Module 1 Flashcards
1
Q
define pharmacology
A
the science of drugs including their uses, effects and mechanisms of action
2
Q
3 influences that have shaped pharmacology
A
- discoveries made by ancient civilians
-roles of poisons
-influence of religion
3
Q
discoveries made in ancient greece
A
- 380 BCE Theoprastus wrote a textbook on theraputics that include opium (obtained from a poppy)
- Serturner, a german pharmacist, isolated crystals of morphine from opium and tested the pure substance on himself and 3 companions to discover its pain relief capabilities
- Opium was found to contain 2 important substances:
- Morphine
- 10% morphine
- able to relieve pain of great intensity
- named after god of dreams
- Codeine
- 0.5% codeine
- Morphine
4
Q
discoveries of ancient egypt
A
- recorded on documents called papyri
- intended to be a textbook of drug use for medical students (called Ebers Papyrus from 1500 BCE)
- contains observations of purgatives (drugs used to cause bowel movements)
- One drug recommended was senna
5
Q
discoveries from ancient china
A
- earliest drug experiments are those emanting from china in 2700 BCE
- Emperor classified all drugs acording to taste
- medium drug Ma Huang was used for cough, influenza & fever
- ephedrine has been isolated from Ma Huang and now used to treat asthma and decongestant
6
Q
role of poisons in history
A
- Paracelsus states all substances are poisons & dosage differentiates a poison from a remedy
7
Q
two examples of poisons
A
- Curare
- Ergot
8
Q
Curare
A
- plant-derrived drug historically used by indigenous
- Use as POISON: Indigenous dipped arrows in curare to use as poison for hunting
- acted upon voluntary muscles of the animal causing paralysis and death by respiration
- Use as DRUG: Indigenous use inspired allopathic medicine and curare was used by anesthetists during surgery
- small doses caused muscle relaxation
- structure modified to make it safer
9
Q
Ergot
A
- poisonous fungus that grows on heads of rye
- ground together with rye finding its way into bread, causing terrible epidemics
- Effects: disrupt nervous, cardiovascular and reproductive systems
- Use as a DRUG: ergotamine and ergonovine are two compounds derived from ergot that have pharmalogical uses
10
Q
Ergotamine
A
treats migranes by constricting blood vessels reducing amplitude of pulsation of blood to head
11
Q
Ergonovine
A
- once used to hasten birth but patients may be injured by too rapid of delivery
- can be used to arrest uterine bleeding after birth
12
Q
influence of religion
A
- traditional healers acted as physicians and priests
- plants containing intoxicating substances were used to alter consciousness and facilitate communication with their gods
- Ex. peytoe cactus widely used in mexico to achieve mysical state
- Contains mescaline causing hallucinations and distorted perception
- Ex. peytoe cactus widely used in mexico to achieve mysical state
13
Q
A drug is…
A
a substance recieved by a biological system not for nutritive purposes
14
Q
what percent of drugs are derrived from plant sources
A
25%
15
Q
two major categories of drugs discoveries in history
A
- Drugs acting on the brain
- Drugs acting against infectious disease
16
Q
LSD
A
- one of the most potent hallucinogenic drugs
- Discovery: Albert Hoffman, from swiss pharmeceutical firm, was involved in trying to synthesize products based on ergot
- In 1943, he synthesized LSD
- supported idea that mental illnesses might be due to the production of potent substances in the brain
- derivatives of LSD might be effective in treating mental illness
- Discovery: Albert Hoffman, from swiss pharmeceutical firm, was involved in trying to synthesize products based on ergot
17
Q
Drugs acting against infectious disease: 1900s
A
Paul Ehrlich designed complexes of arsenic and organic molecules bound to parasites. Led to cure for syphillis
18
Q
Drugs acting against infectious disease: 1930s
A
Gerhard Domagk induced sulfa drugs in Germany. First successful synthetic drugs for treating bacterial disease
19
Q
Drugs acting against infectious disease: 1940s
A
Penicillin. Alexander Flemming discovered first antibiotiv penicillin during 2nd WW and used in therapy of Gram-positive bacterial disease
*gram-positive: bacteria with thick cell walls and no outer membrane
20
Q
Drugs acting against infectious disease: 1950s
A
Selman Waksman discovered streptomycin. Treated tuberculosis and Gram-negative bacteria diseases
*gram-negative: bacteria with thin cells walls and an outer membrane
21
Q
5 steps of drug development:
A
- Basic research and Drug discovery
- Preclinical trials
- Clinical Trials
- Health Canada review and manufacturing
- Post-market surveillance and phase IV clinical trials
22
Q
