module 1 Flashcards
pharmacology can be defined as
the science of drugs, there uses effects and mechanisms
historical influences on modern pharmacology
discoveries of ancient civilization , the roles of poison and the influence of religion
380 BCE
Pupil of Aristotle wrote book that included opium
1803 in germany,
Serturner, a pharmacist isolated crystals of morphine from opium and discovered its pain relief capability
opium contains
10% morphine and 0.5% codeine and was given the name from from morpheus god of dreams
earliest recorded drug experiments
China in 2700 BCE in which ma Huang was used to treat flus and cough. –> today ephedrine has been isolated from the ma Huang plant to treat asthma
ancient Egypt and drugs
ebers papyrus in 1550 BCE was used as a medical textbook
Curare is
plant derived drug in South America that was used as a poison to hunt animals. Causes paralysis of muscles and eventual death my respiratory paralysis
in modern medicine curare was used as
anesthetists in surgery
what is ergot ?
a poisonous fungus found on the head of rye and is found in abundance during wet seasons
ergot effect on nervous system
mental frenzy , hallucination and convulsions
ergot effect on cardiovascular system
can cause constriction of blood vessels , limiting blood supply to fingers and toes and limbs which will eventually become black and die off
ergot and reproductive system
can cause violent contractions of the uterus , was sometimes used for labour
ergotamine
a compound derived from ergot and is useful in treating migraines through contstriction of blood vessels
ergonovine
compound of ergot that is used to hasten birth as to force uterine contractions. can also be used to stop bleeding after birth
religion and drugs
ancient societies healers were doctors and priests , plants were used to alter state of conciusness to be able to talk to the gods
ex) Peyote in Mexico, has LSDA properties
A drug can be defined as
substance received by a biological system that is not received for nutritive purposes and will influence the biological functions on an organism - chemicals , biological agents and herbal products are all considered drugs
drugs that act on the brain
alter the normal signalling ex) LSD
How was LSD discovered
Albert hofman who worked for Swiss pharmaceutical firm , synthesized LSD and chemical structure was similar to ergotamine and ergonovine
LSD contribution to pharmacology
certain mental illness might be due to production of potent substances in the brain and produce psychiatric disturbances
1900’s what drug came out ?
organoarsenicals designed by Paul ehrlich which would bind to parasites and cured syphilis
1930s drug discovery
sulpha drugs which were the first synthetic drugs to treat bacterial infections
antibiotic refers to
specifically to chemical substances produced by microorganism and not synthetic compounds
drug discovery in 1940s
Fleming discovered the first antibiotic known as penicillin and was used for gram positive disease
drug discovery in the 1950s’
Waksman discovered discovered streptomycin antibiotic which was a turning point of tuberculosis and gram negative bacterial disease
what are the 5 key steps of drug discovery ?
basic research/ drug discovery, preclinical trials , clinical trials, health Canada review , post market surveillance and phase IV clinical trial
what is the first stage in basic research
identification of the target, where a receptor is identified
step 2 in basic research
studying the target, in which a lead compound is identified and enters into more testing to look at safety and efficacy
pharmacological studies of new drugs are used to
determine the detailed mechanism of action of the new drug
toxicology studies of new drug entail,
the possible risk or harm of new drug , acute toxicity and chronic toxicity are looked at
if company wants to test new drug on people what 3 things need to fist take place
1) investigation - submission to highly qualified scientists who will approve admission
2) methodology, of the proposed clinical trial in humans
3) proof of safety- must be shown to be safe with several animal models and be submitted to the health products and food branch
what are phase 1 clinical trials
carefully evaluate absorption, distribution and elimination and adverse effects of new drug - efficacy is not assessed however tolerability is looked at with 20- 80 volunteers
phase 2 clinical trial
trying to determine if the drug is effective in a limited number of people ( 100- 500). drug safety is carefully looked at
phase 3 clinical trial
also known as randomized control trials and are the main studies used for marketing of drug
number of participants and phase 3 trial and duration
test drug in larger number of people( 1000+) and range from months to years
goals of phase 3 trial
to determine how safe and effective the drug is compared to no treatment ( placebo)
location and cost of phase 3 trials
are considered multicenter and take place in many cities and can cost from 1 million to 50 million
what are the 3 larger stages of phase 3 clinical trials
1- determining enrolment prior to the study
2-allocating participants to treatment groups
3-monitoring and analyzing results
the target population includes
group of patients for who the drug is intended ex) drug to treat hypertension , adults who have been clinically diagnosed with it would be target population
study population is
subset of the target population , 2 factors that influence this is inclusion/ expulsion criteria and consent
why are comorbities often included ?
to be representative of target population
obtaining consent means that
document which outlines purpose of study , the procedures that will be used and possible risks and benefits
what is meant by double blind design
neither investigator or participant is aware of treatment assignment group
- bias can occur otherwise
what is randomization ?
