Pharmaceutics Flashcards
Describe the main properties of peptides/proteins compaterd to Traditional small molecule medicines
Link the challenges in protein drug delivery to the intrinsic properties of proteins and the anatomical physiological barriers in the body
Absorbtion of the drug - proteins are large hydrophillic molecules
Extravascular access is difficult, even if we inject proteins into the vein it will circle around
Poor stability
Complex pharmacological action
The ability of proteins to cross the endothelial barrier is a major limiting facor in determining protein drug biodistribution
Explain the elimination of proteins
Small peptide molecules are removed via glomerular filtration, though the cut off is 60kDa and they cannot be negatively charged
One example of protein elimination is the removal of old serum glycoproteins and unwanted macromolecules via the Asialoglycoprotein receptors. The terminal sugar residue on the protein is not recognised, howeber when it is cleaved off, it is a signal that the protein is no longer desirable and can be eliminated by lysomal degradaion
why are specific preformulation choices are made in relation to the physical, chemical and biological instabilities of proteins
In terms of physical stability, proteins can easily lose their native 3D structure(denature) whuch will result in the proteins aggregating and then precipitaing which can happen as a result of hydrophobic conditios, pH, temp etc.
In terms of Chemical stability, multiple different amino acid functional groups which make the proteins have many functional groups which can react with the chemical components inthe body which may lead to unfolding, misfolding, aggregation, or increased susceotibility to protease degradation
In terms of biological stability, proteins are biologically unstable as they are greatly affected by the enzymes in the digestive system and the gastric acid
Proteins are not stable molecules there are a few changes we may need to make to achieve stable, active formulation
Salts can be used to stabilise ionic residues, choice of appropiate conditions need to be considered when formulation
indicate and explain the recommended route of administration of protein drugs and discuss why other routes are not suitable
- Parenteral routes are the only way of successfully administering protein drugs
- Problems are repeated administration makes it inconvenient, Patient compliance as patients may not like to have insulin injections, Stability of dosage form over time
Non-parenteral routes have only a few exceptions that work This is due to poor absorption and metabolic instability due to the plethora of proteases arount the GIT which can break down the enzyme
What is the Parenteral drug route
A route of administation other than the oral route
It is compsed of IV, IM, SC, Intradermal
They require steriliy as they bypss infection barriers therfore should be of the highest purities.
Most of the aforementioned routes only tolerate small volumes of injections with IV taking the most
Why do we use Parenteral routes
Rapid onset, Possible local effect, 100% availabilty which is preferrable to drugs that would be degraded in the gut
What are possible issues of parenteral administration
Air embolism, if there are air bubbles in the injection
Bleeding in patients wih haemophilia
Cost in terms of training professionals and specialised formulation production
Fever from pyrogens if the injection is not completely pure
Overdosage
Sepis
Thrombosis
What are the advantages and disadvantages of IV delivery
Advantages include: Rapidity - almost immediate effect - liquids injected into the arm of a human appear in the leg within 20-30 seconds
More predictable response than other routes - no issue with poor or incomplete absorption; blood levels are more predictable
The preferred route for orally inactive drugs
However IV delivery Requires extensive training to place the right amount of drug in the correct
Steriliy must be maintained
Dosage errors can lead to serious injury or death.
The complications are very serious(e.g air embolism)
What is the biopharmaceutics of IV drug delivery
- The drug is injected into the vein → Passes to the heart → then through pulmonary circulation → then the heart pumps it around tissues
- Blood flow is slow in tissue so the absorption is efficient
- Drug returns to the heart through the liver where metabolism begins
- A round trip takes 10-30 seconds
A Bolus injection is a single dose of a drug given over a short period of time which leads to a rapid increase in plasma drug concentraion
- In contrast to an intravenous Bolus injection, an IV infusion administers a large volume of fluid at a slower rate
- This ensures that the drug enters general circulation at a constant rate
What is the difference between IV injections and IM
IM injections do not need to be water miscible
IM injections are as far as possible form major blood vessels to avoid injuries, commonly in the abdomen or Gluteus maximmus. In infants he gluteus is mainly formed of fat so instead it given in the deltoid of the upper arm.
Im involvess. the release of drug into intercellular fluid and from their absorbtion into the blood and lympahatics.
- Extremely hydrophobic drugs do not dissolve in the intercellular fluid
- Strongly ionised or extremely water-soluble drugs will not be able to cross the capillary membrane there fore it needs to be a mix of the two
How is insulin usually given
Subcutaneously into the fatty and connective tissues between the skin
