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Y2S1 - Drug Action > Drug Action 3 > Flashcards

Drug Action 3 Flashcards

1
Q

What alternative anxiolytics exist?

A

Bezodiazepine partial agonists and non-benzidiazepines

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2
Q

What non-benzodiazepines can be used to treat anxiety?

A

Buspirone - 5HT-1 agonist; CCK-R; mGLU-R

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3
Q

What is CCK-R?

A

Cholecystokinin receptor

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4
Q

What is mGLU-R?

A

Metabotropic glutamate receptor

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5
Q

What are the possible causes of epilepsy?

A

Genetic, head injury, local lesions, neoplasms, infections, febrile seizures

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6
Q

Outline genetic causes of epilepsy.

A

Mutations in ion channels - GABA-A, Na-v, AChR

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7
Q

What are the three main areas of epileptic activity?

A

Motor cortex - convulsions; hypothalamus - autonomic discharge (salivation and incontinence); reticular formation - loss of consciousness

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8
Q

What factors aggravate epilepsy?

A

Stress, fatigue, flashing lights, sudden loud noises, altered blood glucose levels, pH

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9
Q

What are the three main treatments for epilepsy?

A

Benzodiazepines, GABA uptake inhibitors, GABA metbolic inhibitors

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10
Q

Name four benzodiazepines used in the treatment of epilepsy.

A

Clonazepam, clobazam, diazepam, barbiturates

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11
Q

What are diazepam, clonazepam and clobazam used to treat?

A

Used IV for status epilepticus

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12
Q

What are the problems with diazepam, clonazepam and clobazam?

A

Sedation, tolerance and withdrawal

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13
Q

What are the problems with barbiturates?

A

Low therapeutic index, sedation, complez pharmacokinetics

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14
Q

Name a GABA uptake inhibitor.

A

Tiagabine

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15
Q

What is tiagabine?

A

GABA uptake inhibitor

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16
Q

What is tiagabine used to treat?

A

Convulsion

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17
Q

Name two GABA metabolic inhibitors

A

Vigabatrin and valproate

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18
Q

What are the problems with vigabatrin usage?

A

Depression

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19
Q

What are the problems with valproate usage?

A

High protein binding, rarely hepatotoxic, teratogenic

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20
Q

What does teratogenic mean?

A

Causing malformations to the embryo

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21
Q

From which respiratory pathway is GABA deriven?

A

Krebs cycle

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22
Q

Describe the deviation from the Krebs cycle that produces GABA.

A

Alpha-ketoglutarate + glutamine = glutamate; glutamate (+ GAD) = GABA

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23
Q

What three states do Na channels cycle through?

A

Closed - open - inactive

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24
Q

How do Na channel blockers treat epilepsy?

A

Block excitatory transmission at focus and limit spread of epileptiform activity with use-dependent Na channel inhibitors

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25
Q

Name three Na channel blockers.

A

Phenytoin, carbamazepine and lamotrigine

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26
Q

What are the problems with phenytoin use?

A

Complex pharmacokinetics, vertigo, ataxia, headaches, rashes

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27
Q

What are the problems with carbamazepine use?

A

Microsomal enzyme induction, shouldn’t be combined with other drugs

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28
Q

What are the problems with lamotrigine use?

A

Nausea, dizziness, ataxia and rashes

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29
Q

What type of drug is phenytoin?

A

Anti-epileptic

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30
Q

What is the MOA of phenytoin?

A

Na channel blocker

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31
Q

What type of drug is carbamazepine?

A

Anti-epileptic

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32
Q

What is the MOA of carbamazepine?

A

Na channel blocker

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33
Q

What type of drug is lamotrigine?

A

Anti-epileptic

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34
Q

What is the MOA of lamotrigine?

A

Na channel blocker

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35
Q

What are Ca channel blockers used for?

A

Epileptic absence seizures

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36
Q

Name two Ca channel blockers.

A

Ethosuzimide and GABApentin

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37
Q

What new targets are there for anti-epileptic drugs?

