Module 1 Flashcards
1
Q
historical influences to pharmacology
A
- discoveries by ancient civilizations
- role of poisons
- influence of religion
2
Q
ancient greece drug development
A
textbook on therapeutics including opium
opium obtained from opium poppy (pain relieving capabilities)
opium contains morphine (10%) and codeine (0.5%)
2
Q
ancient egypt drug development
A
documents called papyri intended to be a textbook of drug use
observations of drug use specifically purgatives (cause bowel movement)
recommended drug was senna
3
Q
ancient china drug development
A
classified drugs according to taste
ma huang (medium drug) used for coughs, influenza and fevers
modern era ephedrine isolated from ma huang and used to treat asthma, and a derivative of ephedrine used as a decongestant
4
Q
curare (poison) drug development
A
plant derived drug used by indigenous people
used in hunting to paralyze animals and cause death
used by anaesthetists in surgery
5
Q
ergot (poison) drug development
A
poisonous fungus growing on the heads of rye
was mixed with rye and found in bread causing epidemics
6
Q
peyote religious use
A
peyote cactus causes mystical state (hallucinations, feeling of well being and distortion of perception) which was linked to spiritual and ritualistic use
7
Q
broad definition of drugs
A
any substance received by a biological system that is not received for nutritive purposes and which influences the biological function of the organism
8
Q
two major categories of drugs
A
- drugs that act on the brain
- drugs that act against infectious disease
9
Q
drugs acting on the brain
A
dugs that alter normal chemical signalling in the brain
LSD is the most potent hallucinogenic drugs
10
Q
LSD (lysergic acid diethlylamide)
A
synthesized by a albert hofmann in 1943
discovery support idea that certain mental illnesses may be due to production of potent substances in the brain causing psychic disturbance
classified as a controlled substance
evidence it may be effective in treating certain mental illnesses (depression, anxiety, addiction)
11
Q
drugs acting against infectious disease
A
any disease caused by an organism
1900s
- drug to cure syphilis
1930s
- sulfa drugs to treat bacterial drugs
- now called antibiotics
1940s
- discovery of penicillin
- used in gram positive bacterial disease
1950s
- discovery of streptomycin
- treated tuberculosis and gram negative bacterial diseases
12
Q
gram positive/negative bacterial disease
A
positive: bacteria with thick cell walls and no outer membrane
negative: bacteria with thin cell walls and an outer membrane
13
Q
drug development process
A
- drug discovery (3-6 years)
- drug development (6-7 years)
14
Q
drug discovery process
A
- basic research and drug discovery
- preclinical trials
14
Q
drug development process
A
clinical trials
- phase 1 (10 patients)
- phase 2 (100s)
- phase 3 (1000s)
health canada review and manufacturing
post market surveillance and phase IV clinical trials
15
Q
basic research and discovery
A
identification of target
- receptor that when activated causes relief or pain
- research about target to determine pharmacological effects at various levels
studying target
- compound with promise lead compound
- tests for efficacy and safety
16
Q
efficacy definition
A
max pharmacological response that can be produced by a specific drug in a biological system
17
Q
preclinical studies
A
tested in molecular / cellular studies, tissues and whole animal
pharmacology studies determines mechanisms of action of the drug
toxicology studies potential risks or harmful effects of the drug (expensive)
18
Q
clinical trials initial steps
A
- proof of safety in several animal species
- proposed methodology
- submission evaluated by scientists and permission given to investigate
19
Q
phase 1 clinical trials
A
evaluate absorption, distribution, elimination and adverse effects of drug
test one of two doses of the drug to test tolerability
conducted on healthy volunteers (20-80)
20
Q
phase 2 clinical trials
A
determine if the drug is effective and evaluates safety
conducted with patients with disease drug is treating
21
Q
phase 3 clinical trials
A
large number 1000+ and multi centred (dif locations)
determine how safe and effective drug is compared to no treatment (placebo) or current therapy
longer than phase 2 (months to years)
most expensive (1-50 million)
22
Q
design of phase 3 clinical trials
A
- determining enrolment prior
- allocating participants to treatment groups and conducting the trial
- monitoring and analyzing results
23
phase 3 enrolment
people drug is tested on needs to be defined
target population group of patients the drug is intended for
inclusion/exclusion criteria + consent
24
phase 3 treatment allocation
double blinded, investigator nor study subject aware of treatment the study subject is assigned to (randomization)
treatment or control (placebo or gold standard)
bias can occur if subject believe drug will work or investigator expects positive results lead to bias results
25
phase 3 results
