PHAR 100 Module 1 Flashcards
drugs
any substance received by a biological system that is not received for nutritive purposes, and which influences the biological function of the organism
pharmacology
the science of drugs, including their uses, effects and modes of action
ancient China
classified drugs according to taste
ancient Greece
opium, morphine
influence of religion
medicine men were physicians and priests
curare
- acts on animals voluntary muscles, causing paralysis and death
- used by anesthetists during surgery, helps relax muscles
ergot
- incorporated in bread in Middle ages, killing many
- symptoms: mental frenzy, convulsions, constriction of blood vessels that led to limbs causing them to die, violent contractions of uterus
- in modern era, 2 active principles have been isolated from ergot
- ergotamine → treatment of migraines, constricts blood vessels to head
- ergotovine - arrest uterine bleeding after birth
drugs acting on brain → reserpine and chlorpromazine
- reduce tension, anxiety, lower BP
- chlorpromazine is preferred to reserpine for management of the mentally ill
- makes people placid
drugs acting on brain → lysergic acid diethylaminde (LSD)
psychedelic effects
drugs acting on brain → anaesthetics
- nitrous oxide → useful for extracting teeth
- ether → used in surgery
drugs acting against infectious diseases → organoarsenicals
- Paul Ehrlich (father of chemotherapy)
- bound to parasites
drugs acting against infectious diseases → sulfa drugs
1st successful synthetic drugs for treatment of bacterial disease → termed antibacterial compounds
drugs acting against infectious diseases → penicillin
- 1st antibiotic
- use in therapy of gram-positive bacterial diseases
drugs acting against infectious diseases → streptomycin
treatment of tuberculosis and gram-negative bacterial diseases
drug development process
- identify a biological target
- determine pharmacological effects
- if compound shows promise, it will be identified as a lead compound
- enters more studies for safety and efficacy
stages in drug development → drug discovery
- 3-6 years
- research and discovery of target (25,000 compounds)
- preclinical testing → safety & efficacy (30 compounds)
stages in drug development → clinical trials
- 6-7 years
- phase 1 → safety & tolerability (5-30 compounds)
- phase 2 → effectiveness, safety & pharmacokinetics (2-3 compounds)
- phase 3 → effectiveness & safety (1 compound)
stages in drug development → health Canada/FDA approved drug
- health Canada review and manufacturing → drug approval and production
- phase 4 → long-term safety
toxicology studies
determine the effect of the new drug on organ systems other than the targeted organ
pharmacology studies
determine the detailed mechanism of action of the new drug
phase 1 clinical trials
- 20-100 healthy volunteers
- absorption, distribution, elimination and adverse effects are studied
phase 2 clinical trials
- conducted in patients who have the disease/condition (100-500 ppl)
- looks at safety
phase 3 clinical trials
- controlled randomized clinical trials
- test 1000+ ppl
- conducted at city centres for diversity
- goal is to determine whether drug is safe/effective
target population
group of patients for whom the drug is intended
inclusion/exclusion criteria
define characteristics of patients to be used in the study; try to eliminate all other variables
ethical considerations and consent
informed consent
study population randomized allocation
- randomization ensures that patients with different characteristics are equally distributed between the treatment and control group, maximizing the comparability of the groups and removes bias
treatment and control groups
- treatment groups receives drug
- control group → placebo or gold-standard drug
blinded assessment
double-blind
outcome
results of treatment measured in an objective, reliable manner
compliance
how often the patient takes the drug
quality of life
important when considering usefulness of drug
analysis of results
experimental drug compared to control drug using stats
generic vs. brand name
- if a drug undergoing development shows promise and a manufacturer wants to put it on the market, then a generic name for the drug is selected (and apply for a patent for 20yrs)
- after patent expires, other manufacturers can make copies of the original brand name drug and sell it under their own brand name
- brand name and generic drug will contain the identical active ingredient as the original brand name drug, in the same amount and dosage form
bioavailability studies
- compares blood levels after administration of both the brand name drug and the new brand name/generic drug to healthy volunteers
- ensures the 2 drugs are bioequivelent
drug advertising techniques
- catch audience attention
- use celebrities or authorities to endorse product
