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PSYCH 478 > Pharmacodynamics > Flashcards

Pharmacodynamics Flashcards

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

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2
Q

What is a ligand?

A

any molecule that binds to a receptor

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3
Q

what is a drug?

A

an exogenous ligand

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4
Q

What are some endogenous ligands?

A

neurotransmitters, hormones, peptides

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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)

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6
Q

TRUE or FALSE: biological agents are endogenous ligands

A

FALSE: endogenous and exogenous

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7
Q

What are the criteria for defining a receptor?

A

saturability, specificity, and reversibility

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8
Q

What can be used to reveal the saturability of a receptor?

A

Dose-response

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9
Q

TRUE or FALSE: In terms of saturability, there are a finite number of receptors per cell.

A

TRUE

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10
Q

Describe the specificity of a receptor.

A

high binding affinity necessary to elicit a biological response

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11
Q

Describe the reversibility of a receptor.

A
  • binding to receptors should be reversible
  • ligand should be DISSOCIABLE and RECOVERABLE
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12
Q

Reversibility distinguishes ______________ interactions from ______________ interactions.

A

receptor-ligand; enzyme-substrate

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13
Q

TRUE or FALSE: The saturability of a receptor remains constant over time.

A

FALSE: saturability can change over time

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14
Q

What kind of ligands do extracellular receptors bind? What is an example?

A
  • water-soluble ligands
  • e.g. neurotransmitters
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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
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16
Q

Extracellular receptors are a common target for _____________.

A

psychoactive drugs

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17
Q

Intracellular receptors are a common target for _____________ and _________________.

A

steroid hormones; lipophilic compounds

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18
Q

what are the mechanisms of signalling for extracellular receptors?

A
  • ligand-gated ion channels
  • G-protein coupled receptors (GPCR)
  • receptor kinases
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19
Q

What is an example of ligand-gated ion channels?

A

postsynaptic neurotransmitter receptors

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20
Q

What is an example of GPCR? What mechanism do they involve?

A
  • metabotropic receptors
  • intracellular second messenger (mechanism)
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21
Q

What are receptor kinases common for?

A

cytokine and peptide hormone receptors (e.g. insulin)

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22
Q

Where are intracellular receptors located?

A

in the cytoplasm

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23
Q

Are hormone receptors intracellular or extracellular?

A

intracellular

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24
Q

Where do hormone receptors translocate to upon hormone binding?

A

to the nucleus

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25
Q

What is the function of hormone receptors?

A

function as transcription factors

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26
Q

TRUE or FALSE: GPCRs directly induce changes in gene expression by binding to specific response element

A

FALSE: hormone receptors

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27
Q

What is the key to receptor function?

A

specific recognition of ligand

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28
Q

What are agonist interactions?

A

elicit a biological effect on the receptor

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29
Q

What are antagonist interactions?

A

prevent or block a biological effect

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30
Q

What is another term used to define potency?

A

ED50

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31
Q

What is ED50?

A

the dose required to elicit a half-maximal effect

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32
Q

Agonist activity at a receptor can be measured by examining the __________.

A

dose-response

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33
Q

TRUE or FALSE: with increasing concentration of agonist, the biological response is lower.

A

FALSE: increase the dose, increase the response

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34
Q

What kind of shape does the dose-respond follow?

A

sigmoidal

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35
Q

What is the difference between potency and efficacy?

A
  • potency depends on ED50
  • efficacy depends on the maximum response
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36
Q

What is TD50 a measure of?

A

potency of a drug at eliciting a toxic response

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37
Q

What is LD50?

A

measures the potency at elicity a lethal effect

38
Q

What is therapeutic index?

A

reflects the margin of safety between drug efficacy and adverse effects

39
Q

How do you calculate therapeitic index (TI)?)

A

TI = TD50 / ED50

40
Q

TRUE or FALSE: A larger therapeutic index means the drug is safer

41
Q

TRUE or FALSE: In contrast to antagonists, agonists can be reversible or irreversible

A

FALSE: antagonists are reversible or irreversible

42
Q

What is competitive antagonism? How does it affect potency and efficacy of the agonist?

A
  • reversible antagonists can be displaced by the endogenous agonist
  • reduces agonist potency
  • does not affect agonist efficacy
43
Q

What is non-competitive antagonism? How does it affect agonist potency and efficacy?

A
  • antagonist binds irreversible to the same binding site as an endogenous ligand
  • reduce drug efficacy
  • SOMETIMES reduce drug potency
44
Q

What are allosteric modulators?

A
  • bind to a different site on the receptor than the endogenous ligand
  • affects receptor function through other conformational effects on the protein
45
Q

TRUE or FALSE: toxins are reversible

A

FALSE: toxins are irreversible

46
Q

What are partial agonists? How does it affect the efficacy of the endogenous agonist?

A
  • binds same site as endogenous ligand but elicit a less than maximal response
  • can decrease efficacy of the endogenous agonist
47
Q

What is an inverse agonist?

A
  • binds receptor with constitutive activity
  • has opposite effect to full agonist
48
Q

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?

A
  • diminished effect of a given does of drug over time
  • reversible
  • dependent on frequency and dose
  • varies across drugs
  • multiple mechanisms
49
Q

What is cross-tolerance?