determines if the treatment was more or less effective than the control
outcome of the trial that measures effectiveness and compares it (objective and reliable manner)
compliance, quality or life and statistics
26
drug patent and naming
manufactures come up with a drug name (generic) and a brand name for the drug
patent gives company exclusive rights to market the drug for 20 years (filed during preclinical development)
27
drug bioqeuivlence
strict regulations in place to ensure all market drugs are as effective as the original brand name drug and are bio equivalent (same ingredients and give similar blood levels)
comparative bioavailability study conducted to compare blood levels in healthy volunteers
28
phase 4 clinical trials
delayed or less frequent risks missed so surveillance of effects needed
post marketing surveillance
29
placebo definition
substance masquerading as a drug
identical in appearance, colour, taste and administration method to active drug
30
drug action factors
- drug target
- drug response
- efficacy and potency
- therapeutic range
31
drug targets
usually receptors, also interact non specifically with biological system
many receptors exist and are distributed through body, location determines where drug acts and if response is beneficial or detrimental
32
opioid receptors activation
activation in brain causes pain relief
activation in gastrointestinal tract causes constipation (adverse effect)
33
drug target chemical reactions/forces
antacids neutralize stomach acid through acid base neutralization reaction
cholestyramine binds to bile acids in gastrointestinal tract preventing reabsorption and increasing elimination of bile salts used to make cholesterol
34
drugs and receptors
drugs mimic action or block effects of ligands at the receptors
agonists stimulate receptor
antagonists block receptor
35
drug response
intensity of effects by a drug increases in proportion to dose (dose response relationship)
36
factors when comparing drugs
- quantity
- frequency of use
- user demographic
- environmental factors
37
dose amounts and effects
low dose, little response observed as few receptor activated
threshold, effect seen as more receptor activated
therapeutic dose, threshold reached small increased results in large increase response
maximal effect, once max is reached increasing amount will have no increase in therapeutic response
38
effective dose
ED50 - dose that is effective in 50% of population
result in 50% of maximal effect
39
efficacy
max pharmacological response produced by a specific drug in that biological system
40
potency
dose of drug required to produce a response of a certain magnitude
usually 50% maximal response
41
therapeutic range
dose that keeps blood concentration of a drug above the minimum concentration that produces desirable response but below concentration that produced unacceptable toxicity
42
pharmacokinetic
refers to movement of a drug into, through and out of the body
for a drug to produced desired effect is must reach cellular site of action at the right concentration, exert its effect and then be removed from the body
43
administrations of drugs
- topical
- enteral
- patenteral
44
processes after administration
ADME
- absorption
- distribution
- metabolism
- excretion
factors determine concentration of drug in blood which determines concentration of drug at the site of action
45
topical administration
applied directly to particular place on or in the body
- on skin
- through skin
- inhalation
46
enteral administration
administration via the gastrointestinal tract
- mouth
- rectum
- sublingual (under tongue) and buccal (cheek)
47
parenteral administration
administration bypassing the gastrointestinal tract
- intravenous
- intramuscular
- subcutaneous
48
drug skin application
large number of drugs applied to the skin to treat mild to moderate severity skin conditions
can be absorbed and produce a systemic effect (affects the whole body or multiple organ system)
49
transdermal drug delivery
through the skin
application if a drug to the skin for absorption into the general circulation for a systemic effect
- convenient
- delivers steady supply for several days
- bypasses enzymes of stomach, intestine and liver
can be expensive and cause local irritation
50
inhalation
prescription or recreational, requires proper use
rapidly absorbed by lungs for local and systemic effect
small quantities required for systemic effect avoiding toxicity with oral administration
51
oral drugs
90%+ drugs oral
most convenient and least expensive
non invasive and self administered
variable absorption between patients due to differences in intestinal motility and disease
52
rectum drugs
systemic or local effect
can be used in patients who are nauseated or vomiting or for those in comas
digestive enzymes of stomach and intestine bypassed
limited number medication available and suitable for rectal
absorption from rectal mucosa slow, incomplete and variable depending on the time the medication is retained
53
sublingual and buccual
enzymes of stomach intestines and liver bypassed