A

Proteins such as SV2A control the sensitivity of synaptic machinery

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38
Q

Name a drug that binds SV2A.

A

Levetiracetam

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39
Q

What does levetiracetam bind?

A

SV2A

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40
Q

What does levetiracetam do?

A

Alters the sensitivity of synaptic machinery

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41
Q

What is levetiracetam used to treat?

A

Epilepsy

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42
Q

What type of drug is felbamate?

A

Anti-epileptic

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43
Q

What type of drug is topiramate?

A

Anti-epileptic

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44
Q

What is the MOA of felbamate?

A

Weak NMDA channel blocker

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45
Q

What is the MOA of topiramate?

A

AMPA channel blocker

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46
Q

Name a weak NMDA channel blocker used to treat epilepsy.

A

Felbamate

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47
Q

Name an AMPA channel blocker used to treat epilepsy.

A

Topiramate

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48
Q

What are the two kinds of depression?

A

Unipolar and bipolar

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49
Q

Characterise unipolar depression.

A

Mood swing always in the same direction

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50
Q

What are the two kinds of unipolar depression, and what are their proportionate incidence?

A

Reactive - 75%; endogenous - 25%

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51
Q

Characterise bipolar depression.

A

Depression alternates with mania - characterised by excessive exuberance, enthusiasm, self-confidence that may be combined with irritability, impatience and/or aggression

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52
Q

Outline the typical symptoms of depression.

A

Low mood, negative thoughts, misery, pessimism, apathy, sever loss or gain in weight/appetite, low self-esteem, feelings of worthlessness or guilt, sleep disturbance, loss of libido, diminished ability to think/concentrate

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53
Q

What is the male:female ratio of depression patients?

A

Two to one

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54
Q

Outline the typical outcomes of depression on the individual.

A

15-30% commit suicide; mortality is generally greater that healthy people due to increased incidence of cardiovasular disease and cancer

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55
Q

Characterise post-natal depression.

A

Usually occurs 2-8 weeks after delivery and can stay up to a year after birth; babies’ brain waves can become altered if the mother is depressed

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56
Q

Outline why treatment for depressed patients is important.

A

Depression can cause changes in brain chemistry that can only be reversed by drugs, and depression can remain long after cause due to the biochemical changes at synapses

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57
Q

What possible physiological causes are there for depression?

A

Hormonal function disturbance, alteration to the pre-frontal cortext/hippocampus & amygdala, NA and 5HT deficits, reduced BDNF neurogenesis, NMDA neurodegeneration

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58
Q

What hormonal function disturbances can cause depression?

A

CRH hyperfunction, high blood cortisol levels (stress)

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59
Q

What can a functional deficit in NA & 5HT cause?

A

Depression and long term trophic effects

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60
Q

What does BDNF stand for?

A

Brain derived neurotrophic factor

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61
Q

What are the four main classes of antidepressants?

A

Selective serotonin reuptake inhibitors, classical tricyclic antidepressants, monoamine oxidase inhibitors, monoamine receptor antagonists

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62
Q

Name a selective serotonin reuptake inhibitor.

A

Fluoxetine

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63
Q

Name a classical tricyclic antidepressant.

A

Imipramine

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64
Q

Name two monoamine oxidase inhibitors.

A

Phenylzine and moclobemide

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65
Q

What type of drug is fluoxetine?

A

Antidepressant

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66
Q

What is the MOA of fluoxetine?

A

Selective serotonin reuptake inhibition

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67
Q

What type of drug is imipramine?

A

Classical tricyclic antidepressant

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68
Q

What type of drug is phenylzine?

A

Antidepressant

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69
Q

What is the MOA of phenylzine?

A

Monoamine oxidase inhibition

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70
Q

What type of drug is moclobemide?

A

Antidepressant

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71
Q

What is the MOA of moclobemide?

A

Monoamine oxidase inhibition

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72
Q

What are the two types of cholinergic receptor?

A

Nicotinic and muscarinic

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73
Q

What agonists stimulate ALL autonomic ganglia?

