Drug Action 3 Flashcards
1
Q
What alternative anxiolytics exist?
A
Bezodiazepine partial agonists and non-benzidiazepines
2
Q
What non-benzodiazepines can be used to treat anxiety?
A
Buspirone - 5HT-1 agonist; CCK-R; mGLU-R
3
Q
What is CCK-R?
A
Cholecystokinin receptor
4
Q
What is mGLU-R?
A
Metabotropic glutamate receptor
5
Q
What are the possible causes of epilepsy?
A
Genetic, head injury, local lesions, neoplasms, infections, febrile seizures
6
Q
Outline genetic causes of epilepsy.
A
Mutations in ion channels - GABA-A, Na-v, AChR
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
8
Q
What factors aggravate epilepsy?
A
Stress, fatigue, flashing lights, sudden loud noises, altered blood glucose levels, pH
9
Q
What are the three main treatments for epilepsy?
A
Benzodiazepines, GABA uptake inhibitors, GABA metbolic inhibitors
10
Q
Name four benzodiazepines used in the treatment of epilepsy.
A
Clonazepam, clobazam, diazepam, barbiturates
11
Q
What are diazepam, clonazepam and clobazam used to treat?
A
Used IV for status epilepticus
12
Q
What are the problems with diazepam, clonazepam and clobazam?
A
Sedation, tolerance and withdrawal
13
Q
What are the problems with barbiturates?
A
Low therapeutic index, sedation, complez pharmacokinetics
14
Q
Name a GABA uptake inhibitor.
A
Tiagabine
15
Q
What is tiagabine?
A
GABA uptake inhibitor
16
Q
What is tiagabine used to treat?
A
Convulsion
17
Q
Name two GABA metabolic inhibitors
A
Vigabatrin and valproate
18
Q
What are the problems with vigabatrin usage?
A
Depression
19
Q
What are the problems with valproate usage?
A
High protein binding, rarely hepatotoxic, teratogenic
20
Q
What does teratogenic mean?
A
Causing malformations to the embryo
21
Q
From which respiratory pathway is GABA deriven?
A
Krebs cycle
22
Q
Describe the deviation from the Krebs cycle that produces GABA.
A
Alpha-ketoglutarate + glutamine = glutamate; glutamate (+ GAD) = GABA
23
Q
What three states do Na channels cycle through?
A
Closed - open - inactive
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
25
Name three Na channel blockers.
Phenytoin, carbamazepine and lamotrigine
26
What are the problems with phenytoin use?
Complex pharmacokinetics, vertigo, ataxia, headaches, rashes
27
What are the problems with carbamazepine use?
Microsomal enzyme induction, shouldn't be combined with other drugs
28
What are the problems with lamotrigine use?
Nausea, dizziness, ataxia and rashes
29
What type of drug is phenytoin?
Anti-epileptic
30
What is the MOA of phenytoin?
Na channel blocker
31
What type of drug is carbamazepine?
Anti-epileptic
32
What is the MOA of carbamazepine?
Na channel blocker
33
What type of drug is lamotrigine?
Anti-epileptic
34
What is the MOA of lamotrigine?
Na channel blocker
35
What are Ca channel blockers used for?
Epileptic absence seizures
36
Name two Ca channel blockers.
Ethosuzimide and GABApentin
37
What new targets are there for anti-epileptic drugs?
Proteins such as SV2A control the sensitivity of synaptic machinery
38
Name a drug that binds SV2A.
Levetiracetam
39
What does levetiracetam bind?
SV2A
40
What does levetiracetam do?
Alters the sensitivity of synaptic machinery
41
What is levetiracetam used to treat?
Epilepsy
42
What type of drug is felbamate?
Anti-epileptic
43
What type of drug is topiramate?
Anti-epileptic
44
What is the MOA of felbamate?
Weak NMDA channel blocker
45
What is the MOA of topiramate?
AMPA channel blocker
46
Name a weak NMDA channel blocker used to treat epilepsy.
Felbamate
47
Name an AMPA channel blocker used to treat epilepsy.
Topiramate
48
What are the two kinds of depression?
