mod 1 - principles of pharmacology Flashcards
1
Q
definition of drugs
A
- substance received by the biological system not for nutritive purposes
2
Q
definition of pharmacology
A
study of drugs, including their uses, effects, and mechanisms of action
3
Q
influences on modern pharmacology (3)
A
- ancient civilizations
- poisons
- religion
4
Q
ancient Greece
A
opium from opium poppy –> pain relief
- morphine: opium contains 10% of morphine
- codeine: opium contains 0.5% of codeine
5
Q
ancient egypt
A
- papyrus: medical textbook
- senna: cause bowel movements
6
Q
ancient china
A
- classified by taste
- Ma Huang: treat influenza, coughing, fever
- ephedrine (isolated from Ma Huang): used to treat asthma
7
Q
poisons (2)
A
- curare
- ergot
8
Q
curare as a poison
A
- indigenous amazonians would use curare on their arrowheads to hunt
- caused paralysis and eventual death in animals
9
Q
curare as a drug
A
- anesthetics during surgery
- muscle relaxation
10
Q
ergot as a poison
A
- found on heads of rye caused epidemic in Russia
- neuro: causes hallucinations and mental frenzy
- cardio: constricts blood vessels causing them to blacken and die off
- reproductive: hastens labour
11
Q
ergot as a drug (2)
A
- ergotamine
- ergonovine
12
Q
ergotamine
A
- treats migraines
- constricts the blood vessels that pulsate when carrying blood to the head
13
Q
ergonovine
A
- arrests uterine bleeding after childbirth
14
Q
influence of religion
A
- healers acted as physicians and priests
- therapy heavily influenced by religion and magic
- plants used to alter state of consciousness to talk to gods
- peyote
15
Q
how many modern drugs are derived from plants
A
25%
15
Q
peyote
A
- cactus in mexico
- achieves mystical state similar to LSD experiences
16
Q
drugs that act on the brain
A
LSD – alters the brain’s chemical signalling
17
Q
LSD discovery and contributions
A
discovery: Albert Hofmann (Swiss) synthesized based on components of ergot
contributions: treating mental illnesses from derivatives of psychedelic compounds
18
Q
drugs acting against infectious diseases (4)
A
- organoarsenicals
- sulfa drugs
- penicillin
- streptomycin
19
Q
organoarsenicals
A
- bind to parasites
- treat syphilis
20
Q
sulfa drugs
A
- first synthetic drug
- led to antibacterial compounds
- treat bacterial diseases
21
Q
penicillin
A
- treats gram-positive diseases (bacteria with thick cell wall and no outer membrane)
22
Q
streptomycin
A
- treats gram-negative diseases (bacteria with thin cell wall and has an outer membrane)
23
Q
ex of gram-pos and gram-neg disease
A
gram-pos: diphtheria
gram-neg: cholera
24
5 steps of drug development
1. basic research and discovery
2. preclinical trials
3. clinical trials
4. review + manufacturing
5. post-market surveillance
25
events in basic research and discovery (2)
1. identify target -- what is the drug targetting (ex. receptor?)
2. study target -- identify lead compound and test for safety and efficacy
26
events in preclinical studies phase (2)
1. pharmacology studies --- mechanism of action of the new drug
2. toxicology studies -- safety of the new drug (potential side effects -- carcinogens, mutagens,...)
