CH1 Flashcards
1
Q
The study of the actions of drugs and their effects on living organisms
A
Pharmacology
2
Q
Prescribes medicinal drugs, knows therapeutic effects, side effects, contraindications
A
pharmacist
3
Q
Creates molecules that bind to targets in body/brain
A
medicinal chemist
4
Q
Identifies chemical substances that act on the nervous system to alter behaviour
A
Neuropsychopharmacology
5
Q
Neuropsychopharmacology uses ______ agents as _____ to gain an understanding of the neurobiology of behaviour. It ranges from ______ (studies in cells/animals) to _____ (working with human patient populations)
A
chemical, probes, pre-clinical, clinical
6
Q
Primary goals of neuropsychopharmacology
A
- understand the neural/neurochemical basis of normal behaviour, 2. identify the causes / treatments of behaviour abnormalities in psychiatric illnesses
7
Q
Study of drug induced changes in the nervous system cell functioning
A
neuropharmacology
8
Q
emphasizes drug-induced changes in mood, thinking and behaviour
A
psychopharmacology
9
Q
molecular changes produced when a drug binds to a receptor/target
A
drug action
10
Q
alterations in physiological/psychological functions induced by drug action
A
drug effect
11
Q
the drug-receptor interaction produces desired physical or behavioural changes
A
therapeutic effects
12
Q
Physiological/biochemical interactions of drug with target site in living tissue; what the drug does to the body that nothing else can do (e.g. alcohol depressing neural activity)
A
specific effects
13
Q
based on unique characteristics of individual background, mood, expectation of effect, perceptions (e.g. alcohol can augment pleasant moods or amplify unpleasant ones, placebo effect)
A
nonspecific effects
14
Q
Factors that contribute to bioavailability
A
pharmacokinetics
15
Q
the amount of drug free to bind at target sites
A
bioavailability
16
Q
five main factors contributing to bioavailability
A
- route of administration, 2. absorption / distribution, 3. binding, 4. inactivation, 5. excretion
17
Q
drug effect also depends on how ____ the drug reaches its target, and ____/______ of prior drug use
A
rapidly, frequency, history
18
Q
Oral administration is the most popular method, because it is ____, ______ and economical. The disadvantages are that it is _____, has variable _____, and _____ levels. Drugs taken orally are absorbed from the ____ into circulation. Some are absorbed from the ____ but most are taken up through the ____ ____. These drugs must be resistant to destruction by ____ ____ and _____.
A
safe, self-administered, slow, absorption, plasma, gut, stomach, small intestine, stomach acid, enzymes
19
Q
through oral administration, the factors that influence absorption include
A
- amount/type of food in the stomach, 2. rate that stomach empties, 3. physical activity
20
Q
potentially harmful chemicals (taken orally) pass through the liver (via portal vein) where they are chemically altered
A
first pass metabolism
21
Q
the liver may render some drugs _______, with the need to administer by _____ or in higher doses. Other drugs are metabolized into _______ forms by the liver and need to be taken orally to have an effect
A
inactive, injection, active
22
Q
Injection routes deliver drugs into the _____, which bypass the _____. The advantages are that it is ______, and has the most accurate blood _______. The disadvantages is that there is the greatest risk of _______.
A
bloodstream, first pass metabolism, fast, concentration, overdose
23
Q
______ or _____ methods of intake allow absorption through capillaries around skin/muscles which allow for _____ and _____ absorption
A
subcutaneous, intramuscular, slow, even
24
Q
_______ is when the drug is absorbed rapidly from the lungs, which can provide ______ and _____ to nasal passages and ______
A
inhalation, irritation, damage, lungs
25
The route of administration alters the rate of ____ and ___ ____ of a drug. The ______ that a drug is dissolved in can impact how long it stays in the system after _______. Other factors affecting absorption are the _____ and ____ of an individual
absorption, blood levels, vehicle, injection, size, sex
26
An intramuscular injection delivered through oil takes _______ to take effect, and drug concentration in the blood declines at a ______ rate. The same method but using ______, results in faster _______ and ______
longer, slower, saline, drug concentration, decline
27
A larger person has more ______ to dilute a drug, thus needing a higher dose. Likewise, women tend to have less, and a different physiology, resulting in a ______ dose required
body fluid, lower
28
A key factor determining plasma brain drug levels is the rate of passage by molecules through _____ ______. These prevent most molecules from passing through unless they are ______ soluble. ______ are completely soluble.
cell membranes, lipid, steroids
29
_______ (heroin), is more lipid soluble than _____, has a more rapid ____ and more potent reinforcing properties
diacetylmorphine, morphine, onset
30
Once the drug is in the bloodstream, it is carried throughout the body within _______ minutes. Capillaries in the body are very _____, allowing drugs to enter tissues regardless of _____ ______. However, in the brain, many substances would have ____ effects on brain function if permitted to cross freely. The ______ reduces the diffusion ______ particles, as brain capillaries have no _____/_________ sites.
