ISA Thiruvarur and ISA Thanjavur - PowerPoint Presentation

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ISA Thiruvarur and ISA ThanjavurFRIDACE Melatonin and anesthesia

Dr. S. Parthasarathy

MD, DA, DNB, Dip Diab.MD ,DCA, Dip software based statistics,

PhD (physiology) FICA IDRA

www.painfreepartha.com

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What is it ?? The pineal gland was first identified as the source of melatonin in 1958 by Aaron Lerner, and colleagues.N-acetyl-5-methoxytryptamine from beef pineal extracts – melatonin ability to aggregate pigment granules in amphibian melanophores

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This tiny is this ??

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From tryptophan Nocturnal synthesis

Sympathetic drive

Sup.

Cerv

. Ganglia input

Lipid soluble

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Peak in the night Serum melatonin reaches a peak value (80-150 pg/mL) between midnight and 3 a.m., while its concentration during the day is low (10-20 pg/mL). 

 The calculated serum half-life of melatonin is about 30-50 minutes. 

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Metabolism Circulating melatonin is metabolized extensively by the liver mixed-function oxidase system (the CYP system or the

cytochrome

P-450 system) to 6-hydroxymelatonin, then conjugated (via

sulpho

- and to a lesser extent

glucurono

-conjugation); conjugated melatonin and small quantities of

unmetabolized

melatonin are excreted in the urine

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Physiological role Regulation of circadian rhythms Regulation of the reproductive axisantioxidant, oncostatic

,

anti-inflammatory

anticonvulsant effects

Neuroprotective

role

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MT 1 and MT 2 receptors Pineal gland Pituitary Hypothalamus KidneysTestes

Pancreas

May be in vessels

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pharmacology 5 mg tablets Maximum of 20 – 40 mg / day

IV - 5 – 10 mg

Ramelteon

Agomelatine

– 25 – 50 mg tablets

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So many routes Apart from per

os

administration, melatonin is currently under research with respect to other routes of administration, such as

sublingual,

transbuccal

/transmucosal, and intranasal for topical and systemic exposure, injectables (intravenous,

i.v.

bolus infusion, intramuscular, subcutaneous, and implant), topical

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How to give infusion The intravenous melatonin will be dissolved in an ethanol/saline solution (2 ml 99.9 % ethanol/23 ml 0.9 % saline) containing 25 mg of melatonin.

The infusion of melatonin will be performed over 10 minutes

the infusion rate being 2.5 mL per minute.

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Rare routes

Melatonin encapsulated in solid lipid nanoparticles enterally administered in critically ill patients has useful pharmacokinetics;

transdermal microemulsion has concentration‐time profile more similar to endogenous one

.

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Innumerable uses described Hypnosis Pain relief

Jet lag

Alzhiemers

Sleep disorders

Bed time urination

Skin – sun tan damage

And so on

No in pregnancy

Autoimmune diseases, caffeine

warfarin

– careful

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What can be mechanism of action ?? Possible GABA facilitation Beta endorphin release

Decreased expression of

cyclooxygenase

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Roles in anesthesia

Premedicant

or calming agent

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Melatonin Vs midazolam melatonin was not only as effective as midazolam

in alleviating preoperative anxiety in children, but

faster recovery,

lower incidence of excitement at post op 10 min

Children --

MRI scan

- 0.2 – 0.4 mg / kg melatonin

Successfully scanned without problems

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premedicantSublingual melatonin ( 3 Mg) premedication for patients undergoing cataract surgery under topical anesthesia reduced the anxiety scores in patients and provided excellent operating conditions.It rather produces a state of

calming

rather than sleep as in

midazolam

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Premed and anesthesia Oral premedication with 0.2 mg/kg melatonin significantly reduces the propofol and thiopental doses required for loss of responses to verbal commands and eyelash stimulation .

The relative potency of

propofol

after melatonin premedication was 1.7–1.8 times greater than that of

propofol

after placebo

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See the year 2019

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Can we use to blunt hemodynamic response – intubation or pneumoperitoneum ?? Melatonin has a mild hypotensive effect. The mechanism of action on the circulation is complex and unclear.

Melatonin may bind to specific melatonin receptors in the blood vessels, interfering with the vascular response to

catecholamines

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2016

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Anesthesia I.V. administration of melatonin induced a profound dose dependent hypnotic state in rats that was characterized by a rapid loss of righting reflex, and an anti nociceptive effect.

These properties are desirable in anesthetic agents or anesthetic

adjuvants

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Protects Brain – already working less !! Neurobiol Dis. 2006 Mar;21(3):522-30. Epub

2005 Nov 10.

Melatonin reduces the severity of anesthesia-induced apoptotic

neurodegeneration

in the developing rat brain.

Yon JH

, 

Carter LB

, 

Reiter RJ

, Jevtovic-Todorovic

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What is the difference ?? Melatonin hypnosis Not associated with hangover

Addiction

Dependence

EEG changes are similar to IV and Inhalational agents

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IJA 2013

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What does anesthesia do to melatonin ? spinal and general anesthesia significantly decreased melatonin secretion during the first postoperative evening when compared with the preoperative evening; they also noticed a postanesthesia

phase delay in melatonin secretion.

a few studies failed to demonstrate any significant changes in melatonin secretion in patients who underwent major surgery.

Can we Give melatonin

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Analgesia Intrathecally administered melatonin is active against the formalin and thermal-induced nociception at the spinal level in rats.

No data on post op pain relief

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Miscellaneous Melatonin is an effective premedication before intravenous regional anesthesia since it reduces patient anxiety, decreases tourniquet-related pain, and improves perioperative analgesia

Treatment of patients undergoing major aortic surgery with intravenous melatonin in a dose up to 60 mg

intraoperatively

was demonstrated to be safe and lacks adverse effects

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Miscellaneous Melatonin may be a valuable agent in preventing peritoneal adhesions in rats.preoperative melatonin, as a potent immune-modulator and antioxidant, would decrease postoperative infectious and noninfectious complications induced by major abdominal surgery

(liver resection)

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Miscellaneous PDPH Surgical stress

Wound healing

stimulatory effects on

osteogenesis

.

Treatment with melatonin suppresses the release of the

proinflammatory

cytokines, tumor necrosis factor-α and interleukin– hemorrhage decreased

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YES -- -- 2020

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Chronic pain Fibromyalgia Decreased neonatal pain IBD abdominal bloating and pain decreasedMigraine

Procedural pain

Betters sleep in cancer pain - !!

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Postoperative period Postoperative delirium is affected with the drug used for preoperative sedation. Melatonin was successful in decreasing postoperative delirium when used preoperatively

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Miscellaneous  The antioxidant properties of melatonin are being investigated for use in sepsis and reperfusion injuriesNeuro protection IOP reduction Hypertension cases

Antitumour

, sedative and analgesic actions – palliative care in cancer patients

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Critical care – 300 patient study Received melatonin for delirium Better than clonidine or midaz

But current recommendations

It is still not found

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Side effects Dizziness,excessive daytime somnolence, headache, nausea.

Risk of seizures in children with

neuro

disease

Side effects are relatively rare

Even 6 gm – only drowsiness

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Summary Pineal gland Light dependent secretion Effects Drug.. Uses Anesthesia

Side effects

FRIDACE

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Available in AMAZON !!

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FRIDACE

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Thank you all

All the slides are freely downloadable from www.painfreepartha.com