midazolam intranasal

Action and Spectrum

Actions and Spectrum: 

Action: 

Sedation: midazolam acts as a central nervous system depressant, producing sedative effects. It works by enhancing the activity of a neurotransmitter called gamma-aminobutyric acid (GABA) in the brain, which leads to sedation and relaxation. 

Anxiolysis: midazolam also has anxiolytic properties, meaning it can reduce anxiety and induce a sense of calmness. It helps to alleviate feelings of apprehension or nervousness in individuals undergoing certain medical procedures or experiencing anxiety-related conditions.  

Spectrum:  

Sedation: midazolam can induce varying levels of sedation, ranging from mild relaxation to deep sedation or even general anesthesia in higher doses. The degree of sedation achieved depends on the dosage administered and the intended purpose of use. 

Amnesia: midazolam can cause temporary anterograde amnesia, meaning it impairs the formation of new memories. This effect can be useful in certain medical procedures where it is desirable for the patient not to remember the event. 

Drug Interaction

Adverse Reaction

Frequency defined  

1-10% (Single 5-mg Dose) 

Lacrimation increased (1%) 

Dysarthria (2%) 

Throat irritation (2%) 

Rhinorrhea (3%) 

Abnormal taste (4%) 

Nasal discomfort (5%) 

Headache (7%) 

Somnolence (10%) 

Black Box Warning

Black Box Warning:  

Dangers associated with simultaneous opioid usage  

Dependency, misuse, and abuse 

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: Individuals with a known hypersensitivity or allergy to midazolam or other benzodiazepines should not receive midazolam intranasally, as it may cause an allergic reaction. 

Acute narrow-angle glaucoma: midazolam can cause pupillary constriction, which may worsen acute narrow-angle glaucoma. It is contraindicated in individuals with this condition. 

Respiratory depression: midazolam can cause respiratory depression, particularly when used in higher doses or in combination with other central nervous system depressants. It should be used with caution in individuals with compromised respiratory function or respiratory disorders, such as severe chronic obstructive pulmonary disease (COPD). 

Severe hepatic impairment: midazolam is metabolized in the liver, and individuals with severe hepatic impairment may have difficulty metabolizing the drug. In such cases, alternative routes of administration or dose adjustments may be necessary. 

Pregnancy and breast-feeding:  

midazolam falls under pregnancy category D, indicating potential fetal harm when given to expectant mothers. Moreover, it is excreted in breast milk and may adversely affect nursing infants. The administration of midazolam to pregnant or breastfeeding women should be approached cautiously, with a thorough evaluation of the potential benefits and risks. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: AU TGA pregnancy category: C
US FDA pregnancy category: D 

Lactation: Excreted into human milk is known 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

midazolam is a benzodiazepine medication that is commonly used for its sedative, anxiolytic (anti-anxiety), and amnesic properties. 

Pharmacodynamics:  

The pharmacodynamics of midazolam intranasal are similar to those of other routes of administration. midazolam acts on the central nervous system (CNS) by binding to the benzodiazepine receptors, which are located throughout the brain. This binding enhances the inhibitory effects of gamma-aminobutyric acid (GABA), a neurotransmitter that reduces neuronal activity in the brain.   

Pharmacokinetics: 

Absorption 

Intranasal administration allows midazolam to be absorbed through the nasal mucosa and enter the bloodstream. The absorption rate is generally faster compared to oral administration.   

Distribution 

Once absorbed, midazolam is distributed throughout the body via the bloodstream. It readily crosses the blood-brain barrier, leading to its central nervous system effects. The distribution of midazolam is rapid due to its lipophilic nature. 

Metabolism 

midazolam undergoes extensive metabolism in the liver through various enzymatic pathways, primarily by the cytochrome P450 (CYP) enzyme system.  

Excretion and Elimination 

midazolam and its metabolites are eliminated from the body primarily through urine. The main excretory route is via the kidneys.

Adminstartion

Administration:  

Intranasal administration of midazolam can be useful in situations where IV access is difficult or unavailable, especially in emergency situations or when treating seizures. The intranasal route offers a non-invasive and relatively rapid way to deliver the medication into the bloodstream. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: midazolam Intranasal 

Why do we use midazolam Intranasal?  

Seizure management: Intranasal midazolam can be used to treat seizures, especially in emergency situations or when intravenous access is not readily available. It provides rapid sedation and anticonvulsant effects, making it useful for controlling prolonged or recurrent seizures. 

Pre-operative sedation: midazolam intranasal administration can be used for pre-operative sedation, particularly in children or individuals who have difficulty swallowing or are resistant to taking oral medication. It helps to reduce anxiety and induce sleep before surgery. 

Anxiolysis and sedation for dental procedures: Intranasal midazolam is sometimes employed to achieve anxiolysis (reduced anxiety) and sedation during dental procedures, particularly in pediatric patients who may have a fear of needles or struggle with oral administration. 

Behavioral management in pediatrics: midazolam intranasal administration can be utilized to manage acute behavioral disturbances or agitation in pediatric patients, such as those with autism spectrum disorder or other developmental disabilities.