nasal Transdermal
What enables most drugs to have biological action
Drugs must enter the blood stream and be distributed to a site of action
There is always a correlation between plasma concentration of a drug and what
The therapeutic response
What is Tmax
Time to peak concentration
What is Cmax
The peak concentration
What is AUC
Area under the drug concentration-time curve which represents the amount of drug which reaches the systemic circulation
If the rate of absorption is rapid what happens to the drug concentration peak
It will be earlier (Tmax)
If the drug dose is increases what happens
Time to peak concentration will not be affected (Tmax)
Peak concentration will increase (Cmax)
What is a therapeutic range
A drug is active over a range of concentrations
What happens below and above the therapeutic range
Below: insufficient or no pharmacological action
Above: toxicity
What is a therapeutic index
A measure of the range at which a drug is safe and active
What is bioavailability
The amount of drug which reaches circulation and which is available for action
How can bioavailability be estimated
Using AUC
How much bioavailability does a drug given intravenously have
100%
State the factors which can affect bioavailability
Formulation
Ability of drug to pass physiological barriers
Gastrointestinal effects
First pass metabolism
How does formulation affect bioavailability
Due to the slow release preparations
What physiological barriers are there that can affect bioavailability
It is dependent on:
Particle size
Lipid solubility
pH and ionisation
What gastrointestinal effects affect bioavailability
It is dependent on:
Gut motility
Food
Illness
What does the degree of ionisation of drugs depend on
Most drugs are weak acids or bases so they depend on the pH of the environment
What forms of the drug will be present in solution
Ionised and un-ionised forms
What can the ionised form of the drug not cross
Membrane
What will the un-ionised form of the drug do
Distribute across the membrane until equilibrium is reached
What is ion trapping
An acidic drug being more concentrated in the compartment with high pH
**What equation describes the relationship between the local pH and the degree of ionisation
Henderson-Hasselbalch equation
How can a small change in pH affect the drug
May significantly influence the ionisation of a drug, so the rate of absorption or diffusion.
What is required for a drug to be able to pass a lipid layer
Must be in solution and be lipid soluble
What is a lipid-water partition coefficient
The ability of a drug to diffuse across a lipid barrier
It is the ratio of the amount of drug which dissolves in the lipid and water phase when they are in contact
What will happen to a highly lipid soluble drug
It will rapidly diffuse across a cell membrane to reach the brain, ovaries, testes and liver
What will happen to a non lipid soluble drug
May not be absorbed at all e.g. gentamicin
Describe the features of passive diffusion
Occurs along concentration gradient. Non selective Not saturable Requires no energy No carrier is needed Depends on lipid solubility and degree of ionsation
How common is passive diffusion
Its very common
How is common is active diffusion
Relatively unusual
Describe the features of active absorption
Occurs against concentration gradient Requires carrier and energy Specific Saturable Iron ,K , Na , Ca Uptake of levodopa by brain
What is active absorption
Energy dependent transport across membranes against a concentration gradient
What features must drugs have to undergo active absorption (transport)
Resemble naturally occurring compounds
Drug must be reversibly bound to a carrier system
Describe the features of facilitated diffusion
Occurs along the concentration gradient Require carriers Saturable Structure specific No energy required Mixed order kinetics
Where does filtration normally occur
Through channels in the cell membrane
What should the molecular weight of drugs be to undergo filtration
Low molecular size (smaller than the diameter of the pore)
Mmolecular weight of 100 or less
What is the driving force for the passage of drugs in filtration
Hydrostatic or the osmotic pressure difference across the membrane
What type of drugs normally undergo filtration
Water-soluble drugs e.g. urea, water & sugars, renal excretion, removal of drug from CSF & entry of drug into the liver
How can motility affect drug absorption
Speed of gastric absorption will affect speed at which drug reaches site of absorption
Can be affected by other drugs, food/drink and illnesses
Where are most drugs absorped
Small intestine
How can food affect drug absorption
Can enhance or impair rate of absorption
How can illness affect drug absorption
Malabsorption (e.g. Coeliac disease) can increase or decrease rate of absorption
Migraine reduces rate of stomach emptying and therefore rate of absorption of analgesic drugs
How are most drugs given
Orally
What is first pass metabolism
Metabolism of drug prior to reaching systemic circulation
Where can first pass metabolism occur
Gut lumen (acid, enzymes) Gut wall (metabolic enzymes) Liver (hepatic enzymes)
Which factors should be considered when administering drugs using subcutaneous/intramuscular methods
The rate of absorption from these sites change with different physical properties of formulation
Depends on blood flow to site
Needs small volume
Avoids first pass metabolism
Some drugs not well absorbed from this route
What is sublingual absorption
Under the tounge
How does sublingual absorption work
Sublingual absorption from the buccal mucosa bypasses first pass metabolism which will inactivate the drug
The drugs given this way enter the circulation directly e.g. GTN for angina
Describe rectal administration
Drugs given via the rectum bypass first pass metabolism
Absorption tends to be slow
Why are some drugs administered through the rectum
Rectum is often used for drugs which cause irritation of the stomach
What is inhalation/nasal administration dependent on
Type of delivery system, particle size, patient technique
What are the advantages of inhalation/nasal administration
Better for volatile agents
Can be metabolism in lungs
Relatively rapid action
What are the disadvantages of inhalation/nasal administration
About 5-10% absorbed
When is inhalation/nasal administration normally used
For topical effect
To avoid problems of oral absorption (e.g. nausea)
Describe transdermal administration
Avoids first pass metabolism
Can provide controlled release
Few substances well absorbed
Need to be non-irritant
What needs to be considered when deciding for the mode of administration
Purpose and site of drug action (local absorption, avoid first pass metabolism) Disease effects Patients ability to take medicine Speed of action Reliability of absorption