not all drugs are adequately absorbed
drugs may be swallowed and then drug behaves as if it were taken orally
54
first pass effect
when drug is absorbed into the blood from the gastrointestinal tract it is first delivered to the liver which contains enzymes that decreases the amount of active drug left to enter general circulation
55
intravenous
directly into the blood, immediate effect
used for drugs poorly absorbed if they can be made into a solution in purified water for injection
response is irreversible, highest risk for drug reactions
required human resources
preparation must be sterile and free of fever producing substances
56
intramuscular
drug injected deep into muscle
volume is limited to 2 to 3 ml in adult
57
subcutaneous
injected into deepest layer of skin
allows for modification of drug preparations to control timing of release of the drug from injection site
58
bioavailability definition
fraction of an administered dose that reaches the systemic circulation (blood) in active form
59
drug absorption
movement of drug from site of administration into the blood
drug must be able to cross the biological membranes
- diffusion through aqua pores
- diffusion through lipids
- active or carrier mediated transport
60
drug distribution
movement of drug from blood to site of action and other tissues
concentration of drug at sites of distribution are in equilibrium with its concentration in the blood
drug distribution rate depends on blood flow of organs
61
drug metabolosim
biotransformation - conversion of drug to a different chemical compound to eliminate it
to be eliminated from body by kidneys drug must be water soluble so drugs converted to more water soluble compounds
liver is where most biotransformation reactions occur (some in kidneys, intestines, lungs, skin and most other organs)
62
drug biotransformation reactions
p450 enzymes capable of biotransforming drugs (found in most tissue and lots in liver)
phase 1 - add or unmask functional group of drug to prepare it for the addition of large water soluble molecule
phase 2 - add water soluble moiety
63
drug excretion
moving drug and its metabolites out of the body
all body fluids will contain drugs and their metabolites
64
kidney excretion
majority of drugs eliminated by kidney
drugs of sufficient water solubility excreted in urine
lipid soluble drugs reabsorbed from the kidney back into the blood
65
gastrointestinal tract excretion
some drugs excreted through feces after they undergo biotransformation in the liver
66
lungs excretion
volatile or gaseous form drugs excreted by lungs
anesthetics and alcohol
67
breast milk excretion
drugs found in breast milk of nursing parents
minor route but infant can be exposed to therapeutic or toxic dose of drug
68
saliva and sweat excretion
presence of drugs can be detected in the saliva of those who have taken it
69
half life of a drug
the time needed for the liver and kidney to remove half the drug from the body
70
factors for drug response variation
- genetics
- environmental factors
- disease states
- altered physiological states
- presence of other drugs
71
genetic drug response
variability in receptors and the way the body handles and eliminates drugs
enzymes vary between individuals, some fast and some slow biotransformers
72
environmental drug response
exposure to certain chemicals increase liver responsible for biotransformation
72
disease states disease response
presence of disease state may alter manner in which drugs are handled by body
73
altered physiological states drug response
changes can influence drug response (age, pregnancy)
74
toxic effects of drugs
- adverse effects
- drug-drug and drug-food interactions
75
drugs present drug response
multiple drugs taken together one drug can change the effect of a second drug
drug-drug interactions
76
adverse effects of drugs
- extension of therapeutic effect
- unrelated to the main drug action
- allergic reaction
- withdrawal and addiction
- teratogenesis
- adverse biotransformation reaction
77
extension of therapeutic effect
occurs if there is too much of the drug in the blood
common in drug overdose
78
unrelated to main drug action
cause unrelated effects to intended action (nausea)
may or may not be expected
79
allergic reaction
mediated by immune system
antigen-antibody combination provokes an adverse reaction in patients
very mild or very severe
80
withdrawal and addiction
unwanted physiological and psychological effects of the drug
81
teratogenesis
drug produced defects in the developing fetus
82
adverse biotransformation reaction
drug is converted to a chemically reactive metabolite that can bind to tissue components and cause tissue or organ damage
83
predicting adverse drug reactions
drugs with little or no adverse effects when first introduced can later have significant toxicities
toxin reaction may be rare, difficult to predict
toxin reaction may only appear after prolonged use
toxin effect may not be detectable in animals only appears in humans
toxic effect may be unique to particular period in time
84
