Week 1 - Pharmacokinetics Flashcards
Define Pharmacokinetics
The study of the passage of a drug through the body.
- ‘What the body does to the drug’
What are the processes of Pharmacokinetics
- Absorption
- Distribution
- Metabolism
- Excretion
What is Absorption
The process by which an unchanged drug proceeds from the site of administration into the blood.
Why is drug formulation important
The drug formulation is important because the faster the rate of dissolution, the more rapidly the drug can be absorbed.
What type of oral drug is absorbed the fastest
Liquids
How does a drug get absorbed
A drug needs to cross a membrane and enter the blood vessels to reach the target site
What are the two main processes for the drug to cross membranes
- Passive diffusion
- Carrier-medicated transport
Explain the structure of membranes which facilitates passive diffusion
- The membrane typically consists of a lipid bilayer
- E.g lipid soluble drugs can easily pass through the lipid membrane
- While Ionised (charged) drugs have difficulty passing the membrane.
Define solubility in drugs
- The more soluble the drug is, the more rapidly it is absorbed
- E.g high lipid solubility increase drug absorption
Define the difference between Ionised and Un-ionised
- Ionised (charged polar) are water-soluble, it’s lipid-insoluble which means it does not diffuse readily through the cell membranes of the body
- Un-ionised (non-polar) are more lipid-soluble and can easily cross membranes
What drugs can easily pass the ‘blood-brain barrier’
Lipid-soluble drugs can easily pass the BBB, while water-soluble drugs are ionised and cannot enter the brain
Explain how the surface area affect drug absorption
- A larger absorbing surface area results in a greater drug absorption and the more rapid effects.
- E.g Small Intestine - Large surface area which means drugs are efficiently absorbed
Provide an example where the surface area affect the drug absorption
- Sublingual route has a rich blood supply which enhances absorption
- Subcutaneous route has poor vascular sites which delays absorption
Explain how the drug formulation affect drug absorption
- Drug formulation can be manipulated to achieve absorption characteristics
- E.g Enteric coated drugs allows sustained release which are useful for drugs that have shorter elimination half-life
Explain how the route of administration affect drug absorption
It affects both the rate of onset of action and the magnitude of the therapeutic response
Explain why medication are administered on an empty stomach
- The stomach is not a major site for drug absorption
- Ensure dissolution of the drug and rapid passage into the small intestines
Define the first-pass effect
Metabolisation of the drug (mostly by the liver), resulting in a reduced concentration of the active drug
Define Bioavailability
The proportion of the administered does that reaches the systemic circulation intact
Explain the first-pass metabolism
- Orally administered drugs are absorbed in the small intestine.
- Then travel through the portal vein to the liver.
- The liver metabolizes a portion of the drug (first-pass metabolism)
- The remaining amount enters systemic circulation.
Provide an example of the first pass metabolism
- You take a drug that contains 100mg
- 80mg of the drug reaches the liver as 20mg isn’t absorbed
- 60mg is extracted in the first pass through the liver
The bioavailability of the drug:
- 20% - As only 20mg is available for distribution and to produce an pharmacological effect
Define Distribution
The process of reversible transfer of a drug between one location and another (one of which is usually blood) in the body
Explain Plasma Protein Binding
- When the drug enters the systemic circulation, a proportion of the free drug molecules binds to proteins which is the ‘drug-protein complex’
- The free drug then enters the tissues to exert a pharmacological effect.
- Drug-protein complex acts a reservoir, slowly releasing more free drug as needed.
Explain the Plasma Protein Binding of Warfarin
- Warfarin has the highly protein bound drug (99%)
- 99% is bound to plasma proteins while 1% of free drug is for distribution
Why can low levels of albumin in the blood be dangerous when administering protein-bound drugs
- Low albumin levels increase free drug concentration, leading to stronger effects and a higher risk of toxicity.
- Dose adjustments may be needed (e.g., for phenytoin, warfarin).
What is tissue binding in lipid-soluble drugs, and how does it affect their duration of action?
Tissue binding occurs when lipid-soluble drugs bind to adipose tissue because it is stable and has low blood flow. This leads to the drugs being stored in the fat, which results in a longer duration of action due to the drug being released slowly over time.
Explain the structure of Blood-brain barrier
- Comprises the endothelial cells of brain capillaries, which are joined to each other by tight junctions
- It provide further protection to the brain
- The lipid-soluble drugs does penetrate into the brain and cerebrospinal fluid
In what situations can other drugs cross the blood-brain barrier
- In meningitis, the blood–brain barrier can become ‘leaky’ (inflammatory process)
- Allowing access of drugs such as penicillin (that would not normally) > allow treatment of meningitis
What is Drug metabolism
The process of chemical modification of a drug, mostly by enzymes
- The liver is the primary site of drug metabolism
What is the difference between pro drug and active drug
Active Drug
- Drug takes effect directly
Pro drugs
- Most drugs are less active after drug metabolism.
- However, pro drug require activation (in the
liver) in order to elicit a therapeutic action
- E.g. Anti-rheumatic- leflunomide
What is excretion
- The loss of a parent molecule or a metabolite* in, for example, urine or bile.
- The kidneys> the main organs of excretion.
- Once in the hepatocyte, the drug becomes available for metabolism by enzymes or for excretion into bile
Define metabolites in hepatocyte
- Diffuse
- Be transported across back into blood for excretion in urine
- Be transported into the bile> passed into the duodenum > excreted in faeces
Define half life
The time required for the concentration of a drug in the body to reduce by half.
What are two processes that influence half life
- The smaller volume of distribution (degree of a drug distributing in the body) > shorter half-life
- The higher clearance > shorter half-life