Step 1: Basic Drug research and Drug Discovery
A
- 2 substeps
1. Identification of footage
2. Studying the target
23
Q
Substep 1: Identification of the target
A
- could be a receptor that, when activated, causes pain relief
- Once a cmpd that binds well to target is identified, it will be studied to determined pharmacological effects at molecular, cellular and whole animal level
24
Q
Substep 2: Studying the Target
A
- if a cmpd shows promise, it is identified as a LEAD COMPOUND and enters more detailed studies for safety and efficacy
- ex. effect of the drug on pain would be studied
25
Step 2: Preclinical Trials
- Is the drug safe and effective?
- after target discovered, drug enters preclinical trials
- conducted prior to testing the new drug in humans
- Two main categories of preclinical trials:
1. Pharmacology studies
2. Toxicology studies
26
Pharmacology Studies
- determine the detailed mechanism of action of the new drug
- ex. HOW a drug lowers blood pressure
27
Toxicology studies
- Determine the potential risks or harmful effects of the drug
- all drugs have some toxicity at some dose in some ind.
- studies will look at acute and chronic toxicity and effects on reproductive, carcinogenic and mutagenic potential
- expensive and may take years to complete
28
Step 3: Clinical trials
three main steps are required before a manufacturer can test a new drug on humans in clinical trial:
1. Proof of safety
2. Methodology
3. Investigation
29
Proof of safety
- submit proof of safety and efficacy of drug in several animal species
30
Methodology
methodology of the proposed clinical trial in humans is required
31
Investigation
- submission evaluated by qualified scientists in the regulatory agency
- if satisfied with submission, permission will be given for highly qualified investigators
- Particular care taken since animal studies will not always predict drug behaviour
32
Phases of Clinical Trials
- once initial steps are complete and permission granted
- clinical trials are studies performed on humans
- split into 3 phases
33
Clinical Trial: phase 1
- evaluate absorption, distribution, elimination and adverse effects of the new drug
- test one or two doses of the new drug to determine the tolerability of the drug
- efficacy is NOT tested during this phase
- usually conducted in a limited number of volunteers (20-80)
34
Clinical Trials: Phase 2
- looking to determine whether the drug is effective in treating the condition for which it is recommended in a limited number of people (100-500)
- pay careful attention to safety of the drug
- conducted in patients with the disease for which the drug is designed to treat
35
Clinical Trials: Phase 3
- Randomized controlled trials
- mains studies used for licensing and marketing of a drug
- tested in larger number of people (1000+) in diverse pop
- goal is to determine how safe and effective a drug compared to placebo/no treatment
- usually months to years
- multi-centered
- most expensive part of drug development; 1-50 million
- Split into 3 stages
36
Stage 1 of Phase 3 clinical Trial
1. Determining enrolment prior to the study
- People drug is tested on is carefully defined
- Target population
- Study Population
- two major factors influence who can be included in study population:
1. Inclusion/exclusion
- who is and who is not eligible
- study population carefully defined to eliminate conflicting variables
- common comorbidities are often included
2. Criteria and consent
- informed (document) consent obtained
37
Target population
who drug is intended for
38
Study population
is subset of target population that meets all required criteria
39
Clinical trials phase 3 stage 2
Allocating participants to treatment groups and conducting the trial
- Double blind design
- assigned to experimental treatment or control group via randomization
- ensure confounding variables are distributed equally
40
Types of control treatments:
- Placebo; identical but does not contain active drug (only used if no gold standard)
- Gold Standard; best available treatment for disease at that time
41
Phase 3 clinical trial stage 3
- outcome of trial that measures how much drug worked needs to be measured and compared
- should be measured in objective, reliable manner
- 3 factors to consider when analyzing clinical trial:
1. Compliance
2. Quality of Life
3. Statistics
42
Compliance
- if results are valid, patient compliance must be determined
- count of tablets remaining shows overall compliance OR by nurse signing off after administering drug
43
Quality of life
- measure impact of drug on QoL
- just because a drug may be effective in treating disease, it may have adverse effects not increasing QoL
44
Statistics
measured outcome for experimental drug compared to measured outcome for control drug
