Antiglycemic medication Flashcards
What is type 1 diabetes
Insulin dependent DM
Inability of b-islets of pancrease to produce insulin
What is type 2 diabetes
Non-insulin dependent DM
- reduced ability of pancreas to produce or secrete insulin
- reduced ability of target cells to respond to insulin (insulin resistance)
Mention types of DM
T1D
T2D
Gestational diabetes
What are the input sources of sugar
- Abs from diet
- biosynthesis in the liver
is insulin a first choice in t2d
No
last choice
is insulin a first choice in T1D
yes
Is insulin a biological drug
No
because it is SMALL in size
MOA of a-Glucosidase inhibitors
blocks a-glucosidase (which is an enzyme that hydrolyzes maltose to glucose)
Mention drugs that fall under the class of a-Glucosidase inhibitors
Acarbose
Miglitol
Voglibose (new)
MOA of Acarbose
a-Glucosidase inhibitor
SE of acarbose
Flatulence
Diarrhea
Colonic gas production from sugar fermentation
bloating
cramping
NOT well tolerated
CI of Acarbose
- chronic GI diseases
- Renal impairment
- Hepatic dysfunction
Acarbose ________ ________ state
mimic transition state
Miglitol _________ ________
Mimic product
is miglitol reversible or not
Reversible a-glucosidase inhibitor
Is miglitol well absorbed
Yes
but no systemic effect ( extremely hydrophilic -> renally excreted)
Is miglitol well tolerated
NO
but still better and less GI effects than a carbose
Why did the USFDA not approve voglibose
Because the studies were only done on asian individuals
Do a-glucosidase inhibitor work on endogenous biosynthesis pathway
No, only on sugars from diet
What is the MOA of sulfonyl ureas
They open potassium channel in B-cells which affect k+ balance -> open Ca+2 channel -> Insulin secretion
What are the generations of sulfonylureas and what are some example drugs
FIRST gen
- Tolbutamide
- Chlorpropamide
- Tolazamide
-Acetohexamide
SECOND gen
- Glyburide
-Glipizide
What are the SE of Sulfonylureas
Weight gain
SAR of sulfonylureas
- R1
- Aromatic ring
- Sulfone
- Urea
- R2 (responsible for activity)
Adding a high hydrophibicity group on R1 will..?
Increase duration of action
What will happen if we add an easily metabolized group like CH3 on R1 and what will happen if we add a slow metabolized group like Cl on R1
in sulfonylureas?
Easily metabolized CH3 like in Tolbutamide
FAST ONSET, SHORT DOA
Slowly metabolized Cll like in CHLORPROMAIDE, GLYBURIDE,GLIMPERIDE,GLIPIZIDE
SLOW ONSET, LONG T1/2 (60hr)
What is the minimum side chain in R1 of sulfonylureas accepted?
What is the maximum
3-C side chain
less than that, no action
3-6 carbons increase activity —–> the BEST
6-12 carbon, NO INCREASE activity
> 12 NO ACTIVITY
Most of sulfonylureas contain cyclic hexane not aliphatic, why
Because cyclic is more soluble and stable than aliphatic
In sulfonylureas, R1 increases —– while R2 increase ——-
R1 -> ACTIVITIY
R2 -> PK
Since Sulfonylureas affect the potassium chanels, can they be given to heart patients
NO
except Glimperide, doesnt affect the cardiac tissue
What is the main concern with sulfonylureas?
HYPOGLYCEMIA
since sulfonylureas increase insulin levels regardless of its level, so we need to organize it with meals
Which have more protein binding, first or second generation sulfonylureas
Second generation glipizide, glimperide… have a high protein binding than first
Signs of HYPOGLYCEMIA
Sweating
Shaking
Irratibility
Sonfusion
Tachycardia
feeling hungry
If sulfonylureas are taken with medication that displace sulfonylureas (LIKE SULFONAMIDE, GEMFIBROZIL, WARFARIN) from their plasma protein binding side what will happen
HIGHER RISKS OF HYPOGLYCEMIA
What is the DOA of chlorpropamide
60 hours! the longest
Do first and second generation sulfonylureas have the same MOA
YES
Sulfonylureas are mostly used in juvenile-onset diabetes?
NOT IN T1D
but it adulthood onset T2D
Is tolbutamide short or long acting ?
SHORT
What % of tolazamide is found in the urine
85%
Is glyburide safe in pregnancy
CATEGORY C
Studies showed that pregnant woman who took glyburide in pregnancy, their children were more likely to be diabetic
not teratogenic
What are the safe glycemic medication in pregnancy
Insulin
Metformin
glyburide
Biguanides contain guanidine group, is it acidic, basic?
BASIC
PKA = 12.5
Why does biguanides cause lactic acidosis?
They block the krebs cycle in mitochondira which lead to pyrovate accumulation in the cell
pyruvate will be converted to lactate
it is not an issue in normal kiney function, it is however a problem in kidney dysfunction
Does phenphormin cause lactic acidosis
YES
Which caused more death cases? metformin or phenformin
phenformin > metformin
Are biguanides only used alone? or can they be in combo
they can be either alone or with sulfonylureas
What is the MOA of metformin
not known but maybe
increase insulin binding to its receptor (increase insulin sensitivity)
At physiological pH, how is the guandinium group
Positively charged -> poorly protein bound
What is the drug reporposing of metformin
Polycyctic ovary cancer
Weight loss (NOT FDA APP)
What is the duration of action of metforn? short long?
Short, 1.7 - 4.5 hr
SE OF metformin
Lactic acidosis
low B12
SAR of thiazolidinediones?
- ACIDIC RING
- LINKER phenyl alkyl
- Lipophilic ring
Where does pioglitazone target
PPAR-Y
PPAR-A
Where does rioglitazone targer
PPAR-Y
SE of pioglitazone
Increase risk of MI
BLADDER CANCER
What does DPP4 break down
Incretins
What is the MOA of sitagliptin
DPP4i (breaks down increitn)
Is Sitaglitptin well tolerated
YES
Is Ozempic a biological peptide
NO
Scientific name of ozempic
Semaglutide
What is Ozempic
GLP1RA
Is ozempic approved for T2D
yes
What is the first GLP1RA approved by fda
Exenatide in 2005
What is the difference between ozempic and wegovy
Same semaglutide but wegovy has double the dose
Which is approved by FDA, ozempic or wegovy
only wegoey is approved
