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90 Cards in this Set
- Front
- Back
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What are autacoids?
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Endogenous molecules with powerful pharm effects, that don't fall into the traditional ANS groups:
Histamine and Serotonin |
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What are ergot alkaloids?
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Interact with serotonin receptors, dopamine receptors, and Alpha receptors.
They are not autacoids |
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* Disease caused by Excess ergot alkaloids
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St. Anthony's Fire
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* Endogenous substances commonly interpreted as histamine, serotonin, prostaglandins, and vasoactive peptides
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Autocoids
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* Syndrome of hypersecretion of Gastric acid and pepsin usually caused by gastrinoma; it is associated wiht severe peptic ulceration and diarrhea
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Zollinger-Ellison Syndrome
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* Drug that causes contraction of the uterus
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Oxytocin
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Histamine is formed from what amino acid?
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Histidine
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Where is histamine found in high quantities in the body?
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Mast cells
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Histamine is metabolized by what?
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MAO and DAO
Monoamine Oxidase Diamine Oxidase |
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How can you detect the levels of histamine in the body?
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Imidazoleacetic acid levels in the urine
(Histamine's main metabolite) |
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What stimulates the release of Histamine from mas cells?
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IgE-mediated allergic reactions
Type I |
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H1 Receptor MOA and effects
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Gq
IP3 & DAG - BronchoCONSTRICTION - VasoDILATION - via NO - Local EDEMA - Capillary endothelial cells contract and Increase permeability. |
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H2 Receptor MOA and effects
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Gs
Stim. Adenylyl cyclase, Increase cAMP - Mediates Gastric acid secretion in parietal cells - Cario-stimulatory effect - Causes negative feedback of Histamine release from mast cells |
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* Distribution of histamine receptors, H1, H2, and H3
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- Smooth muscle
- Stomach, heart, and mast cells - Nerve Endings, CNS Respectively |
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What is Histamine used for clinically?
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Histamine has not therapeutic effects. We usu. want to block Histamine release for clinical uses.
H1 and H2 receptors are usu the targets. No blockers of H3 & 4 receptors exist. |
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* Prototype H1 receptor antagonist
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Diphenhydramine
Gq, IP3, DAG |
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* Prototype H2 receptor antagonist
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Cimetidine
Gs, + cAMP |
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* Older 1st generation antihistamine that is highly sedating
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Diphenhydramine
(H1 blocker) |
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* Newer 1st generation antihistamine that is least sedating
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Chlorpheniramine and cyclizine
(H1 blockers) |
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* 2nd generation antihistamines
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Fexofenadine, loratidine, and cetirizine
(H1 blockers) |
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* Generation of antihistamines that has the most CNS effects
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First generation due to being more lipid-soluble
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MOA of H1 blockers
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Competetive antagonists
No effect on Histamine release from storage sites. More effective if given before histamine release occurs |
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H1 blockers closely resemble what
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Muscarinic blockers and Alpha adrenoceptor blockers - so block ANS sites
Some block serotonin receptors too. |
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Main effects of H1 blockers
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- Sedation
- Anti-motion sickness effects (Some) - Potent local anesthetics Side effects: dry mouth and blurred vision |
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* Major indication for H1 receptor antagonist
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Immediate-type (Type 1), IgE mediated allergic reaction
Hay Fever & Urticaria |
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*Which H1 blockers are used for motion sickness?
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diphenhydramine
*dimenhydrinate cyclizine *meclizine promethazine |
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Which H1 blocker is used for management of chemo-induced vomiting
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diphenhydramine
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* Most common side effect of 1st gen. antihistamines
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Sedation
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* Antihistamine that can be used for anxiety and insomnia and is not addictive
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hydroxyzine (Atarax)
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Which antihistamine would you see orthostatic hypotension with?
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Promethazine
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* Azole antifungals and other CYP3A4 inhibitors, taken with which antihistamines, will cause Lethal arrhythmias
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Terfenadine & astemizole
( Have been removed from the market ) |
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What are the 4 H2 blockers out there?
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Cimetidine (PROTOTYPE)
Ranitidine Famotidine Nizatidine Think -tidine, except Loratidine - which is a 2nd gen. H1 blocker |
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* H2 blocker that causes the mos tinteractions wtih other drugs
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Cimetidine
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* Clinical use for H2 blockers
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Acid reflux, duodenal ulcer and peptic ulcer disease
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i.v. H2 blockers are useful in preventing gastric erosions in what patients?
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Stressed patients in ICU
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H2 blockers used in Zollinger-Ellison and GERD are not as effective as..
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Proton pump inhibitors
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What symptoms might an older H1 blocker like promethazine cause?
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Orthostatic hypotension
Acute angle closure glaucoma (antimuscarinic action M3) Urinary retention in old man |
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What are the side effects of Cimetidine?
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- Antiandrogen effects
- Reduces blood flow to liver, and reduces liver metabolism of drugs |
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What amino acid is Serotonin made from?
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Tryptophan
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Where is Serotonin stored in the body?
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Vesicles in the enterochromaffin cells of the GUT, and neurons of CNS, and ENS, also in PLATELETS
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How is Serotonin metabolized?
What is its main metabolite? |
Metabolized by MAO
Metabolite = 5-HIAA, used to measure excess serotonin production |
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What condition causes excess serotonin production?
