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Drugs as exogenous molecules
Any material that is present and active in an individual organism or living cell but that originated outside that organism. Drugs are exogenous molecules that mimic or block the actions of endogenous molecules.
Drug binding
"A drug will not work unless it is bound"
The vast majority of drugs bind to molecular targets that are important proteins within the body. Most bind reversibly to the target protein through hydrophobic and hydrogen bonds plus weaker van der Waals interaction. Some bind irreversibly through covalent interactions.
Ultimately this leads to the formation of a ligand-protein complex which will alter the activity of the protein in some way.
PK - distribution
Where the drug goes after it has been absorbed.
Usually drugs are distributed around the body by circulating in blood plasma and diffusing through the tissues dissolved in the extracellular fluid (ECF).
The ability of a drug to dissolve in plasma or ECF is determined by its aqueous solubility
When studying drug action we usually measure its concentration in blood plasma, assuming that the concentration in blood plasma will be related to the concentration of the drug at its site of action.
Target protein examples
- Receptors for neurotransmitters or hormones
- Enzymes
- Ion channels
- Carrier or transporter molecules
Toxicology
That branch of pharmacology that focuses on the harmful effects of chemicals, including drugs.
In silico modelling of drugs
Chemical companies use modelling techniques to understand complex structure of a target molecule so they can develop drugs that are complimentary in shape so they can fit to the binding site.
Pharmacology
The science of drugs; their mechanisms of action, how their effects can be measured, their discovery, design and development, their actions on the organism and the actions of the organism on them.
Pharmacy
How drugs are formulated and dispensed for use as medicines. Includes the law governing the medicinal use of drugs.
Pharmacodynamics (PD)
“What the drug does to the body” ie the consequences of the drug's actions at a molecular level on the physiology of an organism.
Therapeutics
The medicinal use of drugs to treat or relieve the symptoms of disease. Not all drugs
are medicines.
When distribution is purposefully minimised
Sometimes localisation of a drug is best, as it reduces side effects. Drugs that act throughout the body has systemic actions. Knowledge of PK distribution is used to reduce side effects when using local anaesthetics and “non-sedating” antihistamines.
PK Metabolism and excretion
These determine how long a drug will last for. Drugs are metabolized by the liver into metabolites and then excreted by the kidneys.
Things to consider:
- Liver health
- How effective liver enzymes are (varies due to genetics)
- Whether metabolites are active (eg codeine is broken down into morphine)
- Whether metabolites are toxic
Excretion occurs through urine, faeces, breath, sweat and bile. These factors affect the drug's half life.
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