00:01
Let’s take a look at metformin.
00:03
Mechanism… you’re doing everything in
the power these drugs are so that it can properly
exhaust the glucose within your circulation.
00:12
How does it go by doing that?
It actually inhibits the liver from releasing
glucose, inhibits gluconeogenesis and also
peripherally may then increase the uptake
of glucose.
00:26
Metformin, the clinical use, typically first
line of treatment in overweight patients.
00:32
Before you do any of this, what’s your first
step of management?
I’ve mentioned this over and over again,
lifestyle modification, exercise, diet…
exercise, diet.
00:41
It is associated with modest weight loss,
no risk of hypoglycemia as monotherapy.
00:48
But,, there is an interesting side-effect
that you want to know from metformin, it’s
lactic acidosis.
00:54
It is also very importantly contraindicated
in a renal disease, severe hepatic disease
and congestive heart failure.
01:00
Put liver and kidney together contraindicated
when such diseases are concomitantly present.
01:08
The GI side effects of metformin are the following.
01:11
Nausea, diarrhoea; minimized by starting low
with dose type of titration.
01:17
Metformin and its complete, complete picture
of what you want to know for your boards and
wards.
01:23
Now, we come to a family and this family,
well, maybe your uncle’s name is thiazolidine
and your aunt’s family’s name is dione,
put them together you have thiazolidine-dione.
01:34
What’s up with that?
We have two of them the drugs that you want
to know, rosiglitazone and we have pioglitazone.
01:42
Look for the suffix glitazone.
01:47
How does this decrease your glucose?
Increase in peripheral sensitivity of the
receptors for insulin thus enhances and increase
the uptake of glucose.
01:58
Once again, here under monotherapy, no hyperglycemia
and reduces the insulin requirement.
02:03
Remember this is type II diabetic.
02:06
This is contraindicated in class II and IV
CHF or active liver disease… the glitazones
are.
02:16
Monitor liver function test extremely important
may then… remember a lot of effects in the
liver here; causes weight gain and edema because
it may actually release insulin and insulin
is anabolic.
02:28
Concern over increased cardiovascular event
seen with especially rosiglitazone; associated
with bone fracture risk in women.
02:38
Important side-effects here for both your
metformin and thiazolidinediones.
02:43
Let’s continue with our discussion and here,
we have sulfonylureas.
02:47
Well, sulfonylureas include the following.
02:49
We have glyburide, we have glimepiride and
we have glipizide.
02:54
You want to know the suffix -ide, -ide, -ide.
02:56
What’s sulfonylureas?
We’ve talked about the mechanism of action,
blocks the potassium channel, increase the
release of insulin and you are absolutely
at risk of hypoglycemia.
03:08
Here, however, remember you have increase
in insulin release, you can have increase
in C-peptide and you will find here sulfonylurea
perhaps in serum or the urine.
03:21
There is a hypersensitivity that you want
to be very familiar with sulfonylureas, sulfonamides…
sulfo, sulfo, sulfo drugs.
03:29
Next, we take a look at our glinides, if you
see this suffix glinide then you’re thinking
about pancreatic insulin secretion, reduces
post prandial hyperglycemia that your most
obvious, important clinical application of
your meglitinides.
03:54
Mild type of glycemia risk, liver disease,
multiple daily dosing with meals, meals, meals…
that’s what your focus should be on please
with the suffix glinides.
04:03
And we have acarbose.
04:07
Now, for the most part ,rarely used; however,
you need to know it because of mechanism of
action.
04:15
It delays glucose absorption by inhibiting
intestinal alpha-glucosidase… they love
that.
04:23
If you inhibit intestinal alpha-glucosidase
then what are you doing?
You’re not taking up the glucose from the
intestine.
04:32
Now because of this, its indication would
be with once again post-prandial, there’s
no hyperglycemia here with monotherapy.
04:41
However, if you block the glucose being taken
up by the intestine after meal, you can expect
there to be, well, I’m not sure as to whether
or not you want to be near this patient.
04:53
Flatulence, cramps and diarrhoea is what you’re
paying attention to.
04:58
Where are you with acarbose?
Think about this way, a – without carbohydrate
reabsorption… acarbose… flatulence and
diarrhoea.
05:10
Then we have something called DPP-IV inhibitors
and these are gliptines.
05:16
So, a couple of suffixes that you want to
pay attention to, you have –gliptines, we
have our –ides, we have –glinides, and
we have our –glitizides.
05:28
Here, if you are to inhibit your dipeptidyl
peptidase DPP-IV which then inactives GLP-1.
05:38
That’s the mechanism of action for this
newer agent, but really at this point, none
of the studies clinically at this juncture
for need to comment any further.
05:49
Please note 1 DPP-IV and this is a gliptin
drug.
05:54
Now, we have a drug, we’ll talk about a
few drugs in greater detail here and this
known as your exenatide incretin effect…
incretin is an important topic, a lot of research
on this.
06:07
Oral glucose has a greater stimulatory effect
on insulin secretion than IV glucose for sure
because you must be able to get that glucose
metabolized and get from the intestine into
circulation so that you can then allow for
that glucose to work on the beta-islet cell
to release the insulin.
06:24
Hence, any type of test that you do here…
have you heard of an IV glucose tolerance
test?
No, oral glucose tolerance test… incretin
effect.
06:35
Now, this effect is mediated by severe or,
excuse me, several GI peptides particularly
what’s known as your glucagon-like peptide
1.
06:43
GLP-1 is produced in small intestine known
as the L cell GLP in response to nutrients.
06:51
The action of GLP is the following.
06:53
Stimulates pancreas to make insulin, slows
gastric emptying and inhibits inappropriate
post-meal glucagon release and reduces your
food intake, will give you a feeling it’s
incretin effect, a GLP-1 type of issue.
07:10
Exenatide naturally occurring component of
your, well, here we have what’s known as
the heloderma suspectum saliva and sequence
identified with GLP-1.
07:22
Resistant to DPP-IV degradation and therefore
exhibits a prolonged half-life.
07:26
Remember DPP-IV, the –gliptine that I was
talking to you on that table earlier, this
is resistant to DPP-IV so that you can have
more of your incretin effect.
07:40
Used twice daily, same effect as GLP-1 which
is glucose dependent augmentation associated
with weight loss.
07:48
Side effect nausea; acute pancreatitis is
a big deal.
07:52
Approved for use for type II diabetes without
concurrent insulin use obviously otherwise
you’re risking the risk of hypoglycemia.
08:02
It may result to HbA1C up to one percent…
that is significant.
08:07
Remember HbA1C of less than seven percent
is equivalent to approximately a glucose level
of 150.
08:15
Let’s take a look at another one in greater
detail and we have our pramlintide.
08:21
Amylin, 37-amino acid detail beta islet cell;
deficient in type I diabetes mellitus.
08:28
Relative deficiency in type II; action slows
gastric emptying, reduces inappropriate glucagon
secretion and weight loss… welcome to pramlintide.
08:41
It’s an amylin analog, mealtime subcutaneous,
same effect as amylin itself as we just mentioned
in the previous slide.
08:51
Side effect - nausea, here once again may
decrease AbH1C up to one percent.
08:57
I would know pramlintide only so that you
have one analog of amylin.