Ch. 1 Principles of Psychopharmacology Flashcards
1
Q
Pharmacology definition
A
study of the actions and effects of drugs on living organisms.
2
Q
what are we primarily studying in pharmacological studies?
A
binding affinity of drugs to different important functional proteins in the body
‘stickiness’
3
Q
what subdivisions of pharmocology evolved from the development of synthetic drugs?
A
pharmacist
medicinal chemist
neuropsychopharmacology
4
Q
pharmacist definition
A
one whoprescribes medicinal drugs and knows the effects, side effects and contraindications
5
Q
medicinal chemist definition
A
one who creates molecules that bind to targets in the body/brain
6
Q
neuropsychopharmacology definition
A
one who identifies chemical substances that act on the nervous system to alter behaviour
7
Q
what are the primary goals of neuropsychopharmacology
A
understand the neural basis of ‘normal behaviour’
identify causes/treatments of behavioural abnormalities in psychiatric illnesses
8
Q
what are the two subdivisions of neuropsychopharmacology
A
neuropharmacology
psychopharmacology
9
Q
neuropharmacology definition
A
study of drug-induced changes in nervous system cell functioning
more cellular level vs behavioural
10
Q
psychopharmacology definition
A
study of drug-induced changes in mood, thinking, and behaviour
more behavioural level vs cellular
11
Q
drug action definition
A
molecular change produced when drug binds to a receptor/target
12
Q
drug effect definition
A
alterations in physiological/psychological function induced by drug action
13
Q
example of the drug action and effect of cocaine
A
action; blocks monoamine transporters
effect; increases self-esteem, reduces apetite, etc.
14
Q
true or false; drug action and effect occur in the same location
A
false, action could happen in a completely different spot than the effect
15
Q
true or false; different drugs can have the same effect through different actions
A
true
16
Q
therapeutic vs side effect
A
desired physical or behavioural effect from the drug vs all the other possible effects
17
Q
what is the relationship between balances in the body/brain and use of drugs?
A
drugs for therapeutic functions are fixing an existing imbalance, but in turn will cause an imbalance in another area that was fine before
18
Q
how can we control the side effects of drugs on the body’s homeostatis
A
through proper dosing
19
Q
specific effects definition
A
physiological/biochemical interaction of drug with target site that always happens
20
Q
non-specific effect definition
A
effect based on unique characteristics of an individual
21
Q
what characteristics can influence non-specific effects?
A
drug-taking background
mood
expectations of effect
perceptions
22
Q
placebo effect definition
A
non-specific effect based on your expectations of the drugs effect
23
Q
pharmacokinetics definition
A
factors that contribute to bioavailability
24
Q
bioavailability definition
A
amount of drug free to bind at target sites
25
what are the 5 main factors of bioavailability
route of administration
absoprtion/distribution
binding
inactivation
excretion
26
what other factors besides bioavailability influence the drug effect?
speed of the drug reaching the target
prior drug use
27
routes of drug administration
oral
injection
inhalation
28
oral administration characteristics
most popular method
absorbed in gut circulation
resistant to stomach acid enzymes
slow
29
what factors affect oral drug administration
amount of food in stomach
rate stomach empties
physical activity
30
first-pass metabolism definition
chemicals/molecules in the gut first filtered by the liver before entering the bloodstream
31
why do we have first-pass metabolism?
to break down any potential harmful chemicals before they can cause us harm
32
what effect does first-pass metabolism have on drugs?
render drug inactive by breaking down, need high does to overcome liver
render active through metabolite, must be taken orally
33
injection administration characteristics
delivered directly to bloodstream
fastest method
greater risk of overdose
can also be subcutaneous or intramuscular
know exactly what dose you get
34
difference between intravenous and subcutaneous/intramuscular
slower and more even absorption
35
inhalation administration characteristics
absorbed through lungs
irritates nasal passage/lungs
36
what physical aspects affects the absorption rate of a drug?
route of administration
vehicle used
fluid in individual (size, sex affect this)
37
what chemical aspect affects the absorption rate of a drug?
rate of passage through cell membranes
38
what molecules pass through cell membranes the best and with what mechanism
lipid soluble compounds
passive diffusion
39
what are lipid soluble compounds?
hydrophobic molecules
40
examples od lipid soluble compounds
steroids
diacetylmorphine (heroine)
41
how long does it take a drug to makes its way through the whole body through the blood stream?
