Oral hypoglycemic agents
-
Upload
siham-gafer -
Category
Health & Medicine
-
view
58 -
download
1
Transcript of Oral hypoglycemic agents
![Page 1: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/1.jpg)
Oral Hypoglycemic Agents
dr. Siham G. AltayibMSc. Community Pharmacy
Queen’s University Belfast
![Page 2: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/2.jpg)
Achieve adequate glycaemic control. Avoid short term complications:- hypoglcaemia hyper glycaemia DKA Prevent long term complications Improve quality of life
Goals of diabetes management
![Page 3: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/3.jpg)
The means of controlling blood glucose is 1\ Life style modifications :- 1- diet 2- exercise 3- weight loss2\ Drugs
Con.
![Page 4: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/4.jpg)
The medication available to treat type 2 diabetes can be grouped according to their chemical class and function :
Medications that improve insulin action :1- biguanides 2- thiazolidenedones
Medications that slow glucose absorption:Alpha – glucosidase inhibitors
Options of the therapy
![Page 5: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/5.jpg)
Medication that increase insulin secretion :1- sulphonylureas 2- meglitinide3- D-phenaylalanine drevatives
Medication that restore or duplicate incretion action on insulin secretion and glucagon suppression :
1- GLP-1 agonist2- DPP-4 inhibitors
con
![Page 6: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/6.jpg)
Medication that provides additional insulin exogenous pharmacological insulin
It is important to note that insulin is included in this list not because oral medication faild to work or when patient is not adherent BUT insulin is typically used when
1- there is deceased endogenous insulin secretion OR
2- to decrease glucose toxicity
con
![Page 7: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/7.jpg)
There are many clinical markers that can reflect the predominance of the various pathophysiologic component that contributes to type2 diabetes SO this can guide the selection of the treatment by the doctor . These include :
1- body habits :Apple-shaped body suggest insulin resistanceOverweight also suggest insulin resistance
Medication selection for treatment of type2 diabetes
![Page 8: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/8.jpg)
2- Age : Aging promotes insulin resistance ( therefore the
older the person the more likely he/she is to have insulin resistabce
3- weight change : Recent loss of weight , particularly concurrent
wirth poor diabetes control suggest insulin deficiency
BMI more than 27 suggest insulin resistance
con
![Page 9: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/9.jpg)
4 - duration of diabetes: The longer the patient has had diabetes , the
more like hood that there is insulin deficiency
5- gender: Women with type 2 diabetes lose the protection
against macrovascular disease , so attention to macrovascular risk factors is important
Con.
![Page 10: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/10.jpg)
6- co-existing disease: Presence of other component of the insulin
resistant syndrome suggest the presence of insulin resistance (dyslipediemia , hypertension or gout)
7- side effect profile: Development of side effect from use of medication
might preclude its use e.g. metfornmin
Con.
![Page 11: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/11.jpg)
1-duration of diabetes 2- age of the patient 3- Patient's Life style consideration 4- Degree of glycemic control( severity of
postprandial hyperglycemia) 5- other illnesses 6- Access to drug
The choice of oral therapy should be based on :
![Page 12: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/12.jpg)
7- Economic status of the person with diabetes 8- Mutual agreement between the patient &
doctor ( willingness and ability to use the drug or inject insulin
The choice of oral therapy should be based on :
![Page 13: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/13.jpg)
The ideal OHGA is that which ; 1- conserve islets cell function . i.e . Delay the
subsequent use of insulin
2- improve patient’s compliance ( single daily dosing )
3- reduce the incidence of oral hypoglycemic events
What is the ideal oral hypoglycemic agent?
![Page 14: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/14.jpg)
1- oral agents are never indicated for typ1 diabetes
2- type 2 patients with acute illness 3- surgery 4- state of gastrointestinal disorders ( nausea ,
vomiting or diarrhea )
Contraindications f OHGAs.
![Page 15: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/15.jpg)
Monotherapy should be the initial choice
The step care approach is recommended because of the progressive nature of diabetes
Important points
![Page 16: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/16.jpg)
1- combination of OHGAs with different mechanisms can be indicated if MONOTHERAPY failed to control BG.
NEVER use 2 drugs from the same class
2- when oral therapy failed to achieve glycemic control ISULIN should be added to the regimen OR alternatively replace treatment with OHGAs.
Important points con. :
![Page 17: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/17.jpg)
1 ] sulphonylureas:
Mechanism of action :Stimulates basal as well as glucose - mediated insulin
secretion. Thus resulting in continuous stimulation of the beta cells to release insulin
With progressive betacell failure sulphonyluras fails to control BG So additional OHGA is added or insulin may be required for glycemic contol
1\ drugs that stimulates insulin relase from pancreas ( secretogogus):
![Page 18: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/18.jpg)
1] pancreatic effect :a) Increase insulin release from the pancreas by : stimulating the release of insulin from functioning
beta cell by blocking ATP –sensitive K chanells resulting in depolarization and calcium influx which causes microtubular contraction and release of insulin
b) Suppress the secretion of glucagon from alpha cells
Con. Mechanism of action SU.