A

Nicotinic ligand-gated ion channel agonists

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74
Q

What is another name for muscarinic agonists?

A

Parasympathomimetics

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75
Q

Outline the five steps in cholinergic transmission.

A

NT synthesis, storage in synaptic vesicles, release upon neuronal activation, post-synaptic receptor activation, breakdown and/or reuptake

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76
Q

What synthesises cholinergic NTs?

A

Choline acetyltransferase

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77
Q

What does CAT stand for?

A

Choline acetyltransferase

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78
Q

What does CAT do?

A

Synthesises cholinergic NTs

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79
Q

What breaks down cholinergic NTs?

A

Acetylcholinesterase

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80
Q

What does AChE stand for?

A

Acetylcholinesterase

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81
Q

What does AChE break cholinergic NTs down into?

A

Choline and acetate

82
Q

What does acetylcholinesterase do?

A

Breaks down acetylcholine into acetate and choline

83
Q

What must drugs that enhance cholinergic transmission do?

A

Inhibit cholinesterases

84
Q

What are the two key cholinesterases?

A

Butyrylcholinesterase and acetylcholinesterase

85
Q

What does BChE stand for?

A

Butyrylcholinesterase

86
Q

How are anticholinesterase drugs classified?

A

By duration of action

87
Q

Name a short acting anticholinesterase.

A

Edrophonium

88
Q

Name three medium acting anticholinesterases.

A

Neostigmine, pyridostigmine, physostigmine

89
Q

Name three groups of long acting anticholinesterases.

A

Nerve gases, organophosphates, pesticides

90
Q

What type of drug is neostigmine?

A

Medium acting anticholinesterase

91
Q

What type of drug is pyridostigmine?

A

Medium acting anticholinesterase

92
Q

What type of drug is physostigmine?

A

Medium acting anticholinesterase

93
Q

What type of drug is edrophonium?

A

Short acting anticholinesterase

94
Q

What are the three key areas that drugs interfering with cholinergic transmission would target?

A

ACh receptors, ACh release, ACh breakdown/reuptake

95
Q

What are the four principle groups of cholinergic transmission drugs?

A

Receptor agonists and antagonists, transmitter breakdown, transmitter reuptake and packaging, exocytosis

96
Q

What type of drug is suxamethonium?

A

Depolarising blocking agent

97
Q

What does suxamethonium amplify?

A

Depolarisation of post-synaptic ACh receptor - increases cholinergic transmission

98
Q

What type of drug is tubocurarine?

A

Non-depolarising blocking agent

99
Q

What does suxamethonium diminish?

A

Depolarisation of post-synaptic ACh receptor - decreases cholinergic transmission

100
Q

What type of drug is hemicholinium?

A

Choline carrier blocker

101
Q

What does hemicholinium do?

A

Prevents choline carrier reuptake

102
Q

What type of drug is botulinum?

A

Exocytotic toxin

103
Q

What does claustridium botulinum neurotoxin do?

A

Bind to cholinergic nerve cells, enter the interior of the cells, cleave specific proteins which blocks vesicle mediate secretion

104
Q

Describe an nAChR.

A

Nicotinic receptor with 4TM where both N & C termini are extracellular; agonist/antagonist binring is in ectodomain (N-terminus)

105
Q

What two drugs have an agonistic effect on nAChR?

A

Nicotine and ACh

106
Q

What drug has an antagonistic effect on nAChR?

A

Curare

107
Q

Describe the structure of nAChR.

A

Heteromeric pentameric assembly of alpha, beta, delta, gamma and epsilon subunits

108
Q

How many genes code for nAChR subunits?

A

16 - alpha 1-9, beta 1-4, delta, gamma, epsilon

109
Q

How many molecules of agonist must bind to nAChR to activate it?

A

2

110
Q

Where do nAChR agonists bind?

A

EC at interfaces between alpha subunits

111
Q

What three things will ganglionic nAChR activation cause?

