Revtew of Pharmacology

• Lactic acidosis (more with phenformin) ,md megaloblastic was witlulrawn due to serious hepatotoxicity and monitoring
anemia (more with metformin) dul' to \ itanun 13 I' of he patic function i<> recommended for other glitazones
deficiency an.• the major ad' ersl' 1.' ffeds l,f these dtug" also. G lita.wnes hav e been reported to cause weight gain,
• Ml•tformin interferes with cakium dep~.·ndl•nt ab.,orption t'dl'llm a11d plasma volume expansion. Therefore, these should
of vitamin B 1J-intrinsi1. f<Ktor nm1pll''\ m ll.'lll1in.11 ikum. be ,w oich.•d in Cf IF patients. (NY.HA class lll and fV) .
Long-term use oi nwtformin L<\11 n•sult in 111l'~,,lnhl,,slt c • Rosiglitazonc i11creases total and LDL cholrsterol as well as
anemia that may bl• pu'<'t'll ft•d l•y mu c•a..,cd 111 take tif dwtary HDL-choks tcrol whereas pioglitazone increases HDL-
calcium. cholcsterol without affecting total and LDL-cholesterol.
• Biguanides incn'<l"l' tlw mtl•stin,\1 production of lactate So, pioglitazone is preferred agent from this group.
by anaerobic gl) colysis. ln norm.1lmdiv tduab, the lactate • There were concerns of Pioglitazone to be associated
produced in the mtestine 1s com erll•d to glucose by with increased risk of bladder cancer on long term use.
gluconeogenesis in tlw liYeL Btgu.midcs put p.1tients at llowcver, long term s tudies failed to establish this fact.
risk of lactic ,lddc,sis b\ inhibiting thts ver\ s.1me process • Both of these can result in:
of gluconeogene.;is. Lactic acidosis '" more likely to Weight gain
occur m the presence of hepatic and renal impairment or Edema
New onset or worsening of macular edema
alcohol ingestion.
Increase in fracture risk in women
Risk factors for lactic acidosis include: Anemia
• I kkrly
• Renal insufficiency r-
Effect of antidiabetic drugs on weight
• Li\ C'r disease Increase:
• Se\ en• hypo-..emia - Sulfonylureas
• An) form of acidosis - Insulin
• Unstable CHF - Pioglitazone
• Alcoholic patients Decrease:
- GLP - I agonists
• Other contra-indications include cardiac failure, ::~nd - Pramlintide
chronic hypoxic lung disease. SGLT2 inhibitors
• Metformin ts al~o useful for polycystic ovarian disease No effect:
(PCOD). - DPP-4 inhibitors
• Metformin is the only oral agent that has been - Metformin
demon,.tratcd to reduce macrovascular events in type 2 DM.
• Metformin is first-line therapy for type 2 diabetes and (c) a-Glucosidase inhibitors
cause maximum reduction in HbAlc levels. Complex carbohydrates (polysaccharides and sucrose) are
•
absorbed after conversion to simple carbohydrates by u

•
'4
glucosidase. . . .
Muemonic Inhibitors of this enzyme (acarbose, voglrbose a11d mrgl1tol)
•
M- Metformin preferred in decrease carbohydrate absorption from the en.
0 - Obese patients Major adverse effect of these drugs is flatulmce due to
S- Sulfonylureas preferred in
•
fermentation of unabsorbed carbohydrates. (therefore,
T - Thin Pat1ents
contra-indicated in inflammatory bowel disease)
(b) Thl•zolidinedlones • I hcsc do not cau"c h} poglycemia. However, if hypogly-
. . t us" of .;ulfonvlureas,
ccmta occurs due to concomt· 1.1n " · •
• Troglttazonc, pioglit.vorw ~nd rosigltt,vone .ue tht> drugs
stmple carbohydrates like glucose (not sucros~ or other
m tht group that. ad as ngonil>ts of ,, nudt•t~r rt•n•ptor ;
peroxtsome proltfcrator activah•d n•u•ptor g., 111111 ,1 comple:.. carbohydrntcs) c.u, be used to reverse. tt. .
(PPARy). It regulates the tranS( ription ol gl'lll'S involved • According to :;oml' trials, these drugs can help tn .restoru~g
in glucose and ltptd metabolism. hnport,ml ~t•rws that .trt' l\-cl'll function .-md pn•vt•nt new cases of type 2 dtabctcs tn
up regulated by PPAR"'Y arc: pre -d iabt'tic.;.
Al·.u-bost• c.1n decwasl' blood glucose in both type 1 as well
.1s typl' 2 diabl'tes. Howt•ver, apart from insulin, the only
drug approved for treatment of both type 1 as weU as
typ(> 2 diabt-te!> is pramlintide.
• Acarbose is not absorbed from C IT whereas miglitol can
drup are used to rever~ msulin resistanc£> tn I) pc
be ubsorbed. Therefore, miglitol is contra-indicated in
T'beee drugs also tend to mcreaJK• HDL. Troglllt•zo11r renal failure.