Psychopharmacology Test I

Front 1

How can you effect the synthesis of dopamine? what are the pharma agents and what do they do?

Back 1

a. Precursor transport: tyrosine competes with other amino acids ie via tryptophan
b. More tyrosine supplied to the diet
c. Block conversion of tyrosine by tyrosinse hydroxylase with AMPT (alpha-methyl-para-tyrosine)  indirect antagonist (rate limiting step)
d. Block decarboxylation of L-DOPA by carbidopa or alpha-methyl-dopa are indirect antagonists

Front 2

What drugs effect the release of dopamine?

Back 2

a. Amphetamines cause vesicles to release DA  amphetamine is an indirect agonist of DA

Front 3

How can you affect the metabolism of dopamine?

Back 3

a. MAO inhibitors prevent the breakdown of DA into aldahyde and ammonia. This means that DA accumulates (even though metabolism is not the main form of inactivation). Examples are clorgyline inhibits MAO A, deprenyl and paragyline inhibit MAO B  indirect agonist

Front 4

what are is the main way to inactivate dopamine? How can you affecct this with pharma?

Back 4

Dopamine Transporter (reuptake)
a. Inhibited by imipramine, cocaine and amatryptaline  no reuptake of Dopamine  dopamine remains in post synaptic cleft longer  indirect agonist

Front 5

What are methods of inactivating dopamine permanantly?

Back 5

Anti dopamine neurotoxins are 6-OHDA and MPTP
6-ODHA is rapidly taken up into the catecholoamine terminals except the adrenal medulla. In the periphery 6-OHDA leads to the degradation and destruction of the sympathetic nervous system. Given intracerebrally it selectively has a long lasting depleting effect of NE and DA neurons. Selective protection of NE from 6-OHDA can be conferred by uptake blockers. Microinjection of 6-OHDA into cell bodies of DA cells causes them to die off.
MPTP selectively destructs nigrostriatal dopamine neurons and confers Parkinsonian type symptoms upon the subject

Front 6

What does AMPT (alpha-methyl-para-tyrosine)do?

Back 6

Block conversion of tyrosine by tyrosinse hydroxylase with AMPT rate limiting step in dopamine and NE synthesis

indirect antagonist of DA and NE

Front 7

What does Carbidopa do?

Back 7

Indirect antagonist of DA and NE

Block decarboxylation of L-DOPA

Front 8

What does alpha-methyl-dopa do?

Back 8

Indirect antagonist of DA and NE

Block decarboxylation of L-DOPA

Front 9

What does Methylphenidate (ridaline) do?

Back 9

Indirect agonist of DA

Releasing agent

Front 10

What does D-Amphetamine do?

Back 10

Indirect agonist of DA

cause vesicles to release DA

Front 11

What do MAOIs do? Name some

Back 11

clorgyline inhibits MAO A
deprenyl and paragyline inhibit MAO B

indirect agonists of dopamine

Inhibit the breakdown of DA into aldahyde and ammonia. This means that DA accumulates (even though metabolism is not the main form of inactivation)

Front 12

What does imipramine do?

Back 12

indirect agonist of DA

Inhibit dopamine transporter reuptake

Front 13

What does Cocaine do?

Back 13

indirect agonist of dopamine

Inhibit dopamine transporter reuptake

Front 14

What does amatryptaline do?

Back 14

indirect agonist of dopamine

Inhibit dopamine transporter reuptake

Front 15

What does 6-OHDA do?

Back 15

anti dopamine and NE neurotoxin

rapidly taken up into the catecholoamine terminals except the adrenal medulla. Given intracerebrally it selectively has a long lasting depleting effect of NE and DA neurons. Microinjection of 6-OHDA into cell bodies of DA cells causes them to die off.

Front 16

What does MPTP do?

Back 16

Neurotoxin againt DA
selectively destructs nigrostriatal dopamine neurons inducing Parkinsonian type symptoms

Front 17

What does SKF82958 do?

Back 17

Agonist of the DA D1 receptor

Front 18

What does dihydrexidine do?

Back 18

Agonist of the DA D1 receptor

Front 19

What does fenoldopan do?

Back 19

Agonist of the DA D1 receptor

Front 20

What does Quinpirol do?

Back 20

Agonist of the DA D2 receptor

Front 21

What does 7-OH DPAT do?

Back 21

Agonist of the DA D3 receptor

Front 22

What does SCH23390 do?

Back 22

antagonist of the DA d1 receptor

Front 23

What does SKP83566, do?