45
Phase 4 clinical trial
post-market review is constant surveillance of any adverse reactions after the drug has reached the market
46
Step 4: Health canada review & manufacturing
- the manufacturer will submit to the regulatory body (Health Canada) a new drug application containing the detailed results of clinical trials
- results reviewed again by regulatory scientists
- If drug deemed effective, and toxicity acceptable, drug will be granted approval
47
manufacturing
- generic vs brand name
- Bioequivalence
48
Bioequivalent
two drug products, generic and brand name, which contain the same active ingredients and give similar blood levels are said to be bioequivalent
- to achieve bioequivalence a comparative bioavailability study is conducted comparing blood levels
49
Factors to consider when looking at drug action:
1. drug targets
2. drug response
3. efficacy and potency
4. therapeutic range
50
drug targets
majority of targets for drugs are receptors, however, there can be other targets
51
Drug targets: receptors
- molecule(s) located on the outside or inside of a cell that has a regulatory function role in the organism
- many copies of same receptor exist
- Receptors are normally bound to and activated by endogenous ligands, substances found in the body such as hormones or neurotransmitters
- Location of receptors determines where a drug will act and whether the response is beneficial or detrimental
52
Other drug targets
- some drugs interact non-specifically with the biological system and not via receptors
- 2 EXAMPLES:
- chemical reactions
- Physical Chemical Forces
52
Chemical reaction drug targets
antacids neutralize stomach acid through simple acid-base reaction
53
Physcial chemical forces drug targets
Cholestyramine works by chemically binding to bile acids in GI tract, prventing reabsorption and increase elimination of bile salts that are used to make cholesterol
54
Agonist drugs
Drugs that bind to and stimulate a receptor are AGONISTS
55
Antagonist drugs
Drugs that bind and block response at a receptor are ANTAGONISTS
56
what do most drugs do at the receptor
most drugs mimic action of or block the effect of the endogenous ligand at the receptor
57
dose-response relationship
the intensity of effects produced by a drug increases in proportion to the dose:
58
questions asked to compare drugs
- Quantity
how much alcohol was compared to how much cannabis?
- Frequency of use
used how often?
- User demographics
By what people?
- Environmental Factors
under what circumstances?
59
types of dose response relationships
- Low doses
- THreshold
- therapeutic doses
-maximal effect
60
Dose response: Low doses
at low doses, little response observed as not many receptors activated
61
Dose response: Threshold
- as the dose increases, more receptors activated, until desired response seen
- a threshold exists, where a certain # of receptors need to be activated for an effect to be seen
62
Dose response: Therapeutic doses
once threshold reached, a small increase in dose results in a large increase in response
63
Dose response: maximal effect
- increase in response not indefinite but our bodies have maximal effect
- once reached, continuing to increase dose with have no further increase in therapeutic response
64
X axis of dose response curve
we make this log Dose so it transforms from a curve to a S with linear portion
65
Dose response curve y axis
Percent response of a rxn in the body
65
Linear portion of therapeutic range of dose response curve
Increasing dose will increase response linearly
65
Dose response curve threshold of effect
initial time when increasing dose but no response
65
Efficacy
- maximum pharmacological response that can be produced by a specific drug in that biological system
- AMOUNT of drug does not matter, what matters is the max effect the drug can produce
- Clinically more important than potency
65
Effective dose 50
dosage at percent response of 50% (y axis)
65
plateau of dose response curve
- maximum effect
- no greater response regardless of dosage
66
potency
- dose of a drug that is required to produce a response of a certain magnitude,
- usually 50% of the max response for that drug
- refers only to the amount of drug that must be given to obtain a particular response
- saying Drug A more potent than drug B means one must take more of drug B to see the same effects as drug A
- AMOUNT of drug matters
- does not matter as much clinically as the dosage can be adjusted for desired response
- easy to adjust
66
2 properties of a drug that describe its ability to produce a response
Efficacy and Potency
67
what axis does efficacy deal with
Y axis
68
What features of dose response curve does potency deal with?