![Page 19: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/19.jpg)
![Page 20: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/20.jpg)
2] Extra pancreatic effect: Potentiating of insulin action in target tissues :1- increase the number of insulin receptors2- increase post receptor insulin sensetivity 3- increase glycolysis4- increase glycogenesis ( glycogen storage in liver
and muscles )5- decrease the gluconeogensis ( glucose out put
from the liver
Con. Mechanism of action SU.
![Page 21: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/21.jpg)
Measurement of C-peptide level gives indication of residual ß-cell function
Early use of combination has been shown to reduce glucose toxicity & preserve ß-cell mass
Pharmakokinetics :1- SU. Are well absorbed orally .2- peak plasma concentration within 2-4 hours3- they circulate by binding to plasma protein and can be
potentially interact with other drugs such as sailcylates and sulphonamides which binds to albumin
Con. sulphonylureas
![Page 22: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/22.jpg)
4- elimination is through kidneys .so the half life can be significantly prolonged in the elderly and those with renal diseases
5- SU. Cross placenta & can stimulate foetal beta cell to secret insulin
Clinical use of SU:SU . Is indicated for type2 D. when diet alone is
insufficient to achieve glycemic control.
Treatment should be commenced at low doses and titrated every 4-7 days as needed
Con. sulphonylureas
![Page 23: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/23.jpg)
SU. Can be used alone or in combination with other OHGA or insulin .
Early use of combination has been shown to reduce glucose toxicity & preserve ß-cell mass
A higher effect is observed with high fasting BG. And with high A1c levels
There are 2 generations of SU. The second generation agents are more potent , have
more rapid onset of action & longer duration of action
Con. sulphonylureas
![Page 24: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/24.jpg)
Drugs that incrase sulphonyl urease action :1] by displacing from the protein binding :Phenylbutazone , sulphonamides ( trimethoprime)
2} inhibit metabolism\ excretion :Cimetidin (H2 blockers) , warfarin , chlorampheincol
3] synergize or prolong plasma pharmacodynemic action :
Salicylate ( aspirin) , probranolol , theophelline
Sulphonylureas drug interactions
![Page 25: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/25.jpg)
Drugs which reduce sulphonylureas action :1] drugs which induce SU metabolism :Phenobarbitones , chronic alcohiolism
2] drugs that oppose \ suppress action ( insulin release ):
Corticosteroids, thiazide diuretics , furosemide . Oral contraceptives
Sulphonylureas drug interactions
![Page 26: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/26.jpg)
1] hypoglycemia :The most serious complication ( often result from
law coloric intake )Risk of HG increase in :- elderly &Those with hepatic or renal impairemnt so
long acting SU. Should be avoided in this group of patients
- The highest incidence occures with chlorobromide & glibencalmide ( donil)
Sulphonylureas \ adverse effects
![Page 27: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/27.jpg)
2] stimulate appitaite & weight gain 3] gasteric upset ( nausea , flatulance , diarrhoea
or constipation )4] allergic skin reaction 5] headache 6] rarely bone marrow damage
Sulphonylureas \ adverse effects
![Page 28: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/28.jpg)
1) Pregnancy2) Hepatic or renal insufficienty 3) Major surgary 4) Severe infection 5) Sesetivity to sulpha
Sulphonylureas \ contraindication
![Page 29: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/29.jpg)
First generation :1- Chloropromide 2- tolbutamide
Second generation :1- Gliclazide 2- glibenclamide ( donil)3- glipizide
Third genteration :Glimepride
Con. sulphonylureas
![Page 30: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/30.jpg)
1] Glibinclamide ( donil)
2] Glimipride ( amary)
3]Gliclazide ( dimicrone)
Sulphonylureas \ commonly used
![Page 31: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/31.jpg)
![Page 32: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/32.jpg)
![Page 33: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/33.jpg)
![Page 34: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/34.jpg)
2] Non-sulphonylureas insulin secretogogues: [Meglinitides ]
Meglinitides stimulating the release of insulin from bancreas by binding to the SUR at a site different from the sulphonylurea –binding site .
They inhibit ATP dependant potassium channels in the beta cell membrane which depolarize the cell leading to opening of calcium channels and insulin secretion .
In contrast to SU this release of insulin is glucose dependant , it diminishes at low glucose concentration
1\ drugs that stimulates insulin relase from pancreas ( secretogogus):
![Page 35: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/35.jpg)
These agents stimulate first phase insulin release in glucose dependent manner {reducing the risk of hypoglycemia}
Drugs in this group are : 1- repaglinide 2- Nateglinide Pharmakokinetics : Fast acting Short duration of action (2-6 hours) doses 2-4
dose per day
![Page 36: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/36.jpg)
Designed to minimize meal time blood glucose peaks .( taken before the main meal) , as they help control prandial glucose) so these agents is suitable options for those who need flexible meal timing and in the elderly
Patients are advised to skip dose if meal is missed Metabolize in liver ( to inactive product ) and
excreted in bile
Con .