Back 23

antagonist of the DA d1 receptor

Front 24

What does haloperidol do?

Back 24

antagonist of the DA d2 receptor (anti- psychotic)

Front 25

What does SB-277011a do?

Back 25

antagonist of the DA d3 receptor (blocks drug seeking behavior maybe)

Front 26

What drugs can you use to agonize the DA d1 receptor?

Back 26

SKF82958, dihydrexidine, fenoldopan

Front 27

What drugs can you use to agonize the DA d2 receptor?

Back 27

Quinpirol

Front 28

What drugs can you use to agonize the DA d3 receptor?

Back 28

7-OH DPAT

Front 29

What drugs can you use to antagonize the DA d1 receptor?

Back 29

SCH23390, SKP83566,

Front 30

What drugs can you use to antagonize the DA d2 receptor?

Back 30

haloperidol (anti psychotic)

Front 31

How can you block the conversion of tyrosine by tyrosinse hydroxylase

Back 31

AMPT (alpha-methyl-para-tyrosine)

Front 32

how can you Block decarboxylation of L-DOPA

Back 32

Carbidopa

Front 33

How can you pharma induce the release of dopmaine

Back 33

Methylphenidate (ridaline), D-Amphetamines

Front 34

How can you Inhibit the breakdown of DA into aldahyde and ammonia. This means that DA accumulates (even though metabolism is not the main form of inactivation)

Back 34

MAOIs (clorgyline inhibits MAO A, deprenyl and paragyline inhibit MAO B)

Front 35

How can you inhibit dopamine reuptake

Back 35

imipramine, cocaine, amatryptaline

Front 36

Under what conditions do you get postive reinforcement?

Back 36

when a consequence is presented after a behavior and it increases the probability of behavior

Front 37

Under what conditions do you get punishment?

Back 37

When a consequence is presented and it decreased the probability of a behavior

Front 38

Under what conditions do you get Negative reinforcement

Back 38

When a consequence is removed and the probability of behavior is increased

Front 39

under what conitions does extinction occur

Back 39

when a consequence is removed and the probability of behavior is decreased

Front 40

Why is operant behavior useful in pharmacological studies?

Back 40

Operant behavior is useful to the study of pharmacology because it is a species general phenomenon, there is technology that allows for the automated, objective, and precise measurement of the behavior, operant behavior provides us with a stable and drug sensitive baseline.

Front 41

What effect does chloropromazine have on aversive control?

Back 41

1. Clinical antipsychotic chloropromazine preclinically reduces avoidance but does not alter escape. No effect on punished responding

Front 42

what effect do benzodiazepine (like chlordiazapine aka librium), barbiturates and alcohol habe on acersive control

Back 42

2. Chlordiazapoxide aka Librium a benzodiazepine (as well as diazepam (valium))and barbiturates are clinically anti anxiety drugs. Preclinical they have no effect on avoidance or escape but they do increase punished responding.

Front 43

What drug(s) reduces avoidance but does not alter escape. No effect on punished responding

Back 43

chloropromazine

Front 44

What drug(s)have no effect on avoidance or escape but they do increase punished responding.

Back 44

Chlordiazapoxide aka Librium a benzodiazepine (as well as diazepam (valium))and barbiturates

Front 45

What is the relationship between schedual of reinforcement of a behavior and drugs? Give examples

Back 45

Behavior can be reinforced on different time course or frequency based schedules. A drug may have a different and/or varying effect on the same behavior depending in the schedule in which the behavior was reinforced.
For example:
Amphetamine increases avoidance behavior more when the behavior is reinforced on a fixed interval schedule than when it is reinforced on a fixed ratio schedule.
Pentobarbital increases punishment suppression behavior more when the behavior is reinforced on a fixed interval schedule than when it is reinforced on a fixed ratio schedule.

Front 46

What are the two features that define the action of a drug? How can you prove their exsistance experimetaly?

Back 46

Two features define the action of a drug on the biological system: affinity and the intrinsic activity of the drug (Ariens)Affinity- describes how well a substance binds to its receptor and can be described by the law of mass action. This is where receptor occupancy is important. Intrinsic activity of a drug is how well does a drug that is bound to a receptor produce the given effect. The Ariens experiment: receptor occupancy and intrinsic activity dose effect curves. Ariens found that even if you antagonize with an irreviersible antagonist (and inactivate) a certain portion of histamine receptors, histamine agonist can still produce a maximal effect even when only 25% of the receptors are active. When only 2.5% of histamine receptors are active there is 70% response. This tells us that it is NOT necessary to activate 100% of all receptors in order to get 100% efficacy. Therefore relationship between receptor occupancy and effect is NOT linear.