- Potency generally deals with ED50 (50% response) and X axis
- what dose of drug you need to produce a certain effect
- the more drug you need to reach ED50, the less potent a drug is
69
Therapeutic range
the aim of drug therapy is to give a dose that keeps the blood concentration of a drug above the minimum concentration that produces the desirable response but below the concentration that produces unacceptable toxicity
70
Duration of action
time above minimum concentration for therapeutic response
71
Minimum concentration for therapeutic response:
time one feels effects of drug
72
Minimum concentration for unacceptable toxic response:
toxic effects
73
what does size of therapeutic range indicate
how safe a drug is, wider = safer
74
pharmokinetics
refers to movement of a drug into, through and out of the body
75
3 routes of drug administration
1. Topical
2. Enteral
3. Parenteral
76
Topical administration
- drugs applied or placed on body
- through skin, on the skin, inhalation
77
topical administration through the skin
- transdermal drug delivery is application of a drug to the skin for absorption into the general circulation FOR a systemic effect
- ex. nicotine patch
- convenient, steady supply delivered, bypasses enzymes
- expensive and cause local irritation
78
topical administration on the skin
- treat mild to moderate skin conditions (eczema, acne, infections)
- drugs applied to skin for local effect can be absorbed and produce a systemic (whole body) effect
79
topical administration via inhalation
- rapidly absorbed from the lungs for local and systemic effects
- gaseous anaesthetics for systemic effect
- steroid for local effect
- local effect, quantities are small avoiding toxicity
-requires proper use
80
enteral administration
administration enters blood via the GI tract, either directly or via the mouth/artificial opening
81
rate of enteral administration via mouth
- >90% drugs taken from this route
82
Advantages of administration via mouth
- convenient and least expensive
- non-invasive and can be self-administered
83
Disadvantages of administration via mouth
variable absorption between patients due to differences in intestinal motility and disease
84
enteral administration via rectum advantages
- systemic or local effect
- can be used in patients who are nauseous or vomiting
- less invasive for those who are comatose
- digestive enzymes are bypassed
85
enteral administration via rectum disadvantages
- limited # of meds are available/suitable
- absorption from rectal mucosal is slow, incomplete, variable, dependant on time medication is retained
86
enteral administration via sublingual and buccal advantages
enzymes are bypassed
87
enteral administration via sublingual and buccal disadvantages
- not all drugs adequately absorbed
- may be swallowed, then behaves if as taken orally
88
Parenteral administration
administration by bypassing the GI tract
89
Parenternal by intravenous (IV)
- drug placed directly into the blood and has immediate effects
- used for poorly absorbed drugs provided they can make a solution
- response is irreversible
- requires significant human resources
90
parenternal via intramuscular
- drug injected deep into a muscle
- volume of drug is limited to 2-3 mL
91
parenternal administration via subcutaneous
- drug injected into deepest layer of the skin
- allows for modification of drug preparations to control the timing of the release from injection site
92
what differs between drugs
bioavailability (dose administered compared to concentration in blood)
