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Isoflurane anesthetics

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Salvia divinorum

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/2012/10/19/putme-to-sleepanesthesiology/

History

https://vetpharma.com

/producto/isoflurane/

The need for a new generation of nonflammable volatile anesthetic originated around 1960 when Ohio Medical Products initiated a research project with the goal to synthesize non-flammable fluorinated ethers and hydrocarbons anesthetic with less cardiovascular toxicities and more ideal metabolism than the first generation of fluorinated compounds. Ohio Medical Products assigned two senior chemists, Louise Speers Croix, Ph.D. and Ross C. Terrell Ph.D. to synthesize fluorinated methyl ethyl ethers and fluorinated methyl isopropyl ethers, which resulted in the discovery of isoflurane. After meeting all required standards of volatility, nonflammability, stability, it was improved for clinical use in 1972.

Background

Primary therapy for preoperative sedation and adjunctive anesthesia maintenance to intravenous anesthetic agents in the perioperative setting. It induces muscle relaxation and reduces pains sensitivity by altering tissue excitability. Inhaled anesthetics allow for rapid introduction of an agent into arterial blood via the pulmonary circulation, essentially the significance of rapid therapeutic effects allows for efficient induction and discontinuation of sedation induced by these agents.

Drug Abuse

Flurane anesthetics cause effects such as dysphoria, intoxication, and hallucinations. Abusers may sniff or snort fumes from a dispenser or aerosol directly into their nose. The high from inhalants only last a couple of minutes so abusers prolong repeating sniffing over several hours. Some abusers may pour inhalants onto their shirt collar and sniff it periodically.

Slang terms: Poppers, Snappers

Pharmacology

www.dnaindia.com/india/reportdna-exclusive-children-glued-toinhalants-as-drugs-1860440/amp

The mechanism of action of inhaled anesthetics consists of deregulating neurotransmission of excitatory paths involving acetylcholine, glutamate, and serotonin within the central nervous system triggering respiratory depression. It may depress myocardial contractility, decrease blood pressure through a decrease in systemic vascular resistance, and decrease sympathetic nervous activity.

Onset- 7-10 minutes post-inhalation, Metabolism: Minimally hepatic (<0.2%), predominantly CYP2E1,minimal biotransformation in man, Excretion: Exhaled gases, Renal Excretion 0.17%

Drug interactions

Risk X: Avoid combinations due to enhanced CNS depression, hypertensive effect, or arrhythmhttps://www.istockphoto.com/ illustrations/anesthesia-mask-cartoonogenic effects: azelastine, bromperidol, dexmethylphenidate, ephedra, ephedrine, flunarizine, isoproterenol, Kratom, levoketoconazole, metaraminol, olopatadine, orphenadrine, oxomemazine, paraldehyde, pimozide, sertindole, thalidomide

Minor decrease in metabolism occurs with CYP2E1 inhibitors and minor increased metabolism with CYP2E1 inducers

Toxicology

Acute exposure- Nephrotoxicity, dizziness, loss of consciousness, asphyxia, due to airway irritation. Chronic exposure-nausea, dizziness, fatigue, headache, irritability, reduced mental performance, liver and kidney disease, carcinogenicity, teratogenic/ birth defects (crosses the placenta), and reproductive effects: sterility or infertility. Warning- All anesthetic gases have shown a depression of cardiac contractility. Decrease in BP is dose dependent due to peripheral vasodilation; cardiac output is maintained. Use caution in patients who are hypovolemic, hypotensive, or hemodynamically compromised; use caution in patients with coronary artery disease to avoid risk of myocardial ischemia. May prolong the QT interval and rarely torsades de pointes; use caution in patients at risk of QT prolongation https://medicare24.onlin e/details/disease/1097

Laws

The average of 50 ppm for isoflurane has been defined as a non-regulatory occupational exposure limit by the American Conference of Governmental Industrial Hygienists (ACGIH). The exposure limit for isoflurane is 50 ppm since OSHA has not developed a regulation permitted exposure level for it.

