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Alprazolam; Uses, Dosage, Side Effects, Interactions, Pregnancy

Alprazolam is a triazolobenzodiazepine agent with anxiolytic, sedative-hypnotic and anticonvulsant activities. Alprazolam binds to a specific site distinct from the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) binding site on the benzodiazepine-GABA-A-chloride ionophore receptor complex located in the limbic, thalamic and hypothalamic regions of the central nervous system (CNS). This binding causes an allosteric modification of the receptor and enhances the affinity of GABA to the receptor leading to an increase in the frequency of chloride-channel opening events. This leads to an increase in chloride ion conductance, neuronal hyperpolarization, inhibition of the action potential and leads to a decrease in neuronal excitability.

Alprazolam is a potent, short-acting benzodiazepine anxiolytic a minor tranquilizer.It is commonly used for the treatment of anxiety disorders, especially of panic disorder, but also in the treatment of generalized anxiety disorder (GAD) or social anxiety disorder.A triazolobenzodiazepine compound with antianxiety and sedative-hypnotic actions, that is efficacious in the treatment of panic disorders, with or without agoraphobia, and in generalized anxiety disorders.It was the 12th most prescribed medicine in the United States in 2010.

Mechanism of Action of Alprazolam

Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABA_A) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

CNS agents of the 1,4 benzodiazepine class presumably exert their effects by binding at stereo specific receptors at several sites within the central nervous system. Their exact mechanism of action is unknown. Clinically, all benzodiazepines cause a dose-related central nervous system depressant activity varying from mild impairment of task performance to hypnosis.

Anxiolytic and possibly paradoxical CNS stimulatory effects of benzodiazepines are postulated to result from release of previously suppressed responses (disinhibition). After usual doses of benzodiazepines for several days, the drugs cause a moderate decrease in rapid eye movement (REM) sleep. REM rebound does not occur when the drugs are withdrawn. Stage 3 and 4 sleep are markedly reduced by usual doses of the drugs; the clinical importance of these sleep stage alterations has not been established.

Benzodiazepines appear to produce skeletal muscle relaxation predominantly by inhibiting spinal polysynaptic afferent pathways, but the drugs may also inhibit monosynaptic afferent pathways. The drugs may inhibit monosynaptic and polysynaptic reflexes by acting as inhibitory neuronal transmitters or by blocking exitatory synaptic transmission. The drugs may also directly depress motor nerve and muscle function.

Indications of Alprazolam

1st choice sleeping pill for diabetes & constipation induce anxiety & insomnia disorder

Generalized Anxiety Disorder
Panic Disorders
Management of anxiety disorder or the short-term relief of symptoms of anxiety
Agoraphobia.
Feeling Anxious
Treatment in combination with other medications for chemotherapy-induced nausea and vomiting.
Tinnitus
Borderline Personality Disorder
Dysautonomia
Panic Disorder
Depression
Rapid eye movement sleep disorder
Restless legs syndrome
Tardive dyskinesia
Tremor
Acute manic episode
Myoclonic seizures
Refractory absence Seizures
The treatment of acute and chronic akathisia induced by neuroleptics, also called antipsychotics.
Spasticity related to amyotrophic lateral sclerosis.
Alcohol withdrawal syndrome
For the management of anxiety disorder or the short-term relief of symptoms of anxiety and for the treatment of panic disorder, with or without agoraphobia.

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Contra Indications of Alprazolam

Abnormal liver function tests
Susceptible to breathing fluid into the lungs
Pregnancy
kidney disease with a likely reduction in kidney function
Having thoughts of suicide
Alcohol intoxication
Drug abuse
Wide-angle glaucoma
Closed angle glaucoma
Decreased lung function
Chronic lung disease
Liver problems
Severe liver disease
Temporarily stops breathing while wleeping.

Dosage of Alprazolam

Strengths: 0.5 mg, 1 mg, 2 mg, 3 mg

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine.

Anxiety

Adults—At first, 0.25 to 0.5 milligram (mg) 3 times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 4 mg per day.

Older adults—At first, 0.25 mg 2 or 3 times a day. Your doctor may increase your dose as needed.
Children—Use and dose must be determined by your doctor.

Panic disorder

Adults—At first, 0.5 to 1 milligram (mg) taken in the morning once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 10 mg per day.
Older adults—At first, 0.5 mg taken in the morning once a day. Your doctor may increase your dose as needed.
Children—Use and dose must be determined by your doctor.

Depression or Insomnia

Adults—At first, 0.5 milligram (mg) 3 times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 10 mg per day.
Older adults—At first, 0.25 mg 2 or 3 times a day. Your doctor may increase your dose as needed.
Children—Use and dose must be determined by your doctor.

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Immediate-release tablet, orally disintegrating tablet, or oral solution

Typical starting dosage: 0.5 mg three times daily.
Dosage increases: Your doctor may increase your dosage every 3–4 days in amounts of no more than 1 mg/day.
Maximum dosage: 10 mg daily, in divided doses.
Dosage reduction: When you’re stopping treatment, your dosage should be decreased slowly. Your doctor may decrease it by no more than 0.5 mg every 3 days.

Side Effects of Alprazolam

The most common

Common

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
hallucinations
headache
irritability
lightheadedness
cold and clammy skin
fast and shallow breathing
swelling of your feet, legs, or hands purple spot on your skin caused by internal bleeding
fast or abnormal heart rate or palpitations
loss of appetite
lower back, side, or stomach pain
mental depression
muscle pain or cramps
Swelling of your feet or ankles
Shortness of breath
Nausea, fever, dark urine, loss of appetite
Depression
Ataxia
Somnolence (difficulty staying awake)
Mental confusion
Hypotension
Respiratory arrest
Vasomotor collapse

Drug Interactions of Alprazolam

Alprazolam may interact with following drugs, supplements, & may change the efficacy of drugs

Antacids
antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
aripiprazole
“azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
baclofen
barbiturates (e.g., butalbital, phenobarbital)
benzodiazepines (e.g.diazepam, lorazepam)
calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
carbamazepine
estradiol (birth control pills)
gabapentin
macrolide antibiotics (e.g., clarithromycin, erythromycin)
mirtazapine
Oral contraceptives (birth control pills)
muscle relaxants
phenytoin
proton pump inhibitors (e.g., lansoprazole, omeprazole)
quinolone antibiotics (e.g., ciprofloxacin, ofloxacin)
selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
tapentadol
theophylline
tramadol
tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)

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If you take one of these drugs with alprazolam, you may have increased drowsiness or other side effects.

Pregnancy & Lactation of Alprazolam

FDA Pregnancy Category D

Pregnancy

This drug should not be used unless there are no safer alternatives, especially during the first trimester of pregnancy. The patient should be warned of the potential risks to the fetus and instructed to discontinue the drug prior to becoming pregnant.

Lactation

This drug may pass into breast milk and may cause side effects in a child who is breastfed. Your child may become lethargic (drowsy) and lose weight. Talk to your doctor if you breastfeed your child. You may need to decide whether to stop breastfeeding or stop taking this medication.T his medication has not been studied in children. It should not be used in people younger than 18 years.