93
Topical: Organ/tissue administered to
skin, eye, ear, nose and lungs
94
Topical: Onset of action
rapid to slow (depends on organ)
95
topical: bioavailability
5% to 100%
96
Enteral organ/ tissue administered to
mouth, rectum, under tongue, in cheek
97
Enteral: Mouth: Onset of action & Bioavailability
slow; 30m - 1hr, 5% to 100%
98
enteral: rectum: onset of action and bioavailability
slow and incomplete, 30# to 100%
99
enteral: under tongue: onset of action and bioavailability
rapid (1-2mins), 30% to 100%
100
enteral: in the cheek: onset of action and bioavailability
immediate (3-4mins) 30%-100%
101
4 processes that occur after administration
1. absorption
2. Distribution
3. Metabolism
4. Excretion
102
what determines the concentration of drug in the blood and in turn, concentration of drug at site of action
ADME
103
Absoprtion
- movement of a drug from the site of administration into the blood
- for a drug to be absorbed and distributed to sites of action, stored and excreted must be able to cross biological membranes
- Drugs can be absorbed from the lumen to the interstitium in several ways:
1. Diffusion through aqueous pores
2. Diffusion through lipids
3. Active/carrrier mediated transport
104
absorption: diffusion through aqueous pores
- drugs with small molecular weights that are water soluble can move across membranes by dissolving aqueous fluids surrounding a cell then passing through small openings between cells
- flows from a area of high concentration (lumen) to an area of lower concentration (intersititum)
105
Absorption: diffusion through Lipids
- dissolve in lipid portion of membrane
- flow through concentration gradient
- the ability of a drug to cross a membrane via this method is dependent on its lipid solubility
106
Absorption: Active/carrier mediated transport
- drugs bind carrier proteins that carry molecules across membranes
- becomes carrier protein-drug complex that releases the drug on the other side of the membrane
- CAN move down gradient but can also be an active process up a gradient requiring energy
- important role in removing drugs and metabolites from liver and kidneys
107
Drug distribution
- movement of a drug from the blood to the site of action and other tissues
- the concentrations of drug at the sites of distribution are in equilibrium with its concentration in the blood
- if the concentration in the blood drops below the concentration at any of the distribution sites, the drug will move from the site to the blood to maintain equilibrium
108
rate of drug distribution to an organ depends on
Blood flow to that organ
109
distribution can result in
termination of therapeutic effect of some drugs
110
Metabolism of a drug
- aka biotransformation
- conversion of a drug to a different chemical compound in order to eliminate it
- products of metabolism are called metabolites
- to be eliminated by the kidneys, a drug must be water soluble
- most metabolism occurs at the liver but some also occur in kidneys, intestines, lungs, skin and most other organs
- Divided into phase 1 and 2 reactions
111
Metabolism phase 1
purpose is to add or unmask a functional group to prepare for addition of water soluble molecule
112
Metabolism phase 2
add a large water soluble moiety (glucuronic acid or sulfate) to the product resulting from phase 1, making the metabolite water soluble for excretion by kidney
113
P450
enzymes capable of metabolizing drugs. found in most tissues, but high concentrations in the liver.