Unipolar and bipolar
49
Characterise unipolar depression.
Mood swing always in the same direction
50
What are the two kinds of unipolar depression, and what are their proportionate incidence?
Reactive - 75%; endogenous - 25%
51
Characterise bipolar depression.
Depression alternates with mania - characterised by excessive exuberance, enthusiasm, self-confidence that may be combined with irritability, impatience and/or aggression
52
Outline the typical symptoms of depression.
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
53
What is the male:female ratio of depression patients?
Two to one
54
Outline the typical outcomes of depression on the individual.
15-30% commit suicide; mortality is generally greater that healthy people due to increased incidence of cardiovasular disease and cancer
55
Characterise post-natal depression.
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
56
Outline why treatment for depressed patients is important.
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
57
What possible physiological causes are there for depression?
Hormonal function disturbance, alteration to the pre-frontal cortext/hippocampus & amygdala, NA and 5HT deficits, reduced BDNF neurogenesis, NMDA neurodegeneration
58
What hormonal function disturbances can cause depression?
CRH hyperfunction, high blood cortisol levels (stress)
59
What can a functional deficit in NA & 5HT cause?
Depression and long term trophic effects
60
What does BDNF stand for?
Brain derived neurotrophic factor
61
What are the four main classes of antidepressants?
Selective serotonin reuptake inhibitors, classical tricyclic antidepressants, monoamine oxidase inhibitors, monoamine receptor antagonists
62
Name a selective serotonin reuptake inhibitor.
Fluoxetine
63
Name a classical tricyclic antidepressant.
Imipramine
64
Name two monoamine oxidase inhibitors.
Phenylzine and moclobemide
65
What type of drug is fluoxetine?
Antidepressant
66
What is the MOA of fluoxetine?
Selective serotonin reuptake inhibition
67
What type of drug is imipramine?
Classical tricyclic antidepressant
68
What type of drug is phenylzine?
Antidepressant
69
What is the MOA of phenylzine?
Monoamine oxidase inhibition
70
What type of drug is moclobemide?
Antidepressant
71
What is the MOA of moclobemide?
Monoamine oxidase inhibition
72
What are the two types of cholinergic receptor?
Nicotinic and muscarinic
73
What agonists stimulate ALL autonomic ganglia?
Nicotinic ligand-gated ion channel agonists
74
What is another name for muscarinic agonists?
Parasympathomimetics
75
Outline the five steps in cholinergic transmission.
NT synthesis, storage in synaptic vesicles, release upon neuronal activation, post-synaptic receptor activation, breakdown and/or reuptake
76
What synthesises cholinergic NTs?
Choline acetyltransferase
77
What does CAT stand for?
Choline acetyltransferase
78
What does CAT do?
Synthesises cholinergic NTs
79
What breaks down cholinergic NTs?
Acetylcholinesterase
80
What does AChE stand for?
Acetylcholinesterase
81
What does AChE break cholinergic NTs down into?
Choline and acetate
82
What does acetylcholinesterase do?
Breaks down acetylcholine into acetate and choline
83
What must drugs that enhance cholinergic transmission do?
Inhibit cholinesterases
84
What are the two key cholinesterases?
Butyrylcholinesterase and acetylcholinesterase
85
What does BChE stand for?
Butyrylcholinesterase
86
How are anticholinesterase drugs classified?
By duration of action
87
Name a short acting anticholinesterase.
Edrophonium
88
Name three medium acting anticholinesterases.
Neostigmine, pyridostigmine, physostigmine
89
Name three groups of long acting anticholinesterases.
Nerve gases, organophosphates, pesticides
90
What type of drug is neostigmine?
Medium acting anticholinesterase
91
What type of drug is pyridostigmine?
Medium acting anticholinesterase
92
What type of drug is physostigmine?
Medium acting anticholinesterase
93
What type of drug is edrophonium?
Short acting anticholinesterase
94
What are the three key areas that drugs interfering with cholinergic transmission would target?
ACh receptors, ACh release, ACh breakdown/reuptake
95
What are the four principle groups of cholinergic transmission drugs?
