Name the two types of cells that secrete histamine. Where are these cells located?
Mast cells - skin, lungs & Gi tract
Basophils - circulation
What are the effects of histamine on the H1 versus the H2 receptor?
H1: Allergy
- smooth muscle contraction in respiratory and GI systems - pruritus & sneezing
- NO release -> peripheral vasodilation
- Dec. AV node conduction -> bradycardia; coronary vasoconstriction
H2: GI
- stimulate gastric H+ secretion
- increased myocardial contractility and HR
- coronary vasodilation
What is the effect of histamine at the H3 receptor?
Negative Feedback. It inhibits histamine synthesis/release. May have an overlap with H2 receptor
What happens if a patient gets an H2 blocker that also blocks the H3 receptor?
they will synthesize excess histamine. this is dangerous if the pt also gets a drug that evokes histamine release
What are the CV effects of histamine release?
- flushing
- hTN
- decreased SVR
- capillary permeability- > edema **
- pos chronotropic and inotropic effects
- possible dysrhythmias
What are symptoms of histamine antagonist toxicity?
Looks like anticholinergic poisoning, seizures, cardiac dysrhythmias
Anticholinergic effects= SLUDGE inhibitor like atropine (tachy,dry,blurred vision,urinary retention)
What is the difference in first and second generation H1 antagonists?
1st gen = crosses the BBB => sedating, cognitive impairment, somnolence, sig. anticholinergic effects (SLUGE inhibitor like atropine)
2nd gen = non-sedating, do not cross BBB, minimal effects at muscarinic, cholinergic, and serotonin receptors
Identify the following as 1st or 2nd gen H1 bocker:
Alegra
Benadryl
Claritin
Benedryl - 1st gen
Aelgra and Claritin - 2nd gen
What is Ranitidine (Zantac)?
H2 antagonist - inhibits gastric H+ secretion, decreased gastric volume has been shown as well
dosing = 50mg IV
What is Famotidine (Pepcid)?
H2 antagonist - inhibits gastric H+ secretion, decreased gastric volume has been shown as well
dosing = 20mg IV
What is the mechanism of action of Omeprazole (pilosec) ?
Proton pump inhibitor
True or false..Antacids increases pH and decreases gastric volume.
False. They neutralize GI acid content but have no effect on gastric volume
How does giving bicitra lower mortality associated with acid pneumonitis?
increases the pH and decreases the volume of the aspirate
In which patients is reglan contraindicated in and why?
Parkinson’s disease patients - it is a dopamine antagonist and can worsen symptoms an produce dystonic extrapyramidal side effects and akathesalso avoid in pts with seizures, MAOIs, TCAs
What receptor does zofran work at?
5HT3
What are the two uses for Droperidol and Haloperidol (Butyrophenones)?
anti-psychotics and anti-emetics
What is benedryl’s anti-emetic mechanis of action?
suppresses neuronal firing + anti-muscarinic+ sedative effects = effective for motion sickenss
What are the side effects of phenergan?
- sedation
- extrapyramidal symptoms (akathesia, dystonia)
- vascular necrosis - must be given IM or IV infusion
What is the mechanism of action of reglan?
Pro-kinetic: Binds to or sensitizes cholinergic (muscarinic) receptors in GI system and stimulates upper GI motility -> accelerated clearance which decreases gastic volume
Anti-emetic: Central D2 receptor antagonist
Dopamine antagonist, but dopamine inhibition is NOT primary mechanism of action - May partially explain anti-emetic effect – binding D2 receptors in the CTZ
What are the side effects of scapolamine?
blurred vision, dry mouth, dizziness, agitation
Antacids should be used with caution in what group of patients? Why?
Renal patients bc they are usually Mg, Al, or Ca salts
What magnesium hydroxide (“Milk of Magnesia”), what is it taken for and what does it cause?
it is taken for constipation bc it causes osmotic diarrhea (Mg=Must Go)
it is an antacid - neutralizes GI acid content (no effect on gastric volume)
What is aluminum hydroxide, what is it used for and what could it cause?
Also called Mylanta - is an antacid that is used for heartburn, sour stomach, peptic ulcer pain…some risk of constipation
True or false..Metoclopramide increases pH and decreases gastric volume.
False. It stimulates upper GI motility and decreases gastric volume by accelerating clearance. It has no reliable effects on gastric acid pH. It binds to or sensitizes cholinergic (muscarinic) receptors in GI system
What are the two uses for Droperidol and Haloperidol?
anti-psychotics and anti-emetics
What is promethazine (phenergan)? What is its mechanism of action?
