Antihistamines Flashcards
What are the different types of antihistamines that have antiemetic properties?
- Promethazine (Phenergan)
- Dimenhydrinate (Dramamine)
- Meclizine (Antivert)
- Diphenhydramine (Benadryl)
What does histamine evoke?
GI smooth muscle contraction via H1 receptors and inositol phospholipid hydrolysis
Define Histamine inositol phospholipid hydrolysis.
Inositol phospholipid hydrolysis has been implicated in the mobilization of cytosolic calcium following receptor activation in several neurotransmitter and hormonal systems
Where are histamine receptors present?
Histamine receptors present in the CTZ (area postrema) and vomiting center (nucleus of the tractus solitarius)
What are some Nonspecific antihistamines used as antiemetics?
diphenhydramine, dimenhydrinate, meclizine, promethazine
What are the sit of action of many H1 receptor antagonists?
have anticholinergic effects & block muscarinic receptors in the vestibular system
What is Dimenhydrinate (Dramamine)?
used to treat motion sickness and decrease incidence of N&V with children after strabismus surgery (0.5 mg/kg IV)
What is Diphenhydramine (Benadryl) used for?
used in PONV mgmt.
What are the most side effects of antihistamines?
anticholinergic effects (dry mouth, somnolence)
What are examples of Neurokinin-1 Antagonists?
- Aprepitant
- Fosaprepitant
Define neurokinin-1.
is a centrally & peripherally expressed G-protein-coupled receptor, primary ligand: substance P
Where is neurokinin-1 expression?
Neurokinin-1 expression in nucleus tractus solitarius & area postrema: vomiting center and CTZ
What is the availablity of Aprepitant?
Aprepitant available only as an oral capsule; dose – 40mg within 3 hours of induction of anesthesia for PONV prophylaxis
What is the recommendation for Aprepitant & Fosaprepitant?
- Expensive
- recommended only for high-risk PONV patients for whom vomiting would compromise surgical repair
What is the metabolism of Aprepitant & Fosaprepitant?
Metabolized by P450 CYP3A4 enzyme
What are Antacids & GI Motility Drugs used to prevent?
Used for prevention of aspiration
Define aspiration.
inhalation of gastric or oropharyngeal contents into the lungs
What does aspiration increase?
increases risk of ICU admission, longer hospital length of stay, and increased mortality
What do Antacids & GI Motility Drugs control?
Antacids & GI motility drugs control the volume and acidity of gastric contents
What is the MOA of Oral Antacids?
Medications that neutralize H+ ions from gastric contents or ↓ secretion of HCL into the stomach
What are the components of oral antacids?
Oral antacids are salts of Al, Mg++, Ca++; hydrogen ions in the stomach react with the base; as hydrogen ions are consumed, the pH of stomach contents increase
What antacids are preferred?
Nonparticulate antacids such as sodium citrate (Bicitra) preferred
Why is sodium citrate preferred?
- Less likely to induce foreign body reaction in the lungs if aspirated
- Mixing with gastric fluid (neutralizes) more complete & rapid than particulate antacids
What is the dose of sodium citrate?
15-30 ml 15-30 minutes before induction effective in increasing gastric fluid pH
What is the contraindication of sodium citrate?
Contraindicated in patients with renal impairment
What does histamine cause?
Histamine causes contraction of smooth muscles in airways, ↑ secretion of stomach acids, ↑ CNS neurotransmitter release
How are Histamine-receptor Antagonists classified?
H1 to H4 receptors identified – drugs classified as H1 to H4 receptor antagonists
What do histamine antagonists bind to?
Histamine antagonists bind to receptors on effector cell membrane; these drugs don’t inhibit release of histamine but rather bind to receptors to prevent histamine mediated responses
Which Histamine-receptor Antagonists are important in anesthesia?
H1 & H2 receptors
What is the components of 1st generation histamine-1 antagonists?
produce sedation/impaired cognition and may activate other receptors (i.e., anticholinergic - dry mouth, blurred vision, urinary retention, tachycardia)
What is the components of 2nd generation histamine-1 antagonists?
more selective for H1 receptor
What is examples of 2nd generation histamine-1 antagonists?
cetirizine, fexofenadine, loratadine, azelastine
What is the toxicity of 2nd generation histamine-1 antagonists?
Less CNS toxicity (less sedation & less impaired cognition)
What are the clinical uses of Histamine Receptor Antagonists?
