Drug information of Droperidol

Mechanism of effect

The exact mechanism of action is unknown, however, droperidol causes a CNS depression at subcortical levels of the brain, midbrain, and brainstem reticular formation. It may antagonize the actions of glutamic acid within the extrapyramidal system.

 It may also inhibit cathecolamine receptors and the reuptake of neurotransmiters and has strong central antidopaminergic action and weak central anticholinergic action. It can also produce ganglionic blockade and reduced affective response. The main actions seem to stem from its potent Dopamine(2) receptor antagonism with minor antagonistic effects on alpha-1 adrenergic receptors as well.

Pharmacodynamic

Droperidol produces marked tranquilization and sedation. It allays apprehension and provides a state of mental detachment and indifference while maintaining a state of reflex alertness. It lowers the incidence of nausea and vomiting during surgical procedures and provides antiemetic protection in the postoperative period. Droperidol potentiates other CNS depressants.

It produces mild alpha-adrenergic blockade, peripheral vascular dilatation and reduction of the pressor effect of epinephrine. It can produce hypotension and decreased peripheral vascular resistance and may decrease pulmonary arterial pressure (particularly if it is abnormally high). It may reduce the incidence of epinephrine-induced arrhythmias, but it does not prevent other cardiac arrhythmias.

Pharmacokinetics

• Half-Life elimination: 2 hr (parent drug), 8-12 hr (metabolites)
• Onset: 3-10 min
• Duration: 2-4 hr, may persist up to12 hr
• Peak Response Time: 10-30 min
• Peak Plasma Time: 60 min (IM)
• Protein Bound: extensive
• Metabolism: extensively in the liver
• Metabolites: [Benzimidazolone, p-Fluorophenylacetic acid, p-Hydroxypiperidine] (inactive)
• Vd: 2 L/kg (Adults); 0.58 L/kg (Children)
• Excretion: Urine (75%); feces (22%)

Drug indications

Anxiety , nausea , vomiting , Restlessness , Nausea/Vomiting - Chemotherapy Induced

Dosage

Adult

Antiemetic

Initial: No more than 2.5 mg IV/IM; additional doses of 1.25 mg may be given if benefit outweighs potential risk

Delirium (Off-label)

5 mg IM

Pediatric

Antiemetic

2-12 years: 0.03-0.07 mg/kg IV/IM over 2-5 minutes q4-6hr PRN 

Not to exceed 0.1 mg/kg IV/IM, additional dose (no more than 2.5 mg) may be given ONLY IF benefit outweighs potential risk

Drug contraindications

Hypersensitivity

Side effects

Anxiety , nausea , Tachycardia , dizziness , vomiting , Seizures , hallucinations , extrapyramidal effects , difficulty urinating , Restlessness , Gain weight

Interactions

Octreotide acetate , Propofol , Tetrabenazine , Methocarbamol , Midazolam , Hydroxyzine , Chlordiaze poxide , Chlorpheniramine , formoterol , Methazolamide , Histrelin , Dolasetron , Palonosetron , Amitriptyline , Amiodarone , Epinephrine , Erythromycin , Ondansetron , Itraconazole , vemurafenib , Fluticasone and Vilanterol , lumefantrine , lofepramine , Arsenic trioxide , Terfenadine , Dosulepin , Romidepsin , lisuride , Mianserin , Panobinostat , Dofetilide , Ibutilide , Eribulin , Ivacaftor , Lumefantrine / artemether , protriptyline , dronedarone , saquinavir , Apomorphine , vandetanib , Sertindole , astemizole , Pentamidine , Sodium Oxybate , Quinidine , Amoxapine , Ziprasidone , Haloperidol , Cabergoline , Clarithromycin , Chlorpromazine , Clomipramine , Levodopa , Fluconazole , Maprotiline , Methyldopa , Moxifloxacin , Nortriptyline , Nilotinib , Doxepin , Disopyramide , Ropinirole , Sotalol , Cisapride , Fluphenazine , Trazodone , Trifluoperazine , Trimipramine , Thioridazine , Desipramine , Dopamine , Imipramine , Bromocriptine , Pramipexole , perphenazine , Promethazine , Pimozide , sparfloxacin , Procainamide , Indapamide , Inotuzumab‎ , Goserelin , Butalbital and Acetaminophen , Promazine , Vasopressin , Chlorthalidone , Panitumumab , Halofantrine , Grepafloxacin , Abarelix , Asenapine , Alfuzosin , Amisulpride , Perflutren , Ramelteon , Secobarbital , lenvatinib , Apalutamide , Tolcapone , Temazepam , Estazolam , Pitolisant , Entrectinib , Clorazepate , Quazepam , Cariprazine , Oxymorphone , gilteritinib , Opium , glasdegib , Bepridil , bedaquiline , Dasatinib , Gemtuzumab , ethotoin , Halaven

Alerts

May cause potentially fatal QT interval prolongation/torsades de pointes at or below recommended doses; should be used only in patients who have failed to respond to other drugs

Use as sedative or anesthesia adjunct no longer recommended

Shares the toxic potentials of phenothiazines

Risk factors for prolonged QT interval

• Use with extreme cautions in patients at risk for development of prolonged QT syndrome
• CHF, bradycardia, diuretic use, hypokalemia, hypomagnesemia, cardiac hypertrophy
• Use of drug known to cause prolonged QT interval: class I or III antiarrhythmias, some antihistamines, antimalarials, calcium channel blockers, neuroleptics, antidepressants or drugs which may induce hypokalemia or hypomagnesemia
• >65 years, alcohol abuse, concomitant use of benzodiazepines or IV opiates, impaired hepatic/renal function

Black Box Warnings

• Patients with dementia-related psychosis who are treated with antipsychotic drugs are at an increased risk of death as shown in short-term controlled trials. The deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature
• This drug is not approved for the treatment of patients with dementia-related psychosis

Points of recommendation

Check blood pressure and heart rate as the doctor has told you. Talk with the doctor.

Pregnancy level

C