50% effect comes before 50% receptor occupancy

Front 47

What are the routes of administration of a drug? what are the benefits and downstides of each? What is the time course?

Back 47

i. Entral (into the GI system) usually by mouth (per os) i. Plus: convenient
ii. Minus: interacts with food which can imped the drug, can de digested by enzymes in the GI, taste is an issue, requires cooperation and compliance
iii. Absorbtion depends on:
1. pH: weak acids are well absorbed (barbiturates are an example)
2. lipid solubility: high lipid solubility is good for absorption
3. susceptibility to enzymes
iv. Time course: fairly slow but depends
ii. Parenteral
a. Subcutaneous (S.C) is an injection under the skin
i. Plus: Allows for slow even absorption
ii. Minus: local necrosis may occur, antiseptic conditions are necessary so it is generally expensive, it can be irritating
iii. Time course: slow and even
b. Intramuscular (I.M.) usually given in deltoid or glut in humans
i. Preferred in monkeys, humans, and pigeons (less in rodents)
ii. Plus: rapid absorption, less pain than S.C., is in suspension the absorption slows
iii. Minuses: also expensive, drug can get caught up in adipose tissue which can result in ineffectiveness in the immediate time course or can lead to overdose
iv. Time course: slow and even
iii. Intrperitoneal (I.P.) the abdominal cavity
a. Mostly for rodents, not used in primates because of the high risk of infection
b. Plus: large absorption cavity
iv. Intraveneus (I.V.)
a. VERY FAST: This can be both a plus and a minus. It is a plus because an immediate effect can be seen. It can be a minus because there is no time to counteract the drug once its in.
b. Plus: accurate, adjustable does, catheters make administration easier and safer
c. Minus: risk of embolism, huge risk of infection, sterile conditions are completely necessary
d. Time course: can have a huge immediate peak in effect but is also is fast to stop acting
v. Lungs (inhalation)
vi. Intracerebrally
a. Only in research animals
b. Into ventricles, spinal cord, cistenea

Front 48

What are the routes of administration of a drug?

Back 48

Entral (into the GI) usually per os (by mouth0

Parenteral includes subcutaneous and intramuscular

Intraparitoneal is into the abdominal cavity

Intraveneus is into the blood steam that goes to the hear

inhalation via lungs

intracerebrally

by the nasal cavity

Front 49

What factors play a role in the transpost of a drug across general membranes?

Back 49

i. Drugs must cross a cellular lipid bilayer
ii. Lipid solutions and fat soluble substances pass easily
iii. Pores in the membrane are protein transport channels
iv. Active uptake into the intersticial fluid is the most common form of transport and requires energy

Front 50

What are the features of the BBB? What drugs cross the BBB?

Back 50

i. The BBB is an extra membrane that surrounds the capillaries made of glial cells (Schwann cells and astroglia)
ii. Characteristic of drugs that can pass the BBB easily are:
a. Low ionization (no charge)
b. Low binding to proteins
c. A high lipid to water coefficient (like ethanol)
d. Lipid and fat solubility

Front 51

What drugs cross the BBB?

Back 51

ii. Characteristic of drugs that can pass the BBB easily are:
a. Low ionization (no charge)
b. Low binding to proteins
c. A high lipid to water coefficient (like ethanol)
d. Lipid and fat solubility

Front 52

Other the the BBB what effects the distribution of a pharmacological agent into and throughout the brain?

Back 52

i. Cappilaries of the brain are less permeable than the ones in the periphery because of astroglial cells?
ii. Passage into CNS depends of blood supply and flow into the different parts of the brain
a. High in cortex and low in white matter

Front 53

What does curare do?

Back 53

Ach antagonist

Front 54

What does Muscarin do?

Back 54

Ach agonist of muscarinic receptors

Front 55

What does hermicholinium-3 do?

Back 55

Antagonist of Ach (no choline reuptake no to ACh)

Blocks choline transporter (rate limiting step)

Front 56

What does Mg2+ and cobalt do in regards to Ach?

Back 56

Antagonist

Competitively inhibits Ca2+ entrance into the cell, preventing release

Front 57

What does botulism toxin do?

Back 57

antagonist of ach

Blocks release

Front 58

What does aminopyridine do?

Back 58

agonist of Ach Keeps calcium channel open

Front 59

What do Organophosphates (pestisides) do?

