3. Histamine, Serotonin, and Ergot Alkaloids- Eicosanoids Flashcards by iya gerzon

endogenous molecules with powerful pharmacologic effects that do not fall into traditional autonomic groups

Autacoids

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Histamine precursor

histidine

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histamine is metabolized by enzyme

Monoamine oxidase

diamine oxidase

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how to detect excess production by histamine

imidazole acetic acid in urine

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important pathophysiologic roles of histamine

seasonal rhinitis (hay fever )
urticaria
angioedema
control of acid secretion in the stomach

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triple response of Lewis

wheal
flush
flare

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triple response of Lewis

mediated by these receptors

H1 and H2

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Histamine receptors

smooth muscle

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stomach
heart
mast cells

histamine receptor

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nerve endings
CNS

histamine receptor

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Leukocytes

Histamine receptor

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postreceptor mechanism of each histamine receptor subtype

H1 - Gq, Inc IP3, DAG
H2 - Gs, Inc cAMP
H3 - Gi, dec cAMP
H4 - Gi, dec cAMP

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Prototype antagonist

Diphenhydramine

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Prototype antagonist

cimetidine

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Prototype antagonist

clobenpropit

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H1 effects

pain and itching
bronchoconstriction
vasodilation
local edema

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effects

gastric acid secretion

cardiac stimulation

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H3 effects

modulation of other neurotransmitters

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H4 effects

leukocyte chemotaxis

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why are H1 receptor antagonists not given to neonates

susceptible to antimuscarinic effects

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H1 receptor antagonists SE

sedation
drowsness
blurred vision
dry mouth 
urinary retention
anorexia 
orthostatic hypotension

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H1 receptor antagonists first -generation

Diphenhydramine
brompheniramine
chlorpheniramine
cyclizine 
meclizne
buclizine
carbonoxamine
dimenhydrinare
hydroxyzine
promethazine
cyproheptadine
clemastine
tripelennamine

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MOA diphenhydramine

competitive block of peripheral and CNS H1 receptors
alpha and M receptor block
antimotion sickness effect

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uses of diphenhydramine

hay fever
angioedema 
motion sickness (cyclizine - more antimotion sickness action, less sedative and less autonomic)
insomnia 
dystonia 
anti-emetic (promethazine)
for serotonin syndrome (cyproheptadine)

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H1 receptor agonists (second - generation)

``` cetirizine loratadine fexofenadine desloratadine levocetirizine terfenadine astemizole ebastine azelastine bilastine rupatadine ```

MOA cetirizine

block of peripheral H1 receptors | no autonomic or anti-motion sickness effects

Uses of cetirizine

hay fever angioedema urticaria

H2 receptor antagonist

cimetidine ranitidine famotidine nizatidine

uses of cimeditine

peptic ulcer disease zollinger ellison syndrome gastroesophageal reflux

cimetidine only SE

CYP450 inhibitor and antiandrogen effects like gynecomastia | dec hepatic flow

used in ICU setting o prevent gastric erosion and hemorrhage

cimeditine

serotonin (5 hydroxytryptamine) | produced from

tryptophan

serotoni metabolized by

monoamine oxidase

excess production of serotonin in the body is detected by

5-hydroxyindole acetic acid in the urine

neurotransmitter in CNS and enteric nervous system | local hormone that modulates gastroinestinal activity

serotonin

serotonin receptor | brain

5HT 1D

serotonin receptor smooth muscle platelets

5HT2

serotonin receptor smooth muscle platelets

5HT2

serotonin receptor area postrema (CNS) sensory and enteric nerves

5 HT3

serotonin receptor | presynaptic nerve terminals in enteric nervous system

5-HT4

5-HT 1D receptor agonists

``` sumatriptan almotriptan eletriptan frovatriptan naratriptan rizatriptain zolmitriptan ```

MOA of sumatriptan

5HT1D agonists vasoconstriction modulates neutrotransmitter release

DOC for acute migraine | cluster headache

``` sumatriptan almotriptan eletriptan frovatriptan naratriptan rizatriptain zolmitriptan ```

SE of sumatriptan

``` paresthesias dizziness chest pain coronary vasospasm injection site reaction ```

5HT1D agonists route of administration and DOA

all are PO except sumatriptain which can also be intranasally, transdermal and IV All has 2-27 hours DOA except sumatriptan DOA 2-4 hours

5HT3 receptor antagonist

``` ondansetron granisetron dolasetron palonosetron alosetron ```

blocks chemoreceptor trigger zone and enteric nervous systm 5 HT3 receptors

ondansetron

``` uses of ondansetron granisetron dolasetron palonosetron alosetron ```

chemotherapy and postoperative vomiting | Irritable bowel syndrome (alostron only)

SE of 5HT 3 antagonist

``` diarrhea headache malaise QRS and QT prolongation (dolasetron only) constipation (alosetron only) ```

St. Anthony’s fire

ergot alkaloid

complex molecules produced by a fungus found in wet or spoiled grain

ergot aklaloids

classification of ergot alkaloids

vasoselective | uteroselective

5HT2 receptor antagonist | vasoselective

ergotamine dihydroergotamine methysergide

5-HT2 antagonist | uteroselective

ergonovine | methyergonovine

MOA ergot alkaloids

partial agonist a alpha and 5HT 2 receptors | some have potent agonist effect at dopamine receptors

uses of ergotamine

migraine | cluster headache

ergonovine uses

postpartum bleeding | migraine

antidote for ergotamine

nitroprusside

SE of vasoselective 5HT2 antagonist