when patients are assigned to either treatment group or to control group in a random fashion
why is randomization used
ensures that confounding variables ( known and unknown ) are distributed equally between the 2 groups - and also removes possible bias in assigning patients to groups
placebo is
identical to experimental drug but does not contain the active ingredient , there is often placebo effect when taking drugs in which symptoms get better
Gold standard drug is known as
accepted by the medical community as the best available treatment for the given condition
when analyzing results what3 things need to be considered ?
compliance, quality of life and statistics
patient compliance refers to ?
how often the participant took the drug
what is meant by bioequivelant ?
both generic and brand name drugs will contain the same active ingredient and give similar blood levels
what is a receptor ?
molecule or complex of molecules located outside or inside the cell that has regulatory or functional role in the organism
receptors are bound to and activated by
endogenous ligands which are substances found in the body like hormones and neurotransmitters
location of receptors will determine
where the drug will act and whether the response that results from the drug - receptor interaction is beneficial or detrimental
how does opioid receptors location result in different effects ?
when they bind to receptors in the brain , causes pain relief , when they bind to receptors in stomach, causes constipation
other drug targets include
chemical reactions and physical chemical forces
chemical reactions include ?
when antacid neutralizes the stomach through aid base neutralization
how does cholestyramine work ?( physical chemical force )
binds to bile acids in GI tract preventing their reabsorption and increasing the elimination of bile salts that are used to make cholesterol
agonists are known as
drugs that bind to stimulate a receptor
antagonists are known as
bind to receptor but block response of receptor –> will not activate receptor
most drugs will
mimic the action or block the endogenous ligand at a receptor
dose response relationship
pharmaocologcial effect will increase in proportion to the dose
problem with the alcohol and cannabis study
there was a wide discrepancy between the doses of cannabis and liquor
what things should be asked when comparing alcohol and cannabis ?
quantity, frequency of use, user demographic, environmental factors
low dose and drug response
very little response will be observed and little receptors will be activated
threshold and drug response
more receptors activation until a desired response is seen - a certain number of receptors are needed to see a response
therapeutic doses
once threshold is reached , small increases in dose will result in large increase in response
maximal effects
once maximal effect has been reached, there will be no difference in the therapeutic response seen
dose response curve
representation of how much drug you need in the body to see a specific effect
Y axis
effect of drug iron Y axis and plotted on a linear scale
receptor threshold
region of the curve , where threshold has been reached and dose of the drug is directly proportional to the response
X axis
dose of the drug is on this axis and is plotted on a log scale
ED 50
dose of the drug that will result in 50% of the maximal effect- also be interpreted as the dose that is effective in 50% of pop
Efficacy
maximum pharmacological response that can produced by a specific drug
Potency
dose of drug that is required to produce a certain magnitude , usually 50% of the maximal response
therapeutic range is referred to as
a dose that keeps the blood concentration of a drug above the minimum concentration that produces the desirable effect but below the toxic response
What is pharmokinetics ?
movement of a drug into and throughout he body and then leaving the body
what are the 3 route of drug administration ?
topical ,enteral and parenteral
what happens after administration ?
absorption, distribution, metabolism and excretion (ADME) which will determine the concentration in the blood
topical administration
drugs that are directly applied directly to the body ( on the skin, through the skin or inhalation )
enteral administration refers to
through the GI tract either directly through the mouth or an artificial opening ( mouth, rectum or sublingual or buccal * under tongue
Parenteral refers to administration through
bypasses the GI tract includes intravenous , intramuscular or subcutaneous
drugs absorbed through the skin can produce
a systemic effect which could be toxicity other parts of the body
what is transdermal drug delivery?
application of drug from the skin to be absorbed into the general circulation ( nicotine patch )- bypasses the enzymes of stomach
inhalation can have
local and systemic effects and can be advantageous because a smaller amount is often needed to see systemic effect which reduces the chances of toxicity
Enteral administration enter the blood through
The GI tract which then brings it to the liver, which decreases the amount of active drug–> known as the first pass effect
mouth administration
most convenient and least expensive and is the most common way drugs are administered
rectum administration
systemic or local effect, less invasive route for those in comatose and digestive enzymes in the stomach are bypassed
disadvantage of mouth administration
variable absorption for patients
disadvantage of rectum administration
limited number of medications are available and absorption is slow and incomplete
sublingual and buccal administration advantages
enzymes in the stomach and liver are bypassed
disadvantages of sublingual and buccal administration
not all drugs are adequately absorbed from, drug may be swallowed in which it behaves as if taken orally
Parenteral administration route
injected into the body and enter blood stream directly
intravenous administration
immediate effects, can be used for drugs that are poorly absorbed however has the highest risk of drug reactions as it is irreversible and free of fever producing substances
intramuscular administration
drug injected into deep muscle where the volume f drug is limited to 2-3 mm
subcutaneous administration
drug is injected into deepest layer of skin, allows for the timing of release of drug to be controlled
bioavailability :
fraction of administered dose that reaches systematic circulation ( blood) in active form , intravenous is 100% bioavailable
what is absorption ?
movement of drug from the site of administration into the blood
Distribution ?
the movement of a drug from the blood to the site of action and tissues
If the concentration of the drug in the blood drops below concentration at any of the sites what will happen ?
drug from the site will move to the blood to try and maintain the equilibrium –> distribution sites and blood concentrations are always in equilibrium
what is metabolism ?
aka biotransformation , is the conversion of a drug to a different chemical compound in order to eliminate it –> products are known as metabolites
where do most biotransformations take place and why ?