1-2, porous, lipid solubility, disruptive, blood brain barrier, ionized, clefts, pinocytotic
31
fills the subarachnoid space around the brain, spinal cord, ventricles, and canals
cerebrospinal fluid
32
separates the brain capillaries and the CSF
blood brain barrier
33
extensions of glial cells that surround brain capillaries restricting movement of non lipid soluble molecules
astrocytes
34
Molecules that the brain needs, such as _____, are carried in via _______ ______ transport
glucose, carrier mediated
35
For a drug to be centrally active, it typically needs to be ________ _____, in both _____ and _____ environments
lipid soluble, acidic, basic
36
Some regions have a weaker blood brain barrier, such as the ____ ______ "vomit center" which senses noxious molecules in the blood, the _____ ___, which release neurohormones in the blood, and parts of the ______
area postrema, median eminence, hypothalamus
37
the elimination of drugs via bio-transformation and metabolites and excretion
drug clearance
38
Drug clearance is usually _______ (first order kinetics), meaning only a small fraction of _____ ____ are occupied, so the rate is __________
exponential, clearance sites, concentration dependent
39
time required to remove 50% of the drug in the system
half life
40
some drugs are eliminated via ______ kinetics, meaning that they are eliminated at a constant rate regardless of concentration. This occurs when drug levels are ____, and routes of metabolism elimination are _______ (aka more ____ than there are clearance sites)
zero order, high, supersaturated, molecules
41
_____ and ____ have relatively long half lives, while _____ ____ and ____ have shorter half lives, requiring frequent administration
caffeine, ibuprophen, nicotine, morphine, cocaine
42
Most biotransformation occurs in the ______. The _______ enzyme family are responsible for oxidizing most psychoactive drugs, making them easier to _____
liver, cytochrome P450, clear
43
modification of a drug by oxidation, reduction, or hydrolysis (non-synthetic); involving adding or removing an ion from the molecule to convert it into a less lipid soluble or less active form
phase I
44
sometimes, phase I metabolism can convert the drug molecule to another _____ form, resulting in a _____ ____ effect
active, long lasting
45
involves conjugation (synthetic) attachment of the drug to other small molecules (glucuronide, sulfate, or methyl groups), which ionizes them and makes them inactive; synthesizes a new molecule
phase II
46
Some drugs are metabolized directly by ___ /____, while others need ____ phase I or III processes
I, II, multiple
47
Inactive metabolites are excreted via the ____ or ______.
kidneys, bile
48
factors that modify biotransformation capacity (3)
1. induction or inhibition of enzymes involves in metabolism, by other drugs, foods, etc., 2. drug competition (when two drugs require the same enzyme to be metabolized), 3. genetic polymorphisms for drug metabolizing enzymes create individual differences
49
molecule that binds to a receptor with some selectivity
ligand
50
amount of attraction between ligand and receptor (concentration needed to achieve a certain amount of firing)
affinity
51
how well the ligand initiates a biological action upon binding to the receptor
drug efficacy
52
absolute amount of ligand necessary to produce a specific effect, typically measured by ED50
drug potency
53
the dose needed to produce 50% of the maximal response
ED50
54
one individual ____ of a drug may have a different ______ than another effect of the same drug
effect, potency
55
_____ curves describe the extent of the effect produced by a given drug. Most curves are _____ shaped. However, some drugs have _____ effects, with a lower dose having one effect, and a higher dose having ___ effect, or even the _____ effect. This is because the drug starts to lose _____, and other parts of the brain are activated that _____ the main effect
dose-response, sigmoidal, biphasic, no, opposite, selective, counteract
56
smallest dose that produces a measurable effect
threshold dose
57
when all the receptors for the drug are occupied
maximum response
58
the dose causing 50% of the population to experience a toxic effect
TD50
59
TD50/ED50; want this to be high to prevent toxic effect at low doses
therapeutic index
60
the range from ED50 --> the TD for a specific toxic effect
margin of safety
61
Most drugs do not ___ into neurons, but instead act on ___ receptors, such as metabotropic or ionotropic receptors
pass, surface
62
receptors that activate second messengers inside the cell, causing multiple effects; is generally slow
metabotropic receptor
63
second messenger effects
1. modulates ion channels to affect neural activity, 2. alters protein synthesis, 3. alters metabolism of the cell
64
Receptors that open or close ion channels, allowing ions to flow through and excite or inhibit neurons; generally fast
ionotropic receptors
65
ligand receptor interactions are ______, meaning after the ligand separates, the receptor is free to ____ again. It is also ______, meaning the likelihood of the ligand binding to a receptor is influenced by the number of molecules of the ______, the ______ of the ligand, and the presence of _______
temporary, bind, probabilistic, ligand, affinity, competitors
66
increase in the number/sensitivity of receptors in response to the absence of ligands
up-regulation
67
reduced number of receptors or their sensitivity after chronic activation
down-regulation
68
the degree to which a drug binds to a particular receptor compared to other receptors; is relative, and highly dependent on dose
drug sensitivity
69
have the best chemical fit and high efficacy, readily attaches to the receptor and produces a biological effect; may even activate or stick to the receptor better than the endogenous ligand
receptor agonists
70
binds to the receptor and activates it but is less potent and have intermediate efficacy
partial agonists
71
initiates an action opposite to that produced by the agonist; ultimate effect is similar to an antagonist, but pharmacological action is different