Back 59

Very strong agonists of Ach

Inhibits acetylcholineesterase which breaks down AcH (most important in ACh inactivation)

Front 60

What does hexaamothonium do?

Back 60

antagonist of ach Nicotinic receptors

Front 61

What does mecamilanine do?

Back 61

Antagonists of ach Nicotinic receptors

Front 62

What does DMDP do?

Back 62

Agonists of ach Nicotinic receptors

Front 63

What does oxotremorine do?

Back 63

Agonists of ach muscarinic receptors

Front 64

What does methabocholine do?

Back 64

Agonists of ach muscarinic receptors

Front 65

What does atropine do?

Back 65

Antagonists of ach muscarinic receptors

Front 66

What does pirencepine do?

Back 66

Antagonists of ach muscarinic receptors

Front 67

What does perenzapine do?

Back 67

Antagonists of ach muscarinic receptors

Front 68

What does telenzapine do?

Back 68

Antagonists of ach muscarinic receptors

Front 69

What drugs are antagonists of the Ach muscarinic receptors?

Back 69

atropine
pirencepine
perenzapine
telenzapine

Front 70

What drugs are the agonists of the ach muscarinic receptors

Back 70

oxotremorine
methabocholine

Front 71

What drug is n agonist of the Ach nicotinic receptor

Back 71

DMDP

Front 72

What drugs are anagonists of the nicotinic receptors

Back 72

hexaamothonium
mecamilanine

Front 73

What drug Blocks choline transporter (rate limiting step)

Back 73

hermicholinium-3 an antagonist of ach

Front 74

What "drug" Competitively inhibits Ca2+ entrance into the cell, preventing release

Back 74

Mg2+ and cobalt

Front 75

what drug blocks Ach release

Back 75

botulism toxin

Front 76

what drug keeps ach calcium channels open?

Back 76

aminopyridine

Front 77

What drug Inhibits acetylcholineesterase which breaks down AcH (most important in ACh inactivation)

Back 77

Organophosphates (pestisides)

Front 78

What does L-amphetamine do?

Back 78

Ne agonist

releasing agent

Front 79

What does Clorgyline do?

Back 79

Ne agonist

Inhibits MAO-A which preferentiably oxidizes NE and 5-HT in locus cirrilius (LC)

Front 80

What does prazosine do?

Back 80

antagonist for Nor epi receptor α1

Front 81

What does Yohimbine do?

Back 81

(a hallucinogen and anxiety producing drug)

antagonist for Nor epi receptor α2

Front 82

What does piperoxame do?

Back 82

antagonist for Nor epi receptor α2

Front 83

What does idazoxan do?

Back 83

antagonist for Nor epi receptor α2

Front 84

What does Clonodine do?

Back 84

agonist for the Nor epi receptor α2

Front 85

What does propandol do?

Back 85

antagonist for Nor epi receptor β1

Front 86

What does Metaprolol do?

Back 86

antagonist for Nor epi receptor β1

Front 87

What does Isoproternol do?

Back 87

antagonist for Nor epi receptor β1

Front 88

What does IPS-339 do?

Back 88

antagonist for Nor epi receptor β2

Front 89

What does Salbotamol do?

Back 89

agonist for the NE receptor β2

Front 90

What drug is an agonist of the Nor epi receptor β2

Back 90

Salbotamol (a cognition enhancer?)

Front 91

What drug is an antagonist of the Nor epi receptor β2

Back 91

ISp-339

Front 92

What drug is an agonsit of the Nor epi receptor β1

Back 92

isoproternol

Front 93

What drugs are antagonist of the Nor epi receptor β1

Back 93

propandol
Metaprolol

Front 94

What drug is the agonsits of the Nor epi receptor α2

Back 94

Clonodine (an antismoking drug)

Front 95

What drugs are antagonists of the nor epi receptor α2

Back 95

Yohimbine (a hallucinogen and anxiety producing drug)
piperoxame

Front 96

What drug is a antagonist of the Nor epi receptor α1

Back 96

prazosine

Front 97

What drug Inhibits MAO-A which preferentiably oxidizes NE and 5-HT in locus cirrilius (LC)

Back 97

Clorgyline

Front 98

what drug is a releasing agent for NE

Back 98

L-amphetamine

Front 99

What is potency? Efficacy?

Back 99

e. Potency describes how many units of a drug in mg/kg it takes to achieve maximum effect and is shown graphicly on the X axis
f. Efficacy describes the magnitude of intensity of an effecy and is shown on the y axis

Front 100

What is potency?