In the liver,( also can happen in the intestines, lungs and skin) a drug must be water soluble to be eliminated by the kidneys
P450
enzymes that are capable of biotransforming drugs, found in most tissues ( lots in liver)
biotransformation is divided into 2 phases:
1 and 2
phase 1 biotransformation
purpose is to add or unmask a functional group on the drug to prepare it for the addition of a large water soluble molecule in phase 2
phase 2 biotransformation
add a large water soluble moiety (molecule ) that is usually sulphate or glucronic acid making it water soluble for the kidney
When taking multiple drugs, what could happen with metabolism
drugs will compete for the same enzyme (p450) which could reduce biotransformation and cause toxic effects
drug excretion is classified as :
moving the drug and metabolites out of the body
kidney and drug excretion
majority of drugs are eliminated by the kidney , water soluble drugs ill be excreted in urine , lipid soluble drugs go back into the blood
Gi tract and excretion
some drugs are excreted in the form of feces after gone through the liver biotransformation
Excretion and the lungs
drugs that are volatile or in a gaseous form, can be excreted in this way ( alcohol and anethsetics )
Breast milk and excretion
a minor way that drugs are excreted however can effect nursing women and exposing toxic levels of drug to baby
saliva and sweat and excretion
presence of drugs can be found here, commonly found with the misuse of certain drugs
half life of drug =
the time that the kidney and the liver need to remove half of the drug from the body , can be used to administer therapeutic doses and make sure that there is enough in circulation in blood
2 ways that drugs get out of body=
biotransformation and excretion
what are the 5 stages the drug goes through after administration
absorption from the site, distribution to the site of action, target interaction, metabolism and excretion
variation in drug response includes
genetic factors, environmental factors, disease states, altered physiological states , presence of other drugs
genetic variability and drugs ?
way in which the boy eliminates the drug and way in which it binds to receptors , biotransformation can vary ( fast vs slow )
environmental factors ?
exposure to certain chemicals can increase liver enzymes –> chronic alcohol consumption will increase enzymes
disease states and metabolism
liver disease= slower metabolism of drugs , and kidney and cvd disease
elderly will see what type of effects with drugs
will have slower acting metabolism due tor educed kidney function and will see increased drug action especially on CNS
adverse drug reaction is defined as
any effect produced by a drug that is not its intended effect
extension of therapeutic effect
when there is too much of the drug in the blood ( overdose )
unrelated to the main action of the drug
side effects that are unrelated to the intended pharmacological effect
allergic reaction
adverse effect mediated by the immune system
withdrawal and addiction
unwanted physiological or psychological effects of the drug
teratogenesis
when drug produces defects in the fetus
adverse biotransformation reaction
conversion to a chemically reactive metabolite that can bind to tissue and cause damage
why is predicting adverse drug reactions hard ?
= may only occur after prolonged periods of use , may be also be very rare , may not be detectable in animals ,certain drugs may have adverse effect at specific times ( during pregnancy )
Therapeutic index
tells you how safe a drug is , compared does for therapeutic effect vs dose where toxic effect are seen, lower the index, the more toxic
therapeutic index formula =
TD50( toxic dose 50- dose that is toxic in 50% of pop
/ effective dose 50- dose that is effective in 50 % of pop
what is a drug to drug interaction ?
one drug changes the pharmacological effect of the second drug
absorption and drug to drug interactions
absorption can be decreased by increasing intestinal movements, and limiting interaction with the intestine wall
how is metabolism effected by drug interactions ?
a drug can block the inactivation of a second drug in the liver , increasing blood level and effect of 2nd drug
how is excretion effected by drug interactions ?
a drug can facilitate the excretion of a second drug by the kidney decreasing the blood levels and effect of second drug
what is the problem with tyramine found in cheese ?
capable of raising blood pressure and is broken down in the liver by MAO–> problem for people taking MAO inhibitors , tyramine will not be broken down and blood pressure effects will be intensified
what is the problem with grapefruit ?
inhibits drug metabolizing enzymes in the GI tract , meaning a greater amount of the drug can be absorbed which could possibly lead to overdose
the limbic system contains
dopaminergic reward centres in the brain that also integrates memory , reward and emotion ( with hypothamulus controls emotion and behaviour
cerebral cortex ( cerebrum)
largest part of brain - sensory, motor, coordination , vision , , judgement , speech ,consciousness
the neuron
generates electrical signals and is the functional unit of brain - neuroplasticity = new connections
neurogenesis = new neurons
cell body / soma
contains the neurotransmitters and is the largest part of neuron and has the nucleus
dendrites :
receiving antennae for incoming signals
axons
single fibre that extends from the cell body and ends at synapse , carries electrical pulses to other neurons
the synapse
junction between 2 neurons
synaptic transmission
aka neurotransmission , chemical in nature , substance that is quickly released that activates next neuron