- when taking 2 drugs simultaneously, they may compete for this enzyme resulting in reduced metabolism of one or both, leading to toxic effects
114
Excretion
- moving the drug and its metabolites out of the body
- Half Life: time needed for liver and kidney to remove half the drug from the body
115
excretion through Kidney
- majority of drugs eliminated here
- drugs of sufficient water solubility will be excreted in the urine
- lipid-soluble drugs can be reabsorbed from the kidney back into the blood
116
Excretion through GI tract
some drugs can be excreted via GI (in the feces) tract after undergoing metabolism in the liver
117
Excretion through Lungs
drugs that are volatile or in gas form can be excreted by the lungs
118
Excretion & breast milk
- drugs often found in breast milk of nursing mothers
- minor route of elimination
- nursing infant can be exposed to a therapeutic or toxic dose of the drug
119
Excretion through saliva and sweat
often in the presence of drug misuse
120
Variation in drug response
- any influence at any stage can contribute to variability in observed response
- concentration can vary up to 10 fold
121
factors for drug response variability
- Genetic
- Environmetnal
- disease states
- altered physiological states
-Presence of other drugs
122
Genetic cause for drug response variability
- genetic variability exists in the receptors to which drugs bind
- enzymes can vary due to individual gene coding
123
Environmental cause for drug response variability
exposure to chemicals can increase enzymes in the liver responsible for metabolism (faster elimination)
124
Disease state cause for drug variability
- alters manner in which drugs are handled
- ex. ppl with liver disease metabolize slower
125
Altered psychiological states cause for drug variability
- elderly more susceptible to drug action
- pregnancy
126
presence of other drugs cause for drug response variability
when drugs taken together, one drug can change biological effect of the second
127
toxic effects of drugs can be divided into:
- adverse effects
- Drug-drug and drug-food interactions
128
Adverse effects
any effect produced by a drug in a patient that is not the intended effect
129
Examples of adverse effects
- Extension of therapeutic effect
-Unrelated to main drug action
-Allergic reaction
-Withdrawal and addiction
- Teratogenesis
- Adverse biotransformation reaction
130
Extension of therapeutic effect
occurs when too much of the drug in the bloo, commonly in drug overdose
131
Unrelated to the Main Drug Action
effects unrelated to pharmalogical action - may or may not be expected
132
allergic reaction
mediated by the immune system, an antigen-antibody combination provokes an adverse rxn (mild or severe)
133
Withdrawl and Addiction
unwanted physiological and psychological effects of the drug
134
Teratogenesis
when a drug produces defects in the developing fetus
135
Adverse Biotransformation Reaction
occurs when a drug is converted to a chemically reactive metabolite that can bind to tissue components and cause tissue or organ damage
136
why when drugs when first introduced into therapy can LATER turn out to have adverse effects
- rarity of occurance
-length of use
-detectability in animals
-time period specificity
137
Rarity of occurrence
- toxic rxn is rare
- ex. antibiotic chloramphenicol was used for years before realizing it can cause fatal bone marrow damage
- this was not picked up in initial testing of the drug
138
Length of usage
- rxn may only appear after prolonged use
- ex. steptomycin was first introduced for treatment of tuberculosis, it was not realized it could cause deafness if used for extended time
139
Detectability in animals
- toxic effect may not be detectable
- only appears once drug is tested in humans
- ex. headache, insomnia, nausea and mental disturbances will not be readily picked up in animal testing
140
Time period specificity
- rxn may be unique to specific time period
- ex. thalidomide (drug to treat nausea) produced animal limb growth in the fetus, was not done on pregnant animals
- even if we test drugs in pregnant animals, this may not reflect a pregnant human
141
assessing drug toxicity
drug toxicity is assessed using therapeutic index
142
formula for therapeutic index
Therapeutic Index = TD50/ED50
143
TD50 (Toxic Dose 50):
the dose of the drug that is toxic in 50% of the population
144
ED50 (Effective Dose 50):
the dose of the drug that is effective in 50% of the population
145
Therapeutic Index:
- how safe a drug is
- relates the dose required to produce a beneficial effect to the dose required to produce an undesirable effect
- the higher the therapeutic index, the safer the drug
- low therapeutic index indicates it is likely toxicities will be observed
146
Drug-Drug Interactions
- occurs when one drug changes the pharmacological effect of a second drug
- can occur at many points of AME
147
drug-drug interactions during absorption
