Druh targets, selective toxicity and therapeutic index Flashcards
What is the etymology of pharmacology ?
What does this imply ?
Pharmakon - from “poison” to “DRUG”
logia - “knowledge/study of”
From describing what drugs do to explaining how they work = the Mechanism of Drug Action
What are the 3 main different ways to name and classify drugs ?
Give examples for each.
Therapeutic use: - Antihypertensive - Antiepileptic Molecular mechanism of action: - beta-blocker - Monoamine oxidase inhibitor - Ca2+ channel blocker Chemical structure: - Benzodiazepine - Catecholamine
What is selective toxicity in pharmacology ?
Selective toxicity refers to the ability of drugs to bind to sites in addition to their main site of action. Such binding may result in unwanted or toxic effects.
Who was one of the first scientists do realize the importance of drug selectivity ?
Ehrlich was one of first to realize the importance of a
drug’s selectivity –> the concept of a “MAGIC BULLET” the idea that a drug might act selectively where its action is wanted.
What did Ehrlich have to say about chemotherapy ?
“In order to use chemotherapy successfully we must search for substances which have an affinity for the cells of the parasite and a power of killing them greater than the damage such substances cause to the organism itself, so that the destruction of the parasite will be possible without seriously hurting the organism. This means we must strike the parasites and the parasites only, if possible, and to do this we must learn to aim, learn to aim with chemical substances!”
How can drug selectivity be achieved (2 principal ways) ?
- Aim to achieve a higher concentration of drug at the desired site of action e.g. eye drops, bronchodilator aerosols, local anaesthetics - Pharmacokinetics = “Drug Motion”
- Design drug to have a higher affinity for desired site of
action. E.g. selective MAO inhibitors, cardioselective beta-blockers - Pharmacodynamics = “Drug Power”
Are drugs targets always invading organisms ?
No, the target may be the patients own tissues (normal or diseased) or an invading organism (bacterium, malaria parasite etc.)
The latter may be very effectively treated by vaccination.
Ar drugs targets always well defined binding sites ?
Support your answer with exemples.
Not always :
- Drug action at a specific binding site e.g. Protein, DNA
- Action not involving a specific binding sitee.g. osmotic diuretic
What are the 5 main classes of specific macromolecular targets ?
- Hormone/neurotransmitter receptors – antagonists or agonists
- Enzymes – cholinesterases, monoamine oxidase
Transporters – e.g. cardiac glycosides acting on Na+/K+ pump.
Ion channels – e.g. local anaesthetics at Na+ channels DNA – some anticancer agents
What can drug specificity be due to ?
The stereochemistry of substrate cofactor binding.
Give an example of a drug without identifiable binding site.
At what concentrations are these less selective drugs usually used ?
The general anaesthetic ether produces surgical anaesthesia only at concentrations above 20mM (much higher concentrations that other drugs with specific binding sites, usually effective at nM/pM concentrations.
The action of these drugs is less affected by changes in
chemical structure. A wide variety of molecules (including
N2) produce general anaesthesia.
How do medical weigh out the benefits and risks of drugs ?
The amount of risk acceptable is influenced by the severity of the medical condition. Significant side effects may be tolerated for life threatening conditions such as cancer.
What is Ehrlich’s Therapeutic Index (TI) ?
Why is in not entirely accurate and what is used instead today ?
Ehrlich’s TI : MAX non-toxic dose / MIN effective dose
–> Difficulties with measurements due to individual variations or sensitivity to drug.
An improved measure uses the better defined doses
producing effects in 50% of subjects:
TI = TD(50) / ED(50)
What is the measure of toxicity in animal studies ?
What does the TI thus become ?
Toxicity = death TI = LD(50) / ED(50)
What is pharmacodynamics ?
“Drug Power”, Potency, Drug Receptor Interaction, Affinity, Efficacy
How does a drug exert its effect, i.e. what does the drug do to the body ?