Receptor agonists and antagonists, transmitter breakdown, transmitter reuptake and packaging, exocytosis
96
What type of drug is suxamethonium?
Depolarising blocking agent
97
What does suxamethonium amplify?
Depolarisation of post-synaptic ACh receptor - increases cholinergic transmission
98
What type of drug is tubocurarine?
Non-depolarising blocking agent
99
What does suxamethonium diminish?
Depolarisation of post-synaptic ACh receptor - decreases cholinergic transmission
100
What type of drug is hemicholinium?
Choline carrier blocker
101
What does hemicholinium do?
Prevents choline carrier reuptake
102
What type of drug is botulinum?
Exocytotic toxin
103
What does claustridium botulinum neurotoxin do?
Bind to cholinergic nerve cells, enter the interior of the cells, cleave specific proteins which blocks vesicle mediate secretion
104
Describe an nAChR.
Nicotinic receptor with 4TM where both N & C termini are extracellular; agonist/antagonist binring is in ectodomain (N-terminus)
105
What two drugs have an agonistic effect on nAChR?
Nicotine and ACh
106
What drug has an antagonistic effect on nAChR?
Curare
107
Describe the structure of nAChR.
Heteromeric pentameric assembly of alpha, beta, delta, gamma and epsilon subunits
108
How many genes code for nAChR subunits?
16 - alpha 1-9, beta 1-4, delta, gamma, epsilon
109
How many molecules of agonist must bind to nAChR to activate it?
2
110
Where do nAChR agonists bind?
EC at interfaces between alpha subunits
111
What three things will ganglionic nAChR activation cause?
Increased arterial BP due to stimulation of sympathetic ganglia, stimulates ADR release from adrenal medulla, increases HR
112
Name three ganglion blockers.
Hexamethonium, trimetaphan, decamethonium
113
What type of drug is hexamethonium?
Ganglion blocker
114
What type of drug is trimetaphan?
Ganglion blocker
115
What type of drug is decmethonium?
Ganglion blocker
116
What are the effects of ganglion blockers?
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
What is the pathology of myasthenia gravis?
Antibodies against AChR bind to extracellular region of ganglionic receptors = increased receptor internalisation + loss of funtional receptors
118
What are the symptoms of myasthenia gravis?
Muscle weakness
119
What treatments are there for myasthenis gravis?
Cholinesterase inhibitiors and immuno-therapy
120
What are M1-5 receptors for?
Muscarine
121
Where are M1 receptors?
Brain
122
Where are M2 receptors?
Heart and bladder
123
Where are M3 receptors?
Bladder, GI tract and salivary glands
124
Where are M4 receptors?
Brain
125
Where are M5 receptors?
Ciliary muscle in the eye
126
What is the role of M1 receptors?
Cognitive function, learning and memory
127
What is the role of M2 receptors?
Regulation of HR (slowing), pre and post synpatic modulation of bladder smooth muscle contraction
128
What is the role of M3 receptors?
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
What is the role of M4 receptors?
Unclear
130
What is the role of M5 receptors?
Visual accomodation
131
What is an agonist of all mAChRs?
Muscarine
132
Name two M1 selective drugs
McNA343 and oxotremorine
133
Name four mAChR antagonists.
Atropine, pirenzepine, darifenacin, mamba toxin 3, mamba toxin 7
134
Name a non-specific mAChR anatagonist.
Atropine
135
What receptors does atropine bind?
mAChR
136
What receptors does pirenzepine bind?
M1
137
What kind of drug is pirenzepine?
M1 selective antagonist
138
What receptors does darifenacin bind?
M2/M3
139
What kind of drug is darifenacin?
M2/M3 selective antagonist
140
What is pirenzepine used to treat?
Peptic ulcers
141
What is darifenacin used to treat?
Incontinence
142
What receptor does mamba toxin 3 bind?
M4 (experimental)
143
What receptor does mamba toxin 7 bind?
M1 (experimental)
144
How many subgroups of ADR receptors are there, and what are they?
2 - alpha and beta
145
What type of receptor are all ADR receptors?