a drug can increase intestinal movement, speeding the passage of a second drug through the intestine, decreases contact of the second drug with instestines, decreasing absorption
148
drug-drug interactions during Metabolism
a drug can block the inactivation of a second drug in the liver, increasing the blood level and effect of the second drug
149
Drug-drug interactions during excretion
a drug can facilitate the excretion of a second drug by the kidney, decreasing the blood level and effect of the second drug
150
Drug-food interactions
Tyramine & grapefruit
151
Tyramine
- found in mature cheese
- capable of raising BP and is broken down in liver by enzyme MAO
- one class of antidepressant drugs are inhibitors of MAO
- if someone being treated with MAO inhibitor and consumes tyramine, tyramine will not be broken down and BP raising effects will be intensified
152
Grapefruit
- grape fruit an some other citrus fruit alter absorption
- a component of grapefruit inhibits drug metabolizing enzymes in GI tract, resulting in greater amount of active drug being absorbed
- results in higher blood levels of the drug, leading to overdose
- no Ontario hospital serves grapefruit products
153
Limbic System
- region of the brain that integrates memory, emotion and reward
- this area of the brain (& hypothalamus) controls emotion and behaviour
- comtains dopaminergic reward centers, which are targets for commonly misued drugs & are associated with addiction
154
Cerebral Cortex
- largest part of the brain
- rich in neurons
- functions: sensory and motor coordination, mental processes, intelligence, memory, vision, judgement, thought, speech, emotions, and consciousness
- Neurons here can be stimulated (excited) or depressed (inhibited) by drugs
155
The neuron
- functional unit of the brain
- a nerve cell capable of generating and transmitting electrical signals
- about 90 billion in brain (differing in shape and size)
- new neurons are generated through **neurogenesis**
- connection between neurons is constantly reshaped through **neuroplasticity**
156
3 structures of the neuron
1. Dendrites
2. Cell body
3. Axon
157
Dendrites
- short with highly complex branching patterns
- receiving antennae for incoming information and accept information through receptors on membranes
- upon receiving information, an electric current is generated and directed down neuron
158
Cell Body
- aka soma
- largest part of neuron and contains nucleus & cytoplasm
- cytoplasm contains abundant pre-packaged neurotransmitters which can be secreted
159
Axon
- single fibre that extends from cell body and ends at synapse
- continues carrying incoming information away from dendrites and cell body by electrical pulses
- this is passed to subsequent neurons
160
The synapse
- junction between two neurons that communicates the electrical impulse
- Synaptic Transmission: passage of a signal from one neuron to another
- rapid and chemical in nature
- the endogenous chemicals that transmit a signal between two neurons are called neurotransmitters
- usually one synapse connects two neurons BUT a single neuron can make synaptic connections with many other neurons
161
Drugs & Synaptic Transmission
- the synapse can be a target site for many drugs, interrupting synaptic transmission OR enhancing it
- this modifies brain activity
162
Neurotransmitters & Receptors
- Glutamate
- Catecholamines
- GABA
- Serotonin
- Acetylcholine
- Opioid Peptides
163
Glutamate
- primary excitatory neurotransmitter in CNS
- found in almost all neurons
- acts on a family of receptors (glutamatergic receptors)
- important for learning
164
Catecholamines
- dopamine and norepephrine are similar in strucutre
165
Dopamine
- pathways involved in the control of hormonal systems, motor coordination, and motivation/reward
- alterations in these are involved in addiction
166
Norepinephrine
- bind to a large number of receptor types, but 2 main are alpha and beta
- activation leads to excitation of cell
- targeted by CNS stimulants
167
GABA
- primary inhibitory neurotransmitter in CNS
- found in high [] in cerebral cortex
- CNS depressants enhance GABA receptor function
168
Serotonin
- hyperactivity involved with anxiety
- hypoactivity implicated in depression
- some classes of CNS stimulants act by increasing serotonin at synapse
169
Acetylcholine
- produces excitatory response in CNS
- 2 types bind acetylcholine and they are termed collnergic receptors: Nicotinic and Muscarinic
170
Nicotinic Receptors:
- found in certain regions of the brain
- stimulated by ACh or nicotine
171
Muscarinic Receptors:
- involved in learning, memory, and cognitive function
- stimulated by ACh or muscarine
- drugs that block action of ACh at these receptors produce amnesia
- loss is associated with alzheimers
172
Opioid Peptides
- 3 main classes
1. Enkephalins
2. Endorphins
3. Dynorphins
- varying degrees of selectivity for three opioid receptors: mu, delta and kappa
- all opioids interact with these receptors
173