27
initial steps in clinical trials
1. proof of safety
2. methodology
3. investigation -- submit proof to regulatory body where their scientists may proceed to hand off to qualified investigators (clinical scientists)
28
phase 1 clinical trial
- evaluates pharmokinetics of the drug
- tested in healthy volunteers
- test tolerance
- 10s of people
29
phase 2 clinical trial
- evaluate efficacy and safety
- tested in people who have the target disease
- 100s of people
30
phase 3
- evaluate efficacy and safety
- tested in those with target disease
- multiple locations = diversity
- 1000s of people
- compares to gold standard drug
- 1-50M $$$
31
enrolment of phase 3 clinical trials
- determined prior to trial
- target population: those with disease
- study population: inclusion, exclusion consent
32
treatment allocation of phase 3 clinical trials
- double blind: investigator and patient don't know who has new drug
- randomization: usually computer generated
- control: gold standard/placebo group
33
results of phase 3 clinical trails
- outcome: compare treatment to control
- compliance: validity >= 50-60%
- QoL
- statistics
34
health canada review + manufacturing
- success of phase 3 clinical trial
- regulatory body review
manufacturing
- generic name: formal chemical name
- brand name: tylenol
35
bioequivalence meaning
- OG drug and generic versions have same active ingredient
- all marketed drugs are as effective as OG drug = bioequivalent
36
post market surveillence (phase 4 clinical trial)
- distribution to population and monitor any adverse effects
- continuous
37
factors of drug action (4)
1. drug targets
2. drug response
3. efficacy and potency
4. therapeutic range
38
drug targets
1. receptors
2. chemical reactions
3. physical chemical forces
39
receptors
- thousands of same receptor in organism
- activated and bound to endogenous ligands (hormones and neurotransmitters)
40
location of opiod receptors
- location of receptor determines where the drug will act
- brain opiod receptors: pain relief
- GI tract opiod receptors: constipation (adverse)
41
drugs in chemical reactions
antacids neutralize stomach acid
42
drugs in physical chemical forces
- cholestyramine: lowers cholesterol
- binds to bile acids in GI tract and prevent their reabsorption, eliminating bile salts that make cholesterol
43
agonists
- drugs that bind to and stimulate a receptor
44
antagonists
- drugs that bind to block responses at receptors
- binds to the receptor, but doesn't activate it
45
drugs interacting with receptors
- increase activity: agonist drug works with endogenous ligand
- decrease activity: antagonist drug competes and blocks endogenous ligand
46
drug response
- analyze the dose-response relationship
- ex. does inc dose = inc response?
47
cannabis vs alcohol
- positive dose-response relationship in cannabis (should've been considered in administering amount)
ask:
- quantity of amount
- ferquency of use
- demographics of user
- environmental factors
48
dose-response relationships (4)
1. low does = little response
2. threshold = dose increases until desired response (amount of receptors need to be activated to have an effect)
3. therapeutic doses = after threshold, small inc in dose means significant responses
4. maximal effect = inc in dose, no effect (plateau)
49
ED50
- dose of drug that results in 50% maximal effect
- dose effective in 50% of population
50
efficacy and potency
1. efficacy: max response by a drug
2. potency: dose of drug required to produce ED50
- efficacy is more important in clinical settings
51
therapeutic range
- range of blood concentration where drug is effective (above threshold) and unacceptable toxicity do not occur
52
administration and ADME of pharmokinetics
administration
- topical
- enteral
- parenteral
ADME = determines blood drug concentration and drug conc at site of action
1. absorption
2. distribution
3. metabolism
4. excretion
53
topical methods
applied directly on the body
- on the skin
- through the skin
- inhalation
54
enteral methods
via GI tract through mouth or artificial opening
- mouth
- rectum
- sublingual and buccal (under tongue and cheek)
55
parenteral methods
bypass GI tract
- intravenous
- intramuscular
- subcutaneous
56
topical on the skin
treat skin conditions -- acne
- causes local effect
- absrobed and produces systemic effect
57
topical through the skin
transdermal: delivery to the skin for absorption into circulation -- nicotine patch
- systemic effect
- convenient, delivers steadily, eliminates frequent oral doses, bypasses enzymes of stomach, intestine, and liver
58
topical inhalation
- absorbed from the lungs for local and systemic
- gaseous anesthetics: systemic
- steroids for lung disease: local effect in lungs
