ANTIDEPRESSANTS; AS ANALGESIC Vs AS ANTIDEPRESSANT

💪🏼The tricyclic antidepressants prevent the reuptake of monoamines, including serotonin and noradrenaline, as both pathways are important in the pain propagation. So the mixed reuptake drugs work better than more selective drugs like SSRIs

💪🏼But serotonin-noradrenaline reuptake inhibitor antidepressants (SNRIs), for example, venlafaxine & duloxetine and the atypical antidepressant group, such as bupropion and mirtazapine are also effective for some chronic pain conditions and are increasingly used because of their improved tolerability

💪🏼The superiority of tricyclics, particularly clomipramine and amitriptyline, in the management of pain may be also explained by their additional action on sodium channels blockade ( which is an action that SNRIs do not exhibit.)

💪🏼The dose of amitriptyline to treat pain is much lower when compared to that needed to treat depression 

💪🏼The analgesic action has a faster onset, whereas antidepressant action takes weeks to start

💪🏼The sedative action of tricyclic antidepressants are helpful in treating the sleep disturbances associated with neuropathic syndromes. Nortriptyline is less sedative than amitriptyline.

#antidepressants , #analgesics , #PainManagement , #ChronicPain 

Reference: Medscape, Pharmacogenetics and Analgesic Effects of Antidepressants in Chronic Pain Management

Frédérique Rodieux; Valérie Piguet; Patricia Berney; Jules Desmeules; Marie Besson, Personalized Medicine. 2015;12(2):163-175. 

Ryder S A, Stannard C F. Treatment of chronic pain: antidepressant, antiepileptic and antiarrhythmic drugs. Contin Educ Anaesth Crit Care Pain 2005; 5: 18–20 . 

A TRAVELOGUE: The long journey of #Insulin

 ✔️Insulin is produced by beta cells of islets of Langerhans. 

✔️It is produced from the pro hormone, 'preproinsulin'® in endoplasmic reticulum. A portion of the structure is cleaved off✂️ and the remaining portion is folded with the help of C-peptide to form 'proinsulin'® 

✔️The C-peptide portion is then removed✂️ to form Insulin 

✔️This active 💪🏼Insulin is transported 🚛 via Golgi apparatus to cytoplasmic granules for exocytosis💦 into plasma

✔️Insulin then binds with its receptor on Insulin sensitive❣️ cells

 ✔️Insulin receptor 🎛 is a tetramer consisting of 2 alpha & 2 beta units. 

✔️Insulin binds to the alpha unit on the cell membrane, while the beta unit, which spans the cell membrane activates🔥 , tyrosine kinase™ and the second messenger system

✔️This activates🔥 cytoplasmic vesicles containing transport molecules🚤

✔️The vesicles fuse with the cell membrane to incorporate the transport molecules🚤 into the cell membrane, which facilitate the transport of glucose into the cell.

Ⓜ️NEMO> MECHANISM OF ACTION: INSULIN Vs GLUCAGON 

🔻Insulin binding to the receptor activates an intracellular second-messenger system via tyrosine kinase. 

🔻Glucagon binding to its receptor activates a G-protein second-messenger system via adenylyl cyclase.

"Insulin is TricKy"

"Glucagon is ACcurate"

#DiabetesMellitus , #endocrinology , #physiology , #pharmacology , #biochemistry , #MedicalExam , #mnemonic , #anesthesia

BUSINESS HACKS: DEALING WITH PEOPLE IN BUSINESS

Medical Etymology : Terms & Root words

➰ Internist - Internus = inside (Latin)

➰Gynecologist- Gyne= woman , Logos = Science (Greek)

➰Obstetrician- Obstetrix = midwife (Latin), ician = expert

➰ Pediatrician - paidos= child , iatreia= medical healing , ician= expert (Greek)

➰Dermatologist - derma= skin (Greek)

➰Ophthalmologist- ophthalmos = eye , logos = science (Greek)