GPCRs
146
What are the four steps in ADR production?
Tyrosine - DOPA - dopamine - noradrenaline - adrenaline
147
What converts tyrosine to DOPA?
Tyrosine hydroxylase
148
What converts DOPA to dopamine?
DOPA decarboxylase
149
What converts dopamine to NA?
Dopamine beta-hydroxylase
150
What converts NA to ADR?
Phenylehtanolamine N-methyltransferase
151
What does COMT stand for?
Catechol-O-methyl transferase
152
What does COMT do?
Converts NA
153
What does MHPEG stand for?
3-methoxy, 4-hydroxyphenylglycol
154
What does VMA stand for?
Vanillylmandelic acid
155
What does alpha methyltyrosine do?
Inihibits NA synthesis
156
What drug prevents the conversion of tyrosine to NA?
alpha-methyltyrosine
157
What does reserpine do?
Inhibits NA packaging into vesicles
158
What are the five types of ADR subunits?
Alpha 1/2, beta 1-3
159
What secondary messengers does ADR alpha 1 activate?
PLC, increased IP-3, increased DAG, increased Ca
160
What secondary messengers does ADR alpha 2 activate?
Decreased cAMP, decreased Ca channels, increased K channels
161
What secondary messengers does ADR beta 1 activate?
Increased cAMP, increased PKA Ca channels
162
What secondary messengers does ADR beta 2 activate?
Increased cAMP
163
What secondary messengers does ADR beta 3 activate?
Increased cAMP
164
Name two selective agonists for ADR alpha 1.
Phenylephrine, methoxamine
165
Name two selective agonists for ADR alpha 2
Clonidine, clenbuterol
166
Name two selective agonists for ADR beta 1
Dobutamine, xamoterol
167
Name four selective agonists for ADR beta 2
Salbutamol, terbutaline, salmeterol, formoterol
168
Name two selective antagonists for ADR alpha 1
Prazosin, doxazocin
169
Name two selective antagonists for ADR alpha 2
Yohimbine, idazoxan
170
Name two selective antagonists for ADR beta 1
Atenolol, metoprolol
171
Name one selective antagonist for ADR beta 2
Butoxamine
172
What is phenylephrine an agonist of?
ADR alpha 1
173
What is methoxamine an agonist of?
ADR alpha 1
174
What is clonidine an agonist of?
ADR alpha 2
175
What is clenbuterol an agonist of?
ADR alpha 2
176
What is dobutamine an agonist of?
ADR beta 1
177
What is xamoterol an agonist of?
ADR beta 1
178
What is salbutamol an agonist of?
ADR beta 2
179
What is terbuatline an agonist of?
ADR beta 2
180
What is salmeterol an agonist of?
ADR beta 2
181
What is formoterol an agonist of?
ADR beta 2
182
What is prazosin an antagonist of?
ADR alpha 1
183
What is doxazocin an antagonist of?
ADR alpha 1
184
What is yohimbine an antagonist of?
ADR alpha 2
185
What is idazoxan an antagonist of?
ADR alpha 2
186
What is atenolol an antagonist of?
ADR beta 1
187
What is metoprolo and antagonist of?
ADR beta 1
188
What is butoxamine an antagonist of?
ADR beta 2
189
What is the main physiological effect of ADR beta 1 activation?
Increase HR and force
190
What is the main physiological effect of ADR beta 2 activation?
Smooth relaxation
191
What is the main physiological effect of ADR beta 3 activation?
Lipolysis
192
What is the main physiological effect of ADR alpha 1 activation?
Smooth muscle contraction
193
What is the main physiological effect of ADR alpha 2 activation?
Lipolysis
194
Where are ADR beta 1 receptors?
Heart
195
Where are ADR beta 2 receptors?
Smooth muscle
196
Where are ADR beta 3 receptors?
Adipocytes
197
Where are ADR alpha 1 receptors?
Smooth muscle
198
Where are ADR alpha 2 receptors?
Presynaptic membrane
199
What is dobutamine used to treat?
Heart failure
200
What is salbutamol used to treat?
Asthma and premature labour