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Carcinoid syndrome
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Where do most Serotonin AGONISTS act?
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5-HT 1D receptors
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Where do most Serotonin ANTAGONISTS act?
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5-HT 2 & 5-HT 3 receptors
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* Receptors for Serotonin (5HT-1) are located
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Mostly in the brain, and they mediate synaptic inhibition via increased K+ conductance
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5HT-1 receptors MOA
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Gi
Decreased cAMP |
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5-HT 2 receptors MOA
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Gq
IP3, DAG Decrease K+ conductance Decreased cAMP |
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Where are 5-HT 3 receptors mostly found?
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Area postrema, chemoreceptive area and vomiting center
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5-HT 3 receptors MOA
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Ligand - gated cation channel
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Clinical applications of serotonin
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none
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Prototype 5-HT 1d agonist
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Sumatriptan
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* 5-HT 1d agonists used for migranes and cluster headaches
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Sumatriptan, naratriptan and rizatriptan
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* Triptan available in parenteral and nasal formulation
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Sumatriptan
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* H1 blocker that is also a serotonin antagonist of 5HT2
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Cyproheptadine
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5-HT 2 Blockers
Prototype? |
KETANSERIN - prototype
phenoxybenzamine cyproheptadine |
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5-HT 3 Blockers
Prototype? |
ODANSETRON - prototype
granisetron dolasetron alosetron |
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MOA's of ketanserin & cyproheptadine
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Competetive antagonists of 5-HT 2
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MOA of phenoxybemzamine
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Irreversible blocker of 5-HT 2
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What effects are seen with carcinoid tumor?
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Diarrhea, bronchoconstriction, flushing
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* Agents used in the treatment of Carcinoid tumor
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Ketanserin
Cyproheptadine Phenoxybenzamine |
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* 5-HT 3 antagonist used in chemotherapeutic induced emesis
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Ondansetron
granisetron dolasetron alosetron |
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What is alostron used for
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5-HT 3 antagonist
Women w/irritable bowel syndrome associated with diarrhea |
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Adverse effects of ketanserin
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alpha blocker and H1 blocker effects
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* 5-HT 3 antagonist that has been associated with QRS and QTc prolongation and should not be used in pt's with HEART DISEASE
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Dolasetron
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* DOC to treat chemo-induced nausea and vomiting
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Odansetron
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* Disease causedby excess ergot alkaloids
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St. Anthony's Fire
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* Agents used for reduction of postpartum bleeding
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Oxytocin, ergonovine, ergotamine
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* Drug used in ergot alkaloids overdose, ischemia and gangrene
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Nitroprusside
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Ergot alkaloids are produced from fungus found in
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Wet or spoiled grain
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What are the main actions of Ergot alkaloids?
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Partial agonists of alpha adrenoceptors and 5-HT receptors (serotonin)
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Prototype ergot alkaloid that acts on UTERUS.
Main ergot effect on vessels |
ERGOTAMINE
VasoCONSTRICTION alpha adrenergic mediated |
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Prototype ergot that acts on UTERUS
Main effect on uterus |
ERGONOVINE
Produce powerful uterine contraction ESP. near term. |
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Prototypical semisynthetic ergot in the BRAIN
Main effect on the brain, and via which receptors? |
LSD
Hallucinations via Dopamine receptors (D2) |
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How does LSD act peripherally?
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its a potent 5-HT 2 blocker
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Effect of ergots on pituitary
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potent Dopamine agonists, so inhibit prolactin secretion
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* Reason ergot alkaloids are contraindicated in pregnancy
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Uterine contractions
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*SE of ergot alkaloids
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Hallucinations resembling psychosis
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* Ergot alkaloid used as an illicit drug
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LSD
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* Dopamine agonist used in hyperprolactinemia
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Bromocriptine
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* Peptide causing increased capillary permeability and edema
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Bradykinin & Histamine
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Ergot used as mainstay tx for acute attacks of migraine
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Ergotamine
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These two ergot's are used to treat Parkinson's disease
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Bromocriptine and Pergolide
Dopamine agonists |
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Ergot side effects, again
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> Ischemia and gangrene (tx'd with nitroprusside)
> Hyperplasia of CT --> hydronephrosis or cardio valve problems, and conduction problems > GI upset > Uterine Contractions > Hallucinations |
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What can reverse the effects of increased histamine on smooth muscle?
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Epinephrine - has a physiological antagonist action that reverses histamine's effects on SMOOTH MUSCLE
EPI-PEN. |
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(T/F) Many histamine blockers have general anesthetic effects.
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False: Many H1 blockers have LOCAL anesthetic effects.
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Review
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H1 = Gq: DAG, IP3 (smooth m.)
H2 = Gs: +cAMP (Stomach, Heart, Mast cells) |
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(T/F) LSD is found in spoiled grain
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Nope, its synthetic.
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(T/F) Ranitidine is associated with antiandrogenic effects in some pts.
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False: Cimetidine does
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Review:
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All available H2 blockers have approx. equal EFFICACY, but different POTENCY.
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Review: What are the following each used for?
1. Alosetron 2. Cetirizine 3. Ergonovine 4. Ondansetron 5. Ranitidine |
1. Irritable bowel syndrome
2. Hay fever 3. Uterine bleeding 4. Chemo-induced emesis 5. Peptic Ulcer |