➰Anesthesia- an= without, aisthesis = sensation --> anaisthesia (Greek)

➰Neurologist - neuron = nerve , logos = science (Greek)

➰Geriatrics - geras = old age , iatreia = medical healing (Greek) 

➰ Psychiatry - psyche= mind , iatreia = medical healing (Greek) 

➰Cardiologist - kardia= heart , logos= science (Greek)

➰Orthopedist - orthos= straight, paidos= child (Greek) At the time of coining this word, correction of spinal curvature was a main concern among practitioners of Orthopedics

➰Orthodontist- orthos= straight , odontos= tooth(Greek)

HOMOCYSTINURIA : #Anesthesia IMPLICATIONS

⏫ There is increased(⏫) levels of homocystine and methionine in blood and urine due to the deficiency of Cystathionine B synthetase which catalyses the conversion of homocystine and serine into cystathionine

⏫ Raised cystine levels reduce the resistance of endothelium against thrombosis, reduces the activity of the vasodilator nitric oxide (NO) and increase platelet aggregation. So there is high incidence of thromboembolism. We have to ensure good hydration, good cardiac output,early mobilisation and should provide mechanical +/- pharmacological thromboprophylaxis. Many patients will be on anticoagulation. If untreated 50% of patients will have thromboembolic complications and the mortality is about 20% before the age of 30 years.  So both modification of the dosing of anticoagulants ( especially if regional anesthesia is planned) if patient is receiving them and providing prophylaxis against DVT are important elements of perioperative care. The incidence of thrombotic complications are more in pregnant patients. 

⏫ Blood viscosity and platelet adhesiveness can be reduced by dextran, and the prior administration of pyridoxine

⏫ Reduced cystine results in weak collagen and fragmentation of elastic tissue of large arteries. There is high incidence of vascular diseases like Cerebrovascular diseases, Coronary Artery Disease, Peripheral Vascular Diseases

⏫ Patients may have increased insulin levels resulting in hypoglycemia. Dextrose infusion will prevent hypoglycaemia.

⏫ Acute psychiatritc symptoms, delirium etc have been reported and the altered availability of homocysteine, methionine and cystiene which are having glutamate agonist properties, has been postulated as a factor which promotes this.

⏫ Regional anaesthesia has certain theoretical disadvantages. Penetration of a large epidural blood vessel might initiate thrombosis, as may the accompanying venous stasis of the lower limbs.

Reference: ANAESTHESIA DATABOOK, A Perioperative and Peripartum Manual, 3RD EDITION

Rosemary Mason

#anaesthesia , #dvt , #biochemistry ,

A FEW CLUES IN INTERPRETING AN ISOLATED PROLONGATION OF ACTIVATED PARTIAL THROMBOPLASTIN TIME (aPTT)

👆🏿aPTT tests the intrinsic and common pathways of coagulation 

👆🏿Though it is included commonly as a part of coagulation profile assessment, it's primary uses are to detect coagulation factor deficiency and titration of heparin therapy

👆🏿An isolated elevation of aPTT may indicate 

➖deficiency of Factor VIII or IX or XI or XII

➖acquired clotting factor inhibitors 

➖presence of Lupus anticoagulant 

👆🏿N.B.:- Factor VIII deficiency is Haemophilia A, Factor IX deficiency is Haemophilia B and Factor XI deficiency is Haemophilia C

👆🏿If factor levels are >30% of normal, aPTT may remain normal, for e.g. in mild von Willebrand disease [raised aPTT + prolonged Bleeding Time (BT)], in mild hemophilia etc

Reference: Martlew V. Peri-operative management of patients with coagulation disorders. Br J Anaesth. 2000; 85(3): 446–455.

MULTIPLE SCLEROSIS- ANESTHESIA IMPLICATIONS

# Most often, postop exacerbation, if it occurs is due to surgical complications like fever and infections

# Even minor increases in body temperatures are not tolerated well

# With the use of Suxamethonium, there is a risk of hyperkalemia

# Both resistance and prolongation of NMBA response are seen

# Complications have been reported with spinal anesthesia (Weak myelin sheath and direct neurotoxicity from LAs have been suggested as reason for this)

# Epidural is safe in this regard (As in epidural technique, there will be a lower concentration of LA in white matter)

# We should explain the chance of exacerbation of symptoms before any form of regional anesthesia

#multiplesclerosis , #anesthesia , #anaesthesia

A FEW FACTS ABOUT COAGULATION FUNCTION, IT’S MONITORING & #RegionalAnesthesia IN OBSTETRIC PATIENTS

🏳️🌈 During routine epidural or spinal anaesthesia, accidental puncture of epidural veins occurs in 1–18% of patients

🏳️🌈The incidence after epidural techniques is estimated to be in the order of 1:150,000 after epidural placement and 1:220,000 after spinal injection in the general population

🏳️🌈removal of epidural catheters posed an equal risk to insertion ( Van- dermeulen et al)

🏳️🌈Surgery on spinal haematoma should ideally be performed within 8–12 h of the identification of symptoms in order to improve the chances of recovery. 

🏳️🌈The overall risk of death in those having general anaesthesia for caesarean section was quoted in 2007 as being just over 1:25,000.

🏳️🌈The levels of factors VII, VIII and fibrinogen increase and those of anticoagulation factors decrease, causing augmented coagulation and decreased fibrinolysis.

🏳️🌈There is no evidence to support routine full blood count (FBC) or coagu lation tests in women before the performance of a regional block in those who have had  

🏴normal FBC results

🏴no bleeding history

🏴no signs or symptoms of liver disease

🏴no signs or symptoms of pre-eclampsia, abruption or clinical signs of disseminated intravascular coagulation

🏴no recent anticoagulant treatment.

🏳️🌈In women with known thrombocytopaenia, a Full Blood Count (FBC) should be checked within 24 h of a regional procedure. 

🏴In women with mild to moderate pre-eclampsia, the course of the disease can be unpredictable and so  FBC be checked within 6 h. In addition, coagulation tests should be performed if platelets are <100000/mcL or if there is abnormal liver function. 

🏴In severe disease, FBC and clotting should be checked immediately before a procedure, as platelet levels in particular can decline rapidly. 

🏴Women with pregnancy-induced hypertension alone do not require an FBC before a regional procedure

🏳️🌈Activated partial thromboplastin time ratio (APTTR) and international normalised ratio (INR) are slightly decreased in late pregnancy.

🏳️🌈In a patient who receives LMWH, if he/she is simultaneously taking NSAID+Aspirin, there is an increased risk if last dose of LMWH is between 12-24 hours; it further increases if last dose is <12 hours 

🏳️🌈In patients with pre-eclampsia and platelet count between 75000-100000/mcL, there is an increased risk even if coagulation tests are normal; but it increases further if the counts has not been stable (= decreasing platelet count)

#obstetrics , #anesthesia , #coagulation , #anaesthesia

Reference: Abnormalities of Coagulation and Obstetric Anaesthesia, Hilary Swales, AAGBI Core Topics in Anaesthesia 2015

🔃COMPATIBILITY IN BLOOD TRANSFUSIONS🔃: RBC Vs FFP Vs PLATELETS

COMPATIBILITY: RBC TRANSFUSION 

In red cell transfusion, there must be ABO and RhD compatibility between the donor’s red cells and the recipient’s plasma. 

All healthy normal adults of group A, group B and group O have ANTIBODIES IN THEIR PLASMA against the red cell types (antigens) that they have not inherited

Among the ABO blood groups: 

Group A individuals have antibody to group B

Group B individuals have antibody to group A

Group O individuals have antibody to group A and group B

Group AB individuals do not have antibody to group A or B. So,

1 Group O individuals can receive blood from group O donors only ( as the antibodies against A or B in their plasma will react with any A or B antigens which enter the circulation)

2 Group A individuals can receive blood from group A and O donors 

3 Group B individuals can receive blood from group B and O donors

4 Group AB individuals can receive blood from AB donors, and also from group A, B and O donors ( as their plasma don't have any antibodies against any antigens)

RhD RED CELL ANTIGENS AND ANTIBODIES

Individuals very rarely make antibodies against these antigens, unless they have been exposed to them (‘immunized’) by previous transfusion or during pregnancy and childbirth.

