Ziprasidone

BRAND NAMES

Zeldox –It contains the active ingredients of Ziprasidone. It is available in the form of tablets used to treat schizophrenia and bipolar disorder. 

Geodon- It contains the active ingredients of Ziprasidone. It is available in the form of capsules. 

MECHANISM OF ACTION

Ziprasidone is an atypical antipsychotic that binds to dopaminergic, serotonergic, adrenergic, and histamine receptors. It also shows minimal action on the norepinephrine and serotonin transporters. Antagonizing histaminergic and adrenergic receptors can cause drowsiness and orthostatic hypotension. In terms of schizophrenia therapy, antagonism of the dopamine receptor in the mesolimbic pathways is effective in reducing positive symptoms, but antagonism of the 5H2A receptor in the mesocortical route reduces negative symptoms of psychosis. The drug's effectiveness and mode of action for treating bipolar disorder remain uncertain. 

PHARMACOKINETICS

Absorption

Oral formation Tmax is around 6 to 8 hours. Within 1 to 3 days of treatment, plasma concentrations reach steady-state levels. When taken orally with meals, the bioavailability is around 70 percent. IM dosing provides close to 100% bioavailability. The IM formulation shortens the time required to achieve peak plasma concentration.

Distribution

Ziprasidone's mean apparent volume of distribution is 1.5 liters per kilogram.

Metabolism

Glutathione and aldehyde oxidase mediate the major metabolism of ziprasidone; CYP1A2 and CYP3A4 play a small part in this process. Benzothiazole sulfoxide and benzothiazole sulfone are among the active metabolites produced. 

Excretion

A minimal amount of Ziprasidone is excreted in the urine.

PHARMACODYNAMICS

Ziprasidone acted as an antagonist at the D2, 5H2A, and 5HT1D receptors and an agonist at the 5HT1A receptor. Ziprasidone decreased serotonin and norepinephrine reuptake at synapses. Other receptor/binding sites tested showed no significant affinity, including the cholinergic muscarinic receptor.

DOSAGE AND ADMINISTRATION

• Ziprasidone is available as a capsule to be taken orally. It is often taken twice a day with food. Take ziprasidone at the same times every day.

• It is available in capsules with doses of 20mg, 40mg, 60mg, and 80mg.

• It is available in the form of powder for injection at a dosage of 20mg. 

DRUG INTERACTIONS

Drug interactions with ziprasidone may include

• Pain relievers – codeine and hydrocodone

• Anti-anxiety drugs – alprazolam, lorazepam and zolpidem

• Muscle relaxants – carisoprodol and cyclobenzaprine

• Anti-allergic drugs – cetirizine

• Common cold medicines – diphenhydramine

• Antidepressants – escitalopram, fluoxetine and sertraline

• Antipsychotics – quetiapine

• Fits medicines – topiramate

• CNS stimulates - lisdexamfetamine  

CONTRAINDICATIONS

Patients having a recent acute myocardial infarction. Patients have a prior history of QT prolongation, including congenital long QT syndrome. Patients with uncompensated cardiac failure.

SIDE EFFECTS

Ziprasidone may cause side effects

• Headache

• Restlessness

• Anxiety

• Lack of energy

• Constipation

• Diarrhea

• Loss of appetite

• Muscle pain

• Stomach pain

• Runny nose

• Cough

• Weight gain

• Decreased sexual ability

Some side effects can be serious

• Fast, irregular, or pounding heartbeat

• Itching

• Rash

• Mouth sores

• Fever

• Chills

• Shaking

• Muscle stiffness

• Confusion

• Sweating

• Loss of consciousness

OVERDOSE

Symptoms of overdose may include the following

• Drowsiness

• Slurred speech

• Sudden movements that you cannot control

• Anxiety

• Uncontrollable shaking of a part of the body

TOXICITY

Ziprasidone has a binding affinity for histamine H1 receptors, which can cause somnolence, especially at hazardous doses. Priapism, body temperature regulation, and suicide can all result from hazardous medication levels if proper patient and case management is done. An overdose ensures the patient's breathing, and intubation may be required. If the patient is unconscious, IV access is essential for doing gastric lavage intubation. Charcoal can also be used in conjunction with a laxative to help with medication clearance.