Monitoring/drug screens

Blood pressure, electrocardiogram, serum potassium, oxygen saturation, respiration, end-tidal CO2 and QT interval in patients at risk for QTc prolongation. Isoflurane concentrations should be monitored prior to and throughout anesthesia QT interval in patients at risk for QTc prolongation

Professional opinion

I believe this form of volatile gas inhalant anesthetics are more beneficial than harmful. They are less abuse prone than the majority of other inhaled anesthetics such as nitrous oxide or chloroform. This class of inhalants are mostly present in surgical settings oppose to easily accessible items such as cleaners or sprays.

~ J. Young

References

1. Anesthetic gases - statpearls - NCBI bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK537013/. Accessed October 14, 2022.

2. Pubs.asahq.org. https://pubs.asahq.org/anesthesiology/article/108/3/531/8240/TheInvention-and-Development-of-Enflurane. Accessed October 13, 2022.

3. Isoflurane. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed October 13, 2022. http://online.lexi.com https://www.123rf.com/clipartvector/anesthesia_anaesthesia.htm

4. Isoflurane Anesthetic Gas Guidelines. Isoflurane Anesthetic Gas Guidelines | Environmental Health and Safety. https://ehs.research.uiowa.edu/isofluraneanesthetic-gas-guidelines. Accessed November 7, 2022.

5. Luo A, Zhang X, Li S, Zhao Y. Sevoflurane addiction due to workplace exposure: A case report and literature review. Medicine (Baltimore). 2018;97(38):e12454.

SARAH PENSYL Student pharmacist

SLANG TERMS:

1. Spice/K2

2. Bliss

3. Black Mamba

4. Blaze

5. Bombay Blue

6. Snax

7.Fake Weed

8.Legal Weed

9.Genie

10.Zohai

11.Red X

12.Dawn Scooby Skunk

PHARMACOLOGY:

“Spice” binds to and acts on the same receptor as marijuana These receptors are known as cannabinoid receptors (CB1 and CB2). Currently, synthetic cannabinoids like Spice/K2 are not well tested or well understood resulting in very minimal understanding of its pharmacology. Despite minimal research, scientists do know that Spice/K2 binds to cannabinoid receptors more strongly than marijuana. This gives it the capability to produce much stronger effects on the human body. The drug appears to be metabolized via the liver and excreted through the urine and feces.

DRUG EFFECTS:

Spice/K2 has a range of effects. Some of these are similar to the effects of marijuana. These effects include elevated mood, relaxation, altered perception, and symptoms of psychosis. Psychotic effects have also been seen with synthetic cannabinoid usage. These effects include extreme anxiety, confusion, paranoia, and hallucinations.

HISTORY:

“Spice” is another term for synthetic marijuana which was first used in Europe and the United States in 2004 and 2008, respectively, although; the chemicals used to make Spice were first created in laboratories decades prior. Components of synthetic marijuana created by experimentation include CP 47,497 (developed by Pfizer in the 1980’s), HU-210 (developed in 1988 at Hebrew University in Jerusalem), and JWH-018 (founded at Clemson University in 1995). Its use has been difficult to track Once a chemical was illegalized, a new chemical, not tested for on a drug screen, would be made in the lab to replace it.

BACKGROUND:

“Spice” is a synthetic form of tetrahydrocannabinol (THC), a psychoactive ingredient that is typically found in marijuana. It often comes as an herbal mixture that contains a mixture of plant material that has been sprayed with chemical additives that create its psychoactive effects. It can resemble the appearance of potpourri, so it is often labeled with “not for human consumption”. Users consume this substance by smoking it or inhaling it through ecigarettes or other devices.

U S. Army. Accessed November 9, 2022. https://www.army.mil/article/157559/substance_abuse_coodinator_ warns_of_spice_dangers

PROFESSIONAL OPINION:

The capability of manufacturers to develop new synthetic cannabinoids in a laboratory quickly and the inconsistency in the make-up of Spice/K2 makes this substance both dangerous and unpredictable. This combined with the drug’s capability to effect the mind with delusions severe agitation and violence makes this drug a danger to the public leading me to the conclusion that this drug should stay illegalized and not be used for medical treatment.