A

Increased arterial BP due to stimulation of sympathetic ganglia, stimulates ADR release from adrenal medulla, increases HR

112
Q

Name three ganglion blockers.

A

Hexamethonium, trimetaphan, decamethonium

113
Q

What type of drug is hexamethonium?

A

Ganglion blocker

114
Q

What type of drug is trimetaphan?

A

Ganglion blocker

115
Q

What type of drug is decmethonium?

A

Ganglion blocker

116
Q

What are the effects of ganglion blockers?

A

CVS - decreased BP (SS); eye - loss of accomodation, pupil dilation (PSS); GI - inhibits motility and secretion (PSS); bladder - urine retention (PSS); genitals - erection/ejaculation failure

117
Q

What is the pathology of myasthenia gravis?

A

Antibodies against AChR bind to extracellular region of ganglionic receptors = increased receptor internalisation + loss of funtional receptors

118
Q

What are the symptoms of myasthenia gravis?

A

Muscle weakness

119
Q

What treatments are there for myasthenis gravis?

A

Cholinesterase inhibitiors and immuno-therapy

120
Q

What are M1-5 receptors for?

A

Muscarine

121
Q

Where are M1 receptors?

A

Brain

122
Q

Where are M2 receptors?

A

Heart and bladder

123
Q

Where are M3 receptors?

A

Bladder, GI tract and salivary glands

124
Q

Where are M4 receptors?

A

Brain

125
Q

Where are M5 receptors?

A

Ciliary muscle in the eye

126
Q

What is the role of M1 receptors?

A

Cognitive function, learning and memory

127
Q

What is the role of M2 receptors?

A

Regulation of HR (slowing), pre and post synpatic modulation of bladder smooth muscle contraction

128
Q

What is the role of M3 receptors?

A

Regulation of ACh release from PSS endings in bladder, mediation of bladder smooth muscle contraction, bladder afferent nerve modulation, GI motility and secreation, slicary secretion

129
Q

What is the role of M4 receptors?

A

Unclear

130
Q

What is the role of M5 receptors?

A

Visual accomodation

131
Q

What is an agonist of all mAChRs?

A

Muscarine

132
Q

Name two M1 selective drugs

A

McNA343 and oxotremorine

133
Q

Name four mAChR antagonists.

A

Atropine, pirenzepine, darifenacin, mamba toxin 3, mamba toxin 7

134
Q

Name a non-specific mAChR anatagonist.

A

Atropine

135
Q

What receptors does atropine bind?

A

mAChR

136
Q

What receptors does pirenzepine bind?

A

M1

137
Q

What kind of drug is pirenzepine?

A

M1 selective antagonist

138
Q

What receptors does darifenacin bind?

A

M2/M3

139
Q

What kind of drug is darifenacin?

A

M2/M3 selective antagonist

140
Q

What is pirenzepine used to treat?

A

Peptic ulcers

141
Q

What is darifenacin used to treat?

A

Incontinence

142
Q

What receptor does mamba toxin 3 bind?

A

M4 (experimental)

143
Q

What receptor does mamba toxin 7 bind?

A

M1 (experimental)

144
Q

How many subgroups of ADR receptors are there, and what are they?

A

2 - alpha and beta

145
Q

What type of receptor are all ADR receptors?

A

GPCRs

146
Q

What are the four steps in ADR production?

A

Tyrosine - DOPA - dopamine - noradrenaline - adrenaline

147
Q

What converts tyrosine to DOPA?

A

Tyrosine hydroxylase

148
Q

What converts DOPA to dopamine?

A

DOPA decarboxylase

149
Q

What converts dopamine to NA?

A

Dopamine beta-hydroxylase

150
Q

What converts NA to ADR?

A

Phenylehtanolamine N-methyltransferase

151
Q

What does COMT stand for?

A

Catechol-O-methyl transferase

152
Q

What does COMT do?

A

Converts NA

153
Q

What does MHPEG stand for?

A

3-methoxy, 4-hydroxyphenylglycol

154
Q

What does VMA stand for?

A

Vanillylmandelic acid

155
Q

What does alpha methyltyrosine do?

