Target based drug discovery Flashcards
What is target based drug discovery?
This means that a certain biomolecule has been identified as problematic, and a drug will be developed to change its behaviour, with the aim of certain final effect.
What is pharmacokinetics?
Pharmacokinetics (How does the body deal with drugs?)
- Fate of drugs once they have been ingested
- Variability of response between patients
- How drugs move through the body in the processes of absorption, distribution, metabolism, and excretion - (ADME).
What is pharmacodynamics?
Pharmacodynamics (What effect drugs have on the body?)
- Is the study of how a drug binds to its binding site
- The drug not only has to bind to its target, it has to reach it in the first place
- For an oral drug that involves a long journey with many hazards to be overcome.
Drugs may be…
- Acidic
- Neutral
- Basic
- Small organic molecules
- Large polymers
- Other compounds with completed chemistries
What does the route of administration depend on?
- Physical & chemical property of the drug (e.g. pH, solid, liquid, solubility)
- Site of desired action – localised or generalised
- Effect of digestive juices and first pass metabolism of drug
- Accuracy of dosage required
- Condition of the patient e.g. unconscious, vomiting, etc.
What are the different types of local routes?
- Topical
- Deeper tissue
- Arterial supply
What are examples of topical administration?
- Lotion
- Cream
- Spray
- Drops
What are examples of deeper tissue administration?
- Intra-articular (joint)
- Intra-medullary (bone marrow or spinal cord)
- Intrathecal pump (spinal fluid)
What are examples of arterial supply administration?
- Angiography
- Anti-cancer drugs
What is topical administration?
External application of the drug to the surface
What is deeper tissue administration?
Certain deep areas can be approached by syringe and neede
What is arterial supply administration?
Closed intra arterial injection
What are local routes?
When you put the drug where you want it to go.
What are systemic routes?
Getting the drug into the whole system
What are the different types of systemic routes?
- Oral
- Sublingual
- Inhalation
- Intradermal & subcutaneous
- Intravenous
What is sublingual?
- Kept under the tongue or crushed and spread over the mouth
- Absorption through mucous membrane with good access to arteries
What are the advantages od sublingual?
- Rapid absorption (< 1 minute)
- Liver is by passed – directly in the systemic circulation
- Can be used on unconscious patients
What are the disadvantages of sublingual?
- Can only be lipid and saliva soluble drugs
- Uncooperative patients
- Irritate the mucosa
What is intravenous?
Its injected directly into the vein
What are the advantages of intravenous?
- Quick action – good for emergencies
- Desired concentration easily obtained
- Doesn’t pass through the liver so it won’t be metbolised
- Can be used on unconscious and uncooperative patients
- Onset of action between 15-30 seconds.
What are the disadvantages of intravenous?
- Costly – special apparatus
- Local irritation
- Self medication not possible
- Action cannot be stopped
- Aseptic and antiseptic measures must be maintained
- Extravasation (escape of drug into tissue )may cause severe irritation
What are intradermal, subcutaneous, and intramuscular?
Other types of injections
What is intradermal?
- Least invasive
- Involves getting into the layers between the skin
- Used for testing allergies
- Onset of action between 10-30 mins
What is subcutaneous?
- Deeper than intradermal
- Below the skin but not reaching the muscle.
- Used for insulin
- Can be done themselves.
- Onset of action between 10-30 mins
What is intramuscular?
- Deepest of the 3
- Where RNA vaccines go
- Onset of action between 10-30 mins
What are the advantages of oral?
- Self medication possible
- Large area for absorption
- Procedure simple- no additional cost
- Slow action – safe for some risky drugs
- Both solid and liquid forms of drugs can be administered
What are the disadvantages of oral administration?
- Irritant and unpalatable drugs cannot be administered
- May induce nausea and vomiting
- Not useful when vomiting and diarrhoea present
- Or patient unconscious
- Can be destroyed by gastric juices e.g. penicillin G and insulin
What does Lipinski’s rule of 5 state?
States that in general an orally active compound has no more than one violation of the following criteria.
< 5 hydrogen bond donors (typically NH + OH)
< 10 hydrogen bond acceptors (all N and O atoms)
A molecular weight < 500
Octanol-Water partition coefficient (log P < 5)
P = [Aorg]/[Aaq]
