Drug No 1:-Alpha
Glucosidase Inhibitors
Acarbose miglitol and voglibose are available in India. They act
locally on the surface of small
intestine . By inhibiting enzymes which convert complex carbohydrates in
to disaccharides they delay digestion
of carbohydrates and convert them in to glucose gradually thus its absorption
in circulation is slowed down and post
prandial peaks are blunted. These agents
are not very effective in controlling
fasting blood glucose and thus
are usually used as an adjuvant to other
anti diabetic agents They
tend to produce abdominal
distention borbigmy and diarrhea
in many patients particularly when given in higher doses . These
side effects are more common in Indians as compared with western people
because we take a lot of fiber
in our diet Usual dose is one to
two tablets three
times a day with meals the pill to be taken with first bite of food
In west many patients are
prescribed higher dosages but these are
not tolerated by Indians.
Indication Of Alpha Glucosidase Inhibitors
1)
As
a monotherapy in patients with mild and predominantly post prandial hyperglycemia
if metformin is contra indicated or not tolerated.
2)
As
an adjuvant to insulin metformin
glitazones and insulin secretogogues for improvement in post prandial glucose control.
3)
Contraindications
4)
Alpha
glucosidase inhibitors are contraindicated in inflammatory bowel disorders and in pregnancy and lactation
Precautions
If a patient develops
hypoglycemia he should be treated by administering glucose even if hypoglycemia is mild because in patients on these agents complex carbohydrates take longer
time for conversion to glucose
1)
.
Contra indications OF Glitazones:
Glitazones are contra indicated in hepatic insufficiency
and in cardiac failure . they are ineffective in type 1 diabetics .
.
Type 2 drugs:-Incretion
Mimetic and Incretion Enhancers
Recently two new classes of anti diabetic agents with novel
and totally different mechanism
of action as compared to insulin and traditional OADs
have been introduced in clinical
practice Incretion
mimetic are injectable agents
while incretion
enhances which are also known as DPP IV inhibitors or Gliptin are oral
agents. Their mechanisms of
action partially overlap each other Before
looking in to these agents let us review
incretion physiology
Incretin physiology
Incretins are hormones secreted by small intestine in
response to food intake. The two important
incretins are GLIP 1, and
GIP . Circulating levels of these hormones
particularly GLP 1 are
reduced in type 2 diabetics. They respond to iv infusion
of GLP 1 but are resistant to action of
GLP Thus it has no therapeutic value.
Thus let us now concentrate on GLP its
four important physiological actions are :
1)
Glucose dependant
enhancement of insulin secretion by beta cells.
2)
Glucose dependant suppression of posts prandial
glucagon secretion by alpha cells.
3)
Delaying gastric
emptying
4)
Stimulation
of satietary centre in hypothalamus leading
to reduction in appetite.
All these actions lead to control of post prandial blood
glucose in normal persons In type 2 diabetics recued levels f GLP is one of the
contributing patho physiological factors
responsible for hyperglycemia GLP 1 has
very short biological half life because
immediately after its formation and secretion in ileum, it is degraded by DPP IV enzyme
locally secreted in small
intestine. Thus in order to e
therapeutically effective it has to be given in continuous iv infusion which is not practicable.
Incretin emetics
Extenuative which is a
synthetic derivative of extending found in saliva of Zila monster has a biological half life of 2 hours
and remains effective for about 12 hours
after sc administration in human
begins. It is available in our country
as Byetta since 2007 It shares all the physiological actions
of GLP 1 ad is not degraded by DPP IV enzymes. It’s administration in the dosage
of 5 to 10 mcg in those type 2 twice a day 30-60 minutes before meals
in those type 2 diabetics with viable
beta cells leads to
significant reduction in post
prandial blood glucose about 1%
reduction in HbA1c and some
reduction in fasting plasma glucose. Its main advantages over SU are weight reduction and absence of
hypoglycemic episodes since it acts only in presence of hyperglycemia. These two properties have led to its vast popularly in western
countries. It is a good alternative to SUs in the management of type 2 diabetes particularly
those who are overweight and can afford to spend around 8000 Rs per month The main side effects
seen in about 10% patients are
nausea and vomiting starting with the
dose of 5 mcg for four weeks and
then increasing to 10 mcg if
required helps to reduce
g I side effects.