1-2 minutes
42
what is the blood brain barrier?
separation of brain capillaries from CSF that surrounds the brain
43
special characteristics of brain capillaries
no clefts/pinocyotic sites
no non-lipid soluble molecules can enter
surrounded by glial feet
surrounded by CSF
44
another name for glial feet
astrocytes
45
weak areas of the blood brain barrier
area prostrema
median eminence
parts of hypothalamus
46
why is the BBB weak around the area prostrema
vomit center, needs to sense noxious molecules in blood
47
why is the BBB weak around the median eminence
needs to release neurohormones into the blood
48
why is the BBB weak around parts of the hypothalamus?
so it can access contents of the blood to look for bad/infectious molecules
49
what does pharmacodynamics encompass?
physiological and biochemical interactions of drug molecules with target receptors
50
what are characteristics of drug clearance
metabolites of drugs area excreted through urine
mostly excreted according to first order kinetics
quantified by their half life
51
what are first-order kinetics?
the exponential clearing of drugs from the system
52
why is drug clearance exponential
enzymes that break down the drug are more abundant than the drug and therefore their removal is concentration dependent
53
what are zero-order kinetics?
linear removal rate of a drug because metabolism enzymese are supersaturated with it
54
half-life definition
time required to remove 50% of the drug in system
55
what are the different classes of biotransformation for drug clearance?
Phase 1
Phase 2
56
phase 1 definition
removal of drug through oxidation, reduction, or hydrolysis
57
how does phase 1 biotransformation work?
ionizes the drug which makes it less active and therefore more readily excreted
sometimes leads to another active form of the drug
58
example of a drug that is converted to another active form after phase 1 biotransformation
Diazepam (valium) becomes Oxazepam
59
phase 2 definition
removaal of drug through conjugation (attaching drug to other small molecule)
60
how does phase 2 biotransformation work?
additional molecule ionizes the drug and therefore makes it more readily excreted
61
which type of biotraansformation is non-synthetic?
phase 1
62
which type of biotraansformation is synthetic?
phase 2
63
True of False: drugs must go through phase 1 and 2 biotrnaformtations to be inactive and secreted
False; different drugs will need one, the other, or both in either order to be excreted
64
factors that modify biotransformation capacity:
induction/inhibition of metabolism enzymes
drug competition
genetic polymorphisms
65
how does induction/inhibition of metablism enzymes affect biotransformations?
less or more metabolism enzymes will determine how much drug gets cleared
66
how does drug competition affect biotransformations?
drugs that use the same enzymes to metabolise will compete for them if in the body at the same time, therefore prolonging taken dose
67
how do genetic polymorphisms affect biotransformations?
genetics determine how well the drug-metabolizing enzymes work
68
receptor definition
proteins on/in cells. all drugs bind to some kind
69
ligand definition
molecule that binds to a receptor with some selectivity
70
endogenous ligand definition
molecule produced by the body that binds to a receptor
71
drug affinity definition
concentration of drug needed to achieve a certain amount of binding
72
affinity definition
amount of attraction between ligand and receptor
73
what is the relationship between drug affinity and drug concentration
drugs with higher affinity will need lower concetrations in the blood stream to achieve maximal binding
74
drug efficacy definition
how well the ligand initiates a biological action upon binding to receptor
75
true or false: drug affinity and efficacy have no established relationship and are more or less independent
true
76
drug potency definition
absolute amount of ligand necessary to produce a specific effect
77
what is ED50
measure of drug potency using dose needed to produce 50% of maximal response
can vary depending on effect
may also be point where 50% of population experiences a therapeutic effect
78
what are the two dose-response functions possible?
