Drug names :
- Chemical name : describe type of molecule and location of chemical group
- The generic name or non-proprietary name: commonly used and can be used by any
company marketing the drug
- Trade name or proprietary name: given and only used by the same company
- Street names: derivatives of trade names
Administration => absorption => distribution (via circulatory system) => X => metabolism
(metabolized to an inactive form) => elimination
Pharmacodynamics: X = drug reaches the SA and interact with the Rc.
Routes of administration:
- Oral: must pass from stomach or small intestine then bloodstream
o Stomach: highly acid so might destroy drugs
o If alkaline drugs: they are ionized and cannot pass out in bloodstream so
o Exit to small intestine (more alkaline environment: diffusion (high Cm to low Cm) into
o Liver: might metabolized a part of the drug:
Cytochrome P-450 in endoplasmic reticulum of liver cells (enzyme). This
enzyme is inducible, is activity might be potentiated.
- Snorting: Albert Hoffman found LSD (first acid trip)
- Inhalation: effective method but lung damage (e.g. bagging, huffing)
o Faster than IV. Reaches the brain in 5-8 sec.
- Injection: likely dependent on the blood flow in the injection’s area
o Peritoneal > muscles
o Muscles > skin
o Interperitoneal > intramuscular > subcutaneous
Drug vocabulary: subcutaneous injection = Skin popping
Medical injection: implanting a pellet (boulette) or a depot (e.g. antabuse)
Experimentation: with animals, directly into brain or ventricules.
Distribution of drugs:
- Injection or pulmonary route: diffusion by pores in capillary walls.
- Orally: must be lipid soluble to be absorbed
A volume of blood is totally circulated once every minute so drugs quickly reach the SA.
Which factors affect a drug into the circulation:
o Weak acids drug: ionized in alkaline environment / less ionized in acidic environment.
o Weak base drug: ionized in acidic environment…
o Rate of absorption: percentage of nonionized molecules
o Ph of digestive system: 1.5 (acidic) to 7 (neutral)
o Ionized particles penetrate cell membranes poorly (less fat soluble)
- Lipid solubility:
o Lipid soluble penetrate cell more easily o Lipid soluble are usually unionized.
o E.g. heroin more lipid soluble than morphine.
o Brain: 2% of body weight and 15-20% of blood pumped and protected by BBB.
o BBB reduces diffusion of water soluble or ionized molecule but not impede lipid
soluble or unionized molecule.
o BBB= placenta: 75-100% of drug reach the fetal blood.
- Receptor Binding:
o Drug and receptor bind by opposite charges
o Drug effect is proportional to the fraction of Rc occupied
o Antagonist: bind and block the pharmacological effect
o Naloxone: opiate Rc antagonist
o Drug mixed: bind and produce some pharmacological effect (lower level)
o Nalorphine is a mixed opiate agonist-antagonist
Dose –response curve
- The amount of drug administered (in mg or mg/kg)
- Vertical axis: % of subjects exhibiting the measured effect
- Horizontal axis: the dose
- One response curve for ONE effect
- The ED50: the drug produce an effect in 50% of the subjects
- The LD50: dose kills 50% of the subjects (heroin=350mg, nicotine=60mg)
- Therapeutic index: LD50/ED50, higher the ratio is, and less likely the drug is lethal
- The margin of safety: LD1/ED99
- Tolerance: progressive attenuation of drug effect (shift to the right in DRC)
- Sensitization: augmented repeated administration (shift to the left)
Termination of drug action
- Might be eliminated by the skin, the lungs or the kidneys, sweat (small %), exhalation, urine
- Liver: cytochrome P450, and a lot of different enzyme differing by the level of CYP enzyme
activity. Drugs depress the activity of CYP (SSRI inhibit CYP enzymes)
- Young and aged people: hepatic metabolizing system is less efficient.
- E.g. fluoxetine (Prozac): 2/3 of effects => norfluoxetine: over a week => excreted.
- Renal absorption: pH dependent (weak acid more excreted if urine is alkaline and conversely)
- To treat an overdose we might change the pH of the urine but it’s a slow process
- Eliminate half-life (t1/2): time needed for half of a drug dose to be eliminated.
o E.g. benzodiazepine with short elimination: good as sleep inducing and long