Medical Pharmacology Chapter 12:  Anxiolytics and Sedative-Hypnotics

• Antihistamines¹

  • Overview:

    • ¹Occasional use for preoperative medication due to sedative and antiemetic characteristics. 

      • For example meperidine (Demerol) + promethazine (Pherergan) produces additive sedation without enhancing the likelihood of nausea/vomiting or respiratory depression.

  • Specific applications:

    • Purpose of premedication -- prevention of intraoperative allergic reactions for those patients who have a history of chronic atopy (predisposition towards hypersensitivity reactions) or who will be undergoing a procedure associated with allergic reaction such as a radiographic studies requiring the use of a dye.

      • For these applications diphenhydramine (Benadryl) [0.5-1 mg/kg orally) may  be combined with H₂ receptor antagonist (blocker).  An example of an H₂ receptor antagonist would be cimetidine (Tagamet) [4-6 mg/kg]. 

      • The combination of an H₁ blocker (diphenhydramine (Benadryl)) and the H₂ antagonist (cimetidine (Tagamet)) reduces the likelihood of physiological responses to endogenous histamine release.

      • An additional agent, a steroid such as prednisone (Deltasone) (50 mg orally every six hours for the 24-hour period preceding the surgical procedure) may be helpful in combination with the above antihistamines.

      • Despite the use of these agents preoperatively, allergic reactions may still occur and may have to be managed intraoperatively

    • Other applications for histamine receptor blockers:  reduction of gastric acid secretion

      • Mechanism: blockade of histamine-receptor mediated gastric acid secretion by selective, competitive inhibition; as a consequence gastric pH increases

      • No reliable effect on gastric  fluid volume or emptying time

      • Probably appropriate as premedication for patients with aspiration pneumonia risk.  Routine use is probably not appropriate.

        • Patient groups probably at increased pulmonary aspiration risk:

          • Parturients

          • Morbidly obese patients

          • Patients with esophageal reflux symptoms

          • "Difficult airway" patients

      • For patients undergoing elective surgery,  costs associated with preventing a single serious pulmonary aspiration complication may preclude routine use of H₂ blockers (this conclusion follows from  the very low likelihood of pulmonary aspiration and and serious morbidity in this patient group)-- also note that these drugs would not be expected to be 100% effective anyway.

      • Several doses are likely more effective for increasing gastric pH compared to single preoperative dose

      • Important reminder: Use of medications, such as H₂ receptor antagonists, to reduce aspiration risk is much less important than proper anesthetic technique which ensures for the correct placement of cuffed tracheal tubes

    • Specific medications:

      • Cimetidine (Tagamet),  reduces acid secretion responses to histamine, caffeine, hypoglycemia, gastrin

        • Route of Administration: oral or parenteral

        • Dosage: 150-300 mg (obese patients may require larger doses)

        • Such administration (oral) 60-90 min preceding surgery increases gastric acid pH to > 2.5 in most patients; however gastric fluid volume is not significantly altered.

          • Recall that in adults: possibly, relatively high-risk of pulmonary complications if aspiration volume when gastric fluid volume is > 25 ml with a pH < 2.5.

        • Concerning neonatal effects:

          • Probably limited since, although cimetidine (Tagamet) crosses placental barrier, studies resolved no difference between use of 30 ml of antacid 1-3 hours prior to the surgery and cimetidine (Tagamet) (300 mg) 1-3 hours before the procedure, with respect to neonatal neurobehavorial scores

        • Duration of action: 3-4 hours

        • Prominent side effect: inhibition of hepatic mixed-function oxidase enzyme system (cytochrome P450 system): consequence-

          • Half-life prolongation for drugs including diazepam (Valium), theophylline, propranolol (Inderal), lidocaine (Xylocaine)

          • Serious cardiovascular side effects may occur following rapid IV administration particularly  in critically ill patients (these effects include arrhythmias, hypotension, and cardiac arrests)

      • Ranitidine (Zantac), six times as potent as cimetadine in inhibiting gastric acid secretion

        • Ranitidine (Zantac) compared to cimetidine (Tagamet):

          • Longer acting

          • Increased relative potency is reflected in a lower dosage range (50-200 mg)

        • Dosage:

          • Oral:  50-200 mg

          • Parenteral: 50-100 mg (gastric fluid pH will increase within about our)

          • Duration of action: may last as long as 9 hr, suggesting that for very long cases premedication with ranitidine (Zantac) may reduce aspiration pneumonia is risk during emergence/tracheal tube extubation

        • Side effects: probably fewer CNS or cardiovascular side effects compared to cimetidine (Tagamet);smaller inhibitory effect on cytochrome P450 system than observed with cimetidine (Tagamet)

      • Famotidine (Pepcid)

        • Generally similar to cimetidine (Tagamet) and ranitidine (Zantac)however with a longer elimination  half-life

        • Dosage: (oral) 40 mg administered 1.5-3 hours preoperatively is likely effective in increasing gastric pH

      • Nizatidine (Axid): similar to the above agents in that 150-300 mg (oral) given about two hours before the procedure will increase preoperative gastric pH.