A
  • development of tolerance to structurally similar drugs in the same pharmacologic class
  • can cause drug interactions
50
Q

What is sensitization? Provide an example.

A
  • 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
Q

TRUE or FALSE: sensitization is less common than tolerance

52
Q

What is cross-sensitization?

A
  • development of sensitization to structurally similar drugs
  • occurs between drugs acting on the same receptor (e.g. cocaine and amphetamines)
53
Q

What is metabolic tolerance? What does it lead to? What is another name?

A
  • increased metabolism through enzyme induction
  • decreased bioavailability of drug
  • aka drug disposition tolerance
54
Q

What is pharmacodynamic tolerance? What does it result in?

A
  • changes in nerve cell function in response to drug
  • receptor down-regulation results in saturation and diminished effect
55
Q

What is behavioural tolerance? What does it involve? In what kind of environments does it occur?

A
  • context-specific tolerance
  • involves learning and memory
  • demonstrated by tolerance in familiar but not novel environments
56
Q

What is habituation in terms of behavioural tolerance?

A
  • first administration causes greater alteration of normal behaviour
  • diminished with subsequent administrations
57
Q

What is conditioning in terms of behavioural tolerance?

A

environment or paraphernalia act as a conditioned stimulus to initiate response

58
Q

TRUE or FALSE: administration of drug in a conditioned environement can elicit a different physiological response than in a novel environment

59
Q

TRUE or FALSE: drug tolerance occurs slowly and persistently

A

FALSE: drug tolerance can occur rapidly and transiently OR slowly and persistently

60
Q

What is an example of drug that causes tolerance rapidly and transiently? slowly and persistentl?

A
  • rapid = cocaine
  • slow = alcohol
61
Q

What is the persistence of tolerance heavily influenced by?

A

metabolic and pharmacodynamic mechanisms

62
Q

What is a key component contributing to drug addictions? What does it result from?

A
  • drug dependence
  • results from tolerance mechanisms
63
Q

What is drug dependence most significantly influenced by?

A

pharmacodynamic mechanisms

64
Q

______________ is the requirement for drug use in order to maintain normal function after development of drug tolerance.

A

dependence

65
Q

What kind of tolerance will NOT lead to drug dependence?

A

behavioural tolerance

66
Q

Who developed the classic model of dependence and tolerance to opiates?

A

Himmelsbach in 1943

67
Q

What does tolerance to opiates result from?

A

compensatory mechanisms to restore homeostasis

68
Q

What does acute administration of opiates cause? repeated administration?

A
  • acute –> disrupt homeostasis
  • repeated –> initiate adaptive mechanisms that compensate to restore homeostasis
69
Q

What leads to withdrawal and cravings of opiates?

A

disturbed homeostasis from NO drug administration

70
Q

TRUE or FALSE: acute morphine treatment decreases cellular cAMP

71
Q

TRUE or FALSE: chronic exposure to morphine decreases cellular cAMP

A

FALSE: normalizes cAMP levels to restore homeostasis

72
Q

How does withdrawal of morphine affect cAMP levels?

A

dramatic rebound ABOVE normal cAMP levels

73
Q

What is the key descriptor of addictions?

A

dependence

74
Q

How does the DSM describe addictions?

A

substance abuse disorders

75
Q

Dependence is based on ____________ drug response.

A

physiological

76
Q

When does confusion in diagnosing addictions occur?

A

confusion arises in distinguishing medically normal and problematic dependence

77
Q

Addiction may be better defined as ______________________.

A

COMPULSIVE drug-seeking behaviour (i.e. impulse control disorder)

78
Q

What is addiction confounded by?

A

societal norms and stigmatization

79
Q

Addiction is a medical/psychiatric disorder that results from ________________ norm-violating behaviours and thus is subject to moral judgement regardless of terminology.

80
Q

What is intoxication defined as? What is it a result of? What disturbances does it result in? Is acute and chronic intoxication the same?

A
  • 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
Q

What is withdrawal defined as? What kind of changes does it result in? What kind of urge is it associated with?

A
  • 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
Q

What is the gateway hypothesis? Who was it proposed by?

A
  • progressive and hierarchical staging of drug use - licit, soft illicit, hard illicit
  • proposed by Kanel, 1975
83
Q

What kind of drugs are considered licit according to the gateway hypothesis?

A

alcohol and tobacco

84
Q

What kind of drugs are considered soft illicit according to the gateway hypothesis?

85
Q

What kind of drugs are considered hard illicit according to the gateway hypothesis?

A

cocaine and heroin

86
Q

TRUE or FALSE: the use of drug of a lower stage is sufficient for progression to a higher stage

A

FALSE: necessary but not sufficient

87
Q

TRUE or FALSE: drug initiation does not account for risk of addictive behaviour

88
Q

What is a predictive risk of substance-use?

A

disinhibition (predisposition to impulsivity, hyperactivity, antisociality)

89
Q

TRUE or FALSE: there is a low correlation of genetic risks for various substances

A

FALSE: high correlation

90
Q

TRUE or FALSE: multiple substances have common neurobiology

91
Q

TRUE or FALSE: having one addiction increases the risk of having other addictions

92
Q

Where do all drugs work in the brain?

A

reward pathway

PSYCH 478 (28 decks)

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