``` GI upset vasospasm gangrene uterine spasm abortion ```

effect of ergotamine to epinephrine

epinephrine reversal as a partial agonist

ergonovine SE

GI upset (n,v, diarrhea) uterine spasm abortion

drugs used for vertigo

betahistine cinnarizine dimenhydrinate

strong antagonist at H3 receptor (inc levels of NT histamine, acetylchoine, norepinephrine, serotonin and GABA ) weak agonist at H1 (vasodilation and inc permeability in the inner ear)

betahistine q

an antihistamine and CCB | promotes cerebral blood flow

cinnarizine

first gen antihistamine used for nausea , vomiting, and dizziness caused by motion sickness

dimenhydrinate

betahistine used for

balance disorders | Meniere’s disease

Cinnarizien used for

nausea vomiting due to motion sickness Meniere’s disease vertigo cerebral apoplexy cerebral arteriosclerosis post trauma cerebral symptoms

selective calcium entry blocker with calmodulin binding propreties and H1 antagonist activity

flunarizine

flunarizine uses

prophylaxis of migraine occlusive peripheral vascular disease vertigo adjuvant for epilepsy

major families of eicosanoids include

straight chain: leukotrienes | cyclic: prostacyclin, prostaglandings, thromboxane

cyclooxygenase isoform

COX-1 - many tissue - normal physio processes COX-2 - inflammatory cells - synthesis of prostacycln in vascoular endothelium - synthesis of prostaglandins for renal fx

drug the inhibts phospholipase A2

corticosteroids

inhibits COX-2 COX-2

NSAIDS

inhibits lipoxygenase

zileuton

inhibits leukotrienes

zafirlukast

this eicosanoid promotes | leukocyte chemotaxis

LTB4

this eicosanoid promotes bronchoconstriction , slow reacting substance of anaphylaxis

LTC4 | LTD2

this eicosanoid promotes vascular smooth muscle relaxation protective effects on gastric mucosa maintains PDA

PGE1

this eicosanoid promotes vascular smooth muscle relaxation maintains PDA inc uterine tone

PGE2

this eicosanoid promotes vascular smooth muscle relaxation (peripheral, pulmonary, coronary)

PGI2

this eicosanoid promotes inc uterine tone dec IOP

PGF 2alpha

this eicosanoid promotes | platelet aggregation

TXA2

prostaglandin E1 analog

misoprostol gemeprost alprostadil

MOA of misoprostol

activates EP receptors inc HCO3 and mucus secretion in stomach uterine contraction

indications of misoprostol

peptic ulcer disease prevention of NSAID induced gastric mucosa injury abortifacient

SE of misoprostol

``` abdominal pain diarrhea uterine cramping misacarriage teratogen - moebius sequence ```

misoprostol is used together with ___ as safe abortifacient

mifepristone | methotrexate

MOA of alprostadil

prostaglandin E1 analog activates EP receptors causes vascular smooth muscle relaxation and vasodilation

uses of alprostadil

``` maintenance of PDA for infants with right ventricular outflow obstruction erectile dysfunction (injected into cavornosa) ```

SE of alprostadil

``` apnea hypotension arrythmia priapism lightheadedness ```

Prostaglandine E2 analog

Dinoprostone | Sulprostone

MOA low conc contract higher conc relax uterine and cervical smooth muscle soften cervix at term before induction with oxytocn

Dinoprostone

Uses of dinoprostone

induction of labor | abortifacient (2nd trimester)

Dinoprostone SE

cramping | fetal trauma

Prostaglanding F2 alpha analog

carboprost bimatoprost Travoprost Unoprostone

MOA activates FP receptors

carboprost bimatoprost Travoprost Unoprostone

uses of carboprost bimatoprost Travoprost Unoprostone

control of postpartum hemorrhage for refractory postpartum bleeding abortifacient

carboprost SE

vomiting diarrhea transient bronchoconstriction

prostaglandin I2 analog

epoprostenol beraprost iloprost treprostinil

MOA activates IP receptors causes vasodilation reduces platelet aggregation

epoprostenol beraprost iloprost treprostinil

latanoprost | MOA

prostaglandin F2 alpha analog

Latanoprost MOA

activates FP receptors inc outflow of aq humour reduces IOP

Uses latanoprost

Glaucoma

SE latanoprost

alters color of iris causing permanent eye color change

Sildenafil Tadalafil Vadernafil MOA

Phosphodiesterase 5 inhibitor -> degrades cGMP to inactive GMP -> vasodilation

Uses of Sildenafil

erectile dysfunction pulmonary arterial hypertension raynaud’s phenomenon

Sildernafil SE

``` headache flushing priapism hearing loss optic neuropathy ```

Sildefil should not be taken with ___ it may lead to fatal hypotension

ISDN ISMN NTG