FENTANYL

 

Fentanyl is a powerful synthetic opioid analgesic that is used for various purposes in medical settings, including anesthesia. Its importance in anesthesia can be attributed to several factors:

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1. Potency: Fentanyl is highly potent, about 50 to 100 times more potent than morphine, which makes it a highly effective analgesic. This allows for effective pain relief and anesthesia with relatively small doses, reducing the risk of side effects.

2. Rapid onset and short duration: Fentanyl has a rapid onset of action (usually within minutes) and a relatively short duration of effect (typically 30-60 minutes). This makes it ideal for use in short procedures and enables better control of the patient's pain levels during surgery.

3. Hemodynamic stability: Fentanyl is known to maintain hemodynamic stability in patients, which means it has minimal effects on blood pressure and heart rate. This is a desirable characteristic in anesthesia, especially for patients with cardiovascular issues or those undergoing major surgeries.

4. Balanced anesthesia: Fentanyl is used as a component of balanced anesthesia, where multiple drugs are used to provide analgesia, muscle relaxation, and unconsciousness. This approach can minimize side effects, improve patient comfort, and facilitate a smoother emergence from anesthesia.

5. Postoperative pain management: Fentanyl can be used for postoperative pain management through patient-controlled analgesia (PCA) devices or as part of a multimodal analgesia regimen. This helps minimize discomfort and can lead to better patient outcomes.

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Here are the main steps in fentanyl's mechanism of action:

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1. Binding to opioid receptors: Fentanyl primarily acts on mu-opioid receptors, which are G-protein-coupled receptors found throughout the central and peripheral nervous systems. It can also bind to other opioid receptor subtypes (such as delta and kappa receptors) but with lower affinity.

2. Activation of opioid receptors: Upon binding to the mu-opioid receptors, fentanyl activates the receptors, leading to the inhibition of adenylate cyclase. This results in a decrease in intracellular cyclic AMP (cAMP) levels.

3. Modulation of ion channels: The activation of mu-opioid receptors by fentanyl also causes the opening of potassium channels and the closing of voltage-gated calcium channels. The opening of potassium channels leads to hyperpolarization of the cell membrane, reducing the neuron's excitability. The closing of calcium channels inhibits the release of neurotransmitters, including substance P, which is involved in pain transmission.

4. Inhibition of pain transmission: The overall effect of fentanyl's action on opioid receptors is the inhibition of pain transmission in the central nervous system. This results in analgesia, sedation, and a reduced perception of pain.

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                                                                                                      Key points about Fentanyl

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• Phenylpiperidine-derivative synthetic opioid agonist.

 

• 100 times more potent than morphine.

 

• Rapid onset and highly lipid soluble.

 

• Significant first-pass pulmonary uptake- 75% of the initial dose.

 

• Metabolized by N-demethylation to norfentanyl.

 

• Substrate for hepatic P450 enzymes (CYP3A).

 

• Produces potentiation of benzodiazepines.

 

• May produce chest wall rigidity.

 

• Side effects: Depression of ventilation, depression of baroreceptor reflex, bradycardia, hypotension, myoclonus, nausea/vomiting, itching, constipation.

 

• Clinically used to provide analgesia, to blunt sympathetic response to laryngoscopy, and surgical stimulation.

 

• It lacks myocardial depressant effects.

 

• It does not evoke histamine release.

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