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Drug
any substance that alters behavior, disease state; undergoes a metabolic process
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therapeutic vs. toxic
the difference depends on dose. not all drugs are therapeutic
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Paraselsus
1400 Ad found that all substances are poisonous, the dose determines the therapeutic and toxic responses
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Hippocrates
~300 BC; father of medicine
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Socrates
first person publicly executed with drugs. he died from hemlock
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Hemlock
drug that killed Socrates
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Coniine
active substance in hemlock; binds by nicotinic receptor antagonist
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receptor
protein "in or within" a cell where a drug can bind
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Agonist
The drug acts as the agonist (ligand) that bonds to the receptor
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Antagonist
occurs when the effect is blocked
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Antagonist bonds to the opposite side of the receptor of the drug
there is no effect
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Competitive antagonist
drug bonds to the same side as the antagonist
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Sympathetic
releases Ach at the nicotinic receptor at pre-ganglionic synaps and then NE and Epi at the smooth muscle
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Parasympathetic
releases Ach at nicotinic receptor at skeletal muscle
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Claude Bernard
1856; investigated curare (works similar to coniine in that it binds to a nicotinc receptor modulator)
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Muscarinic receptor
smooth muscle
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Nicoinic receptor
skeletal muscle
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acetylcholinesterase
breaks AcH into choline
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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
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Langley and Ehrlich
Receptor theorem in ~1900 AD
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Henry VIII
royal company of physicians
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1938; what did congress pass?
the food, drug and cosmetic act because of sulfur based drugs
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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
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Kefaver Harris Amendment (1962)
forced companies to perform pre-clinical studies which meant there was an increase in animal studies
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What was the reason why Kefaver Harris Amendment was passed?
thalidomide caused birth defects in pregnant women mainly in the U.K.
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How much money does it take to bring a drug to the market form start to finish?
800 million to 3 billion dollars
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Four stages of marketing a drug from start to finish
Pre clinical RND, Clinical, ADA, Post-marketing survellance
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Pre-clinical RND
discovery of drug by chemists to find new durg, animal testing and synthesiss
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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)
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Clinical
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
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ADA
new drug application to FDA
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Post-marketing surveillance
anything that happens at this stage the company is held liable by the FDA for any adverses
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Why are beagles used?
for cardiovascular studies
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How can drugs reach the receptor?
orally, rectally, IM, IV, sub Q, internasally, sublingal, inhaling
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ADME
absorption, distribution, metabolism and excretion
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What is the best way to distribute drugs all over the body?
bloodstream
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Before a drug reaches target, it must be absorbed by?
passive diffusion (very small amount will travel by active transport)
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Passive diffusion
lipid rich- must be lipid soluble because of the lipid bilayer int he membrane
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charged drugs
have a more difficult time crossing the membrane weak acid (-) and weak base (+)
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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
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Weak acid (ex. ibuprofen)
acid drugs absorb in the stomach (ph ~12) because stomach is an acidic environment
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Weak base (ex. propanonol)
absorbs in the intestine
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