Phenothiazines Anticholinergics

Amantadine is used cautiously in patients with seizure disorders, psychiatric problems, renal impairment, and cardiac disease. Amantadine is a Pregnancy Category B drug and is used cautiously during pregnancy and lactation. Concurrent use of antihistamines, phenothiazines, tricyclic antidepressants, disopyramide, and quinidine may increase the anticholinergic effects (dry mouth, blurred vision, constipation) of amantadine... 

Administration of atropine with meperidine (Demerol), flurazepam (Dalmane), diphenhydramine (Benadryl), phenothiazines, and the tricyclic antidepressants may increase the effects of atropine. There is a decreased effectiveness of haloperidol when administered with the anticholinergic dragp. 

The answer is a. (Katzung, pp 471, 473, 482.) The phenothiazines as a class are the most potent anticholinergics of the neuroleptics. Tolerance to their anticholinergic effects occurs in most patients Cholinomimetic agents may be used to overcome symptoms that persist. 

Closed-angle glaucoma Topical anticholinergics Topical sympathomimetics Systemic anticholinergics Heterocyclic antidepressants Low-potency phenothiazines Antihistamines Ipratropium... 

Phenothiazines with fewer anticholinergic effects can be substituted in some patients it erectile dysfunction is a problem. 

Antagonists. Most of the so-called Hi-antihistamines also block other receptors, including M-cholinoceptors and D-receptors. Hi-antihistamines are used for the symptomatic relief of allergies (e.g., bamipine, chlorpheniramine, clemastine, dimethindene, mebhydroline pheniramine) as antiemetics (meclizine, dimenhydrinate, p. 330), as over-the-counter hypnotics (e.g., diphenhydramine, p. 222). Promethazine represents the transition to the neuroleptic phenothiazines (p. 236). Unwanted effects of most Hi-antihistamines are lassitude (impaired driving skills) and atropine-like reactions (e.g., dry mouth, constipation). At the usual therapeutic doses, astemizole, cetrizine, fexofenadine, and loratidine are practically devoid of sedative and anticholinergic effects. Hj-antihistamines (cimetidine, ranitidine, famotidine, nizatidine) inhibit gastric acid secretion, and thus are useful in the treatment of peptic ulcers. 

Drugs that interact with oxybutynin include atenolol, digoxin, haloperidol, phenothiazines, amantadine, and anticholinergic agents. 

Drugs that may affect maprotiline include thyroid hormones, benzodiazepines, and phenothiazines. Drugs that may be affected by maprotiline include anticholinergics. 

Concomitant conditions Use with caution in the following patients exposed to extreme heat or phosphorus insecticides atropine or related drugs because of additive anticholinergic effects those in a state of alcohol withdrawal those with dermatoses or other allergic reactions to phenothiazine derivatives because of the possibility of cross-sensitivity those who have exhibited idiosyncrasy to other centrally acting drugs. 

Drugs that may affect phenothiazines include anticholinergics, beta-blockers, meperidine, paroxetine, ritonavir, and thiazide diuretics. 

Drugs that may interact with Gl anticholinergics include amantadine, atenolol, digoxin, phenothiazines, and tricyclic antidepressants. 

Uses Allergic Rxns itching Action Phenothiazine antihistamine serotonin antagonist Dose Adults. 4-20 mg PO qSh max 0.5 mg/kg/d Feds. 2-6 y 2 mg bid-tid (max 12 mg/24 h) 7-14 y 4 mg bid-tid in hepatic impair Caution [B, ] BPH Contra Neonates or <2 y NAG BOO acute asthma GI obst Disp Tabs, syrup SE Anticholinergic, drowsiness Interactions T Effects Wf CNS depressants, MAOIs, EtOH X effects OF epi, fluoxetine EMS Use other CNS depressants w/ caution concurrent EtOH use can T CNS depression higher epi doses may be needed if used OD May cause mood changes, Szs, CNS depression, or CNS stimulation symptomatic and supportive... 

Hyoscyamine (Anaspaz, Cystospaz, Levsin, Others) [Antispasmodic/Anticholinergic] Uses Spasm w/ GI bladder disorders Action Anticholinergic Dose Adults. 0.125-0.25 mg (1-2 tabs) SL/PO tid-qid, ac hs 1 SR cap ql2h Caution [C, +] T Effects w/ amantadine, antihistamines, antimuscarinics, haloperidol, phenothiazines, TCA, MAOI Contra BOO, GI obst, NAG, MyG, paralytic ileus, ulcerative colitis, MI Disp Caps, tabs SE Dry skin, xerostomia, constipation, anticholinergic SE, heat prostration w/ hot weather Interactions T Effects W/ amantadine, antimuscarinics, haloperidol, phenothiazines,... 