A

Inihibits NA synthesis

156
Q

What drug prevents the conversion of tyrosine to NA?

A

alpha-methyltyrosine

157
Q

What does reserpine do?

A

Inhibits NA packaging into vesicles

158
Q

What are the five types of ADR subunits?

A

Alpha 1/2, beta 1-3

159
Q

What secondary messengers does ADR alpha 1 activate?

A

PLC, increased IP-3, increased DAG, increased Ca

160
Q

What secondary messengers does ADR alpha 2 activate?

A

Decreased cAMP, decreased Ca channels, increased K channels

161
Q

What secondary messengers does ADR beta 1 activate?

A

Increased cAMP, increased PKA Ca channels

162
Q

What secondary messengers does ADR beta 2 activate?

A

Increased cAMP

163
Q

What secondary messengers does ADR beta 3 activate?

A

Increased cAMP

164
Q

Name two selective agonists for ADR alpha 1.

A

Phenylephrine, methoxamine

165
Q

Name two selective agonists for ADR alpha 2

A

Clonidine, clenbuterol

166
Q

Name two selective agonists for ADR beta 1

A

Dobutamine, xamoterol

167
Q

Name four selective agonists for ADR beta 2

A

Salbutamol, terbutaline, salmeterol, formoterol

168
Q

Name two selective antagonists for ADR alpha 1

A

Prazosin, doxazocin

169
Q

Name two selective antagonists for ADR alpha 2

A

Yohimbine, idazoxan

170
Q

Name two selective antagonists for ADR beta 1

A

Atenolol, metoprolol

171
Q

Name one selective antagonist for ADR beta 2

A

Butoxamine

172
Q

What is phenylephrine an agonist of?

A

ADR alpha 1

173
Q

What is methoxamine an agonist of?

A

ADR alpha 1

174
Q

What is clonidine an agonist of?

A

ADR alpha 2

175
Q

What is clenbuterol an agonist of?

A

ADR alpha 2

176
Q

What is dobutamine an agonist of?

A

ADR beta 1

177
Q

What is xamoterol an agonist of?

A

ADR beta 1

178
Q

What is salbutamol an agonist of?

A

ADR beta 2

179
Q

What is terbuatline an agonist of?

A

ADR beta 2

180
Q

What is salmeterol an agonist of?

A

ADR beta 2

181
Q

What is formoterol an agonist of?

A

ADR beta 2

182
Q

What is prazosin an antagonist of?

A

ADR alpha 1

183
Q

What is doxazocin an antagonist of?

A

ADR alpha 1

184
Q

What is yohimbine an antagonist of?

A

ADR alpha 2

185
Q

What is idazoxan an antagonist of?

A

ADR alpha 2

186
Q

What is atenolol an antagonist of?

A

ADR beta 1

187
Q

What is metoprolo and antagonist of?

A

ADR beta 1

188
Q

What is butoxamine an antagonist of?

A

ADR beta 2

189
Q

What is the main physiological effect of ADR beta 1 activation?

A

Increase HR and force

190
Q

What is the main physiological effect of ADR beta 2 activation?

A

Smooth relaxation

191
Q

What is the main physiological effect of ADR beta 3 activation?

A

Lipolysis

192
Q

What is the main physiological effect of ADR alpha 1 activation?

A

Smooth muscle contraction

193
Q

What is the main physiological effect of ADR alpha 2 activation?

A

Lipolysis

194
Q

Where are ADR beta 1 receptors?

A

Heart

195
Q

Where are ADR beta 2 receptors?

A

Smooth muscle

196
Q

Where are ADR beta 3 receptors?

A

Adipocytes

197
Q

Where are ADR alpha 1 receptors?

A

Smooth muscle

198
Q

Where are ADR alpha 2 receptors?

A

Presynaptic membrane

199
Q

What is dobutamine used to treat?

A

Heart failure

200
Q

What is salbutamol used to treat?

A

Asthma and premature labour

Y2S1 - Drug Action (4 decks)

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