PHARMAKON – Drug
LOGOS – Study
All substances are poison, there is none that isn’t a poison and the right dose
differentiates a poison and a remedy
Paul Ehrlich ▯father of chemotherapy
Advertising is done to a doctor rather than to the public or individual buying the drug
To conduct a trial, manufacturer must
◦ Submit proof of efficacy and safety (Animal data)
◦ Methods to be used in the trial
◦ Drug given to qualified investigators
Placebo effects – placebo is defined as an inert substance masquerading as a drug.
Phases of Trials in Drug Development
Phase I – One or two doses in healthy volunteers
◦ Absorption, distribution, elimination and adverse effects (limited)
Phase II – Shortterm efficacy study. Determine dose for phase III. Safety.
Proof of concept.
Phase III – Longterm study for efficacy and safety.
◦ Randomized controlled trials.
Phase IV – Often referred to as postmarket surveillance – look for possible rare
◦ How many to detect a certain difference (10%)
◦ Who – patient characteristics?
◦ What is being measured? Is it valid? Is it the appropriate outcome?
◦ Quality of Life. Do we improve quality of life.
◦ Remove bias, neither the physician who does the assessment nor the patient
knows the treatment the patient is receiving.
◦ Compare two drugs – Group A gets drug A and Group B gets drug B for three
weeks and then they switch such that Group A now gets drug B.
Lecture 3: Potency ▯how much drug must be given to obtain particular response?
Efficacy à how much pain can I relieve with the drug?
Efficacy is more important than potency
As dose increases so does the response.
◦ Variability in the response between individuals.
◦ Variability between drugs.
Therapeutic dose must be less than the toxic dose (chemotherapy at toxic levels)
Toxic dose 50 ▯Dose toxic to 50% of animals
Median effective dose 50 ▯Dose effective in 50% of animals
Therapeutic Index = TD50/ED50
Higher number = lower probability drug will cause toxicity
Selective Toxicity ▯started from chemotherapy d▯ iscovered by Paul Ehrlich
Definition – Harm to one organism without harming some other kind.
◦ Weed killer without harming the crop
◦ Kill a parasite without harming the host (human) lice, helminths, bacterial infections,
Antimetabolites ▯Design of anticancer drugs
◦ Designed to take advantage of differences between cancer cell and normal cell.
◦ Cancer cells continuously divide as compared to normal cells, thus can take
advantage by blocking DNA synthesis, affects both normal and cancer cell but more
effect on cancer cell
Bacteria have a cell wall, mammalian cells do not. Penicillins block cell wall
synthesis in the bacteria, no effect on human cells.
Acute à short term
Chronic à 3 months or longer
Age à very young and the elderly respond to drugs very differently
Babies do not have proper and developed organ functions to take drugs
Disease à liver is the main organ that handles drugs…impaired liver functions leads to the
drug being handled impaired
Types of Adverse Effects
1. Extension of therapeutic effect
◦ Oversedation with barbiturates or benzodiazepines
◦ Nonselective action of the drug.
2. Unrelated to main drug action
◦ Digitalis and nausea ◦ NSAID – GI Erosions
3. Idiosyncrasy ▯drug response out of population norm
◦ Usually genetically mediated – eg. lack an enzyme or changes in the
manner in which the drug is handled.
4. Drug allergy
◦ Need prior exposure to form antibodies to the drug – penicillin
Why did Michael Jackson die?