59
enteral first pass effect
- drug first delivered to liver, enzymes decreases the amount of active drug left to enter circulation
60
enteral mouth pros and cons
pros
- common + convenient
- least expensive
- non invasive
cons
- variable in absorption
61
enteral rectum pros and cons
pros
- systemic or local effect
- used in patients who are nauseaus -- less invasive -- or in a coma
- bypasses enzymes of stomach and intestine
cons
- limited medications
- slow absoprtion or incomplete; variable
62
enteral sublingual/buccal pros and cons
pros
- bypass stomach/intestine enzymes
cons
- low quality of absorption
- possibility of swallowing, ends up just being oral
63
parenteral intravenous
- directly in the blood
- immediate + irreversible effects = high risk
- requires more resources and preparation
- used for drugs that are poorly absorbed
64
parenteral intramuscular
- injected deep into a muscle
- vol of drug limited to 2-3mL in adult
65
parenteral subcutaneous
- injected into deepest layer of skin
- allows for modification to control timing of the release of the drug from the injection site
66
bioavailability
- relationship between dose of drug administered and concentration of drug in the blood
67
topical bioavailability
onset: slow to rapid depending on organ
b/a: 5-100%
68
enteral bioavailability
mouth:
- slow
- 30-100%
rectum:
- slow and incomplete
- 30-100%
under tongue:
- rapid
- 30-100%
cheek:
- intermediate
- 30-100%
69
parenteral availability
veins (intravenous):
- 15-30s
- 100%
muscle (intramuscular):
- 10-20 min
- 75-100%
under skin (subcutaneous):
- 15-30 min
- 75-100%
70
ADME
1. absorption
2. distribution
3. metabolism
4. excretion
71
absorption
- movement of drug from site of administration into blood
- must cross biological membranes (lipid membranes)
72
distribution
- movement of drug from blood to site of action and tissues (always reaches all tissues)
- maintains equilibrium with blood concentration (dec in blood concentration causes drug to move from site to the blood)
- greater blood flow to an organ, more rapidly the drug reaches there
73
metabolism
biotransformation
- conversion of drug to a different chemical compound in order to eliminate it
- products are called metabolites and devoid of pharmacological action
74
termination of thiopental (termination of effect)
1. administrated using i.v; brain has high conc (asleep), muscles and fat is low conc
2. distribution: conc of drug in muscle and fat inc and levels out causing drug to leave brain and move into the blood (wakes up)
3. termination: drug redistribution caused the action of the drug (sleep) to be terminated
75
sites of biotransformation
liver: where majority occurs
other: kidneys, intestine, lung, skin, other organs
kidney: eliminates from the body but drug needs to be converted to a water soluble compound
76
biotransformation reactions
- p450
- phase 1
- phase 2
- excretion
77
p450 in biotransformation
- the majority family of enzymes that do the biotransforming
- found in most tissues
- found in high conc in the liver (responsible for most biotrans)
78
phase 1 biotransformation
- add or unmask functional groups
- prepares for addition of water-soluble molecule in phase 2
79
phase 2
- adds large water soluble moiety (glucuronic acid or sulfate)
- makes metabolite water soluble for the kidney
80
excretion organs
- kidneys
- gi tract
- lungs
- breast milk
- saliva and sweat
81
kidney excretion
- majority of drug excretion
- water soluble exits through urine
- lipid soluble reabsorbed back into the blood
82
gi tract excretion
- some drugs exit here after biotransformation in the liver
83
lung excretion
- volatile or gaseous drugs
84
breast milk excretion
- minor route
- exposes nursing infant
85
saliva/sweat excretion
- found here
- detectable
86
what is the half-life of a drug
- time needed for liver and kidney to remove half the drug from the body
87
drug response variation factors
1. genetic
2. environmental
3. disease states
4. altered physiological states
5. presence of other drugs
88
genetic variability
- drug binding receptor variability in how the body handles and eliminates drugs
- different genes that encode for the enzyme
- people can be slow or fast biotransformers (based on acitivity of enzymes)
89
environmental variation
- exposure to certain chemicals alter enzymes in liver for biotransformation
90
other disease states
- presence of other disease alter manner in how drugs are handled in the body
91
altered physiological states
- influences drug response
- ex. age of patient
- older = greater effect
- pregnancy
92
other drugs present
- multiple drugs taken together can change effect of a drug leading to variability in drug response
