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Block 5 Jones Flashcards

1
Q

how is histamine produced?

A

L-histidine is decarboxylated by histidine decarboxylase

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2
Q

where is most histidine stored

A

mast cells

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3
Q

describe the 4 receptor subtypes of histidine, including their post-receptor mechanism and where they’re found

A

H1 - smooth muscle, endothelium, brain; Gq coupled (IP3 and DAG increase)

H2 - gastric mucosa, cardiac muscle, mast cells, brain; Gs coupled, increase cAMP

H3 - presynaptic autoreceptors and heteroreceptors, brain, myenteric plexus; Gi coupled (decrease cAMP)

H4 - eosinophils, neutrophils, CD4s; Gi coupled (decrease cAMP)

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4
Q

H1 receptors are similar to _____ and H2 receptors are similar to ______

A

muscarinic

serotonergic

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5
Q

H1 stimulation leads to ______ and inhibition leads to ______

A 
stimulation = arousal
inhibition = sedation
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6
Q

H2 receptor antagonists are used for

A

blocking histamine release from ECL cells, which decreases the stimulation and subsequent release of protons into the stomach
- this decreases stomach acid in treatment of GERD/acid reflux and peptic ulcers

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7
Q

IgE binds to _______ on mast cells

A

FC-epsilon-R1 receptors

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8
Q

____ receptors have very important chemotactic effects on eosinophils and mast cells

A

H4

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9
Q

____ receptors in the vestibular system send stimuli to the vomiting center to generate motion sickness

A

H1

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10
Q

contrast 1st and 2nd generation histamine antagonists

A

1st - better sedative effects and have better MR affinity and BBB permeability

2nd - are substrates for P-glycoprotein and are rapidly effluxed; less MR affinity

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11
Q

2nd generation H1 antagonists are used for

A

seasonal allergies

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12
Q

H2 receptor antagonists are used exclusively for

A

stomach acid reducers due to their MOA

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13
Q

give examples of H2 receptor antagonists

A

Axid (nizatidine)
Pepcid (famotidine)
Tagamet (cimetidine)
Zantac (ranitidine)

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14
Q

deficiency in _______ results in depression

A

serotonin

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15
Q

serotonin is synthesized from ______ by hydroxylation of the indole followed by decarboxylation of the amino acid

A

L-tryptophan

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16
Q

which serotonin receptor is not GPCR coupled

A

5-HT3

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17
Q

where are 5-HT3 receptors located?

A

in the GIT and the VC and CTZ, allowing them to participate in the vomiting reflex

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18
Q

the release of serotonin by EC cells from the gut stimulates EPANs via _______, which are ligand gated ion channels that signal the VC

A

5-HT3

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19
Q

stimulating which receptors will cause a response in IPANs?

A

5-HT1P

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20
Q

what happens when IPANs are activated?

A

it activates the enteric neurons responsible for peristaltic and secretory reflex activity

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21
Q

5-HT4 receptors are heteroreceptors with ______ feedback; they release ____ which causes…

A

positive

Gs

enhanced release

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22
Q

antiemetics that target 5HT receptors target which one?

A

5-HT3

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23
Q

what disease state do partial agonists of 5-HT4 treat?

24
Q

treatment of depression is done by…

A

enhancement of endogenous 5HT postsynaptic activity by inhibition of pre-synaptic reuptake via SERT inhibitors
- SSRIs = sleective serotonin reuptake inhibitors

25
what kind of lipase removes AA from the membrane?
PLA2
26
identify the three forms of PLA2 that play a role in removing AA from the membrane.
cPLA2 - cytosolic, calcium dependent, does most of the actual removal sPLA2 - secretory (inducible), calcium dependent, can be induced when you need lots of AA iPLA2 - independent; most of the AA removed by it is put back in the membrane
27
what are the 4 pathways by which AA is oxygenated?
COX LOX CYP450 nonenzymatically - isoeicosanoid
28
which COX enzyme provides for "housekeeping" functions
COX1
29
what kind of inducers can "induce" COX2
shear stress growth factors tumor promoters cytokines
30
due to the nature of its main producers, ____ is the main source of prostanoids in inflammation and cancer
COX2
31
ibuprofen inhibits
COX1 and COX2 - non selective
32
Celecoxib, diclofenac, and meloxicam inhibit
COX 2 selectively
33
Aspirin inhibits
both COX 1 and 2 irreversibly
34
What are the COX metabolites
prostaglandins prostacyclins thromboxanes
35
what is PGI2 used for
smooth muscle relaxation effects to maintain the ductus arteriosus in patients
36
PGE2 and PGF2-alpha are used to
induce labor
37
latanoprost is
topically active PGF2-alpha used to treat glaucoma/ocular hypertension
38
PGI2 is used by _____ as a _____
vascular endothelium powerful vasodilator (inhibits platelet aggregation)
39
what is the MoA of thromboxane (TXA2)
stimulates platelet aggregation and vasoconstriction
40
why is PGE2 special?
its effects on platelet aggregation are dose-dependent - low concentrations = enhance - high concentrations = inhibit
41
5LOX gives rise to...
leukotrienes
42
four approaches to anti-leukotriene drugs are
1 - inhibit 5 LOX 2 - cysteinyl leukotriene receptor antagonists 3 - FLAP (5-lox activating protein) inhibitors 4 - PLA2 inhibitors (which block all AA derivatives)
43
alpha-melanocyte stimulating hormone (alpha-MSH) is released when
ACTH levels are very high. it results in stimulation of synthesis and distribution of melanin - this is why addison's diease often results in hyperpigmentation
44
secretion of the mineralocorticoid aldosterone is primarily under the influence of
angiotensin 2
45
glucocorticoids are made in the
zona fasciculata
46
all GCs are highly _____
lipophilic
47
what is the main GC?
cortisol
48
what is the effect of GC on serum glucose levels
increase
49
how do GCs affect inflammation and the immune system
inhibit the functions of immune cells and suppress release of pro-inflammatory cytokines and PGs
50
glucocorticoid receptors are found
on the nuclear membrane because they're part of the nuclear receptor family of TFs
51
______ is the most important mineralocorticoid in humans
aldosterone
52
where is aldosterone synthesized?
zona glomerulosa of the adrenal gland
53
_____ is used in the treatment of adrenocortical insufficiency (AKA _______). the MOA is...
fludrocortisone Addison's Disease is an MR with non-selective GR agonist acitivity
54
spironolactone is used in the treatment of
hyperaldosteronism
55
what is Cushing's disease
a pituitary disorder is caused by excessive ACTH causes secondary dysfunction of the adrenal glands

PDSA (6 decks)

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