Ziprasidone Hydrochloride is the hydrochloride salt form of ziprasidone, a benzothiazolylpiperazine derivative and an atypical antipsychotic agent with an antischizophrenic property. Ziprasidone hydrochloride functions as an antagonist at the dopamine D2 and serotonin 5-HT2A and 5-HT1D receptors, and as an agonist at the 5-HT1A receptor. Ziprasidone hydrochloride also inhibits synaptic reuptake of serotonin and norepinephrine. The mechanism of action by which ziprasidone hydrochloride exerts its antischizophrenic effect is unknown but is potentially mediated through a combination of dopamine D2 and serotonin 5-HT2 antagonism. This agent also has antagonistic activity against histamine H1 and alpha-1-adrenergic receptors.
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Ziprasidone is the fifth atypical antipsychotic which is used for the treatment of schizophrenia as well as acute mania and mixed states associated with bipolar disorder. Ziprasidone is Food and Drug Administration (FDA) approved for the treatment of schizophrenia, and the intramuscular injection form of ziprasidone is approved for acute agitation in schizophrenic patients. Ziprasidone has also received approval for acute treatment of mania associated with bipolar disorder. Its immediate release intramuscular injection form is approved for acute agitation in people with schizophrenia. Ziprasidone is also used off-label for depression, bipolar maintenance, and post-traumatic stress disorder (PTSD).
Mechanism of Action of Ziprasidone
Ziprasidone’s antipsychotic activity is likely due to a combination of its antagonistic function at D2 receptors in the mesolimbic pathways and at 5HT2A receptors in the frontal cortex. Ziprasidone is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Ziprasidone acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other therapeutic and side effects of Ziprasidone. Ziprasidone’s antagonism of muscarinic M1-5 receptors may explain its anticholinergic effects. Ziprasidone’s antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Ziprasidone’s antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug. Ziprasidone functions as an antagonist at the Dopamine D2 , 5HT-2A , and 5HT-1D receptors, and as an agonist at the 5HT-1A receptor. Alleviation of positive symptoms is due to antagonism at D2 receptors while relief of negative symptoms are due to 5HT2A antagonism.
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Ziprasidone is a benzisothiazolyl piperazine-derivative antipsychotic agent that is chemically unrelated to other currently available antipsychotic agents (eg, butyrophenones, phenothiazines) and has been referred to as an atypical or second-generation antipsychotic agent. The exact mechanism of antipsychotic action of ziprasidone has not been fully elucidated but, like that of other atypical antipsychotic agents (eg, olanzapine, risperidone), may involve antagonism of central type 2 serotonergic (5-HT2) receptors and central dopamine D2 receptors. As with other drugs that are effective in bipolar disorder, the precise mechanism of antimanic action of ziprasidone has not been fully elucidated. Antagonism of various other receptors (eg, histamine H1 receptors, alpha1-adrenergic receptors) may contribute to other therapeutic and adverse effects (eg, orthostatic hypotension, somnolence) observed with ziprasidone.
Indications of Ziprasidone
- Autism
- Bipolar Disorder
- Body Dysmorphic Disorder
- Obsessive Compulsive Disorder
- Paranoid Disorder
- Schizoaffective Disorder
- Schizophrenia
- Acute Agitation
- Bipolar 1 Disorder
- Mixed manic depressive episode
- Treatment Resistant Major Depressive Disorder
- Acute Manic episode
Contra Indications of Ziprasidone
- Diabetes
- Excessive fat in the blood
- Low amount of magnesium in the blood
- Extreme Loss of Body Water
- Low amount of potassium in the blood
- Overweight
- Decreased Function of Bone Marrow
- Deficiency of granulocytes a type of white blood Cell
- Increased eosinophils in the Blood
- Abnormal movements of face muscles and tongue
- Neuroleptic malignant syndrome
- Lower seizure threshold
- Closed angle glaucoma
- Very Rapid Heartbeat – Torsades de Pointes
- Slow Heartbeat
- Stroke
- Disorder of the Blood Vessels of the Brain
- blood clot in a deep vein of the extremities
- Blood Pressure Drop Upon Standing
- Abnormally low blood pressure
- Paralysis of the Intestines
- Constipation
- Liver problems
- Acute infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">Inflammation of the Pancreas
- Enlarged Prostate
- Seizures
- Cannot Empty Bladder
- High Blood Sugar
- abnormal liver function tests
- Susceptible to Breathing Fluid Into Lungs
- a mother who is producing milk and breastfeeding
- Metabolic Syndrome X
- Dementia in an Elderly Person
- Decreased Motility Function of Stomach or Intestines
Dosage of Ziprasidone
Strengths: 40 mg; 20 mg; 60 mg; 80 mg
Schizophrenia
Oral
- Initial dose: 20 mg orally twice a day
- Maintenance dose: Adjust as clinically indicated at intervals of not less than 2 days
- Maximum dose: 100 mg twice a day
- A dose greater than 80 mg twice a day is generally not recommended.
