The hypotension for this reason these medication
Therecommended starting dose of Canagliflozin is 100 mg once daily, taken beforethe first meal of the day.
In patients tolerating Canagliflozin 100 mg oncedaily who have an eGFR of 60 mL/min/1.73m2 or greater and require additional glycemic Dosage:Chemical structure: A novel thiophene derivate with a C glycoside bearing a hetero-aromaticring formed a metabolically more stable, highly potent and selective inhibitorsfor sodium glucose co-transporter 2 than O glycoside (Nomura et al., 2010).Approved bythe US Food and Drug Administration (US FDA) in 2013 (Vlotides & Mertens, 2014).
Pharmacologicalclass: Sodium glucose co-transporter 2 inhibitors SGL-2 inhibitors. Therapeuticclass: antidiabetic Genericname: CanagliflozinInvokana Further, SGLT2 inhibitors may be associatedwith increased risk for lower limbs amputations; theoretically, these agentsincrease the excretion of serum glucose to the urine thus lowering its osmoticpressure, enhancing the osmotic diuresis and lowering the intravascular volume.To date this effect is under investigation and no clear evidence was made(Yuan et al., 2017) SGLT2 inhibitors may increase the risk of bonefractures; in patients with T2DM, canagliflozinshowed significant reductions in total hip Bone Marrow Density and increases inbone formation and resorption biomarkers(Bilezikian et al., 2016).
Recent data indicate that SGLT2 inhibitors may alter calciumand phosphate homeostasis (secondary hyperparathyroidism induced by increasedphosphate reabsorption) and thereby potentially affect bone mass and fracturerisk.(Scheen, 2016) SGLT2 inhibitors are associated with anincreased risk of euglycemic ketoacidosis (Taylor, Blau, & Rother, 2015) Reviews of DKA in people taking SGLT2inhibitors revealed that a significant proportion of cases occurred in peoplewith type 1diabetes for whom SGLT2inhibitors are not licensed. Other situations that predisposed to DKA in peoplewith type 2 diabetes were those of relative insulin deficiency, including acuteillness, surgery, alcohol abuse and people with an underlying low reserve ofinsulin. Even if most reported episodes of SGLT2 inhibitor-associatedketoacidosis occurred in patients with type 1 diabetes, rare events were alsoobserved in patients with T2DM (Morris, 2017) Glycosuria induces an osmotic diuresis thatmay result in increased urination in people taking SGLT2 inhibitors. Associatedwith this is a slightly raised incidence of side effects related to volumedepletion, dehydration and postural hypotension for this reason thesemedication are contraindicated when glomerular filtration rate less than 30ml/min/1.73 m2.
Acute kidney injury can occur, particularly if eGFR <60mL/min/1.73 m², advance age, existing low systolic BP, or taking eitherdiuretics or drugs that interfere with renin-angiotensin-aldosterone system(RAS) (Morris, 2017). The glycosuria induced by SGLT2 inhibitorspredisposes to an increased risk of genital fungal infection and urinary tractinfection.(Burson & Moran, 2015)General adverse effects,disadvantages and limitations use: Gliflozins are contraindicated in thepresence of hypersensitivity reaction, or Severe renal impairment (glomerularfiltration rate (eGFR) less than 30 mL/min/1.73 m2), endstage renal disease (ESRD), or patients on dialysis.
(Cada, Ingram, Levien, & Baker,2013) Indication and contraindication: Gliflozins are indicatedas an adjunct to diet and exercise to improve glycemic control in adults withtype 2 diabetes mellitus and is not recommended in patients with type 1 diabetes mellitus or forthe treatment of diabetic ketoacidosis. Non-specific inhibition of both SGLT-1and SGLT-2 transporters can result in glucose-galactose mal-absorption, mildglucose urea and severe diarrhea. this limits the utilization of SGLT-1 as a therapeutic target forglucose-lowering treatment (Bhartia, Tahrani, & Barnett, 2011). A selective SGLT2 inhibitor effectivelylowers the renal threshold to around 5 mmol/L Thus enhancing glycosuria; as aresult, around 60–80 g of glucose is excreted per day in the urine. (Morris, 2017) At a blood concentration level of about 10mmol/l, renal threshold for glucose reabsorption is achieved and the glucosebegins to be excreted in the urine.
However in patient with type 2 diabetesmellitus and due to the adaptive mechanisms this threshold is achieved at ablood glucose level of about 14 mmol/l. (Morris, 2017) Innormal healthy individuals, the kidney secrets about 180g of glucose per day bya filtration process in the urine, nearly all this amount is reabsorbed in theconvoluted tubules mainly by SGLT 1 and 2 proteins. SGLT2 is found exclusivelyin the proximal tubules of the nephron and responsible for 90% of glucosereabsorption, whereas SGLT 1 is found in the distal convoluted tubules andresponsible for 10% of the filtered glucose. Also, SGLT 1 is act centrally toenhance the absorption of glucose from the small intestine. (Morris, 2017)Mechanism of action and drug targets:The indications,contraindications, mechanism of action and some of the adverse reactions aresimilar for all gliflozins. Figure (2) The differences in structures ofDapagliflozin, Empagliflozin and Ertugliflozin as well as those ofCanagliflozin and Ipragliflozin are not large, mainly related to thedifferences in the aryl group. Figure (2) (Larson, 2015) The general structures of the gliflozins have in common a glucose sugarto which is attached an aromatic group in the ??position at the anomeric carbon1.
It will be noted that in addition to the glucose sugar moiety and the??isomeric aryl substituent the aryl group is composed of a diarylmethylenestructure. Figure (1) figure (1) Chemical structure: Numerous drugs within this class where synthesized and approved clinicallyin different countries include, Dapagliflozin (Farxiga) considered the first SGLT2inhibitor approved anywhere in the world, Canagliflozin was the first SGLT2inhibitor to be approved for use in the United States, Canada and Europe underthe brand name “Invokana”. Empagliflozin (Jardiance) which approved in the united states. Othersare currently under investigation like Remogliflozin, Sergliflozin,Ertugliflozin, Sotagliflozin. Ipragliflozin, and Tofogliflozin (Apleway or Deberza) (Gilbert, 2014; Larson, 2015). Is a class of drugs which responsible for the inhibition of glucoserenal reabsorption primarily from the proximal convoluted tubules of the kidney.They inhibit sodium glucose transport protein which accountable for a ninetypercent of glucose reabsorption, so they called sodium glucose co-transporter 2inhibitors (SGLT2 inhibitors)(Al Eyadeh & Jennings, 2015).Generic name: Gliflozins.Drug class: Sodium glucose co-transporter2 inhibitors: