The Lay Medical Man: 1/17/16

Friday, January 22, 2016

ROLAPITANT

🔹Its a Neurokinin-1 receptor antagonist . NK-1 receptors are highly concentrated in the vomiting center of the brain and bind a neurokinin termed substance P; activation of NK-1 receptors by substance P plays a central role in eliciting chemotherapy-induced nausea and vomiting

Blocking the interaction of substance P at the NK-1 receptor, NK-1 receptor antagonists improve the management of nausea and vomiting

🔹Comes in Tablet form (90 mg)

🔹Indication: In combination with other antiemetic agents, to prevent nausea and vomiting associated with emetogenic cancer chemotherapy

🔹Especially useful in preventing delayed phase chemotherapy induced nausea and vomiting

🔹Highly emetogenic chemotherapy

Day 1: Rolapitant 180 mg PO 1-2 hr before chemotherapy PLUS dexamethasone 20 mg PO 30 minutes before chemotherapy PLUS 5HT-3 antagonist

Days 2-4: Dexamethasone 8 mg PO BID

🔹Moderately emetogenic chemotherapy

Day 1: Rolapitant 180 mg PO 1-2 hr before chemotherapy PLUS dexamethasone 20 mg PO 30 minutes before chemotherapy PLUS 5HT-3 antagonist

Days 2-4: 5HT-3 antagonist

🔹Contraindicated with the use of thioridazine ( risk of arrhythmias due to increased thioridazine levels)

Safety not established for pediatric use and in pregnancy

🔹SIDE EFFECTS

Decreased appetite (9%), Neutropenia (7-9%)

Dizziness (6%)

🔹Rolapitant vs Aprepitant

Rolapitant has been studied as a one-time dose on day 1 of chemotherapy, while aprepitant is recommended to be given on days 1 through 3. Rolapitant does not inhibit CYP 2C9 or 3A4 enzymes, whereas aprepitant induces CYP 2C9 and 3A4 and moderately inhibits 3A4.3,4 As a result, aprepitant can interfere with warfarin, hormonal contraceptives, and certain chemotherapy, among other drugs.

Ref: WHO DRUG INFORMATION, VOL 29, number 3, 2015

Medscape Reference , http://reference.medscape.com/drug/varubi-rolapitant

Anaphylactic Reactions on Muscle Relaxants

🔅Neuromuscular blocking agents (NMBAs) represent the most frequently incriminated substances for allergic reactions, among all drugs used in the perioperative period, ranging from 50 to 70% (1)

🔅Substances responsible for IgE-mediated anaphylaxis. Among NMBAs, the following substances have been incriminated, in decreasing order of importance: suxamethonium, vecuronium, atracurium, pancuronium, rocuronium, mivacurium and cisatracurium.(1)

🔅incidence of anaphylactic reactions are seen more with suxamethonium and rocuronium. (2) (3)

🔅These reactions are more severe than on latex

🔅seem to occur more frequently in women than in men.

🔅if rapid-sequence induction is not mandatory, safer alternatives like cisatracurium can be used , in place of Rocuronium

🔅Regarding suxamethonium, more frequently it causes histamine release from mast cells and basophils, resulting in flushing and urticaria (without anaphylactic reactions)(4)

🔅Regarding atracurium , histamine release is observed in 40% of patients who receive doses over 0.5 mg/kg, resulting in transient hypotension and tachycardia; this can be prevented by injecting the drug slowly over 75 seconds, reducing the dose or prior treatment with 0.1 mg/kg chlorpheniramine and 2 mg/kg cimetidine i.v. (4)

🔅Cisatracurium will not cause histamine release in clinical dose range. Cisatracurium had the lowest rate of cross-reactivity in patients who had previously suffered anaphylaxis to rocuronium or vecuronium.(4)

🔅 Mivacurium causes transient fall in b.p. due to histamine release with doses above 0.2 mg/kg(4)

🔅The estimated sensitivity of skin tests for muscle relaxants is approximately 94 to 97 %. (1)

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Reference:

(1) www.worldallergy.org , Allergy to Anesthetic Agents, Mertes Paul Michel, Demoly Pascal, Stenger Rodolphe , Updated May 2013 ,Originally posted: October 2007, Reviewed by: Mario Sánchez-Borges

(2)A. Gullo(Editor) Anaesthesia, Pain, Intensive Care and Emergency – A.P.I.C.E.

(3) Proceedings of the 22 nd Postgraduate Course in Critical Care Medicine, Incidents Provoked Specifically by Certain Drugs Used in Anaesthesia M. K LIMEK , T.H. O TTENS ,F.G RÜNE

(4) Lee's Synopsis of Anaesthesia,13/e, p:191-193

(5) Br J Anaesth. 2013 Jun;110(6):981-7. Anaphylaxis to neuromuscular blocking drugs: incidence and cross-reactivity in Western Australia from 2002 to 2011., Sadleir PH1, Clarke RC, Bunning DL, Platt PR.

PAIN IN GUILLAIN BARRE SYNDROME

✔️GBS a number of different subtypes

✔️The most common is an acute inflammatory demyelinating polyradiculoneuropathy

✔️More than half of patients report severe pain.

✔️Severe widespread neuropathic pain may be described, often without the features of a peripheral neuropathy, as well as musculoskeletal pain.

✔️May sometimes have severe acute pain,

✔️Treatment with systemic ketamine and/or lidocaine as well as gabapentin/pregabalin and carbamazepine may be of benefit in the acute phase (ANZCA and FPM, 2010).

Ref: Acute Pain Management: A practical guide,4/e, Pamela E. Macintyre , Stephan A. Schug

Wednesday, January 20, 2016

TRANSFORMATION OF A PREGNANT LADY! (When does the physiology changes back to normal?)

↪️Despite decreased requirements during pregnancy ,spinal anesthesia requirements return to non pregnant levels by 12-36 hours postpartum. Abouleish et al found that patients required 30% more bupivacaine, to achieve a T4 level for post partum tubal ligation , upto 24 hours after delivery. Rapid decline in plasma progesterone levels, after delivery of placenta is one factor, which contributes to this.

↪️Cardiac output rises immediately after delivery because of autotransfusion of 500 to 750 ml of blood from the uterus. Patients with pulmonary hypertension and stenotic valvular lesions are at a particular risk at this time.

↪️Cardiac output returns to slightly above prepregnancy values about 2 to 4 weeks after delivery.

↪️FRC and residual volume rapidly return to normal.

↪️Many of the pulmonary changes caused by mechanical compression by the gravid uterus resolve quickly. Alveolar ventilation returns to baseline by 4 weeks postpartum, and there is a rise in maternal PCO 2 as the progesterone levels decrease.

↪️The dilutional anemia of pregnancy resolves, and the hematocrit returns to normal within 4 weeks secondary to a postpartum diuresis.

↪️Serum creatinine, glomerular filtration rate, and BUN return to normal levels in less than 3 weeks.

↪️Mechanical effects of the gravid uterus on the gastrointestinal system resolve about 2 to 3 days after delivery; however, gastric emptying may be delayed for several weeks as serum progesterone levels slowly decrease.

Reference:

Shnider and Levinson's anesthesia for obstetrics, Maya Suresh; Sol M Shnider; Gershon Levinson, 2013,English : 5th

Ana M. Lobo, Andrea J. Fuller,Marina Shindell, Chapter 59, Anesthesia Secrets, 4/e