inverse agonists
72
drugs that can also act like agonists, even though they may not directly interact with a particular receptors e.g. by increase NT synthesis or release, or increasing binding of NT to a receptor
indirect agonist
73
fit receptors but produce no cellular effect (low efficacy); reduces the effect of the endogenous ligand; ability to block the effect of the agonist depends on the relative concentrations and affinities of the two drugs
competitive antagonists
74
reduces the agonist effect by 1. binding to the receptor at a site other than the agonist binding site (e.g. blocking an ion channel) 2. interfering with second messengers initiated by the agonist, 3. disturbing the cell membrane supporting the receptor (protein shape changed)
noncompetitive antagonists
75
competitive agonists essentially reduce the _____ of an agonist, and shift the dose response curve so that a ____ dose of agonist is needed to achieve the maximal effect. Adding enough agonist can ____ the effects of the antagonist. However, noncompetitive agonists change the _____ of the dose response curve, often preventing the agonist from achieving _____ effect, irrespective of how much more agonist is added
potency, higher, block, shape, maximal
76
two drugs interacting to reduce the effectiveness of both drugs
physiological antagonism
77
When two drugs combine to produce effects that are equal to both drug effectiveness combined
additive effects
78
when the combination of 2 drugs produces effects greater than the sum of their individual effects; important for things like sedation
potentiation / synergistic interactions
79
diminished response to a drug after repeated exposure; dose of drug must be increased to achieve the same magnitude of effect
drug tolerance
80
when tolerance to one drug diminishes effectiveness of another drug, usually ones that work on similar mechanisms
cross tolerance
81
4 characteristics of drug tolerance
1. reversible when drug use stops, 2. dependent on dose/frequency of drug use and drug taking environment, 3. may occur rapidly, after long periods of use, or never, 4. multiple forms explained by different mechanisms
82
repeated drug use reduces the amount of the drug available at the target tissue; by more efficient metabolism (more enzymes), so less drug gets to site of action
metabolic (drug dispositional) tolerance
83
when changes in cell function compensates for repeated drug exposure; typically occurs at the site in the brain or body where the drug exerts its effects (ex. downregulation)
functional (pharmacodynamic) tolerance
84
When the brain makes associations between the drug effects and the context where they occurred; and tolerance is maximal when the drug is given in environments similar to those previously experienced; results in body increasing or decreasing response in advance to prepare for the drug effects
behavioural tolerance / conditioned tolerance
85
The placebo effect can result in both ______ evaluation of relief and measurable ____ changes
subjective, physiological
86
Increase in anxiety and influence in treatment outcome when having negative expectations
nocebo effect
87
movement of drug from the site of administration to the blood circulation
absorption
88
____ administration may avoid some first pass metabolism, but has irregular _____.
rectal, absorption
89
injection used for lab animals that involves injection into the abdominal wall; has rapid effects but variable absorption
intraperitoneal (IP)
90
______ ____ of drugs have local drug effects
topical application
91
______ (under the tongue), _______, or _______ administration all by pass the first pass metabolism
sublingual, intranasal, transdermal
92
_______ (into CSF), ______, _____ or ______ (into ventricles) are central routes of administration
intrathecal, epidural infusion, intracranial, infusion pump
93
Plasma levels of drug gradually fall as it is absorbed into the ____, _____, _____ ___, etc. Drug _______ reduces the drug concentrations in organs again to restore equilibrium and ____ the action of the drug
heart, brain, kidneys, liver, redistribution, terminate
94
inactive sites where no measurable biological effect is initiated (e.g. fat and bone)
drug depots/silent receptors
95
____ binding reduces the concentration of drug at the sites of ______. It results in prolonged drug time in the body
depot, action
96
Drug clearance depends on (3)
1. biotransformation rate, 2. depot binding, 3. storage in fat reservoirs
97
the range of plasma drug levels that are high enough to be effective, but not so high that they cause toxic or intolerable side effects
therapeutic window
98
the desired blood concentration of drug achieved when the absorption / distribution phase is equal to the metabolism / excretion phase
steady state plasma level
99
enzymes on the smooth ER that lack specificity, like cytochrome P450
microsomal enzymes
100
baseline receptor function in the absence of ligand
constitutive activity
101
receptor proteins for a given drug or NT have different characteristics in different target tissues
receptor subtypes
102
The dose of drug that is lethal to 1% of the population compared with the dose that is lethal therapeutically effective in 99% of the population (LD1/ED99)
safety factor index
103
when tolerance develops after a single administration
acute tolerance
104
a physiological state in which the body adapts to the chronic presence of a drug and elicits a drug-specific withdrawal syndrome if the drug is abruptly stopped
physical dependence
105
tasks learned under the influence of a psychoactive drug may subsequently be performed better in the drugged state than in the nondrugged state and vis versa
state dependent learning
106
enhancement of particular drug effects after repeated administration of the same dose of drug
sensitization
107
sensitization is ___ dependent, can have ______ effects, and be conditioned; more sensitization in a ____ environment, and persist for long periods of ______
dose, cross-sensitization, novel, abstinence
