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Fentanyl

Highly lipophilic and is delivered transdermally.

Among the safer opioid drugs to be used with renal insufficiency.

Fentanyl, a synthetic opioid that is so strong that just 2 milligrams can kill a person in a matter of minutes.

 

 

Fentanyl is 50 times stronger than heroin and 100 times stronger than morphine according (Centers for Disease Control and Prevention).

 

 

Fentanyl can be found in pill form.

An opioid used as a pain medication and together with other medications for anesthesia.

Also made illegally and used as a recreational drug, often mixed with heroin or cocaine.

In the US, fentanyl and fentanyl analogs caused over 29,000 deaths in 2017.

Between 2013-2016 overdose deaths involving fentanyl increased 113% per year.

Has a rapid onset.

Effects generally last less than an hour or two.

Used by injection, as a patch on the skin, as a nasal spray, or in the mouth.

Trade names Actiq, Duragesic, Fentora

Pregnancy category US: C (Risk not ruled out).

Routes of administration-Buccal, epidural, IM, IT, IV, sublingual, skin patch

US: Schedule II

Bioavailability 92% (transdermal)

89% (intranasal)

50% (buccal)

33% (ingestion)

100% intramuscular

Protein binding 80–85%

Metabolism

Hepatic metabolism, primarily by CYP3A4

Onset of action is 5 minutes.

Elimination half-life Intranasal: 6.5 hours

Elimination IV: 6 mins.

Elimination Transdermal: 20–27 hours.

Sublingual/buccal (single dose): 2.6–13.5 hours

Duration of action IV: 30–60 minutes.

Excretion is mostly by urinary metabolites, <10% unchanged drug.

Common side effects include vomiting, constipation, sedation, confusion, hallucinations, and injuries related to poor coordination.

Serious side effects may include respiratory depression, serotonin syndrome, low blood pressure, addiction, or coma.

In 2016, more than 20,000 deaths occurred in the United States due to overdoses of fentanyl and fentanyl analogues, half of all reported opioid-related deaths.

Fentanyl works primarily by activating μ-opioid receptors, and It is around 100 times stronger than morphine, also some of its analogues such as are around 10,000 times stronger.

As a Mu-receptor agonist, it binds 50 to 100 times more strongly than morphine.

As of 2017, fentanyl was the most widely used synthetic opioid in medicine.

Intravenous fentanyl is often used for anaesthesia and analgesia.

During anaesthesia it is often used along with a hypnotic agent like propofol.

In combination with a benzodiazepine, such as midazolam, it can produce sedation for procedures such as endoscopy, cardiac catheterization, and oral surgery, or in emergency rooms.

Used in the management of chronic pain including cancer pain.

Sometimes given intrathecally as part of spinal anaesthesia or epidurally for epidural anaesthesia and analgesia.

Has a high lipid solubility, so its effects are more localized.

Fentanyl transdermal patches are used in chronic pain management.

Fentanyl transdermal patch rate of absorption varies with body temperature, skin type, amount of body fat, and placement of the patch.

The application of external heat sources can trigger the release of too much medication and cause life-threatening complications.

Different delivery systems used by different makers affect individual rates of absorption.

Generally, the dermal patch will reach its full effect within 12 to 24 hours.

Transdermal fentanyl has a role for:

Patients requiring palliative care with swallowing problems and cannot tolerate other parenteral routes such as subcutaneous administration.

people with moderate to severe kidney failure.

troublesome side effects of oral morphine, hydromorphone, or oxycodone.

In some cases it can be fatal with just one dose.

A fentanyl nasal spray with a strength of 100mcg per use is available.

The bioavailability of intranasal fentanyl is about 70–90%, but with some imprecision

Intranasal fentanyl is available in doses of 50, 100, and 200 µg.

Intranasal fentanyl with a low rate of side effects and a promising pain reducing effect.

Intranasal fentanyl can be used in children, for the treatment of moderate and severe pain and is well tolerated.

Abstral dissolves quickly and is absorbed through the sublingual mucosa to provide rapid analgesia.

Fentanyl is a highly lipophilic compound which is well absorbed sublingually and generally well tolerated.

Sublingual forms are particularly useful for breakthrough cancer pain episodes, which are often rapid in onset, short in duration and severe in intensity.

Fentanyl lollipop, 400 micrograms lozenges (Actiq) are a solid formulation of fentanyl citrate on a stick that dissolves slowly in the mouth for transmucosal absorption.

Fentanyl lozenges are intended for opioid-tolerant individuals and are effective in treating breakthrough cancer pain.

It is most effective when consumed within 15 minutes.

Fentanyl lozenge absorption is about 25% of through the oral mucosa, resulting in a fast onset of action.

The remainder is swallowed and absorbed in the small intestine, acting more slowly.

The lozenge is less effective and acts more slowly

If swallowed whole, the lozenge undergoes extensive first-pass metabolism, leading to an oral bioavailability of about 33% as opposed to 50% when used correctly.

Intranasal fentanyl is as effective as IV morphine and superior to intramuscular morphine for management of acute hospital pain.

Among the more than 72,000 deaths estimated in 2017, the sharpest increase occurred among deaths related to fentanyl and fentanyl analogs with over 29,000 deaths.

Most common side effects include: diarrhea, nausea, constipation, dry mouth, somnolence, confusion, weakness, sweating, and less frequently abdominal pain, headache, fatigue, anorexia and weight loss, dizziness, nervousness, hallucinations, anxiety, depression, flu-like symptoms, indigestion, shortness of breath, hypoventilation, apnoea, and urinary retention.

Its use has also been associated with aphasia.

It is a more potent analgesic, and induces less nausea, as well as less histamine-mediated itching, than morphine.

Sustained release preparations, such as patches, may produce unexpected delayed respiratory depression, and death.

It has a therapeutic index of 270.

Fentanyl 2 mg is an lethal dose in most people.

Its strong potency relative to morphine is largely due to its high lipophilicity, and can more easily penetrate the central nervous system.

It binds to opioid G-protein coupled receptors (GPCR) which regulate synaptic transmission, and so initiating signalling to result in the inhibition of the release of nociceptive neurotransmitters.

It inhibits the ascending pathways in the CNS to increase pain threshold by changing the perception of pain.

It decreases propagation of nociceptive signals resulting in analgesic effects.

Levels may be measured in blood or urine to monitor for abuse, confirm a diagnosis of poisoning, or assist in a medicolegal death investigation.

Blood fentanyl levels are expected to be in a range of 0.3–3.0 μg/l in persons using the medication therapeutically, 1–10 μg/l in intoxicated people and 3-300 μg/l in victims of acute overdosage.

It is a Schedule II controlled substance per the Controlled Substance Act.

Distributors are required to implement an FDA-approved risk evaluation and mitigation strategy (REMS) program.

Fentanyl analogues may be hundreds of times more potent than heroin.

Fentanyl is used orally, smoked, snorted, or injected.

Fentanyl is sometimes sold as heroin or oxycodone, sometimes leading to overdoses.

Fentanyl is sometimes sold on the black market in the form of transdermal fentanyl patches such as Duragesic, and the gel from inside the patches is sometimes ingested or injected.

Fentanyl. 2 mg is a lethal dose in most people.

Non-medical use of fentanyl by individuals without opiate tolerance has resulted in numerous deaths.

The effects of fentanyl can be reversed with naloxone, or other opiate antagonists.

Some heroin dealers mix fentanyl powder with heroin to increase potency or compensate for low-quality heroin.

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