sigmoidal shape (most common)
biphasic shape
79
threshold dose definition
smallest dose that produces a measurable effect
80
maximum response definition
assumes all receptors are occupied
81
what causes a drug to have biphasic effect?
higher concentrations of the drug lose receptor selectivity and therefore use other receptors that counteract effect
82
what does it mean if a drug has a biphasic effect
higher dose range of the drug either shows no effect or opposite effect
83
what is TD50
dose where 50% of the population experiences toxic effect
84
what is the therapeutic index (TI)
TD50/ED50
85
metabotropic receptor
ligand binding changes the shape of the receptor causing biological action through secondary messengers
86
ionotropic receptor
ligand binding changes configuration to open ion channel
87
which type of receptor has the fastest effects?
ionotropic receptors
88
what are the two types of ligand-receptor binding
temporary
probabilistic
89
temporary ligand-receptor binding
after ligand separates, the receptor is free to bind again
affinity determines how long they're together
90
probabilistic ligand-receptor binding
likelihood of ligand binding is influenced by other factors
91
factors affecting probilistic ligand-receptor binding
how many ligands are available
how sticky the ligand is for the receptor
competition with other molecules
92
up-regulation of receptors
increase in number/sensitivity of receptors in response to absence of ligands
93
down-regulation of receptors
reduces number of receptors/sensitivity after chronic activation
94
drug selectivity
degree to which a drug binds to a particular receptor compared to other receptors
95
true or false: some drugs only selective bind to one type of receptor
false; no drug is truly selective and selectivity is relative
96
what is the relationship between drug selectivity and dose?
higher doses cause loss in selectivity
97
agonist
best fit and high efficacy in receptor that produces biological effect
98
partial agonist
mediocre fit and intermediate efficacy in receptor causing a less potent effect
99
what can a partial agonist be used for?
prevent excessive activation of agonist in situations where an antagonist could have negative effects
100
inverse agonists
initiate action opposite to that produced by agonist
101
indirect agonist
has same effect as agonist but does not interact with a receptor directly
102
how can an indirect agonist affect the receptor?
release more NT
increase binding of NT to receptor (positive allosteric modulator)
103
competitive antagonists
fit receptor but produce no cellular effect (low efficacy)
in competition with the agonist/endogenous ligands
104
noncompetitive antagonist
reduces agonist effect indirectly
e.g. mess with 2nd messenger, block ion channel, etc
105
how do competitive antagonists shift the dose response curve?
shift the curve up or down
106
how do non-competitive antagonists shift the dose response curve?
change the shape, usually preventing maximal effect
107
physiological antagonism
two drugs counteract each other's effects through opposite mechanisms
108
additive effects
two drugs causing the same effect add together
109
potentiation
combination of two drugs produces effects much greater than the sum of their individual effects
110
example of two drugs that cause potentiation
benzodiazepine and alcohol in their repiratory effects
111
examples of functional antagonism/potentiation
physiological antagonism
additive effects
potentiation
112
drug tolerance definition
diminished response to a drug after repeated exposure
body's response to being brought out of homeostasis
113
cross tolerance
tolerance to one drug diminishes the effectiveness of another drug withe similar mechanisms
114
characteristics of drug tolerance
reversible
dependent of dose/frequency and environment
can occur rapidly, slowly, or never
spans many different mechanisms
115
acute tolerance
tolerance after a single administration
116
metabolic tolerance (drug-dispositional)
body becomes more efficient at metabolizing, therefore reducing drug that makes it to target tissue
117
functional tolerance (pharmacodynamics)
changes at drugs site of action, usually involving receptor sensitivity to the ligand
118
example of drug with effects that build tolerance at different rates
opiods:
tolerance to euphoric effects builds rapidly
tolerance to respiratory supression builds slowly
119
behavioural tolerance
pavlovian conditioning makes brain associate the drug effects with the context they occur in
120
conditioned tolerance
tolerance is maximal when drug is given in environments similar to those where drug effects previously experienced
