Drug Action 4 Flashcards
1
Q
What is BRL37344 used to treat?
A
Obesity
2
Q
What is phenylephrine used to treat?
A
Nasal decongestant
3
Q
What is clonidine used to treat?
A
Hypertension
4
Q
What is BRL37344 an agonist of?
A
ADR beta 3
5
Q
Name one selective agonist for ADR beta 3.
A
BRL37344
6
Q
What is prazocin used to treat?
A
Hypertension
7
Q
What is yohimbine used to treat?
A
Erectile dysfunction
8
Q
What is propanolol used to treat?
A
Angina, cardiac dysrhythmia, hypertension
9
Q
What receptors regulate NA release?
A
Presynaptic receptors on postganglionic SS varcosities regulate the release of NA
10
Q
What pre-synaptic neural connection negatively modulates NA synapses?
A
ACh
11
Q
What pre-synaptic neural connection negatively modulates ACh synapses?
A
NA
12
Q
What is released from smooth muscle that negatively modulates the NA neuron innervating it?
A
PG
13
Q
What is released from endothelial cells that negatively modulates the ACh neuron that innervates them?
A
NO
14
Q
What does NANC stand for?
A
Non-adrenergic, non-cholinergic NT
15
Q
What NANC NTs are in the ANS?
A
5-HT, ATP, peptides, NO
16
Q
Name three NANC peptides.
A
VIP, somatostatin, substance-P
17
Q
What does VIP stand for?
A
Vasoactive intestinal polypeptide
18
Q
Why can NANC NTs be referred to as co-transmitters?
A
They are released alongside ACh and ADR NTs to modulate the response chemically
19
Q
What principle does NO break, and why?
A
Dale’s principle - synthesised outside the nerve terminal
20
Q
What is NO synthesized from?
A
O2 and L-arginine
21
Q
What synthesises NO?
A
NOS
22
Q
What does NOS stand for?
A
Nitrogen oxide synthase
23
Q
What does eNOS stand for?
A
Endothelia
24
Q
What does nNOS stand for?
A
NANC
25
Where is eNOS found?
Endothelia
26
Where is nNOS found?
NANC nerves
27
What does activation of NOS result in?
Increased cGMP - decreased IC Ca - increased K channel - hyperpolarization - relaxation
28
What terminates the action of NO?
Phosphodiesterase V
29
How is the action of NO terminated?
Break down of cGMP by phosphodiesterase V
30
How does phosphodiesterase V terminate NO action?
Breaks down cGMP
31
What is the MOA of sildenafil?
Selective inhibitor of phosphodiesterase V
32
What is sildenafil also known as?
Viagra
33
What are the unwanted side effects of sildenafil?
Hypotension, flushing, headache, visual disturbance
34
When was the first compound for migraine treatment discovered?
1868
35
What did the first migraine treatment contain?
Ergotamine
36
What was the first compound for migraine treatment?
Ergot
37
When were the triptans developed?
20th Century
38
What is the incidence of migraines?
1-2%
39
What are the two clinical sub-types of migraine?
With or without aura
40
What is the general treatment strategy for migraines?
All patients require acute treatment, frequent attacks require prophylactic pharmacology
41
What is the socioeconomic cost of migraines?
Approx EU27 billion in Europe
42
What was the ORIGINAL theory of pathophysiology of migraines?
Vasodilation of cranial blood vessels generates pain
43
What is the neurogenic hypothesis of migraines?
Neural events increase noxious sensory transmission through trigeminal system, causing pain directly and through neurogenic inflammation
44
What is the brain theory of migraines?
Linked to CSD, more likely to occur in migraine with aura, but not without
45
What is CSD?
Cortical spreading depression
46
What is CGRP?
Calcitonin gene related peptide
47
What is neurogenic inflammation?
Activation of trigeminal sensory axons causes release of vasodilatory substances such as CGRP; mast cells activate and release more; blood vessels thus leak fluid; afferents are sensitised thus become hypersensitive to physiological stimuli
48
Where to ergot alkaloids occur naturally?
