any substance that alters behavior, disease state; undergoes a metabolic process
therapeutic vs. toxic
the difference depends on dose.not all drugs are therapeutic
1400 Ad found that all substances are poisonous, the dose determines the therapeutic and toxic responses
~300 BC; father of medicine
first person publicly executed with drugs. he died from hemlock
drug that killed Socrates
active substance in hemlock; binds by nicotinic receptor antagonist
protein "in or within" a cell where a drug can bind
The drug acts as the agonist (ligand) that bonds to the receptor
occurs when the effect is blocked
Antagonist bonds to the opposite side of the receptor of the drug
there is no effect
drug bonds to the same side as the antagonist
releases Ach at the nicotinic receptor at pre-ganglionic synaps and then NE and Epi at the smooth muscle
releases Ach at nicotinic receptor at skeletal muscle
1856; investigated curare (works similar to coniine in that it binds to a nicotinc receptor modulator)
breaks AcH into choline
VX and sarin
used in parkinson's disease; they are acetylcholinesterase inhibitors that allows Ach buildup in the synaptic cleft. this buildup leads to respiratory arrest
Langley and Ehrlich
Receptor theorem in ~1900 AD
royal company of physicians
1938; what did congress pass?
the food, drug and cosmetic act because of sulfur based drugs
Sulfur based antibiotics
lipid soluble so they are hard for the body to absorb. Combined ethylene glycol for sulfur based drugs. Ethylene glycol is an antifreeze that causes crystals to form in the liver
Kefaver Harris Amendment (1962)
forced companies to perform pre-clinical studies which meant there was an increase in animal studies
What was the reason why Kefaver Harris Amendment was passed?
thalidomide caused birth defects in pregnant women mainly in the U.K.
How much money does it take to bring a drug to the market form start to finish?
800 million to 3 billion dollars
Four stages of marketing a drug from start to finish
Pre clinical RND, Clinical, ADA, Post-marketing survellance
discovery of drug by chemists to find new durg, animal testing and synthesiss
Animal Testing (LDSO)
usually the first test is done to see how much dosage can be taken; zebra fish (first animals that companies test), mice and rats, dogs (specifically beagles), monkeys (when they are near death; we are nicer to them)
Phase I, II and III. Phase I trials are usually less than 50 people and are usually college men who need money. Phase II and III just have more people
new drug application to FDA
anything that happens at this stage the company is held liable by the FDA for any adverses
Why are beagles used?
for cardiovascular studies
How can drugs reach the receptor?
orally, rectally, IM, IV, sub Q, internasally, sublingal, inhaling
absorption, distribution, metabolism and excretion
What is the best way to distribute drugs all over the body?
Before a drug reaches target, it must be absorbed by?
passive diffusion (very small amount will travel by active transport)
lipid rich- must be lipid soluble because of the lipid bilayer int he membrane
have a more difficult time crossing the membrane weak acid (-) and weak base (+)
neutral drugs with no charges
pass the membrane easily; ex. ethnylesterdiolnorethindione (birth control); since neutral drugs pass easily they take a while to take affect
Weak acid (ex. ibuprofen)
acid drugs absorb in the stomach (ph ~12) because stomach is an acidic environment