Pharmacodynamics Flashcards
(92 cards)
1
Q
what is pharmacodynamics?
A
the study of the PHYSIOLOGICAL and BIOCHEMICAL interactions of drug molecules with their target tissues/receptors responsible for their ultimate drug effects
2
Q
What is a ligand?
A
any molecule that binds to a receptor
3
Q
what is a drug?
A
an exogenous ligand
4
Q
What are some endogenous ligands?
A
neurotransmitters, hormones, peptides
5
Q
What is a receptor?
A
protein molecule on cell surface or within the cell that is the initial site of action of a biological agent (neurotransmitters, hormones, peptides, drugs)
6
Q
TRUE or FALSE: biological agents are endogenous ligands
A
FALSE: endogenous and exogenous
7
Q
What are the criteria for defining a receptor?
A
saturability, specificity, and reversibility
8
Q
What can be used to reveal the saturability of a receptor?
A
Dose-response
9
Q
TRUE or FALSE: In terms of saturability, there are a finite number of receptors per cell.
A
TRUE
10
Q
Describe the specificity of a receptor.
A
high binding affinity necessary to elicit a biological response
11
Q
Describe the reversibility of a receptor.
A
- binding to receptors should be reversible
- ligand should be DISSOCIABLE and RECOVERABLE
12
Q
Reversibility distinguishes ______________ interactions from ______________ interactions.
A
receptor-ligand; enzyme-substrate
13
Q
TRUE or FALSE: The saturability of a receptor remains constant over time.
A
FALSE: saturability can change over time
14
Q
What kind of ligands do extracellular receptors bind? What is an example?
A
- water-soluble ligands
- e.g. neurotransmitters
15
Q
What kind of ligands do intracellular receptors bind? What is an example?
A
- lipid-soluble ligands within the cell
- e.g. steroid hormone receptors
16
Q
Extracellular receptors are a common target for _____________.
A
psychoactive drugs
17
Q
Intracellular receptors are a common target for _____________ and _________________.
A
steroid hormones; lipophilic compounds
18
Q
what are the mechanisms of signalling for extracellular receptors?
A
- ligand-gated ion channels
- G-protein coupled receptors (GPCR)
- receptor kinases
19
Q
What is an example of ligand-gated ion channels?
A
postsynaptic neurotransmitter receptors
20
Q
What is an example of GPCR? What mechanism do they involve?
A
- metabotropic receptors
- intracellular second messenger (mechanism)
21
Q
What are receptor kinases common for?
A
cytokine and peptide hormone receptors (e.g. insulin)
22
Q
Where are intracellular receptors located?
A
in the cytoplasm
23
Q
Are hormone receptors intracellular or extracellular?
A
intracellular
24
Q
Where do hormone receptors translocate to upon hormone binding?
A
to the nucleus
25
What is the function of hormone receptors?
function as transcription factors
26
TRUE or FALSE: GPCRs directly induce changes in gene expression by binding to specific response element
FALSE: hormone receptors
27
What is the key to receptor function?
specific recognition of ligand
28
What are agonist interactions?
elicit a biological effect on the receptor
29
What are antagonist interactions?
prevent or block a biological effect
30
What is another term used to define potency?
ED50
31
What is ED50?
the dose required to elicit a half-maximal effect
32
Agonist activity at a receptor can be measured by examining the __________.
dose-response
33
TRUE or FALSE: with increasing concentration of agonist, the biological response is lower.
FALSE: increase the dose, increase the response
34
What kind of shape does the dose-respond follow?
sigmoidal
35
What is the difference between potency and efficacy?
- potency depends on ED50
- efficacy depends on the maximum response
36
What is TD50 a measure of?
potency of a drug at eliciting a toxic response
37
What is LD50?
measures the potency at elicity a lethal effect
38
What is therapeutic index?
reflects the margin of safety between drug efficacy and adverse effects
39
How do you calculate therapeitic index (TI)?)
TI = TD50 / ED50
40
TRUE or FALSE: A larger therapeutic index means the drug is safer
TRUE
41
TRUE or FALSE: In contrast to antagonists, agonists can be reversible or irreversible
FALSE: antagonists are reversible or irreversible
42
What is competitive antagonism? How does it affect potency and efficacy of the agonist?
- reversible antagonists can be displaced by the endogenous agonist
- reduces agonist potency
- does not affect agonist efficacy
43
What is non-competitive antagonism? How does it affect agonist potency and efficacy?
- antagonist binds irreversible to the same binding site as an endogenous ligand
- reduce drug efficacy
- SOMETIMES reduce drug potency
44
What are allosteric modulators?
- bind to a different site on the receptor than the endogenous ligand
- affects receptor function through other conformational effects on the protein
45
TRUE or FALSE: toxins are reversible
FALSE: toxins are irreversible
46
What are partial agonists? How does it affect the efficacy of the endogenous agonist?
- binds same site as endogenous ligand but elicit a less than maximal response
- can decrease efficacy of the endogenous agonist
47
What is an inverse agonist?
- binds receptor with constitutive activity
- has opposite effect to full agonist
48
What is tolerance? Is it reversible or irreversible? What is it dependent on? Is it the same across all drugs? Is there only one mechanism?
- diminished effect of a given does of drug over time
- reversible
- dependent on frequency and dose
- varies across drugs
- multiple mechanisms
49
What is cross-tolerance?
