GO - Targets identified from studying the effects of drugs and toxins Flashcards
Put these steps for the drug discovery process in order:
- Lead optimisation
- Marketing authorisation
- Target identification
- Formulation development
- Lead generation
- Pharmaceutical and Toxicity profiling
- Target validation
3, 7, 5, 1, 6, 4, 2
For a drug molecule to exert a pharmacological effect, an interaction between the ___ and the _____ must occur.
drug molecule
target molecule
This interaction between the drug molecule and target molecule requires:
1 - functional groups on both target molecule and drug molecule
2 - appropriate orientation in space of the drug functional groups relative to the target molecule functionality.
3. and can be explained in terms of bonding and reactivity between the two molecules.
State the bond types and order them from strongest to weakest.
Covalent Ionic Ion-dipole Hydrogen Hydrophobic VWF
What is a pharmacophore
The combination of parameters essential for activity
Pharmacophoric descriptors are used to define a pharmacophores, including:
ionic, H-bonding, hydrophobic and eletrostatic interaction sites, define by atoms, ring centers and virtual points
The pharmacophore can be considered:
- the largest common denominator shared by a set of. inactive molecules
- the largest common denominator shared by a set of. active molecules
- the largest common numerator shared by a set of. active molecules
- the smallest common denominator shared by a set of. active molecules
- the largest common denominator shared by a set of. active molecules
Structurally relevant (but different) molecules from natural resources frequently have similar ( but subtly different) ________, such as ________
biological activities
duration of action
Where did drugs come from in the past?
Food and toxins
What are two ways in which you can improve pharmacodynamic activity?
- Greater potency –> same effect with lower dose
2. Greater selectivity –> fewer s/es due to interaction with other targets
Most drugs have ‘side effects’. This is often the result of…
activity on other targets.
Opium alkaloids are obtained from the latex of….
Papaver somniferum
What properties are opium alkaloids known for?
sedating and analgesic.
Name a few opium alkaloids.
Noscapine Thebaine Papaverine Morphine Codiene
How is morphine administered
Subcutaneous injection
What activity does morphine show?
- analgesic
- antitussive
- reduced gastric motility
- respiratory depressant
Morphine side effects
- Constipation
- Nausea and vomiting
- Drowsiness
- Respiratory depression
What is an opiate antagonist?
Nalaxone
Order the functional groups in order of polarity.
Amide > Acid > Alcohol > Ketone > Aldehyde > Amine > Ester > Ether > Alkene > Alkane
What is the general term for opioid peptides
Endorphins
Higher affinity for analgesic receptors =
greater potency
Change susceptibility to metabolising enzymes =
change in duration of action
Changing lipophilicity will
change penetration of CNS
u-receptors are associated with all the main pharmacological effects of morphine:
- analgesia
- respiratory depression
- emesis
- tolerance
- withdrawal symptoms
- reduce gastric motility
