#NORADRENALINE : PHARMACOLOGICAL HIGHLIGHTS & COMPARISON WITH #ADRENALINE

🖍Noradrenaline ( norepinephrine) is a directly and indirectly acting sympathomimetic amine which stimulates alpha 1 and β1 adrenoceptors, but, in contrast to adrenaline (epinephrine), has little effect on β2 adrenoceptors.

 🖍These actions produce positive inotropic effects, intense vasoconstriction, increases in arterial pressure, and relative maintenance of cardiac output.

🖍Noradrenaline increases arterial pressure while simultaneously enhancing contractile state and venous return by reductions in venous capacitance, thereby augmenting stroke volume and ejection fraction. In contrast, pure alpha 1 adrenoceptor agonists such as phenylephrine and methoxamine further compromise cardiac output in failing myocardium and contribute to peripheral hypoperfusion despite an increase in arterial pressure.

🖍In contrast to adrenaline , noradrenaline does not substantially affect heart rate because activation of baroreceptor reflexes resulting from arterial vasoconstriction usually counteracts β1 mediated, direct, positive, chronotropic effects.

🖍Its arrhythmogenic potential is considerably less than that of adrenaline. Thus, substitution of noradrenaline for adrenaline may be appropriate in the therapeutic management of cardiogenic shock when atrial or ventricular arrhythmias are present.

🖍Intravenous infusions of noradrenaline (0.03–0.90 mg kg –1 per minute) have been shown to increase arterial pressure, LV stroke work index, cardiac index, and urine output in septic patients with hypotension that was unresponsive to volume administration, dopamine, or dobutamine

🖍Causes relatively greater increases in systemic vascular resistance and diastolic arterial pressure than adrenaline.

🖍The drug has a duration of action of 30–40 minutes; tachyphylaxis occurs with prolonged administration.

🖍Noradrenaline produces coronary vasodilatation, leading to a marked increase in coronary blood flow. However, as myocardial work may increase, the balance of myocardial oxygen consumption and delivery may lead to ischaemia on noradrenaline.

🖍Reflex vagal stimulation leads to a compensatory bradycardia

🖍The cerebral blood flow and oxygen consumption are decreased by the administration of noradrenaline; mydriasis also occurs

🖍The glomerular filtration rate is usually well maintained with noradrenaline; but it decreases the renal blood flow and this represents a major limitation on the prolonged use of high doses of norepinephrine.

🖍Noradrenaline increases the contractility of the pregnant uterus; this may lead to fetal bradycardia and asphyxia

🖍Noradrenaline may decrease insulin secretion, leading to hyperglycaemia

🖍The drug is pharmaceutically incompatible with barbiturates and sodium bicarbonate

#ClinicalPharmacology , #IntensiveCare , #CriticalCare , #EmergencyMedicine , #pharmacology , #anaesthesiology , #anaesthesia , #anesthesiology ,


(Reference: Paul S. Pagel and David C. Warltier, Essential drugs in anesthesia practice   Positive inotropic drugs, Anesthetic Pharmacology, 2nd edition)

TURP SYNDROME AND THE ANESTHESIOLOGIST

🚩#TURPsyndrome is diagnosed based on clinical signs, symptoms and biochemical findings 
🚩The manifestations are due to hypervolemia, hyponatremia and due to the direct toxicity of the irrigation fluids like 1.5% glycine
▪️FACTORS INCREASING THE ABSORPTION OF THE IRRIGATION FLUID ( AND THUS CONTRIBUTING TO THE HYPERVOLEMIA )
🚩Long duration of the surgery: the irrigation fluid is absorbed at the rate of 20-30 mL/ min and so the volume absorbed increases with the duration of the surgery 
🚩High pressure delivery of the irrigation fluid especially from a considerable height; 

The minimum height required for adequate flow should be used (usually 70 cms)
🚩Low venous pressures 
🚩Excessive bleeding (= there are more open veins)
🚩Large prostate (>50g)
▪️CLINICAL FEATURES:
🚩Headache, Restlessness, Agitation, Confusion, Convulsions, Coma; pulmonary oedema may also set in. If patient is under general anesthesia, these symptoms will get masked.
▪️MANAGEMENT FROM SURGICAL SIDE:
🚩Coagulating bleeding points and terminating surgery as soon as possible.
▪️ANESTHETIC MANAGEMENT: 
🚩Reduce / stop fluid administration. Diuretics may be required in the presence of pulmonary oedema
🚩Intubation to protect the airway and mechanical ventilation to support respiration may be required 
🚩Anti-convulsants, if needed, to treat seizures
🚩Hypertonic saline should be considered for severe hyponatremia (<120 mmol L−1) or in the presence of severe neurological symptoms.

👉🏿N.B.- Central pontine myelinolysis or osmotic demyelinating syndrome (ODS) is more likely to occur with correction of serum Na greater than 8-12 mMol/day and in the setting of chronic hyponatremia (greater than 48 h)
👉🏿Faster rates of administration can potentially lead to central pontine myelinolysis. Treatment should stop once symptoms have resolved or the serum sodium is more than 125 mmol L−1. Such therapy is best delivered in a high-dependency environment.