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Autacoids :( Flashcards

1
Q

Histamine precursor and enzyme

A

Histidine

L-histidine decarboxylase

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2
Q

Histamine - stored in? Complexed with?

A

Mast cells and basophils

Complex with heparin-ATP in secretory granules (like suicide bombers)

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3
Q

Triple response of Lewis

A

Flush, wheal, flare

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4
Q

(Localized red spot) action and effect?

A

Flush

Relaxation of vascular smooth muscle

Vasodilation

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5
Q

(Swelling of edema) action and effect?

A

Wheal

Contraction of endothelial cells and post-capillary venule

Increased capillary permeability / leakage

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6
Q

(Brighter red halo) action and effect?

A

Flare

Local axon reflex

Indirect vasodilation

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7
Q

H1 distribution (2)

A

Smooth muscle endothelium, CNS

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8
Q

H1 rep antagonist (2)

A

Chlorphenamine, diphenhydramine

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9
Q

H2 distribution (4)

A

Parietal cells, cardiac muscle, mast cells, CNS

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10
Q

H2 rep antagonist (2)

A

Ranitidine (Zantac), cimetidine

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11
Q

Selective H2 blocker, acts on stomach

A

Ranitidine

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12
Q

H3 distribution

A

CNS: presynaptic, myenteric plexus, other neurons

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13
Q

H3 rep antagonist (3)

A

Thioperamide, cloben, burimamide

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14
Q

H4 distribution

A

Cells of hematopoietic origin (bone marrow)

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15
Q

H4 antagonist (2)

A

Thioperamide (JNJ7777120), zymosan

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16
Q

H receptors distributed widely in periphery and CNS

A

H1, H2

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17
Q

H1 activates _, -> _ pathway

A

H1 activates Gq/11 -> PLC-IP3-Ca pathway

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18
Q

H2 activates _, -> _ pathway

A

H2 activates Gs -> adenylyl cyclase-cAMP-PKA pathway

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19
Q

H3 and H4 activate _ -> inhibit

A

H3 and H4: Gi/o -> inhibit adenylyl cyclase

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20
Q

Betahistine used for?

A

anti-vertigo (*H3, H4)

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21
Q

H receptors involved in neurotransmission, inflammation, circadian rhythm, nausea (vomiting center), vertigo

A

H3, H4

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22
Q

H receptor confined largely to CNS

A

H3

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23
Q

H receptors for lab rat experiments

A

H3, H4

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24
Q

H1 blockers (5)