- fear
- offering easy solution for problems
- before-after technique
- discredit drugs produced by other manufacturers and praise yours
receptors
- normally bound to and activated by endogenous ligands (hormones and neurotransmitters)
- most drugs can mimic the action of, or block the effect of, the endogenous ligand at the receptor
- drugs that bind to and stimulate a receptor are called agonists, and drugs that bind to but block the response at a receptor are called antagonists
- lock and key analogy
dose-response relationship
- intensity of the pharmacological effects produced by a drug increases in proportion to dose
- for a drug to achieve it’s desired response, many receptors need to be activated at once
- as dose/concentration of drug increases, more and more receptors are activated
- a threshold exists, where a certain number of receptors need to be activated before an effect will be seen
dose-response curve
how much drug you need in your body to see a specific effect
efficacy
- the maximum pharmacological response that can be produced by a specific drug in that biological system
- amount of drug needed doesn’t matter, the maximum effect the drug can produce matters
- efficacy is more important than potency
potency
- the dose of a drug that is required to produce a response of a certain magnitude, usually 50% of the maximal response for that drug
- drug A is more potent than drug be (need to take less of drug A to achieve the same effect from drug B)
therapeutic range
the aim of therapy is to give a dose that keeps blood concentration above the minimum concentration, but below the concentration that produces a toxic response
pharmacokinetics
- movement of drug into, through and out of the body
- 4 major processes are involved: absorption, distribution, metabolism, excretion
topical administration
- on the skin → drugs applied to skin for local effect can be absorbed and produce a systemic effect
- through the skin → transdermal drug delivery is the application of a drug to the skin for absorption into general circulation for a systemic effect; steady supply for several days; bypasses enzymes in body
- inhalation → drugs are rapidly absorbed from the lungs; local and systemic effects
enteral administration (enter blood through mouth of GI tract)
- mouth → enzymes in liver can decrease amount of active drug left to enter circulation
- rectum → digestive enzymes of stomach and intestine are bypassed
- sublingual and buccal → enzymes of stomach, intestine and liver are bypassed
parenteral administration
- intravenous (IV) → can be used for drugs that are poorly absorbed; needs to be made into a solution in water for injection
- intramuscular → drug is injected deep into a muscle
- subcutaneous → drug is injected into deepest layer of skin
absorption
- movement of a drug from the site of administration into the blood
- occurs by 3 ways: diffusion through aqueous pores, diffusion through lipids; active or carrier-mediated transport
distribution
- the movement of a drug from the blood to the site of action and other tissues
- can result in termination of the therapeutic effects of some drugs
metabolism
- the conversion of a drug to a different chemical compound
- drug must be water-soluble to be eliminated by the kidneys
biotransformation
- occurs in the liver
- phase 1 → add/unmask a functional group on the drug so phase 2 can add a large water soluble molecule; P450 - enzymes capable of biotransforming drugs are found in most tissues, but are present in [high] in the liver
- phase 2 → add a large water soluble moiety to the product resulting from phase 1, making the metabolite water soluble for excretion
excretion
- moving the drug and its metabolites out of the body
- kidneys, GI tract (feces), lungs, saliva/sweat, breast milk
half-life
- the time needed for the liver and kidney to remove half the drug from the body
variations in drug response
- genetic factors
- environmental factors
- other disease states
- altered physiological states (ex: pregnant)
- other drugs present
adverse effects
- extension of therapeutic effect
- unrelated to main drug action
- allergic reaction
- drug dependence or addiction
- teratogenesis (birth defects)
- adverse biotransformation reactions
drug toxicity
- assessed using a measure called the therapeutic index, which is calculated by the formula: TI = TD50/ED50
- TD50 = toxic dose in 50% of the population
- ED50 = effective dose in 50% of the population
- therapeutic index tells you how safe the drug is
- the higher the therapeutic index, the safer the drug
drug-drug interactions
occurs when one drug changes the pharmacological effect of a second drug; occur during absorption or metabolism
drug-food interactions
involve the interference of food with drugs taken con-currently