- development of tolerance to structurally similar drugs in the same pharmacologic class
- can cause drug interactions
50
What is sensitization? Provide an example.
- enhancement of a particular drug effect on repeated exposure
- e.g. prior exposure to cocaine increases repetitive and hyperactive behaviours in animals (head bobbing)
51
TRUE or FALSE: sensitization is less common than tolerance
TRUE
52
What is cross-sensitization?
- development of sensitization to structurally similar drugs
- occurs between drugs acting on the same receptor (e.g. cocaine and amphetamines)
53
What is metabolic tolerance? What does it lead to? What is another name?
- increased metabolism through enzyme induction
- decreased bioavailability of drug
- aka drug disposition tolerance
54
What is pharmacodynamic tolerance? What does it result in?
- changes in nerve cell function in response to drug
- receptor down-regulation results in saturation and diminished effect
55
What is behavioural tolerance? What does it involve? In what kind of environments does it occur?
- context-specific tolerance
- involves learning and memory
- demonstrated by tolerance in familiar but not novel environments
56
What is habituation in terms of behavioural tolerance?
- first administration causes greater alteration of normal behaviour
- diminished with subsequent administrations
57
What is conditioning in terms of behavioural tolerance?
environment or paraphernalia act as a conditioned stimulus to initiate response
58
TRUE or FALSE: administration of drug in a conditioned environement can elicit a different physiological response than in a novel environment
TRUE
59
TRUE or FALSE: drug tolerance occurs slowly and persistently
FALSE: drug tolerance can occur rapidly and transiently OR slowly and persistently
60
What is an example of drug that causes tolerance rapidly and transiently? slowly and persistentl?
- rapid = cocaine
- slow = alcohol
61
What is the persistence of tolerance heavily influenced by?
metabolic and pharmacodynamic mechanisms
62
What is a key component contributing to drug addictions? What does it result from?
- drug dependence
- results from tolerance mechanisms
63
What is drug dependence most significantly influenced by?
pharmacodynamic mechanisms
64
______________ is the requirement for drug use in order to maintain normal function after development of drug tolerance.
dependence
65
What kind of tolerance will NOT lead to drug dependence?
behavioural tolerance
66
Who developed the classic model of dependence and tolerance to opiates?
Himmelsbach in 1943
67
What does tolerance to opiates result from?
compensatory mechanisms to restore homeostasis
68
What does acute administration of opiates cause? repeated administration?
- acute --> disrupt homeostasis
- repeated --> initiate adaptive mechanisms that compensate to restore homeostasis
69
What leads to withdrawal and cravings of opiates?
disturbed homeostasis from NO drug administration
70
TRUE or FALSE: acute morphine treatment decreases cellular cAMP
TRUE
71
TRUE or FALSE: chronic exposure to morphine decreases cellular cAMP
FALSE: normalizes cAMP levels to restore homeostasis
72
How does withdrawal of morphine affect cAMP levels?
dramatic rebound ABOVE normal cAMP levels
73
What is the key descriptor of addictions?
dependence
74
How does the DSM describe addictions?
substance abuse disorders
75
Dependence is based on ____________ drug response.
physiological
76
When does confusion in diagnosing addictions occur?
confusion arises in distinguishing medically normal and problematic dependence
77
Addiction may be better defined as ______________________.
COMPULSIVE drug-seeking behaviour (i.e. impulse control disorder)
78
What is addiction confounded by?
societal norms and stigmatization
79
Addiction is a medical/psychiatric disorder that results from ________________ norm-violating behaviours and thus is subject to moral judgement regardless of terminology.
voluntary
80
What is intoxication defined as? What is it a result of? What disturbances does it result in? Is acute and chronic intoxication the same?
- clinically significant problematic behavioural and psychological changes associated with substance intake
- result of physiological effects of substance on CNS
- disturbances of: perception, wakefulness, attention, thinking, judgement, psychomotor behaviour, interpersonal behaviour
- differences in acute/chronic intoxication
81
What is withdrawal defined as? What kind of changes does it result in? What kind of urge is it associated with?
- substance-specific problematic behavioural change resulting from discontinuation of use
- physiological and cognitive changes
- clinically significant distress or impairment
- urge to re-administer to reduce symptoms
82
What is the gateway hypothesis? Who was it proposed by?
- progressive and hierarchical staging of drug use - licit, soft illicit, hard illicit
- proposed by Kanel, 1975
83
What kind of drugs are considered licit according to the gateway hypothesis?
alcohol and tobacco
84
What kind of drugs are considered soft illicit according to the gateway hypothesis?
cannabis
85
What kind of drugs are considered hard illicit according to the gateway hypothesis?
cocaine and heroin
86
TRUE or FALSE: the use of drug of a lower stage is sufficient for progression to a higher stage
FALSE: necessary but not sufficient
87
TRUE or FALSE: drug initiation does not account for risk of addictive behaviour
TRUE
88
What is a predictive risk of substance-use?
disinhibition (predisposition to impulsivity, hyperactivity, antisociality)
89
TRUE or FALSE: there is a low correlation of genetic risks for various substances
FALSE: high correlation
90
TRUE or FALSE: multiple substances have common neurobiology
TRUE
91
TRUE or FALSE: having one addiction increases the risk of having other addictions
TRUE
92
Where do all drugs work in the brain?
reward pathway
