Drug Absorption Flashcards
Define Pharmaceutical process
Get the drug into the patient
Define Pharmacokinetic process
Get the drug to the site of action
Define Pharmacodynamic process
Produce the correct pharmacological effect
Define Therapeutic process
Produce the correct therapeutic effect
What determines drug pharmacokinetics
Absorption
Distribution
Metabolism
Elimination
What are the methods of administration?
Oral
Intravenous
Subcutaneous
Intramuscular
Other GI - Sublingual
rectal
Inhalation
Nasal
Transdermal
What is absorption?
the process of movement of unchanged drug from the site of administration to the systemic circulation.
What does ADME allow?
understanding of :
Dosage
Drug administration
Drug handling
Patient variability
Potential for harm.
What is sublingual?
Under the tongue
What is Tmax? Oral absorption
The time to peak concentration, important in relieving pain
What is Cmax? Oral absorption
The peak concentration, important in determining a toxic dose
What is the (AUC)? Oral absorption
The area under the drug concentration-time curve
Does the dose effect the tmax?
No, alters cmax
What does the The area under the drug concentration-time curve represent?
The amount of drug which reaches the systemic circulation
What is the Theraputic range?
The range of concentrations at which a drug is active.
What happens above or below the theraputic range
Toxicity
Insufficient pharmalogical action
What does The AUC allows us to estimate?
The amount of drug which reaches the circulation and which is available for action
BIOAVAILABILITY - Used to compare routes of administration
What is the bioavailability of an intravenous drug?
100%
What are the factors affecting Bioavailability? (oral absorption)
Formulation - Slow release preparations
Ability of drug to pass physiological barriers
- Particle size
- Lipid solubility
- pH and ionisation
Gastrointestinal effects
- Gut motility
- Food-Illness
- First pass metabolism (whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation.)
What is dissolution?
The rate a drug breaks up
What is an example of a physiological barrier?
Transport across membranes
What are the methods of transport across membranes?
Passive diffusion
Filtration
Bulk flow
Active transport
Facilitated diffusion
Ion-pair transport
Endocytosis
What does the degree of the ionisation of the drug depend on?
As most drugs are weak acids or bases the degree of ionisation depends on the pH of the environment
What form of the drug crosses the membrane?
The unionised form
What is the distribution of the un-ionised form of a drug?
Should distribute across the membrane until equilibrium is reached - equal concentration on each side.
Where will an acidic drug be most concentrated?
In the compartment with high pH
What does the Henderson-Hasselbalch equation describe?
The relationship between the local pH and the degree of ionisation
What is The ability of a drug to diffuse across a lipid barrier is expressed as?
lipid-water partition coefficient
What is the lipid-water partition coefficient?
The ratio of the amount of drug which dissolves in the lipid and water phase when they are in contact.
Describe passive diffusion
Very common.Occurs along concentration gradient.
Non selective Not saturable Requires no energy No carrier is needed Depends on lipid solubility and degree of ionsation
Describe Active Absorption
Relatively unusual.Occurs against concentration gradient.
Requires carrier and energy. Specific Saturable. Iron ,K , Na , Ca Uptake of levodopa by brainEnergy dependant
What is the structure of drugs that undergo active transport?
They must resemble naturally occurring compounds
Describe facilitated diffusion
Occurs along the concentration gradient
Require carriers
Saturable Structure specific
No energy required
Mixed order kinetics
monosaccharides, amino acids, vitamins
Where does filtration occur?
Through channels in the cell membrane.
What is the milecular size of the drug in Filtration / Bulk Flow/ Pore Transport?
Low molecular size
What is the driving force in Filtration / Bulk Flow/ Pore Transport?
Hydrostatic or the osmotic pressure difference across the membrane.
What does the speed of gastric absorption affect?
speed at which drug reaches site of absorption
What is the effect of food on absorption?
Can enhance or impair rate of absorption
How does illness affect absorption?
Malabsorption (eg Coeliac disease) can increase or decrease rate of absorption
Migraine reduces rate of stomach emptying and therefore rate of absorption of analgesic drugs.
Decribe the Subcutaneous / Intra-muscular route of administration?
Needs small volume
Avoids first pass metabolism
Describe Sublingual, Buccal administration
Sublingual absorption from the buccal mucosa bypasses first pass metabolism which will inactivate the drug.
Drugs given this way enter the circulation directly i.e. GTN for angina
Describe rectal administraion
Bypass first pass metabolism.
Absorption tends to be slow.The rectum is often used for drugs which cause irritation of the stomach.
Describe the benefits of inhalation/nasal administration
Relatively rapid action
Avoids problems with oral absorption
Although only 5-10% absorbed
Describe Transdermal absorption
Avoids first pass metabolism.
Can provide controlled release.
Few substances well absorbed.
Need to be non-irritant.