In fungi that infect rye
49
What is the ergot alkaloid MOA?
Act mainly on ADR, 5-HT or dopamine receptors
50
What two ergot alkaloids are related to migraine therapy?
Ergotamine and methysergide
51
What type of drug is ergotamine?
Ergot alkaloid
52
What type of drug is methysergide?
Ergot alkaloid
53
What is ergotamine used to treat?
Migraine
54
What is methysergide used to treat?
Migraine
55
What limits the use of methysergide?
Adverse effects
56
What is the MOA of ergotamine?
Acts as antagonist and partial agonist at 5-HT-1 receptors, and partial agonist at alpha-ADR
57
What does ergotamine cause?
Vasoconstriction and uterine contraction
58
What are the side effects of ergotamine?
Emesis, vasospasm and adverse affects during pregnancy
59
What physiological effects implicate 5-HT in the pathogenesis of migraines?
Elevated with vasoconstriction, decreased with vasodilation, increased excretion of 5-HT metabolites during migraine, decreased blood levels
60
What pharmacological effects implicate 5-HT in the pathogenesis of migraines?
Many drugs that are effective against migraines target 5-HT receptor signalling pathways
61
What are the three 5-HT1 receptors associated with migraines?
5-HT1-B/D/F
62
Where are 5-HT1-B receptors found?
CNS, vascular smooth muscle and many others
63
Where are 5-HT1-D receptors found?
Presynaptic location on peripheral and central trigeminal neurons
64
Where are 5-HT1-F receptors found?
Same as 5-HT1-D - presynaptic location on peripheral and central trigeminal neurons
65
What is the signalling function for all 5-HT1 receptors?
G-i/o protein - decreased cAMP - possible modulation of Ca channels
66
Name three triptans.
Sumatriptan, rizatriptan, zolmitriptan
67
What are the triptans used to treat?
Acute migraine attacks
68
What is the MOA for triptans?
5-HT1-B/D/F agonists
69
What do triptans cause?
Constrict large arteries - decreasing vasodilation and reducing sensory signalling; inhibit trigeminal nerve transmission - decreasing pain signalling and neurogenic inflammation
70
What type of drug is sumatriptan?
Triptan
71
What type of drug is rizatriptan?
Triptan
72
What type of drug is zolmitriptan?
Triptan
73
What receptor does sumatriptan bind?
5-HT1-B/D/F
74
What receptor does rizatriptan bind?
5-HT1-B/D/F
75
What receptor does zolmitriptan bind?
5-HT1-B/D/F
76
What are the side effects of triptans?
Coronary vasoconstriction, dysrhythmias, chest pain, neck and jaw pain, muscle pain, CNS effects - functional impairment and reduced productivity
77
What are triptans contra-indicated for?
Patients with symptoms of coronary heart disease
78
What may be an alternative approach to treating migraines, other than with triptans?
Target neuronal release of pain sensitising neuropeptides such as CGRP - target 5-HT1-F receptors expressed on the trigeminal nerve
79
What type of drug is lasmiditan?
Ditan
80
What receptor does lasmiditan bind?
5-HT1-F specifically
81
What are the advantages to the ditans?
No coronary side effects noted
82
What is the new class of drugs being tested for migraine treatments?
Ditans
83
How does lasmiditan act differently to sumatriptan?
Sumatriptan = vasoconstriction; lasmiditan = inhibition of neuronal activity
84
What is the preferred drug for migraine related prophylaxis?
Propranolol
85
Name four emerging migraine treatments.
CGRP receptor antagonists, onabotulinumtoxin, prostanoid receptor antagonism, 5-HT7 receptor antagonism
86
Name two CGRP receptor antagonists.
Olcegepant and telcagepant
87
What is the MOA of olcegepant?
CGRP receptor antagonist
88
What is the MOA of telcagepant?
CGRP receptor antagonist
89
What is olcegepant used to treat?
Migraine
90
What is telcagepant used to treat?
Migraine
91
What does 5-HT7 receptor antagonism do?
Prevents vasodilation in blood vessels in the trigeminal sensory areas