A 
diphenhydramine (Benadryl)
chlorphenamine 
hydroxyzine (urticaria)
meclizine (Bonamine)
promethazine (anesthesia; drug-drug -> arrythmia)
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25
H1 blocker pharmacodynamics (4)
Blocks Type I hypersensitivity reaction Incomplete block of vascular smooth muscle relaxation (H1 & H2 for complete suppression) CNS: sedation, anti-emetic Anti-cholinergic: dryness
26
Antihistamine actions not mediated by H-receptor, ex.
Anticholinergic, via muscarinic receptor Scopolamine for anti-vertigo
27
Kinin Precursors, catalyst
Precursors: HMW, LMW kininogen Catalyst: Plasma and tissue kallikrein
28
Kinin metabolism inhibited by? Half life?
Kininase or converting enzyme 15 secs
29
Endogenous KKK systems supports which part of the clotting system
Intrinsic pathway
30
B1 receptor fxn
Contraction of arteries and most veins
31
B2 receptor fxn (2)
Vasodilation in arterioles (via EDRF) -> drop BP, inc heart rate Contraction of endothelial cell sin venules -> inc capillary permeability, edema
32
Kallikrein inhibitor ex. (used in coronary by-pass)
Aprotinin
33
KKK antagonist therapeutic uses (3)
Cold, pain from burns, allergic asthma
34
Where is serotonin stored
90% enterochromaffin cells, rest in platelets, CNS
35
Serotonin biosynthesis
W (tryptophan-5-hydroxylase) -> 5-hydroxytryptophan (L-amino decarboxylase) -> 5-hydroxytryptamine
36
HT functions (4)
Central chemical transmitter for tryptaminergic neurons in the brain Regulation of GI motility Hemostasis Precursor for melatonin
37
Ligand-gated 5-HT
5-HT3 (others: GPCR)
38
5-HT1A drug action, prototype, clinical use
Buspirone Partial agonist Anxiety, depression
39
5-HT1B/1D action, prototype, clinical use
Sumatriptan Agonist Migraine
40
5-HT2A/2C action, prototype, clinical use
Risperidone Antagonist Migraine, depression, schizo
41
5-HT3 action, prototype, clinical use
Ondansetron Antagonist Chemo emesis, nociception, sympathetic inhibition, pain and itching
42
5-HT4 action, prototype (2), clinical use
Cisapride (banned), metoclopramide Agonist GI peristalsis
43
5-HT transporter action, prototype (2), clinical use
Fluoxetine, sertraline Inhibitor Major depression, OCD
44
Non-selective serotonergic drugs action, prototype (2)
Ergoamine, LSD Agonist
45
Drug choice for migraine
Sumatriptan (5-HT1B/1D)
46
Serotonergic agonists
1A (partial) - buspirone 1B, 1D - sumatriptan 4 - cisapride, metoclopramide
47
5-HT2A antagonist (contracts vascular smooth muscle, platelet aggregation)
Ketanserin (lowers BP)
48
Non-selective serotonergic drug for prophylactic treatment of migraine and vascular headaches
Methysergide
49
Vasoconstrictors
``` Angiotensin II Vasopressin Endothelin Neuropeptide Y Urotensin ```
50
Vasodilators
``` Vasoactive intestinal peptide Substance P Calcitonin gene-related peptide Bradykinin Natriuretic peptide Neurotensin Adrenomodulin ```
51
Renin produced by? Fxn?
JG cells (kidney), angiotensinogen -> angiotensin I
52
Angiotensin is exclusively produced by ACE t/f?
F
53
Angiotensin II antagonist Structures responsible for reduced agonist activity and increased receptor affinity?
Saralasin Ala on 8th AA - reduced agonist activity Sarcosin on 1st AA - inc receptor affinity
54
ACE inhibitor
Captopril
55
ARBs (angiotensin II blockers), ranked by affinity to AT1
CITyViLle Candesartan > Irbesartan > Telmisartan >= Valsartan > Losartan
56
Renin inhibitor
Aliskiren Also, beta blockers (but weaker)
57
Renin inhibitors vs ACE inhibitors
Renin inhibitors don't affect kinin metabolism so no dry cough or angioneurotic edema (characteristic side effect of ACE inhibitors)
58
COX 1 vs COX 2
1 - good, constitutive, housekeeper, widely distributed throughout GIT 2 - bad, inducible, homewrecker
59
Aspirin not used anymore for pain relief but as (3)
Analgesic-antipyretic Anti-inflammatory Antiplatelet (inhibit Thromboxane A2)
60
Aspirin adverse effects
``` Ulcers (inhibit mucus formation) Bleeding neuropathy (reduced GFR due to less PGI?) ```
61
Probably dominate during allergic constriction of airways
LTC5, LTD4, LTE4
62
LTC4, LD4 in low vs high concentration
LOW - exudation of plasma in PCP | HIGH - reduce exudation of plasma by constricting ARTERIOLES
63
COX 2 agonists (4)
cytokines IL-1 TNF1 growth factors
64
COX 2 antagonists (3)
cytokines glucocorticoids IL-4
65
PGE2 or PGF2a
induction of labor at term / aborifacients, cytotek
66
PGE1 analog
misoprostol gastric cytoprotection prevent gastric dry-up with NSAID
67
PGE1
alprostadil impotence
68
PGE1 in some neonates with congenital heart disease
maintenance of PDA
69
PGI2
epoprostenol primary pulmonary hypertension; anti-inflammatory
70
Nonselective COX inhibitors (8)
``` indomethacin diclofenac ibuprofen nabumetome aspirin ``` paracetamol mefenamic acid meloxicam
71
Selective COX 2 inhibitors (4)
rofecoxib etodolac nimesulide celecoxib
72
aspirin vs nsaids
aspirin covalently modifies both cox 1 and 2 -> irreversible inhibition cox 1 -> serine 530 cox 2 -> serine 516 nsaids - competitive inhibitors of COX
73
other therapeutic uses of nsaids (3)
indomethacin - postnatal closure of pda relief of cramps in primary dysmenorrhea emergic use: colon/breast cancer, alzheimer's

Autacoids (1 decks)

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