Diphenhydramine causing

Diphenhydramine causes heavy sedation Terfenadine causes no sedation FIGURE 3.2 Terfenadine does not have sedative effects. 

In 15 healthy men tolerance to diphenhydramine developed rapidly in a randomized, placebo-controUed, crossover study (9). Diphenhydramine 50 mg or placebo was given twice a day for 4 days and tests of objective and subjective sleepiness together with computer-based tests of psychomotor performance were carried out. Compared with placebo on day 1, diphenhydramine caused significant impairment. However, by day 4 sleepiness and impairment of performance were indistinguishable from placebo. 

The answer is e. (Hardmanr p 930.) All the drugs listed in the question are used as antiemetics. Chlorpromazine is a general antiemetic, used orally, rectally, or by injection for the control of nausea and vomiting that is caused by conditions that are not necessarily defined. Ondansetron is indicated in the oral or intravenous route for the prevention of nausea and vomiting caused by cancer chemotherapy Diphenhydramine and dimen-hydrinate are used orally for the active and prophylactic treatment of motion sickness. Scopolamine is a transdermal preparation used in the prevention of motion sickness. The drug is incorporated into a bandage-like... 

Detailed kinetics investigations have shown that the reaction follows pseudo-first-order kinetics. A linear relationship exists between pH and log k (the log of the rate constant), such that log k decreases by 1.7 (i.e., tm increases by a factor of ca. 50) with each increase of one pH unit. For example, the tu2 value of diphenhydramine (11.24, R = R = H, Fig. 11.2) and orphenadrine (11.24, R = 2-Me, R = H) at pH 0 and 25° were found to be 550 and 460 min, respectively, from which f1/2 values of ca. 460 and 360 h could be calculated for pH 1. Each increase of 10° in temperature led to a decrease in the f/2 value of 3 - 4 h. Hence the tV2 value of diphenhydramine and orphenadrine in the stomach at 37°, assuming pH 1 and neglecting any effect caused by ionic strength, should be ca. 4 d. This is clearly too slow for any significant nonenzymatic formation of benzhydrol in the body (see below). 

With long-term use, the most problematic side effect is weight gain. However, many antihistamines including diphenhydramine also possess potent anticholinergic effects. This can cause dry mouth, blurred vision, constipation, confusion, and urinary retention. Because anticholinergic effects are especially problematic for the elderly, we advise against the routine use of antihistamines to treat elderly patients with insomnia. 

Pharmacokinetics Dimenhydrinate has a depressant action on hyperstimulated labyrinthine function. The precise mode of action is not known. The antiemetic effects are believed to be caused by the diphenhydramine, an antihistamine also used as an antiemetic agent. 

Extrapyramidal symptoms Extrapyramidal symptoms, manifested primarily as acute dystonic reactions, occur in approximately 0.2% to 1% of patients treated with the usual adult dosages of 30 to 40 mg/day. These usually are seen during the first 24 to 48 hours of treatment, occur more frequently in children and young adults, and are even more frequent at the higher doses used in prophylaxis of vomiting caused by cancer chemotherapy. If symptoms occur, they usually subside following 50 mg diphenhydramine IM. Benztropine 1 to 2 mg IM may also be used to reverse these reactions. 

Geriatric Considerations - Summary Diphenhydramine is a first-generation etha-nolamine antihistamine with potent Hj-receptor antagonism. It also has significant anticholinergric properties and causes somnolence at normal doses. Older adults taking this drug are at risk of dizziness and hypotension and diphenhydramine would... 

Diphenhydramine (Benadryl) May cause confusion and sedation. Should not be used as a hypnotic, and when used to treat emergency allergic reactions, it should be used in the smallest possible dose. High... 

A large number of prescription and nonprescription drugs, as well as a variety of plants and mushrooms, can inhibit the effects of acetylcholine at muscarinic receptors. Some drugs used for other purposes (eg, antihistamines) also have anticholinergic effects. Many of them have other potentially toxic actions. For example, antihistamines such as diphenhydramine can cause seizures tricyclic antidepressants, which have anticholinergic, quinidine-like, and a-blocking effects, can cause severe cardiovascular toxicity. 

Metoclopramide can cause adverse effects such as sedation, akathisia (motor restlessness), involuntary movements, diarrhea, and dizziness. The extrapyramidal reactions, which are more common in patients < 30 years old, can be relieved by intravenous or oral diphenhydramine or benztropine (Cogentin). 

Seizures, muscular hyperactivity, and rigidity may result in death. Seizures may cause pulmonary aspiration, hypoxia, and brain damage. Hyperthermia may result from sustained muscular hyperactivity and can lead to muscle breakdown and myoglobinuria, renal failure, lactic acidosis, and hyperkalemia. Drugs and poisons that often cause seizures include antidepressants, theophylline, isoniazid (INH), diphenhydramine, antipsychotics, cocaine, and amphetamines. 

Antihistamines are the most frequently used agents in the treatment of sneezing and watery rhinorrhea associated with allergic rhinitis. -Histamine receptor blockers, such as diphenhydramine, chlorpheniramine, loratadine, terfenadine and astemizole (see p. 422), are useful in treating the symptoms of allergic rhinitis caused by histamine release. Combinations of antihistamines with decongestants (see below) are effective when congestion is a feature of rhinitis. They differ in their ability to cause sedation, and their duration of action. 

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