Drug Absorption IA%+ Flashcards
1
Q
First pass metabolisim
A
- Metabolism of drug prior to reaching systemic circulation
- Can be a limit on oral route for some drugs. Oral route not useable for insulin
- Gut lumen (acid, enzymes)
- Gut wall (metabolic enzymes)
- Liver (hepatic enzymes)
- These factors can be changed by drugs and disease
2
Q
4 Factors determining drug pharmacokinetics
A
- Absorption
- Distribution
- Metabolism
- Elimination
3
Q
8 Mode of absorption
A
- Oral
- Intravenous
- Subcutaneous (under skin)
- Transdermal (through skin e.g adhesive patch)
- Intramuscular
- Other GI - Sublingual (under tongue), rectal
- Inhalation
- Nasal (spray)
4
Q
Absorption definition
A
•Absorption is defined as the process of movement of unchanged drug from the site of administration to the systemic circulation.
Note: There is always a correlation between plasma concentration of a drug and the therapeutic response.
5
Q
Oral absorption graph
A
- The time to peak plasma concentration (Tmax)
- The peak plasma concentration (Cmax)
- The area under the drug concentration-time curve (AUC)
6
Q
Oral absorption explained
A
- The more rapid the rate of absorption, the earlier the drug concentration peak (Tmax)
- Increasing dose does not affect the time at which peak concentration is reached but does increase the peak concentration (Cmax)
- The area under the drug concentration-time curve represents the amount of drug which reaches the systemic circulation. AUC (area under curve)
7
Q
Therapeutic concentration
A
- A drug is active over a range of concentrations: Therapeutic Range
- Below this there will be insufficient or no pharmacological action.
- Above this toxicity occurs
- The therapeutic index is a measure of the range at which a drug is safe and active.
8
Q
Bioavailability
A
- The proportion of a drug which enters the circulation when introduced into the body and so is able to have an active effect.
- A drug given intravenously has 100% bioavailability.
- The AUC allows us to estimate the amount of drug which reaches the circulation and which is available for action
9
Q
Factors affecting bioavailability►
A
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
10
Q
Physiological barrier
A
Transport across membranes
- Passive diffusion
- Filtration
- Bulk flow
- Active transport
- Facilitated diffusion
- Ion-pair transport
- Endocytosis
11
Q
Diffusion- ionisation
A
- Most drugs do not completely ionise in water.
- As most drugs are weak acids/bases the degree of ionisation depends on the pH of the environment.
- Both ionised and un-ionised forms will be present. The ionised drug does not cross the membrane.
- The un-ionised form should distribute across the membrane until equilibrium is reached – an equal concentration at each side.
12
Q
Diffusion - Ionisation 2
A
- An acidic drug will be more concentrated in the compartment with high pH (‘ion trapping’ ?)►
- The relationship between the local pH and the degree of ionisation is described by Henderson-Hasselbalch equation.
- The result is that small changes in pH may significantly influence the ionisation of a drug and so the rate of absorption or diffusion.
- Proton pump inhibitors and antacids
13
Q
Diffusion- lipid solubility
A
- To pass across a lipid layer a drug must be in solution and be lipid soluble.
- The ability of a drug to diffuse across a lipid barrier is expressed as a lipid-water partition coefficient.
- This is the ratio of the amount of drug which dissolves in the lipid and water phase when they are in contact.
- A drug that is highly lipid soluble will rapidly diffuse across a cell membrane.
- Reach the brain, ovaries, testes and liver
- A drug that is not lipid soluble may not be absorbed at all, for example gentamicin.
14
Q
Passive transport vs active transport pic
A
15
Q
Filtration
A
- Filtration normally occurs through channels in the cell membrane.
- Low molecular size (smaller than the diameter of the pore) with a molecular weight of 100 or less.
- The driving force for the passage of the drugs is the hydrostatic or the osmotic pressure difference across the membrane.
- Generally water-soluble drugs e.g. urea, water & sugars, renal excretion, removal of drug from CSF & entry of drug into the liver
16
Q
Gastrointestinal factors
A
Motility
- Speed of gastric absorption will affect speed at which drug reaches site of absorption (most drugs are absorbed in small intestine).
- Can be affected by other drugs, food/drink and illnesses (esp pain).
Food
•Can enhance or impair rate of absorption.
Illness
- 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 (pain killers)
17
Q
Factors when considering mode of administration
A
- Purpose and site of drug action: Local absorption
- Avoid first pass metabolism
- Disease effects
- Patients ability to take medicine
- Speed of action
18
Q
Inhalation►
A
- Depends on type of delivery system, particle size, patient technique.
- Better for volatile agents.
- Can be metabolism in lungs.
- Relatively rapid action.
- About 5-10% absorbed.
- Usually used for topical effect or to avoid problems of oral absorption (eg nausea).
19
Q
Rectal►
A
- Drugs given via the rectum bypass first pass metabolism.
- Absorption tends to be slow.
- The rectum is often used for drugs which cause irritation of the stomach.
20
Q
Sublingual and Buccal Mucosa (inside of cheeks lining)
A
- 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-chest pain
21
Q
Subcutaneous / Intra-muscular
A
- Can change the rate of absorption from these sites 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 (water soluble better).
22
Q
Transdermal
A
- Avoids first pass metabolism.
- Can provide controlled release.
- Few substances well absorbed.
- Need to be non-irritant.