A single unit of RhD positive red cells transfused to an RhD negative person will usually provoke production of anti-RhD antibody. This can cause: in a subsequent pregnancy, rapid destruction of RhD positive red cells.

Haemolytic disease of the newborn (HDN):

An Rh D-negative mother may first encounter the D antigen while being pregnant with an Rh D-positive child, or by receiving a blood transfusion of Rh D-positive blood. Now the mother's immune response to the fetal D antigen is to form antibodies against it (anti-D.) The fetal red cells are haemolysed, causing severe anaemia. HDN due to ABO incompatibility is usually less severe than Rh incompatibility.

PLASMA TRANSFUSION: COMPATIBILITY 

In plasma transfusion, group AB plasma can be given to a patient of any ABO group because it contains neither anti-A nor anti-B antibody. 

1 Group AB plasma (no antibodies) can be given to any ABO group patients

2 Group A plasma (anti-B) can be given to group O and A patients 

3 Group B plasma (anti-A) can be given to group O and B patients 

4 Group O plasma (anti-A + anti-B) can be given to group O patients only

FFP does not need to be Rh-compatible  (However, the unit will still be labelled as Rh +ve or Rh −ve); anti-D prophylaxis is not necessary in Rh D-negative recipients of Rh D-positive FFP

PLATELET TRANSFUSION: COMPATIBILITY 

The Platelet Concentrates( PCs ) transfused must be ABO-identical, or at least ABO-compatible, in order to give a good yield. ( ( Ideally, ABO identical units should be used but, in an emergency, ABO non-identical units can be used, although the improvement seen in platelet count post-transfusion may be less.)

Group O PC can be used for patients with blood groups A, B, and AB ONLY IF,  they are resuspended in additive/preservative solutions, or if negative for high titre anti-A/A,B 

ABO-incompatible PCs have reduced efficacy and, preferably, should not be used 

 

Rh-negative patients, in particular women of childbearing age, should receive, if possible, RhD-negative PC 

 

In the case of a transfusion of a RhD-positive PC to a RhD-negative women of childbearing age, 250 UI (50 μg) of anti-D immunoglobulin should be administered, a dose able to cover the transfusion of five therapeutic doses of PC in 6 weeks 

ACUTE EMERGENCY : COMPATIBILITY 

During an acute emergency, the blood bank may send group O (and possibly RhD negative) blood, especially if there is any risk of errors in patient identification. This may be the safest way to avoid a serious mismatched transfusion, in such situations. 

Reference: The Clinical Use of Blood, Handbook, WHO,

 Recommendations for the transfusion of plasma and platelets Giancarlo Liumbruno, Francesco Bennardello, [...], and as Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) Working Party

Succinylcholine aka Suxamethonium

 ⚗️Two molecules of acetyl choline joined together by the acetyl group forms Succinylcholine 

⚗️ It can be presented as chloride, bromide or iodide salt

⚗️ When presented as the chloride salt, it's a solution with concentration 50 mg/ mL

⚗️ When presented as bromide or iodide salts, they are powders, with more stability, shell life and suited for warm climates; but has to be reconstituted before use

⚗️ pH of the solution is around 4

⚗️ So they are destroyed by mixing it with alkaline solutions (e.g. Thiopentone )

Reference: Kestin I. Suxamethonium. Update in Anaesthesia 1992; 1: article 7.  Peck T, Hill S, Williams M. Pharmacology for Anaesthesia and Intensive Care, 3rd edn. Cambridge: Cambridge University Press, 2008; pp. 179–84 .