In a placebo-controlled study, the concomitant administration of sertraline and methadone caused a 40% increase in blood levels of the latter, which is primarily metabolized by CYP2B6.Sertraline had a slight inhibitory effect on the metabolism of diazepam, tolbutamide and warfarin, which are CYP2C9 or CYP2C19 substrates; the clinical relevance of this effect was unclear. As expected from in vitro data, sertraline did not alter the human metabolism of the CYP3A4 substrates erythromycin, alprazolam, carbamazepine, clonazepam, and terfenadine; neither did it affect metabolism of the CYP1A2 substrate clozapine.Sertraline had no effect on the actions of digoxin and atenolol, which are not metabolized in the liver. Case reports suggest that taking sertraline with phenytoin or zolpidem may induce sertraline metabolism and decrease its efficacy, and that taking sertraline with lamotrigine may increase the blood level of lamotrigine, possibly by inhibition of glucuronidation.CYP2C19 inhibitor esomeprazole increased sertraline concentrations in blood plasma by approximately 40%.Clinical reports indicate that interaction between sertraline and the MAOIs isocarboxazid and tranylcypromine may cause serotonin syndrome. In a placebo-controlled study in which sertraline was co-administered with lithium, 35% of the subjects experienced tremors, while none of those taking placebo did.Sertraline may interact with grapefruit juice—see "Grapefruit–drug interactions". Pharmacology
Pharmacodynamics
Sertraline is a selective serotonin reuptake inhibitor (SSRI). By binding serotonin transporter (SERT) it inhibits neuronal reuptake of serotonin and potentiates serotonergic activity in the central nervous system.
Pseudohypoaldosteronism (PHA) is a condition that mimics hypoaldosteronism. However, the condition is due to a failure of response to aldosterone, and levels of aldosterone are actually elevated, due to a lack of feedback inhibition. Types
Presentation
PHA2 is clinically characterised by hypertension, hyperkalaemia, metabolic acidosis and normal renal function. Mechanism
PHA2 is also known as familial hyperkalaemic hypertension, or Gordon syndrome. The underlying genetic defect leads to increased sodium chloride reabsorption in the distal tubule in the kidney, leading to volume expansion, hypertension and lowered renin levels. The hyperkalemia found in PHA2 is proposed to be a function of diminished sodium delivery to the cortical collecting tubule (potassium excretion is mediated by the renal outer medullary potassium channel ROMK in which sodium reabsorption plays a role). Alternatively, WNK4 mutations that result in a gain of function of the Na-Cl co-transporter may inhibit ROMK activity resulting in hyperkalemia. Unlike in PHA1 in which aldosterone resistance is present, in PHA2 the volume expansion leads to relatively low aldosterone levels. Treatment
Treatment of severe forms of PHA1 requires relatively large amounts of sodium chloride. These conditions also involve hyperkalemia.In contrast, PHA2 (Gordons syndrome) requires salt restriction and use of thiazide diuretics to block sodium chloride reabsorption and normalise blood pressure and serum potassium. History
This syndrome was first described by Cheek and Perry in 1958.