Buspirone

BRAND NAMES:

Buspar: Buspar is available in the form of a buspirone hydrochloride tablet (5, 7.5, 10, 15, 30 mg), and this medication is indicated to treat anxiety. It regulates the levels of dopamine and serotonin in the brain.

MECHANISM OF ACTION:

Buspirone's therapeutic efficacy in generalized anxiety disorders is assumed to stem primarily from its interaction with two key 5-HT1a receptor subtypes involved in the brain's anxiety and fear circuitry, which enhances serotonergic activity in these brain locations. While buspirone only partially agonistically interacts with postsynaptic 5-HT1a receptors located in the hippocampus and cortex, it fully agonistically interacts with presynaptic 5-HT1a receptors, also known as 5-HT1a auto receptors, expressed at the dorsal raphe. 5-HT1a receptors act as inhibitory autoreceptors by being expressed in the soma or dendrities of serotonergic neurones, or they facilitate 5-HT's postsynoptic activities by being highly expressed in corticolimbic circuits. They block G-protein receptors that are connected to Gi/Go proteins.

When activated, presynaptic 5-HT1a autoreceptors produce neurone hyperpolarization and reduce the firing rate of serotonergic neurones by lowering extracellular 5-HT levels in the neurones' projection areas. Activated postsynaptic 5-HT1a receptors stimulate hyperpolarization, which leads to the release of 5-HT on pyramidal neurones. 
Buspirone's anxiolytic activity is mostly due to interactions with presynaptic 5-HT1a autoreceptors. Buspirone, acting as a strong agonist in these receptors, activates these auto receptors and inhibits 5-HT release. It is believed that buspirone produces desensitization of somatodendritic auto receptors over time, which could explain the drug's delayed onset of action.

Desensitization of auto receptors eventually leads to increased serotonin neurone excitation and 5-HT release. Buspirone also has a low affinity for the serotonin 5-HT2 receptor and acts as a weak antagonist on dopamine D2 autoreceptors, although there is little evidence that the action at these receptors contributes to buspirone's anxiolytic effects. It is an antagonist of presynaptic dopamine D3 and D4 receptors and may bind to alpha-1 adrenergic receptors as a partial agonist.

PHARMACOKINETICS:

Absorption: Buspirone is rapidly absorbed following oral administration. Bioavailability is low and variable due to extensive first-pass metabolism. While absorption of buspirone is decreased with concomitant food intake, the first-pass metabolism of the drug is also decreased, resulting in increased bioavailability as well as increased Cmax and AUC.

Distribution: The volume of dispersion of buspirone was 5.3 L per kg.

Metabolism : Buspirione is substantially metabolized after ingestion, with hepatic oxidation driven by the CYP3A4 enzyme. Hydroxylated derivatives are formed, including the pharmaceutically active metabolite 1-pyrimidinylpiperazine.

Excretion: About 29–63% of the dose given was eliminated in the urine within 24 hours, mostly in the form of metabolites, according to a single dose pharmacokinetics study employing 14C-labeled buspirione. Approximately 18% to 38% of the dosage was removed by feces.

PHARMACODYNAMICS:

• Buspirone causes desensitization of somatodendritic autoreceptors over time, which could explain the drug's delayed onset of action.
• Desensitization of auto receptors eventually leads to increased excitation of serotonergic neurones and 5-HT release.

DOSAGE AND ADMINISTRATION

• Buspirone tablets are designed for oral use.
• It is typically taken twice a day and must be taken consistently, either with or without meals, as advised by the physician.

DOSAGE AND STRENGTH

• Buspirone pills are used orally.
• Buspirone pills come in five different strengths: 5mg, 7.5mg, 10mg, 15mg, and 30mg.

CONTRAINDICATIONS:

• History of hypersensitivity reactions with buspirone in the past.
• Avoid the use of monoamine oxidase inhibitors within 14 days before or after buspirone therapy.

• Avoid buspirone in patients receiving reversible MAOIs such as linezolid or Ⅳ methylene blue due to the risk of serotonin syndrome.

  DRUG INTERACTIONS

• Buspirone oral tablet may interact with other drugs, vitamins, or herbal supplements that you use. An interaction occurs when a substance alters how a drug functions. This can be hazardous and prevent the drug from working properly.
• Antibiotics such as erythromycin and clarithromycin may interact with buspirone.
• Antidepressants include nefazodone.
• Antifungal medications include itraconazole, ketoconazole, fluconazole, and voriconazole.
• Carbamazepine, phenobarbital, and phenytoin are all antiseizure medications.
• Diltiazem and verapamil are high-blood-pressure medications. 
  Ritonavir, atazanavir, darunavir, and lopinavir are some of the HIV medications available.

SIDE EFFECTS:

• Along with its needed effects, some medicine may cause some unwanted effects.
• Symptoms of side effects include
• Chest pain
• Confusion
• Fast heartbeat
• Fever
• Mental depression
• Muscle weakness
• Numbness, pain in the hands or feet.
• Sore throat
• Skin rash

OVERDOSE:

When you take more than the recommended amount of dose, it leads to an overdose. The symptoms of overdose include:

• Dizziness when getting up from a sitting or lying position suddenly
• Nausea or vomiting
• Drowsiness
• Stomach upset

TOXICITY:

The administration of buspirone at a dose of 375 mg/day caused nausea, vomiting, dizziness, drowsiness, migraines, and stomach distress. The few incidents of overdose that have been reported usually resulted in full recovery. In situations of overdose, general symptomatic and supportive care is advised, coupled with urgent gastrointestinal lavage and monitoring of breathing, pulse, and blood pressure.

STORAGE CONDITIONS:

Buspirone should be stored at room temperature, between 68 F to 77 F (20 C to 25 C). It can be exposed to temperature between 59 F to 86 F (15 C to 30 C) for a shorter period of time, such as when transporting it.