- antiemetic
- blocks D2 receptor in CTZ & other parts of CNS
- also has sig anti-histamine and anticholinergic activity
What is the mechanism of action of scapolamine?
antagonize M1 receptors in cerebral cortex, pons; also block H1 receptor in hypothalamus, vomiting center
T or F. H1 antagonists are very selective and have vey little H2 activity.
TRUE
What is used to block histamine-mediated vasodilation during anaphylactic rxns?
Diphenhydramine (Benedryl) - a 1st generation H1 blocker
What is Hydoxyzine (Vistaril)?
A first generation H1 blocker
- used for sedation/anxiety, motion sickness, vertigo, N/V
- has significant anticholinergic effects
What does an H2 antagonist do?
inhibits gastric H ion secretion - decreased gastric volume has been shown as well
T or F. H2 antagonists have a duration of action of 6-10 hours that is followed by rebound hyper-secretion of gastric acid
TRUE
Which of the following H2 antagonists bind to P-450?
a. Ranitidine (Zantac)
b. Cimetidine (Tagamet)
c. Famotidine (Pepcid)
b. Cimetidine (Tagamet)
What are the side effects of H2 antagonists?
diarrhea, fatigue, HA
rare: cardiac dysrhythmias, mental status changes
What drug is characterized by the following:
- non-particulate antacid
- used often in OB and other “full stomach” cases
- unpleasant flavor (liquid)
Sodium citrate + citric acid (Bicitra)
What are the advantages of non-particulate antacids?
- Lowers mortality associated with aspiration of gastric contents (acid pneumonitis) b/c it
- increases pH
- volume decreases - decreased likelihood of foreign body reactions, faster onset of action
What could happen with rapid administration of Reglan?
cramping
T or F. Reglan increases lower esophageal tone
True. It is also used to treat diabetic gastroparesis and increase gastric emptying
Erythromycin is an antibiotic that many claim upsets their stomach. Why does this occur?
It works much the same way Reglan does. It increases lower esophageal sphincter tone and promotes GI motility
It is also used to treat diabetic gastroparesis and increase gastric emptying (like reglan)
What drug is characterized by the following:
would be first choice for PONV prophylaxis if it was not for its “Black Box” warning
Droperidol
What drug is characterized by the following:
“Black Box” warning: risk of torsades de pointes in pts with QT prolongation
Droperidol
What drug is characterized by the following:
due to risk of vascular necrosis, it must now be given IM or else as an IV infusion
Promethazine (Phenergan)
What drug does Dr. Volts like to give to pts with blood in their stomach (tonsillectomy, ENT stuff etc)?
Reglan
What 2 antiemetics can cause extrapyramidal symptoms?
Reglan and Phenergan
What are side effects of Reglan?
- hypoTN
- tachycardia
- dyskinetic/extrapyramidal symtoms at high doses
(tx w/ benzos and antihistamines)
T or F. Ephedrine has anti-emetic properties.
good evidence is lacking but n/v results from hTN so it may help by inc BP
What are some other antiemetic treatments?
- supplemental O2
- hydration
- inhaled isopropyl alcohol
- ginger
- P6 (wrist) acupressure
- TENS (transcutaneous electrical nerve stimulation)
Name the 2 receptors at the vestibular center that are involved in PONV.
H1, M1
Name the 5 receptors in the CTZ that are involved in PONV.
D2, M1, H1, 5-HT3, & NK1
What 5 things lead to PONV and must be ruled out?
- hTN
- hypoxia
- hypoglycemia
- increased ICP
- gastric bleeding
Name the 3 receptors of the afferent nerves of the periphery (vagal and glossophayngeal nerves, GI tract nerves, and pharyngeal nerves) that are involved in PONV.
5-HT3, D2, NK1
What are the respiratory effects of histamine release?
- bronchoconstriction, esp in pts with asthma/ COPD
- inc prod of nasal/bronchial mucus
What are the GI effects of histamine release?
- constriction of intest. smooth muscle
- inc bowel peristalsis and diarrhea
- inc gastric volume and acidity
T or F. H1 antagonists are not very selective and as a result, have significant H2 action as well.
False. They are very selective and have little H2 action
Due to its binding to many isozymes of cytochrome P-450, _____ has numerous drug interactions and increases plasma levels of warfarin, theophylline, phenytoin, meperidine, nifedipine, and lidocaine.
Cimetidine (Tagamet)
What is the mechanism of action of Pantoprazole (protinix)?
Proton Pump Inhibitor
List the 4 most common PPIs and explain how they work.
Prilosec, Nexium, Prevacid, Protonix
Inhibit the pump that transfers protons across gastric parietal cell membrane
What is Dexamethasone’s dose mechanism of action for PONV prophylaxis?
Mechanism unclear: acts in CNS, likely in medulla
Dose: 4-5 mg IV at induction of anesthesia (efficacy = 4 mg ondansetron). One dose only.