Liraglutide : it is a GLP1
agonist having longer
biological half life and needs to be give
once a day thus is more patients friendly As compared to exenatide its other subtle differences are 1) Less pronounced effect on gastric emptying leading
to lesser reduction of post prandial
blood glucose and also lesser gastro
intestinal side effects 2) It reduces
fasting blood glucose as well as HbA1c
by a greater extent , 3) It has
greater homology with glucagon like polypeptide 1 .
Liraglutide been recently introduced in India. Its dose is 1.2
to 1.8 mg sc once a day. The starting dose is 0.6 mg and if well tolerated the dose should be stepped up
to 1.2 mg after 1 week
Indications of Exenatide and liraglutide
Both the agents are
suitable in affording overweight type
2 diabetics Particularly if they are not responding to combination
therapy with OADs and they still have
some surviving beta cell mass
Long acting
Extenatide : A
longer acting version of extenatide with
effective duration of action up
to one week is being developed . In recently
concluded clinical trial long
acting extenatide in the dose
of 2 mg sc once a week has been
able to reduce HbA1 c by 1.6% in 20 weeks.
Incretin enhancers
As mentioned above DPP IV is an enzyme secreted by small
intestinal mucosa in areas next to incretion
secreting cells . it degrades incretins
including GLP 1 immediately after formation thus making
it ineffective as a therapeutic agent However now orally active agents which inhibit DPP IV enzyme are
available. This action leads to sustained availability of physiological amounts of
incretins including GLP 1. If given to diabetic patients these agents effectively
reduce blood glucose level by working through GLP 1.
Sitagliptin is first
agent from this class which
is available for day to day practice . It is given
in once a day in 100 mg dosage by
mouth just before breakfast it is a bit less potent than extenatide because it does not
have equally potent actions on
gastro intestinal motility and satietary centre Unlike extenatide its use does not lead to significant weight
reduction. It is weight neutral
when used alone or in combination with insulin sensitizers it does not lead to significant hypoglycemia because of its glucose
dependent action on beta cells.
Availability I oral form is its
main advantage over extenatide. It has been in clinical use for 3 years while extenatide is in use for 4 years.
It can be a good
alternative for SUs both as monotherapy
if metformin is unsuitable or in
combination with metformin and /or
glitazones. In mild renal
impairment the dose need not be
changed. In moderate and severe
renal impairment the dose is 50 mg and 25 mg once a day respectively Tablets in 50/25 mg strengths
are available but the cost of both is same as 100 mg tablets Vildagliptin is
another agent from this class which has
been introduced recently in India. It’s
usual dose is 50 mg twice a day and has a profile similar to that of sitagliptin. It is not cleared for use has a
profile similar to that of sitagliptin.
It is not cleared for use in renally impaired
patients. Both sitagliptin and
vildagliptin are available in fixed dose combinations with metormin in our
country.
Another DPPs
inhibitor Saxagliptin has been
recently introduced in India. It
is available as a formulation containing 5 mg tablet and is administered once daily .
Its indications and
contraindications are same as those of other DPP4 inhibitors.
Linagliptin
In may 20111 a new DPP4
inhibitor 4th in series linagliptin was launched in USA, IT has a long biological half life as well as ability to maintain rayed GLP1 level
for about 24 hrs . Thus it is true once a day agent . It is safe in
all grades of renal insufficiency and is
administered in same full therapeutic dose
as in those with normal renal
functions thus frequent
monitoring of renal functions is
not required for those on linagliptin.
The main advantages of extenatide and Gliptins over SUs are Lack of weight
gain and hypoglycemic episodes
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