The hypotension for this reason these medication

The
recommended starting dose of Canagliflozin is 100 mg once daily, taken before
the first meal of the day. In patients tolerating Canagliflozin 100 mg once
daily who have an eGFR of  60 mL/min/1.73
m2 or greater and require additional glycemic      

Dosage:

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Chemical structure:
                                                                                                                                     A novel thiophene derivate with a C glycoside bearing a hetero-aromatic
ring formed a metabolically more stable, highly potent and selective inhibitors
for sodium glucose co-transporter 2 than O glycoside (Nomura et al., 2010).

Approved by
the US Food and Drug Administration (US FDA) in 2013 (Vlotides & Mertens, 2014).

Pharmacological
class: Sodium glucose co-transporter 2 inhibitors SGL-2 inhibitors.

Therapeutic
class: anti
diabetic

Generic
name: Canagliflozin

Invokana

 

 

 

    Further, SGLT2 inhibitors may be associated
with increased risk for lower limbs amputations; theoretically, these agents
increase the excretion of serum glucose to the urine thus lowering its osmotic
pressure, 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 bone
fractures; in patients with T2DM, canagliflozin
showed significant reductions in total hip Bone Marrow Density and increases in
bone formation and resorption biomarkers(Bilezikian et al., 2016). Recent data indicate that SGLT2 inhibitors may alter calcium
and phosphate homeostasis (secondary hyperparathyroidism induced by increased
phosphate reabsorption) and thereby potentially affect bone mass and fracture
risk.(Scheen, 2016)

    SGLT2 inhibitors are associated with an
increased risk of euglycemic ketoacidosis (Taylor, Blau, & Rother, 2015) Reviews of DKA in people taking SGLT2
inhibitors revealed that a significant proportion of cases occurred in people
with type 1diabetes  for whom SGLT2
inhibitors are not licensed. Other situations that predisposed to DKA in people
with type 2 diabetes were those of relative insulin deficiency, including acute
illness, surgery, alcohol abuse and people with an underlying low reserve of
insulin. Even if most reported episodes of SGLT2 inhibitor-associated
ketoacidosis occurred in patients with type 1 diabetes, rare events were also
observed in patients with T2DM (Morris, 2017)

 

    Glycosuria induces an osmotic diuresis that
may result in increased urination in people taking SGLT2 inhibitors. Associated
with this is a slightly raised incidence of side effects related to volume
depletion, dehydration and postural hypotension for this reason these
medication are contraindicated when glomerular filtration rate less than 30
ml/min/1.73 m2. Acute kidney injury can occur, particularly if eGFR <60 mL/min/1.73 m², advance age, existing low systolic BP, or taking either diuretics or drugs that interfere with renin-angiotensin-aldosterone system (RAS) (Morris, 2017).      The glycosuria induced by SGLT2 inhibitors predisposes to an increased risk of genital fungal infection and urinary tract infection.(Burson & Moran, 2015) General adverse effects, disadvantages and limitations use:     Gliflozins are contraindicated in the presence of hypersensitivity reaction, or Severe renal impairment (glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2), end stage renal disease (ESRD), or patients on dialysis. (Cada, Ingram, Levien, & Baker, 2013) Indication and contraindication:      Gliflozins are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus and is not recommended in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.          Non-specific inhibition of both SGLT-1 and SGLT-2 transporters can result in glucose-galactose mal-absorption, mild glucose urea and severe diarrhea. this limits the utilization of  SGLT-1 as a therapeutic target for glucose-lowering treatment (Bhartia, Tahrani, & Barnett, 2011).            A selective SGLT2 inhibitor effectively lowers the renal threshold to around 5 mmol/L Thus enhancing glycosuria; as a result, around 60–80 g of glucose is excreted per day in the urine. (Morris, 2017)    At a blood concentration level of about 10 mmol/l, renal threshold for glucose reabsorption is achieved and the glucose begins to be excreted in the urine. However in patient with type 2 diabetes mellitus and due to the adaptive mechanisms this threshold is achieved at a blood glucose level of about 14 mmol/l. (Morris, 2017)      In normal healthy individuals, the kidney secrets about 180g of glucose per day by a filtration process in the urine, nearly all this amount is reabsorbed in the convoluted tubules mainly by SGLT 1 and 2 proteins. SGLT2 is found exclusively in the proximal tubules of the nephron and responsible for 90% of glucose reabsorption, whereas SGLT 1 is found in the distal convoluted tubules and responsible for 10% of the filtered glucose. Also, SGLT 1 is act centrally to enhance 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 are similar for all gliflozins. Figure (2)        The differences in structures of Dapagliflozin, Empagliflozin and Ertugliflozin as well as those of Canagliflozin and Ipragliflozin are not large, mainly related to the differences in the aryl group. Figure (2) (Larson, 2015)       The general structures of the gliflozins have in common a glucose sugar to which is attached an aromatic group in the ??position at the anomeric carbon 1. It will be noted that in addition to the glucose sugar moiety and the ??isomeric aryl substituent the aryl group is composed of a diarylmethylene structure. Figure (1) figure (1)      Chemical structure:    Numerous drugs within this class where synthesized and approved clinically in different countries include, Dapagliflozin (Farxiga) considered the first SGLT2 inhibitor approved anywhere in the world, Canagliflozin was the first SGLT2 inhibitor to be approved for use in the United States, Canada and Europe under the brand name "Invokana". Empagliflozin (Jardiance) which approved in the united states. Others are 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 glucose renal reabsorption primarily from the proximal convoluted tubules of the kidney. They inhibit sodium glucose transport protein which accountable for a ninety percent of glucose reabsorption, so they called sodium glucose co-transporter 2 inhibitors (SGLT2 inhibitors)(Al Eyadeh & Jennings, 2015). Generic name: Gliflozins. Drug class: Sodium glucose co-transporter 2 inhibitors: