Kinins, Serotonin and Drug Therapy of Migraine headache -Salisbury Flashcards
(100 cards)
1
Q
what are 3 biological effects of Kinins
A
autocoids that induce inflammation, pain and vasodilation
2
Q
what are two kinins
A
Bradykinin
kallidin
3
Q
what is the precursor for kinin
A
Kininogens
4
Q
what are Killikerins
A
serine proteases that cleave Kininogens into kinins
5
Q
High molecular weight kininogens HMWK is cleaved by what and gets turned into what?
A
Plasma Kallikrein into bradykinin
6
Q
Low Molecular weight Kininogen LMWK is cleaved by what
A
Tissue Kallikrein into kallidin which is then cleaved by Aminopeptidase into Bradykinin
7
Q
Autoactivation of Factor XII (Hageman factor) turns into what
A
factor XIIa
8
Q
Factor XIIa converts what into what
A
plasma Prekallikrein to plasma Kallikrein
9
Q
what is the role of Plasma Kallikrein (2)
A
- converts high molecular weight kininogen HMWK to Bradykinin
- activates factor XIIa
10
Q
the first step in the intrinsic clotting cascade enhances what
A
Bradykinin synthesis
11
Q
Are tissue and plasma Kallikrein the same thing
A
no
12
Q
Tissue Kallikrein converts what
A
Low Molecular Weight Kininogen LMWK to Kallidin
Aminopeptidase converts kallidin to Bradykinin
13
Q
Role of Carboxypeptidase N and M (CPN, CPM)
A
cleave kinins into active kinin metabolites
14
Q
what is another name for carboxypeptidase N and M CPN, CPM
A
kinase I
15
Q
another name for Angiotensin I-converting Enzyme (ACE_)
A
Kinase II
16
Q
Role of ACE kinase II
A
hydrolyzes Bradykinin into inactive products
17
Q
when people take ACE inhibitors for lowering blood pressure and cardioprotective reasons, what effect does this have on Bradykinins
A
increases
18
Q
Name two Kinin receptors? what kind of receptors are they
A
B1 and B2
G coupled receptors
19
Q
Native Bradykinin and Kallidin activate what receptor
A
B2
20
Q
Active metabolites of Bradykinin and Bradykinin activate what receptor
A
B1
21
Q
where is B2 mostly expressed
A
in most tissues
22
Q
B1 receptor is induced by what
A
tissue damage and inflammation
23
Q
activation of B receptors stimulates increase synthesis of what
A
prostaglandins
NO
EDHF
24
Q
What effect do NSAIDS have on bradykinin and kallidin and prostaglandin
A
decreases Bradykinin and Kallidin
increases prostaglandin by blocking cyclo-oxygenase
25
What effect do corticosteroids have on bradykinin and kallidin and prostaglandin
decreases Bradykinin and Kallidin
| increases prostaglandin by stimulating Lipocortin ( phospholipase A2 inhibitor)
26
what are 4 effects of kinins
pain
inflammation
cardiovascular
respiration
27
what is the most potent vasodilator peptide in the trigeminal system
CGRP
| induced by kinins
28
Kinins can induce what in the respiratory tract
bronchospasms
| kinin levels can be elevated in asthma
29
what do kinins do to the cardiovascular system
vasodilation and lower BP
30
what are 4 biological effects of Serotonin
platelets
cardiovascular
GI
CNS
31
what role does serotonin play in platelets
platelets do not synthesize serotonin
platelets actively take up serotonin
Serotonin release during platelet aggregation promotes platelet aggregation and vasoconstriction
32
what role does serotonin play in cardiovascular
induces vasoconstriction
| positive inotropic and chronotropic effects on heart
33
what role does serotonin play in GI
Enterochromaffin cells release 5-HT in response to vagal stimulation and stretching with food digestion
5-HT regulates GI motility
34
5-HT producing carcinomas will induce what
diarrhea and abdominal cramps
35
where are 5-HT found in the CNS? role?
raphe nuclei of brain stem
| regulates sensory perception and nociception
36
Serotonin is inactivated by what
monamine-oxidase A (MAO-A)
37
what only expresses MAO-B isoform
platelets
38
what is a urinary metabolite of 5-HT
5-HIAA
| 5-Hydroxyindoleacetic acid
39
what serotonin receptors play a role in migaine
5-HT 1B/1D
40
role of 5-HT 1D
induces vasoconstriction of cranial blood vessels
41
role of 5-HT1B
autoreceptor
| inactivation inhibits nociceptive trigeminal afferents which controls acute migraine attacks
42
what drug are 5-HT1B/1D agonist that controls/reverses acute migraine attacks
Triptans
43
common migraine
headache
44
classic migraine
aura and headache
45
what are the 4 stages of migraine
prodome ( 1-2 days prior to attack) GI effects mood changes
aura (20-60 min prior to attack)
attack ( 4 hrs - 3 days)
postdrome
46
what is a characteristic of a migraine attack
POUND
| Pulsating headache lasting 4-72 hOurs that is Unilateral, Nauseating and Debilitating
47
can patients be genetically susceptible to migraine
yes
48
what is neurovascular headache
disorder in which neural events results in further dilation of cranial blood vessels, which in turn, results in pain and further nerve activation
49
can a migraine be caused by a primary vascular event?
no
50
what causes a migraine
brain-stem nuclei that normally mediate sensory input and exerts neural effects on cranial vessels
51
Beta blockers are what kind of agents for migraines
prophylactic
52
name 2 beta blockers
Propranolol and Atenolol
53
Propanolol and Atenolol is contraindicated in who
patients with ashtma
54
Name two tricyclic antidepressants
Amitriptyline
| Nortriptyline
55
what are side effects of Amitriptyline and Nortriptyline
limit use
| - significant anti-muscarinic properties, weight gain, tiredness
56
tricyclic antidepressants- how are they used to treat migraines
prophylactic agent
57
```
Valproic acid
Topiramate
Gabapentin
Levetiracetam
are what type of drug and use
```
Anticonvulsants
| prophylactic
58
who is Valporic acid contraindicated in
pregnant patients
59
Anticonvulsants are typically prescribed to who
migraine patients with epilepsy or anxiety disorders
60
name a calcium channel blocker and its use
Verapamil
| prophylactic
61
what are side effects of Verapamil
negative inotropic cardiac effects
| hypotension
62
MOA for Cyproheptadine
antagonist of histamine, acetylcholine, serotonin
| Prophylactic
63
side effects of Cyproheptadine
CNS depression
| sleepiness
64
what is used to abort mild to moderate migraines ( rescue)
Acetaminophen, aspirin NSAIDS
65
what is used to abort moderate to severe migraines? how can you administer it? what the longest length of time you can use it? (rescue)
Ketorolac ( IV or oral)
| max 5 days
66
what is used to abort migraines in children ( rescue)
Acetaminophen and ibuprofen
67
what is used to abort migraines in pregnant ladies ( rescue)
Ibuprofen and acetaminophen
| all NSAIDS should be avoided in last trimester
68
Same 2 Ergot alkaloids
Ergotamine and Dihydroergotamine
69
what is MOA for Ergot Alkaloids
agonist effects at 5-HT1 receptors
70
what are the routes of administration of Ergotamine and Dihydroergotamine
Ergotamine- sublingual
| Dihydroergotamine: nasal spray, injection
71
what are side effects of Ergot Alkaloids
Nausea and vomiting
| generalized vasoconstriction
72
Ergotamine and dihydroergotamine are contraindicated in who
pregnancy
peripheral vascular disease
ischemic heart disease
73
Ergot alkaloids can be combined with what to treat what
antiemetic
| curve nausea
74
what cannot you not combine ergotamine and dihydroergotamine with
Triptans
75
compare side effects of Triptan and Ergot alkoids
Triptan causes less nausea and generalized vasoconstriction
76
MOA of Triptan
5-HT 1B/1D receptor agonists
77
Triptan effect on vascular
vasoconstriction of cranial vessles
78
Triptan effect on neurogenic
reduction of trigeminal sensory nerve activation
| inhibition of vasoactive neuropeptide release
79
Triptan effect on central
-inhibition of neurotransmitter release from activated trigeminal nerve in the brainstem and upper cervical spinal column
80
what are good things about Sumatriptan
short onset
| relief within 1hr
81
limitations of Sumatriptan
short duration
low bioavailability
short plasma half life
82
Good things about Naratriptan and Zolmitriptan
lipophilicity: greater distribution to brain
greater bioavailability
longer half life
83
draw back of Naratriptan and Zolmitriptan
onset of action 1 hours
84
what drugs get metabolized by P450
Naratriptan and Zolmitriptan
85
what patients should receive lower doses of Naratriptan and Zolmitriptan
renal dysfunction
86
what has the longest acting Triptan, higher affinity for 5-HT 1B/1D
Frovatriptan
87
How is Rizatriptan given
sublingual
88
adverse effect of Rizatriptan
headache recurrence
| tingling, paresthesia, dizziness, flushing, neck pain, and drowsiness
89
contraindications of Rizatriptan
dont use ergot alkaloid within 24 hrs
- peripheral vascular disease
- ischemic heart disease
90
Drug interactions of Rizatriptan
dont use with SSRI
| - restlessness, hallucinations, loss of coordination, diarrhea
91
Episodic severe unilateral stabbing headaches that tend to appear at the same each ( circadian Rhythm)
cluster headace
92
acute treatment options for cluster headache attacks
oxygen
| triptans
93
prophylactic options for cluster headaches
high dose prednisone
| calcium channel blockers ( verapamil)
94
Headache pain is a squeezing or pressure felt around the head that is not associated with nausea or vomiting
tension
95
abortive medications for tension headaches
acetaminophen and NSAIDS
96
prophylactic medications for tension headaches
tricyclic antidepressants
| antiepileptic gabapentin
97
pain due to increases in intracranial pressure and disorder occurs most frequently in obese young women
idiopathic intracranial hypertension
98
Drug therapy for idiopathic intracranial hypertension includes
carbonic anhydrase inhibitors
| Acetazolamide and Topiramate
99
what is MOA of Acetazolamide and Topiramate
function as carbonic anhydrase inhibitor that reduce CSF production
100
side effects of carbonic anhydrase inhibitors
nausea, tingling in hands and feet, altered taste