Back 100

e. Potency describes how many units of a drug in mg/kg it takes to achieve maximum effect and is shown graphicly on the X axis

Front 101

What is efficacy

Back 101

f. Efficacy describes the magnitude of intensity of an effecy and is shown on the y axis

Front 102

what does the slope of a dose effect curve tell you

Back 102

g. The slope of the log phase of a sigmoidal dose-effect curve describes how fast the drug reached its max effect

Front 103

Can you draw a cruve in which there are 3 drugs:
L is more potent than M and N
L and N have the same efficacy
M is more potent than N
N is more efficacious than M

Back 103

see pic on pg 9 of notes

Front 104

What does the addition of any antagonist do to a dose effect curve of an agonist?

Back 104

a. antagonism shifts the does effect curve of the agonist to the right

Front 105

with what kind of antagonist does an increase in does of the agonist overcomes the effects of the antagonist

Back 105

a competitive antagonist

Front 106

with what kind of a drug does , increasing the dose of the agonist never fully restores 100% of the effect.

Back 106

irreversible or noncompetitive antagonist

Front 107

what are additive effects of two drugs

Back 107

a. Additive affects are when the effect of drug A alone + drug B alone = the effects of A+B together

Front 108

what are potentiating effects of two drugs

Back 108

when the effects of A alone + the effects of B alone are not as great as the effect of A+B together

Front 109

define tolerence

Back 109

a. Tolerance is either defined as
i. the effect of a drug dose diminishes as a result of repeated administration or
1. graphically dose is on x and effect on y
ii. the does that is necessary to produce a given effect must be increased over time
1. time on x and effect on y

Front 110

describe the phenomenon of selective tolerence?

Back 110

b. Tolerance can be selective meaning that only certain effects of a drug, but not necessarily all of them, can experience tolerance. This can be dangerous if the beneficial effects of a drug are tolerated but the deleterious ones are not. By increasing the dose of the drug the margin between the ED50 and ET50 becomes smaller as does the TI

Front 111

what is the name of the phenomemon that is seen when one drug causes the tolerance to another (ex alcohol and barbiturates)

Back 111

cross tolerence

Front 112

What is the phenomenon that is seen when only certain effects of a drug, but not necessarily all of them, can experience tolerance

Back 112

selective tolerence

Front 113

what are the mechanisms of tolerence

Back 113

i. Metabolic- sharing of metabolic enzymes by more than one drug. …?
ii. Cellular pharmodynamic tolerance is the most likely mechanism, the more of a receptor you use the more the receptor is made
iii. Behavioral tolerance is not understood

Front 114

define sensitization

Back 114

the effects of a given drug dose increase over time

a. Tolerance and sensitization to different effects of the same drug are not uncommon

Front 115

what is a key structural feature of serotonin and serotonin direct agonists?
draw it

Back 115

indole nuclues

Front 116

what are the benefits of oral drug admin?
minus?

Back 116

i. Plus: convenient
ii. Minus: interacts with food which can imped the drug, can de digested by enzymes in the GI, taste is an issue, requires cooperation and compliance

Front 117

what factors effect the absorption of drug through the GI tract

Back 117

1. pH: weak acids are well absorbed (barbiturates are an example)
2. lipid solubility: high lipid solubility is good for absorption
3. susceptibility to enzymes

liver metabolism

Front 118

what are the benefits of subcutaneus drug admin? minus?

Back 118

i. Plus: Allows for slow even absorption
ii. Minus: local necrosis may occur, antiseptic conditions are necessary so it is generally expensive, it can be irritating

Front 119

what are the benefits of intra muscular drug admin?

Back 119

usually given in deltoid or glut in humans
i. Preferred in monkeys, humans, and pigeons (less in rodents)
ii. Plus: rapid absorption, less pain than S.C., is in suspension the absorption slows
iii. Minuses: also expensive, drug can get caught up in adipose tissue which can result in ineffectiveness in the immediate time course or can lead to overdose

Front 120

what are the benefits of intraperitoneal drug admin? minus?

Back 120

a. Mostly for rodents, not used in primates because of the high risk of infection
b. Plus: large absorption cavity

Front 121

what are the benefits of IV? minus?

Back 121

a. VERY FAST: This can be both a plus and a minus. It is a plus because an immediate effect can be seen. It can be a minus because there is no time to counteract the drug once its in.
b. Plus: accurate, adjustable does, catheters make administration easier and safer
c. Minus: risk of embolism, huge risk of infection, sterile conditions are completely necessary
d. Time course: can have a huge immediate peak in effect but is also is fast to stop acting