Clinical uses (urticaria, allergic rhinoconjunctivitis, antipruritic, antiemetic, sedative)
Where are histamine receptors rich?
Myocardium and coronary vasculature rich with histamine receptors
Myocardium and coronary vasculature prone to the effects of _________
histamine release
What can H1 and H2 blockers be used with?
Use of H1 and H2 blockers with epinephrine used for anaphylactic reactions
What is the use of H1 and H2 blockers with corticosteroids?
Use of H1 and H2 blockers with corticosteroid used preemptively in patients with increased likelihood of allergic reactions such as with radiographic contrast dye
What are examples of H2- Receptor Antagonists?
cimetidine, ranitidine, famotidine, & nizatidine
What do H2- Receptor Antagonists inhibit?
Inhibit selective H2 mediated secretion of hydrogen ions by parietal cells in the stomach
What is the MOA of H2- Receptor Antagonists?
Histamine released from mast cells activates cAMP within gastric parietal cells which ↑ H+ ion secretion
What is the most potent H2- Receptor Antagonists?
Famotidine
What is the least potent H2- Receptor Antagonists?
cimetidine
What is the elimination of H2- Receptor Antagonists? What disease effects this?
- hepatic & renal
- renal failure increases elim half-life (decreased doses recommended in patients w/renal dysfunction)
What does cimetidine interfere with?
interferes w/drug metabolism by CYP450 enzymes
What are the clinical uses of H2- Receptor Antagonists?
- Duodenal ulcer disease asso/w hypersecretion of gastric H+ ions
- Used to increase pH of gastric fluid before induction of anesthesia
- Routine use as a preop chemoprophylaxis to ↑ gastric pH not recommended
What is not influenced by H2- Receptor Antagonists?
No influence on pH of gastric fluid already in the stomach
What can H2- Receptor Antagonists reduce the risk of? What medications are more likely (2)?
May be used to reduce risk of acid pneumonitis if aspiration were to occur in perioperative period (cimetidine or famotidine)
What can H1 and H2 antagonists be used preoperative for?
Preoperative preparation of patients w/allergic histories or likelihood of allergic reactions (radiographic contrast dye administration) may include prophylactic pretreatment with an H1 and H2 antagonist
What is true about the sie effects of H2- Receptor Antagonists?
Overall, frequency of side effects low
When are side effects at increased risk of occuring with H2- Receptor Antagonists?
Increased risk for adverse side effects w/hepatic or renal dysfunction, advanced age
What EKG effects are associated with H2- Receptor Antagonists?
- Cardiac arrhythmias (sinus brady, sinus arrest, idioventricular escape rhythm, complete heart block) have occurred after chronic oral or IV administration
- Prolonged QTc interval & cardiac arrest w/famotidine has been reported
What hemodynamic effects can occur with H2- Receptor Antagonists?
Bradycardia & hypotension asso/w rapid IV administration (critically ill or older patients)
What is the administration of H2- Receptor Antagonists?
Administer IV over 15-30 minutes
Which H2- Receptor Antagonists is most implicated in numerous drug interactions?
Cimetidine
What is the characteristics of cimetidine drug interactions?
Binds to heme portion of P450 oxidase system
What can H2 blockers interfere with?
H2 blockers can interfere with the gastric absorption and renal excretion of certain drugs
What are examples of proton pump inhibitors?
- Omeprazole
- Esomeprazole
- Lansoprazole
- Pantoprazole
- Rabeprazole
What is the most effect drugs for available for controlling gastric acidty & volume?
Proton Pump Inhibitors (PPIs)
What is the MOA of Proton Pump Inhibitors (PPIs)?
The proton pump (hydrogen-potassium-ATPase) moves hydrogen ions across the gastric parietal cell membranes in exchange for potassium ions
What do PPIs control?
PPIs control gastric acidity and volume by irreversibly blocking the proton pump which reduces gastric HCl acid secretion
What are other clinical uses of Proton Pump Inhibitors (PPIs)?
PPIs are more effective than H2 antagonists in healing esophagitis & relieving heartburn
What is the effect of Omeprazole (Prilosec)?
Effectively increases gastric pH & decreases gastric fluid volume
What is the dse of Omeprazole (Prilosec)?
Oral dose (20 mg) should be administered > 3 hrs before induction of anesthesia to raise gastric pH in patients for whom chemoprophylaxis is desired
What are side effects of Omeprazole (Prilosec)?
Can cause headaches, agitation, confusion, GI side effects