Imipramine (Tofranil) [Antidepressant/TCA] WARNING Close observation for suicidal thinking or unusual changes in behavior Uses Depres-sion, enuresis, panic attack, chronic pain Action TCA t CNS synaptic serotonin or norepinephrine Dose Adults. Hospitalized Initial 100 mg/24 h PO in doses T over several wk 300 mg/d max Output Maint 50-150 mg PO hs, 300 mg/24 h max Peds. Antidepressant 1.5-5 mg/kg/24 h daUy-qid Enuresis >6 y 10-25 mg PO qhs T by 10-25 mg at 1-2-wk int vals (max 50 mg for 6-12 y, 75 mg for >12 y) Rx for 2-3 mo, then tap Caution [D, /-] Contra Use w/ MAOIs, NAG, acute recovery from MI, PRG, CHF, angina, CVD, arrhythmias Disp Tabs, caps SE CV Sxs, dizziness, xerostomia, discolored urine Interactions t Effects W/ amiodarone, anticholinergics, BBs, cimetidine, diltiazem, Li, OCPs, quinidine, phenothiazines, ritonavir, verapamil, EtOH, evening primrose oil t effects OF CNS depressants, hypoglycemics, warfarin T risk of serotonin synd W/MAOIs 4-... 

Uses Endogenous depression Action TCA T synaptic CNS levels of serotonin /or norepinephrine Dose Adults. 25 mg PO tid-qid >150 mg/d not OK Elderly. 10-25 mg hs Peds. 6-7 y 10 mg/d 8-11 y 10-20 mg/d >11 y 25-35 mg/d, 4- w/ hepatic insuff Caution [D, +/-] NAG, CV Dz Contra TCA allergy, use w/ MAOI Disp Caps, soln SE Anticholinergic (blurred vision, retention, xerostomia) Interactions T Effects W/ antihistamines, CNS depressants, cimetidine, fluoxetine, OCP, phenothiazine, quinidine, EtOH T effects OF anticoagulants T risk of HTN W/clonidine, levodopa, sympathomimetics T effects W/barbiturates, carbamazepine, rifampin EMS Concurrent use w/ MAOIs have resulted in HTN,... 

Chlorpromazine is the best known representative of the aliphatic phenothiazines. Although it is considered to be a low potency agent it is still frequently used. It is one of the most sedative antipsychotic agents and is therefore very effective in the treatment of agitated and violent patients. Extrapyramidal effects are seen with a rather low incidence. However it displays marked anticholinergic activity. There have been reports of hepatotoxicity, also in patients with previously normal hepatic function, due to chlorpromazine. Alimemazine and triflupro-mazine are other representatives from this group. 

Huphenazine is a short acting agent. Eor the management of agitated and potentially violent patients its hydrochloride formulation is frequently used for parenteral administration. Fluphenazine decanoate is a widely used depot preparation. Although its principal pharmacological activities are similar to those of the other phenothiazines fluphenazine displays only weak sedative action and it shows little anticholinergic and hypotensive effect. 

A number of drugs in addition to atropine and scopolamine have antimuscarinic properties. Tbese include tricyclic antidepressants, phenothiazines, and antihistamines. Physostigmine has been used in the treatment of acute toxicity produced by these compounds. However, physostigmine can produce cardiac arrhythmias and other serious toxic effects of its own, and therefore, it should be considered as an antidote only in life-threatening cases of anticholinergic drug overdose. 

Mechanism of Action A phenothiazine that blocks dopamine neurotransmission at postsynaptic dopamine receptor sites. Possesses strong anticholinergic, sedative, and antiemetic effects moderate extrapyramidal effects and slight antihistamine action. Therapeutic Effect Relieves nausea and vomiting improves psychotic conditions controls intractable hiccups and porphyria. 

Mechanism of Action A phenothiazine that antagonizes dopamine neurotransmission at synapses by blocking postsynaptic dopaminergic receptors in the brain. Therapeutic Effect Decreases psychotic behavior. Also produces weak anticholinergic, sedative, and antiemetic effects and strong extrapyramidal effects. Pharmacokinetics Erratic absorption. Protein binding greater than 90%. Metabolized in liver. Excreted in urine. Half-life 33 hr. 

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