GI- Histamine/ PUD Flashcards
1
Q
What is histamine?
where is it stored?
when is it released?
A
- a naturally occurring endogenous amine that is synthesized in tissues by decarboxylation of histadine
- Stored in vesicles in mast cells in the skin, lung, and gastric mucosa
- stored in vesicles in circulating basophils
- released in response to antigen-antibody reaction or in response to certain drugs
2
Q
What does histamine do?
A
- Histamine is an inflammatory mediator
- regulated gastric acid secretion
- regulates neurotransmission
- does not easily cross the BBB thus CNS effects are not evident
- effects mediated by H1, H2, & H3 receptors
3
Q
How do histamine antagonists work?
A
- They do not prevent the release of histamine, but instead block the receptor where the histamine binds, blocking the response to histamine
- agents are classified by which receptor the antagonism occurs at
4
Q
What does the H1 receptor do?
Where is the H1 receptro found?
A
- Smooth muscle contraction in lung and GI, vascular endothelium; release of NO, sensory nerve stimulation
- lungs- bronchoconstriction
- vascular smooth muscle- dilation–>hypotension and erythema ***predominant effect of histamine
- vascular endothelium- increased capillary permeability–>edema
- peripheral nerves- sensitization- itching, pain, sneezing
- heart- found in AV node; slows HR by slowing conduction
5
Q
Where is the H2 receptor found?
What is its effect?
A
- Found in gastric parietal cells, cardiac muscle, and mast cells
-
heart- positive inotropic and chronotropic effects–>increase in HR and contractility
- coronary vasculature dilation (offsets constriction of H1)
- relaxes bronchial smooth muscle
-
stomach- Activation cAMP–> activates proton pump of parietal cells to secrete hydrogen ions
- increased gastric acid can lead to PUD, GERD
6
Q
Where is the H3 receptor found?
What does it do?
A
- Located on the heart and presynaptic postganglionic SNS fibers
- stimulation causes inhibition of synthesis and release of histamine
- Some H2 antagonists may affect H3 receptors, which would ultimately cause an increase in histamine release
- Avoid rapid administration of agents known to cause histamine release (ex. atracurium) if pt has been pretreated with an H2 antagonist
- will have greater atracurium induced BP decrease in a pt pretreated with an H2 blocker than a pt pretreated with an H1 blocker
7
Q
What kind of receptors are histamine receptors?
How do H1 and H2 antagonists interact with them?
A
- Seven-transmembrane GCPR
- H1 and H2 antagonists competetively and reversibly inhibit receptros on effector cell membranes
8
Q
What do H1 antagonists treat?
H2 antagonists?
A
- H1 antagonists- allergic rhinitis
- H2 antagonists- inhibit acid gastric fluid secretion
9
Q
How are H1 antagonists classified?
uses?
A
- Classified as first and second generation
- first generation- will also bind to muscarinic, serotonin, and alpha receptors, causing sedation
- second generation- more specific to H1 receptors; non-drowsy, decreases CNS toxicity
- Uses:
- rhinitis
- conjunctivitis
- urticaria
- pruritis
10
Q
First generation H1 antagonist pharmacokinetics?
examples
A
- Pharmacokinetics:
- lipophilic
- neutral at physiologic pH
- examples
- diphenhydramine
- hydroxyzine
- promethazine
- chlorpheniramine
- Doxepin
11
Q
Second generation H1 antagonist pharmacokinetics?
examples?
A
- pharmacokinetics
- Ionized at physiologic pH
- “albumin binding”- not sure what she meant by this, didnt see anything in book
- Examples
- Loratidine
- desloratidine
- acrivastine
- fexofenadine
12
Q
H1 antagonists:
Are they well absorbed?
Concentrtation max?
PB?
metabolization?
E1/2t?
A
- Excellent absorption
- Plasma concentration max in about 2-3 hours
- protein binding 78-99%
- heptaically metabolized by CYP450
- E1/2t is variable
- chlorpheniramine >24 hours
- Acrivastine - 2 hours
13
Q
What are some adverse effects of H1 antagonists?
A
- CNS toxicity- sedative effects
- Cardiac toxicity- QT interval prolongation
- Anticholinergic effects- pupillary dilation, dry eyes, dry mouth, urinary hesitancy
14
Q
Why are H2 antagonists given?
What agents are available?
most potent vs least potent?
A
- Competitive antagonism of H2 receptors used to suppress gastric acid secretion by parietal cells
- Agents:
- The ones we use: Cimetidine, Ranitidine
- must give ahead of time: famotadine
- Nizatidine
- Potency:
- least: Cimetidine
- most: Famotadine
15
Q
What are the clinical uses of H2 antagonists?
Doses
A
- treatment of duodenal ulce disease & GERD
- No effect on pH of fluid already in stomach
- unpredictable effect on volume of fluid present in stomach
- Chemophophylaxis prior to induction of GA
- Cimetidine 300 mg PO or IV 1-2 hours pre-op
- Famotadine 20-40 mg PO/ 20 mg IV am of surgery
- Ranitidine- 150 mg PO or 50 mg IV
19
Q
Cimetidine may slow metabolism of what drugs?
(chart from book)
A
23
Q
PPI pharmacokinetics
absorption
MOA
metabolization
A
- Rapid absorption
- prodrug converted into active drug in parietal cell canaliculus
- forms a covalent bond with Proton pump
- short half life
- Hepatically metabolized by CYP2C19, 3A4
- crosses placenta
25
Q
What is Dicyclomine?
Adverse effects?
A
- An anticholinergic (muscarinic ACh receptor antagonist)
- used to decrease acid secretion
- less effective than H2 antagonist and PPIs
- Adverse effects:
- dry mouth, constipation, blurred vision, cardiac arrhythmia, urinary retention