– S.Pensyl

DRUG INTERACTIONS:

“Spice” is a substrate for various P450 isoforms. These isoforms include CYP2C9 and CYP1A2. Drugs that are inhibitors of these enzymes possess the ability to cause drug-drug interactions with Spice/K2. These drugs include:

1. CYP2C9 inhibitors (valproic acid, sertraline)

2. CYP1A2 inhibitors (ciprofloxacin, fluvoxamine) “Spice” is metabolized in part by CYP2C9 which can affect the metabolism of other drugs that utilize this enzyme like warfarin, phenytoin, tolbutamide, losartan, and ibuprofen.

TOXICOLOGY:

The Centers for Disease Control has associated the use of Spice/K2 to overdose deaths as a result of myocardial infarction. In addition, the smoked substance has led to acute kidney injury requiring hospitalization and dialysis. The drug has an extensive list of adverse effects including tachycardia, elevated blood pressure, tremors, vomiting, hallucinations, and agitation.

LAWS:

Due to the lack of medical benefit and high potential for abuse, there is currently no accepted medical use for Spice/K2 in the United States, and it is illegal to buy and sell. For this reason, 26 synthetic cannabinoids are currently listed as schedule I substances under the Controlled Substances Act, in addition to many other substances that meet the definition for cannabimimetic agent However, there are a few synthetic cannabinoid substances that have been sold as the result of a workaround, selling the product as incense or potpourri. There is an act termed the Controlled Substance Analogue Enforcement Act that has allowed these uncontrolled synthetic cannabinoids to be subject to persecution as a Schedule 1 controlled substance if a list of criteria is met.

REFERENCES:

DRUG SCREENING:

Due to the ever-evolving list of synthetic cannabinoid substances and components, it can be hard to design tests that target this type of drug. There are blood, hair, urine, and saliva tests that can detect levels of Spice. Saliva tests have proved useful and have shown detection 20-60 minutes after inhaling the drug.

“Synthetic Marijuana: A Short History.” Foundation for a Drug-Free World, https://www.drugfreeworld.org/drugfacts/synthetic/syntheticmarijuana-short-history.html.

“Spice/ K2, Synthetic Marijuana.” DEA, https://www.dea.gov/factsheets/spice-k2-synthetic-marijuana.

“Spice (Synthetic Marijuana).” National Institute of Drug Abuse, https://nida.nih.gov/sites/default/files/pdf/nmassist.pdf

“Synthetic Cannabinoids (Spice, K2).” Release, 28 Jan 2019, https://www.release.org.uk/drugs/synthetic-cannabinoids-salvia-spicek2/pharmacology

Tai S, Fantegrossi WE. Pharmacological and Toxicological Effects of Synthetic Cannabinoids and Their Metabolites. Curr Top Behav Neurosci 2017;32:249-262. doi:10.1007/7854_2016_60

Pharmacology

Kava Kava is a depressant drug. It slows down the messages travelingbetween the brain and the body.

Kava Kava works by:

• blockage of voltage-gated sodium ion channelsenchanced ligand binding to GABA type A receptors

• diminished excitatory neurotransmitter release due to calcium ion channel blockade

• reduced neuronal reuptake of noradrenaline

• reversible inhibition of monoamine oxidase B and suppression of the synthesis of the eicosanoid thromboxane A2, which antagonizes GABA-A receptor function

Kava Kava can be used to treat anxiety and insomnia. It can also create a similar effect to alcohol. It has a sedative, anxiolytic, antistress, analgesic, local anesthetic, anticonvulsant, and neuroprotective properties.

Kava Kava can be used to treat anxiety and insomnia1. It also creates a similar effect to alcohol1. It has sedative, anxiolytic, antistress, analgesic, local anesthetic, anticonvulsant, and neuroprotective properties.

Kava Kava has been used in the Pacific Islands as a ceremonial drink^1. It is made from the root or the stump of the keva shrub^2. Kava Kava can cause similar effects as alcohol. The roots of this plant are ground up and then added to cold water that results in a “thick brew.” It is a drink that is prestigious and is offered to guests. It can be used to relax, “elevate mood, well-being, and contentment.” It can also be used to treat some disorders including anxiety, insomnia, and other types ofnervousdisorders^1.

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