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Autacoids > Autacoids :( > Flashcards

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
Q

H1 blocker pharmacodynamics (4)

A

Blocks Type I hypersensitivity reaction
Incomplete block of vascular smooth muscle relaxation (H1 & H2 for complete suppression)
CNS: sedation, anti-emetic
Anti-cholinergic: dryness

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26
Q

Antihistamine actions not mediated by H-receptor, ex.

A

Anticholinergic, via muscarinic receptor

Scopolamine for anti-vertigo

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27
Q

Kinin

Precursors, catalyst

A

Precursors: HMW, LMW kininogen

Catalyst: Plasma and tissue kallikrein

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28
Q

Kinin metabolism inhibited by? Half life?

A

Kininase or converting enzyme

15 secs

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29
Q

Endogenous KKK systems supports which part of the clotting system

A

Intrinsic pathway

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30
Q

B1 receptor fxn

A

Contraction of arteries and most veins

31
Q

B2 receptor fxn (2)

A

Vasodilation in arterioles (via EDRF) -> drop BP, inc heart rate

Contraction of endothelial cell sin venules -> inc capillary permeability, edema

32
Q

Kallikrein inhibitor ex. (used in coronary by-pass)

33
Q

KKK antagonist therapeutic uses (3)

A

Cold, pain from burns, allergic asthma

34
Q

Where is serotonin stored

A

90% enterochromaffin cells, rest in platelets, CNS

35
Q

Serotonin biosynthesis

A

W (tryptophan-5-hydroxylase) -> 5-hydroxytryptophan (L-amino decarboxylase) -> 5-hydroxytryptamine

36
Q

HT functions (4)

A

Central chemical transmitter for tryptaminergic neurons in the brain

Regulation of GI motility

Hemostasis

Precursor for melatonin

37
Q

Ligand-gated 5-HT

A

5-HT3 (others: GPCR)

38
Q

5-HT1A drug

action, prototype, clinical use

A

Buspirone

Partial agonist

Anxiety, depression

39
Q

5-HT1B/1D

action, prototype, clinical use

A

Sumatriptan

Agonist

Migraine

40
Q

5-HT2A/2C

action, prototype, clinical use

A

Risperidone

Antagonist

Migraine, depression, schizo

41
Q

5-HT3

action, prototype, clinical use

A

Ondansetron

Antagonist

Chemo emesis, nociception, sympathetic inhibition, pain and itching

42
Q

5-HT4

action, prototype (2), clinical use

A

Cisapride (banned), metoclopramide

Agonist

GI peristalsis

43
Q

5-HT transporter

action, prototype (2), clinical use

A

Fluoxetine, sertraline

Inhibitor

Major depression, OCD

44
Q

Non-selective serotonergic drugs

action, prototype (2)

A

Ergoamine, LSD

Agonist

45
Q

Drug choice for migraine

A

Sumatriptan (5-HT1B/1D)

46
Q

Serotonergic agonists

A

1A (partial) - buspirone
1B, 1D - sumatriptan
4 - cisapride, metoclopramide

47
Q

5-HT2A antagonist (contracts vascular smooth muscle, platelet aggregation)

A

Ketanserin (lowers BP)

48
Q

Non-selective serotonergic drug for prophylactic treatment of migraine and vascular headaches

A

Methysergide

49
Q

Vasoconstrictors

A 
Angiotensin II
Vasopressin
Endothelin
Neuropeptide Y
Urotensin
50
Q

Vasodilators

A 
Vasoactive intestinal peptide
Substance P
Calcitonin gene-related peptide
Bradykinin
Natriuretic peptide
Neurotensin
Adrenomodulin
51
Q

Renin produced by? Fxn?

A

JG cells (kidney), angiotensinogen -> angiotensin I

52
Q

Angiotensin is exclusively produced by ACE t/f?

53
Q

Angiotensin II antagonist

Structures responsible for reduced agonist activity and increased receptor affinity?

A

Saralasin

Ala on 8th AA - reduced agonist activity
Sarcosin on 1st AA - inc receptor affinity

54
Q

ACE inhibitor

55
Q

ARBs (angiotensin II blockers), ranked by affinity to AT1

A

CITyViLle

Candesartan > Irbesartan > Telmisartan >= Valsartan > Losartan

56
Q

Renin inhibitor

A

Aliskiren

Also, beta blockers (but weaker)

57
Q

Renin inhibitors vs ACE inhibitors

A

Renin inhibitors don’t affect kinin metabolism so no dry cough or angioneurotic edema (characteristic side effect of ACE inhibitors)

58
Q

COX 1 vs COX 2

A

1 - good, constitutive, housekeeper, widely distributed throughout GIT

2 - bad, inducible, homewrecker

59
Q

Aspirin not used anymore for pain relief but as (3)

A

Analgesic-antipyretic
Anti-inflammatory
Antiplatelet (inhibit Thromboxane A2)

60
Q

Aspirin adverse effects

A 
Ulcers (inhibit mucus formation)
Bleeding neuropathy (reduced GFR due to less PGI?)
61
Q

Probably dominate during allergic constriction of airways

A

LTC5, LTD4, LTE4

62
Q

LTC4, LD4 in low vs high concentration

A

LOW - exudation of plasma in PCP

HIGH - reduce exudation of plasma by constricting ARTERIOLES

63
Q

COX 2 agonists (4)

A

cytokines
IL-1
TNF1
growth factors

64
Q

COX 2 antagonists (3)

A

cytokines
glucocorticoids
IL-4

65
Q

PGE2 or PGF2a

A

induction of labor at term / aborifacients, cytotek

66
Q

PGE1 analog

A

misoprostol

gastric cytoprotection
prevent gastric dry-up with NSAID

67
Q

PGE1

A

alprostadil

impotence

68
Q

PGE1 in some neonates with congenital heart disease

A

maintenance of PDA

69
Q

PGI2

A

epoprostenol

primary pulmonary hypertension; anti-inflammatory

70
Q

Nonselective COX inhibitors (8)

A 
indomethacin
diclofenac
ibuprofen
nabumetome
aspirin

paracetamol
mefenamic acid
meloxicam

71
Q

Selective COX 2 inhibitors (4)

A

rofecoxib
etodolac
nimesulide
celecoxib

72
Q

aspirin vs nsaids

A

aspirin covalently modifies both cox 1 and 2 -> irreversible inhibition

cox 1 -> serine 530
cox 2 -> serine 516

nsaids - competitive inhibitors of COX

73
Q

other therapeutic uses of nsaids (3)

A

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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