therapeutic index
assess drug toxicity, how safe a drug is, higher = safer
TI = TD (dose toxic to 50% of population) / ED (dose effective in 50% of population)
85
drug-drug interactions
when on drug changes the effects of a second drugs
86
absorption drug-drug interactions
drug increase intestinal movement speeding movement of second drug reducing contact with intestinal wall thus decreasing absorption
87
metabolism drug-drug interactions
drug can block inactivation of second drug in liver increasing blood level and effect of second drug
88
excretion drug-drug interactions
drug can facilitate excretion of second drug by kidney, decreasing blood level and effect of second drug
89
drug-food interactions
interference of food with drugs taken simultaneously
90
tyramine drug-food interactions
tyramine can raise blood pressure and is broken down in the liver by enzyme MAO (monoamine oxidase) to inactive products
antidepressant drugs are inhibitors of MAO
drug-food interactions causes blood pressure raising
91
grapefruit drug-food interactions
grapefruit and some other citrus fruits alter the absorption of some drugs
grapefruits inhibits enzymes that inactivate drug resulting in a greater amount of active drug
result in higher blood levels and potential overdose
92
cerebral cortex
largest part of the brain, very rich in neurons which can be stimulated or depressed by drugs
functions
- sensory and motor coordination
- mental processes
- intelligence
- memory
- vision
- judgement
- thought
- speech
- emotions
- consciousness
93
limbic system
region of the brain that integrates memory, emotion and reward
with the hypothalamus controls emotion and behaviour
contains dopaminergic reward centre (associated with addiction)
94
neuron
generates and transmits electrical signals
new neurons generated via neurogenesis
connection between neurons reshaped constantly via neuroplasticity
95
structure of the neuron
- dendrites
- cell body
- axon
96
dendrites
short and highly complex branching patterns
function as receiving antennae for incoming information and accept information through receptors on membrane
once information received form another cell, electric current generated and directed down the neuron
97
cell body (soma)
largest part of the neuron
contains nucleus and surrounding cytoplasm
contains abundant pre packaged neurotransmitters which can be secreted
98
axon
single fibre extending from the body and ends at the synapse
carries incoming information away from the cell body by electrical pulses
information passed on the subsequent neurons
99
synapse
junction between two synapse
area where nueron axon ends and a nueron dendrite or cell body begins
100
synaptic transmission (neurotransmission)
passage of signal (endogenous chemicals) from one neuron to another
very rapid and chemical in nature (quickly released and activates next)
usually one synapse connects two neurons, however a single neuron can make many synaptic connections
101
glial cells
role in mechanisms which neurotransmitters are removed from synaptic cleft
102
drugs and synaptic transmission
some interrupt transmissions while other enhance or facilitate it, modifying activity of brain
103
types of neurotransmitters
- glutamate
- serotonin
- catecholamines
- acetylcholine
- gaba
- opioid peptides
104
104
104
105
glutamate
primary excitatory neurotransmitter in the CNS
found in almost all nuerons
acts on glutamatergic receptors
neurons that release glutamate called glutamatergic neurons
106
serotonin
in CNS hyperactivity of the serotonergic system involved in anxiety and hypo activity (depression)
some classes of CNS stimulates increase serotonin in synapse
107
cetecholamines
two types similar in structure
- dopamine
- norepinephrine
108
dopamine
type of catecholamines
involved in
- control of some hormonal systems
- motor coordination
- motivation and reward
alterations in dopamine mediated motivation and reward system linked to addiction
109
norepinephrine
type of catecholamines
bind to large number of receptor types (main alpha and beta)
activation of receptor leads to excitation of cell
pathway targeted by some CNS stimulants
110
acetylcholine
produces excitatory response in CNS
two types of receptors bind to it (cholinergic receptors)
- nicotinic receptors
- muscarinic receptors
111
nicotinic receptors
found in certain regions of the brain
stimulated by acetylcholine or nicotine
112
muscarinic receptors
found in many regions of the brain
involved in
- learning
- memory
- cognitive function
stimulated by acetylcholine or muscarine
drugs that block these produce amnesia (loss of cholinergic neurons, associated with alzheimers)
113
gaba (gamma amino butyric acid)
primary inhibitory neurotransmitter in CNS
neurons release gaba
gaba receptors found in high concentration in cerebral cortex
CNS depressants enhnace gaba receptor function
114
opioid peptides
three main classes
- enkephalins
- endorphins
- dynorphins
classes vary in degree of selectivity for three opioid receptors (all interact w receptors)
- mu
- delta
- kappa
