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Anti-diabetic medications

this is a video on anti-diabetic

medications we're going to be talking

about drugs used to treat diabetes

mellitus by lowering blood glucose

levels before we begin we're going to

break down the list of drug classes that

we have on the left here we have the

insulin sensitizers the

insulin-secreting Oggs the anti

alpha-glucosidase is which allow for

slow absorption of carbohydrates we have

peptide analogs that serve a couple

functions that we'll talk about we have

the glycol so your X which block

reabsorption of glucose in the kidneys

and then we have two random grab-bag

drugs that are approved for

anti-diabetic purposes but really have

other primary purposes that's a bile

acid sequestrants colas civilian and

bromocriptine a dopamine agonist when I

start off by talking about insulin which

is of course a protein that decreases

blood glucose levels insulin comes in

many formulations all of them break down

to find the insulin receptor and the

insulin receptor activates a tyrosine

kinase receptor pathway that does the

many effects

oklets of insulin these insulin variants

can be used for diabetes type 1 type 2

as well as gestational diabetes we're

start with a rapid acting insulins these

are lists Pro s part and glue the seen

these are monomeric insulin analogs they

are monomers in solution they break down

pretty quickly and that's why the rapid

acting so the peak time here is one hour

and there's really no lag before these

rapid acting insulins start to take

effect so that lag is a mnemonic that

can help you remember Lisp Pro s parts

and glue the scene these are used for

postprandial glucose control that means

controlling your glucose after a meal

you might pop these in right after a

meal or right before meal or during a

meal to help control the postprandial

glucose spike next we have short-acting

insulin this is just called regular

insulin it's the same insulin found in

the human body

it's a dimer or hexamer in solution

breaks down a little more slowly

the rapid-acting insulin so it reaches

its peak in two to four hours this is

administered intravenously for people

who come in in diabetic ketoacidosis

next up is the intermediate acting

insulin this is called NPH it Peaks in

four to ten hours so intermediate amount

of time before it reaches its maximum

potential but it's not quite as long

acting as the long-acting insulin which

is glargine and debt Amir which don't

really peak at all they kind of go in

your body and they and they even

precipitate at body pH depending on the

pH s some of them might might not even

be in solution so these don't really

peak as I said earlier the relatively

flat and because they're relatively flat

they're good for mimicking the basal

glucose levels that your pancreas

usually secretes so in people with type

one diabetes they might be given a

long-acting insulin that kind of keeps

up that basal insulin release

next is the Bhagwad eyes big one here is

metformin very commonly used drug for

diabetes metformin mechanism of action

is to sensitize to insulin it does this

by stimulating the liver enzyme amp K

the exact mechanism of action is unclear

but it's definitely through that enzyme

ampk this does not require functioning

beta cells so it means it does work in

DM type 1 as well as DM type 2 it's more

effective in the liver than the muscle

at sensitizing to insulin and that's in

contrast to another drug that we'll talk

about later metformin is an is

administered orally it decreases

hemoglobin a1c by about one to two

percent which is a pretty good decrease

compared to some of the other drugs on

this list we also see mild weight loss

with metformin use some side effects

include diarrhea nausea vitamin b12

deficiency and the commonly tested one

is lactic acidosis so it's important to

to associate metformin with the risk of

lactic acidosis metformin is

contraindicated in liver kidney and

heart failure so somebody's kidneys

aren't working don't give a metformin

metformin is first-line for diabetes

type 2 in addition to or sometimes

slightly after weight loss and exercise

next is the style addenda dones

these are also called T CDs or the

glitter zones to drugs that are worth

knowing or Pio glitter zone and Rosie

glitter zone these like metformin

sensitized to insulin they increase the

number and sensitivity of insulin

receptors they specifically bind to the

PPAR gamma receptor that's the

peroxisome proliferator activated

receptor gamma receptor they are more

effective in the periphery this is the

muscle or the fat tissues than the liver

unlike metformin and they do not require

functional beta cells again so this

could be used in type 1 and type 2 these

glitter zones are also administered

orally and they decrease hba1c by 1 to

1.5 percent also a pretty good decrease

these are uncommon these are unpopular

because they cause mild weight gain

which is usually the opposite in what

we're trying to do in diem patients they

can also increase a LDL which can put

you at risk for coronary problems

they're also pretty expensive and slow

onset so it's easy understand why these

are less popular than metformin side

effects here as we said earlier our

weight gain we see some edema we also

see heart failure liver toxicity and

fractures of the bones but these are

safe with renal failures if you have a

patient with dm2 has some renal failure

you might not be able to give them at

Foreman but you can give them one of the

Glitter zones next up are these two

categories which are the

insulin-secreting dogs they increase the

secretion of insulin directly they both

tend to decrease hba1c by about one to

two percent also pretty effective suffix

here o that they cause weight gain and

they put you at risk for hypoglycemia

which kind of makes sense if you're May

forcing the body to release its stores

of insulin it's possible that too much

insulin would be released and you can

become hypovolemic so people also have

allergies specifically to the

sulfonylureas

people who have sulfa allergies might

not want to give them the Silvano

ureas and they're administered orally so

let's talk about the two groups cell

phone to your wheels these are broken

down into first generation and second

generation the first generation

sulfonylureas are told beautified and

chloro provide and the second generation

sulfonylureas are glipizide

Colibri ride and glimepiride these last

three second generation I'll start with

GL and end with IDE that's how I

remember I'm second generation so funnel

yuri is these bind to the cell phone or

your cell phone or your real receptor on