Intramuscular
- Recommended dose: 10 to 20 mg IM; may repeat 10 mg IM every 2 hours or 20 mg IM every 4 hours up to the maximum daily dose
- Maximum dose: 40 mg IM per day
- Duration of therapy: Use beyond 3 consecutive days has not been studied
Bipolar Disorder
Acute Treatment of Manic or Mixed Episodes
- Initial dose: 40 mg orally twice daily
- Increase dose to 60 mg or 80 mg twice daily on the second day; subsequently adjust dose based on tolerance and efficacy within the dose range of 40 to 80 mg orally twice a day.
Maintenance Treatment (as the adjunct to lithium or valproate)
- Once stabilized, continue on the same dose within the range of 40 to 80 mg orally twice daily.
Side Effects of Ziprasidone
The most common
- Blurred vision
- Aggressive behavior
- agitation
- anxiety
- changes in vision, including blurred vision
- difficulty concentrating
- difficulty speaking or swallowing
- dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
- Chest pain or tightness
- dry mouth
- trembling or shaking of the hands or feet
- stomach pain or cramping
- diarrhea
- a headache
- stomach pain;
- back pain, joint or muscle pain.
- problems with your vision (including color vision);
- sudden chest pain or trouble breathing;
- pain or swelling in one or both legs;
- a migraine headache;
- pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or
- feeling like you might pass out.
More common
- Abdominal or stomach pain, discomfort, or pain when an area is touched or pressed. সহজ বাংলা: চাপ দিলে ব্যথা।" data-rx-term="tenderness" data-rx-definition="Tenderness means pain when an area is touched or pressed. সহজ বাংলা: চাপ দিলে ব্যথা।">tenderness
- chills or fever
- difficulty with moving
- headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in chest
- discomfort in arms, shoulders, neck or upper back
- excessive sweating
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- sudden slow or difficult speech
- sudden drowsiness or need to sleep
- fast breathing
- sharp pain when taking a deep breath
- fast or slow heartbeat
- coughing up blood
- rust colored urine
- decreased amount of urine
Rare
- Anxiety
- change in vision
- chest pain or tightness
- confusion
- cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- fainting
- hallucinations
- headache
- irritability
- lightheadedness
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
- nervousness
Drug Interactions of Ziprasidone
Ziprasidone may interact with following drug, supplements, & may change the efficacy of the drug
- antihistamines (e.g,. cetirizine, doxylamine, diphenhydramine, hydroxyzine,loratadine)
- anti-Parkinsons medications (e.g., amantadine, apomorphine, bromocriptine, levodopa,pramipexole, ropinirole)
- antipsychotics (e.g., chlorpromazine, , haloperidol, quetiapine, risperidone)
- antiseizure medications (e.g., clobazam, ethosuximide, felbamate, levetiracetam, phenobarbital, phenytoin, topiramate, valproic acid, zonisamide)
- aripiprazole
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- baclofen
- barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
- benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
- beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
- bupropion
- calcitriol
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- captopril
- celecoxib
- chloroquine
- cholecalciferol
- cyclosporine
- dantrolene
- domperidone
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- gabapentin
- H2 antagonists (e.g., famotidine, ranitidine)
- ipratropium
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- mirabegron
- mirtazapine
- monoamine oxidase inhibitors (MAOIs; moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine)
- non-steroidal anti-inflammatory medications (NSAIDs; e.g., diclofenac, ibuprofen, naproxen)
- phosphodiesterase 5 inhibitors (e.g., sildenafil, vardenafil)tadalafil,
- proton pump inhibitors (e.g., lansoprazole, omeprazole)
- quinolone antibiotics (e.g., levofloxacin, norfloxacin, moxifloxacin)
- selective serotonin reuptake inhibitors (SSRIs; e.g., paroxetine, fluoxetine,citalopram)
- serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
- tapentadol
- theophylline
- thiazide diuretics (water pills; e.g., hydrochlorothiazide, indapamide, metolazone)
- tramadol
- tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
- tyrosine kinase inhibitors (e.g., dasatinib, imatinib, nilotinib, sunitinib)
- “triptan” migraine medications (e.g., eletriptan, sumatriptan)
Pregnancy Catagory of Ziprasidone
FDA Pregnancy Category C
Pregnancy
This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
It is not known if ziprasidone passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.The safety and effectiveness of using this medication have not been established for children less than 18 years of age.
References