93
toxic effects of drug categories
1. adverse effects
2. drug-drug and drug-food interactiosn
94
adverse effects of drugs
- effect produced that is not the intended effect
95
examples of adverse effects
- extension of therapeutic effect
- unrelated to main mech of action
- allergy
- withdrawal + addiction
- teratogenesis
- advers biotransformation
96
extension of therapeutic effect
too much of drug in the blood
- overdose
97
unrelated to main mechanism of action
- side effects
- can be good or bad
98
allergic reaction
- antigen-antibody combination provokes allergic reaction
99
withdrawal and addiction
- unwanted physiological and psychological effects of the drug
100
teratogenesis
- defects in developing fetus
101
adverse biotransformation reactions
- drug converted into chemically reactive metabolite
- tissue and organ damage
102
challenges in predicting adverse drug reactions
- rarity of occurence (can't be picked up in initial testing)
- length of usage (reaction with extended period of use)
- detectability (some may be undetectable)
- time period specificity (ex. pregnancy)
103
therapeutic index
td50 (toxic in 50% pop)/ed50 (effective in 50% pop)
> ti = safer
< ti = more toxic (smaller ratio)
104
drug-drug interactions ADME
absorption:
- drug can increase intestinal movement, speeds up second drug passage and decreases its contact -- dec absorption
metabolism
- block inactivation of a second drug -- possibly inc blood level and effect of second drug
excretion
- drug can make other drug excreted through kidney -- dec blood level and effect of 2nd drug
105
drug-food interactions (interference of food)
1. tyramine
- found in well matured cheese
- raises bp
- broken down by MAO in liver
- if drug contains MAO inhibitor and one consumes tyramine, it won'y be broken down -- inc in tyramine
2. grapefruit and citrus
- metabolizing enzymes in gi tract inactivate the biotransformation of drugs
- cause inc in drug blood concentration
- may cause overdose
106
drugs on the cns: cerebeal cortex
- largest part of th ebrain
- rich in neurons
- functions: sensory, motor, mental processing, intelligence, memory, vision, judgment, thought, speech, emotions, consciousness
- drugs can stimulate or depress these neurons
107
drugs on the cns:
- brain region
- integrates memory, emotion and reward
- works with hypothalamus to control emotion and behaviour
- contains dopamine reward centers = associated with addiction
108
drugs on the cns: neuron structure
| dendrites? cell body? axon?
- 90 billion in brain
- dendrites: short complex branching, reciever
- cell body: contain neurotransmitters in its cytoplasm to be secreted
- axon: single fibre ending at synapse carrying info
109
neurogenesis
generation of new neurons
110
neuroplasticity
neurons being constantly reshaped
111
synapse
- junction between two neurons
- synaptic transmittion: signal from one neuron to another (rapid and chemical in nature) using neurotransmitters
112
synaptic transmission and termination
| axon? glial cells? neurotransmitters? vesicles? receptors?
axon: electrical impulses to reach end of presynaptic neuron
glial cells: removes neurotransmitters from synaptic cleft
neurotransmitters: endogenous chem msgrs that transmite e signals from nerve cells to target cells
vesicles: transport and release neurotransmitters into synaptic cleft by fusing with presynaptic membrane
receptors: activation of these cause ions to move into postsypnatic neuron by changing permeability of the membrane
113
# what is its receptor and function
neurotransmitter: glutamate
glutamatergic receptor
- primary excitatory neurotransmitter
114
neurotransmitter: catecholamines
2 types:
1. dopamine: control of some hormonal systems, motor coordination, motivation, reward
2. norepinephrine: mainly bind to alpha and beta receptors, excites cells
115
neurotransmitter: GABA
- primary inhibitory neurotransmitter
- neurons that release gaba and gaba receptors are found in high concentrations in the cerebral cortex
- cns depressants enhance gaba
116
neurotransmitter: seratonin
- hyperacitivty of serotonergic system causes anxiety and hypoactivity in depression
- cns stimulants inc seratonin at synapse
117
neurotransmitter: acetylcholine
- excitatory response in cns
2 receptrs (cholinergic receptors):
1. nicotinic -- stimulated by aCoA and nicotine
2. muscarinic -- learning, memory, cognitive function; stimulated by a-CoA and muscarine
118
amnesia
drugs that block acetylcholine at muscarinic receptors produce amnesia
- losing cholinergic receptors is associated with alzheimers
119
neurotransmitter: opiod peptides
3 classes:
1. enkephalins
2. endorphins
3. dynorphins
receptors:
1. mu
2. delta
3. kappa