the ATP activated potassium channel of

beta cells and they do require

functional beta cells so they bind to a

fatass iam receptor they block it

forcing the those beta cells to

depolarize which makes the calcium

channel on those cells open up calcium

rushes in and it releases insulin it's

worth looking into the release mechanism

of insulin to understand this so they

block that potassium channel calcium

influx into the cell and it activates

insulin release similar mechanism of

action in McGlinn ID so these are

rapidly died and the tag line ID so they

end in england ID these bind to another

receptor to block the potassium channel

so it's this it's a different receptor

on the same potassium channel they have

the same mechanism of action after that

so they block the potassium channel

which leads to calcium influx and that

again activates insulin release the

second group the militant IDEs have

faster onset and a slower duration and

they're also more expensive compared to

the sulfonyl ureas next drug is anti

alpha-glucosidase these two drugs are

acarbose

and mcglue tal mechanism here is at the

slow absorption of carbohydrates in the

proximal gut alpha-glucosidase is an

enzyme that hydrolyzes carbohydrates in

the brush border of the gut so if you

inhibit this enzyme they're going to

slow the absorption and slow the

breakdown and slow the absorption of

carbohydrates in the gut so you're going

to delay car break down and thus delay

carb absorption you're also going to

decrease post post prandial

hyperglycemic spikes using these drugs

they're getting administered orally you

want to get them into the GI tract they

increased the they decrease the hba1c

percentage by a modest amount point five

to one percent and one of the big cons

of using these drugs are the severe

flatulence and

other GI disturbances that you get by

using this which kind of makes sense

you're kind of feeding your gut bacteria

a bunch of glucose that you're failing

to absorb so people tend to have gas and

that causes poor adherence to these

drugs they're also pretty expensive next

group of drugs is the in critten

mimetics it's worth reviewing that the

inc Returns which are glp-1 and GIP our

gut derived hormones have a couple

functions they stimulate insulin release

they inhibit glucagon secretion and they

slow gastric emptying they also promote

satiety so we can stimulate inc return

release and by eating by stretching the

stomach in the gut and it's secreted by

the gut there are a couple analogs to

these in cretons or in critten mimetics

that we can administer as medicine to

get these same four effects these glp-1

receptor analogs are eggs and tied low

reglue tied and dual a glue tied so that

again they mimic that ink return and

they produce the same in critten effects

which can result in weight loss which

can be desirable to patients next we're

going to talk about an enzyme called

dipeptidyl peptidase-4 which is the

enzyme that breaks down these in cretons

so you can imagine that if you inhibit

dpp-4 you're going to have your

endogenous in cretons around for a

longer amount of time and that's exactly

what dpp-4 inhibitors do they increase

the blood concentration of your in

cretons so the drugs that do this the

drugs that inhibit dpp-4 are the egg

Lipton's

so we have sittig lipton we have sexy

GLIP 10 and linagliptin these are the

dpp-4 inhibitors that break that block

the breakdown of in cretons and these

are also administered orally next group

of drugs is the emmalin analogs so

there's a synthetic Emaline analog

called pram lin tide now Emlyn is

usually a molecule that's co secreted

with insulin in the body some people

call it the second blood glucose

decreasing drug so it has the following

effects

inhibits glucagon secretion it slows

gastric emptying and it promotes satiety

so these emmalin analogues act like the

endogenous molecule emmalin and it has

these three effects the synthetic

version is called pram land tide and

they decrease hba1c by modest amount

again point five to one percent side

effects here are nausea and hypoglycemia

these can also promote moderate weight

loss which can be desirable and these

are also administered orally or

subcutaneously next is a group of drugs

called the glycosyl Eurex these promote

renal secretion of glucose renal

excretion they are excreted glucose is

excreted through the kidneys so there's

a transporter in the distal convoluted

tubules

called excuse me there's a transporter

in the proximal tubules called the

sodium-glucose cotransport ER - and if

you kind of promote this channels

activity you're going to absorb more

glucose if you inhibit this transporters

activity they're going to be dumping

more glucose into the urine you're going

to be wasting glucose and that's one

method of lowering your blood glucose

level so if you inhibit the sglt2

co-transporter you're going to have an

effect of decreasing blood glucose and

that's what these drugs do so we have

connect the flows in Depok glyph losen

and impact LIF flows in now I remember

these in that they all have flow in them

they all ended flows in and that's

because they allow for the free flow of

glucose through the renal tubules and

out in the urine

these also decrease hba1c by a modest

amount point five to one percent and

there's a whole list of side effects

that are related to peeing out excess

glucose here but your risk UT is

especially in women you can get vulva

vaginal candidiasis which is yeast

infections in the vagina you can get

glycosuria which is kind of the point

you want to be peeing out

glucose you can get renal failure and

this can also decrease your blood

pressure cause dehydration and cause

hyperkalemia so all kinds of other

kidney affects that you get from

purposely peeing out the glucose these

also promote substantial weight loss

because you're essentially ridding your

body of sugar through your urine next is

a drug that's not primarily used for

diabetes but it is approved for use in

diabetes mellitus

this is colas 7 a.m. it's a bile acid

sequestrants and its exact mechanism is

unknown it decreases hba1c by a very

modest amount point 32.4% so not the

best on this list at all some side

effects for this drug are constipation

dyspepsia nausea and

hypertriglyceridemia next is

bromocriptine which is a dopamine analog

this again is not primarily used for

diabetes but it has been approved the

exact mechanism of action is unknown but

it also decreases hba1c by very modest

amount point 4 2.5%

side effects here are headache dizziness

nausea and vomiting this has been a

overview of drugs used to treat diabetes

mellitus I hope this was helpful and

thank you for listening