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Chapter 3

PHAR 100 Chapter Notes - Chapter 3: Thiazide, Multiple Drug Resistance, Victor Ling

Pharmacology and Toxicology
Course Code
PHAR 100
Bill Racz

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Lesson A.3 Dose-Response Curves and Selective Toxicity
- Distinguish between the potency and efficacy of a drug
- Define ‘selective toxicity’
- Describe how organoarsenicals were designed to achieve selective toxicity
- State the reason for selective toxicity of sulfonamide (sulfa) antimicrobial agents
Potency and Efficacy of Drugs
- Potency refers only to the amount of drug that must be given to obtain a particular response
- Efficacy refers to the maximum effect that is obtainable with a given drug (range of treatment);
very important characteristic
o Ie. Aspirin is only effective in relieving mild to moderate pain, while morphine is able to
relieve pain of nearly all intensities hence it has a greater efficacy
- Thiazide diuretic efficacy < Furosemide diuretic efficacy
Selective Toxicity
- Selective toxicity refers to harm of one without harm to another (ie. pesticides)
- In New Brunswick, extensive aerial spraying of forests with insecticides were used to kill the spruce
bud worm
- In Nova Scotia, a mixture of the herbicide 2,4-D and 2,4,5-T were sprayed on forest to eliminate a
plant enabling another more valuable species to grow
- Each of these examples impose threats to surrounding plant and animal life in parallel with the
target species
- Selective toxicity can be achieved via a selective agent. This agent will accumulate within the target
species and eventually kill it
- Sulphuric acid (10%) is a toxic agent of weeds, yet does not influence cereal grass
- A combination of anticancer drugs is often used to treat cancer two different multidrug resistance
proteins have been identified (both by Canadian researchers)
o P-glycoprotein identified by Dr. Victor Ling (Toronto, 1976)
o Multidrug resistance protein (MRP) identified by Dr. Susan Cole and Dr. Roger
Deeley (Queen’s University, 1992)
o These proteins have been found to be responsible for the extrusion of anticancer drugs in
some types of resistant cancer cells; both of these proteins have abnormal function in the
body, but if overproduced by a tumour, can result in drug resistance
- Chemotherapy (example of selective toxicity)
o Is the process by which the use of drugs injures an invading organism without injury to the
o Pasteur and Koch demonstrated that diseases of many types are caused by microbes;
19th century
o Paul Ehrlich (Germany, 1854) the father of chemotherapy
At the time it was believed that drugs acted by stimulating the body’s defense
system Ehrlich proved this wrong
The drug Atoxyl (an agent against parasites in the body but not the test tube) was
shown by Ehrlich to convert from one form into its active form to then attach to
the parasite within the body
Studied arsenic and synthesized many derivatives of these compounds; these
compounds were tested for their ability to cure syphilis in rabbits the 606th
compound Salvarsan (‘to save health’) could do just that
- Sulfonamides
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