![Page 37: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/37.jpg)
Con. Repaglinide : Form available in sudan is NovoNorm Strength 0.5-4.0 mg tablets \ staring dose 0.5-2
mg Given just before each major meal 15 kin. Rapid & short duration of action Improve postprandial glycemia Less likely to develop repeated hunger , frequent
eating and weight gain [unlike sulphonylureas]
![Page 38: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/38.jpg)
Side effects: 1- hypoglycemia { rare} 2- nausea and vomiting 3- arthralgia ( joint pain)
Con.
![Page 39: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/39.jpg)
![Page 40: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/40.jpg)
Very rapid onset of action Shorter duration of action 1-10 minutes before meal Lower incidence of hypoglycemia than repaglinide
Nateglinide
![Page 41: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/41.jpg)
These are drugs that improve the sensitivity to insulin in muscle , liver & fat tissues
Medication in this group share the following characteristics :
1- they require the presence of endogenous or exogenous insulin to have their effects
2- the patient must have insulin resistance 3- hence they reduce insulin resistance rather than
insulin quantity so they have good effects in higher glucose levels ..and not likely to cause significant hypoglycemia as treatments that increase insulin levels
2\ insulin sensitizers :
![Page 42: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/42.jpg)
1- biguanides 2- thiazolidenediones
1] Biguanides : These are class of antidiabetic drugs originate
from the french lilac (flower) The only one used now and is effective is
metformin
Con.
![Page 43: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/43.jpg)
Metformin :Use alone or in combination with other drugs Recommended as first-line drug in patient with
type2 diabetes ( guidelines)
Approved for prevention of type 2 diabetes in high risk individuals
Used for polycystic ovary syndrome : insulin resistance with ovarian hyperandrogenism
Con.
![Page 44: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/44.jpg)
Mechanism of action :
1- decrease the intestinal absorption of CHO2- decrease hepatic glucose production 3- increase insulin-mediated peripheral glucose
uptake4- increase glucose utilization (glycogen synthesis5- increase glycolysis through anaerobic pathway
( lactic acidosis)
Con. Metformin
![Page 45: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/45.jpg)
6- dcrease fasting plasma glucose conc. By about 60-7-mg\dl
7- lower blood glucose but not cause hypoglycemia
NB: metformin is appropriate for obese patient with type2 diabetes
Con. Mechanism of action :
![Page 46: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/46.jpg)
pharmakokinetics :1- well absorbed from small intestine2- stable 3- doesnot bind to plasma protein 4- excreted unchanged in urine 5- can be taken in 3 doses with meal6- maximum recommended daily dose is 3g\day ( currently we don’t give more than 2g\day in divided
doses with meal )
Con. Metformin
![Page 47: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/47.jpg)
Secondery beneficial effects : on libids :1\ small reduction in total cholestrol level2- small reduction in triglycerides 3- reduction in LDL4- increase in HDL
Con. Metformin
![Page 48: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/48.jpg)
Side effects :Occurs in 20-25% of patientsGastrointestinal side effects:1- abdominal discomfort , bloating , nausea ,
metallic taste 2- weight loss and diarrhea observed in 10-15% of
patient , depending on dose 3- decrease absorption of vit,B 12
Con. Metformin
![Page 49: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/49.jpg)
adverse effects :1- hypoglycemia : occurs only when combined with
other drugs 2- rarely : severe lactic acidosis particularly in
patients with CHF
Drug interaction:Cimetidine , nifedipine , frusemide
Con. Metformin
![Page 50: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/50.jpg)
Contraindications:1- should be avoided in patients who predisposed to
lactic acidosis ( renal & hepatic disease , heart failure ..) impaired renal function serum cr. >1.4mg\dl for woman or 1.5 mg\l male
2- past history of lactic acidosis 3- chronic lung diseaseThese conditions predespose to increase lactate
production which cause hepatic lactic acidosis which is fetal.
4- all other situatios where OHGAs is contraindicated
Con. Metformin
![Page 51: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/51.jpg)
Contraindications:5- type1 diabetes 6- surgary 7- myocardial infraction 8- elderly 9- pregnancy
Con. Metformin
![Page 52: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/52.jpg)
Metformin in market
![Page 53: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/53.jpg)
Metformin in market \combination
![Page 54: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/54.jpg)
Also known as :1- PPRAs ( peroxisome prolifelator activated
receptors )2- glitazones ( TZDs.)Untilrecently there were 3 TZDs :1- pioglitazone ( Actos)2- posiglitazone ( Avandia)3- troglitazone ( rezulin)
2] Thiazlidenediones
![Page 55: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/55.jpg)
Mechanism of action :Antihyperglycemic : 1- increase insulin sensetivity in liver and
muscle 2- do not increase insulin secretion3- reduce hepatic glucose output4-improve lipid profile 5- may induce weight gain
Con. Thiazlidenediones
![Page 56: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/56.jpg)
Rosiglitazone :
Bioavailability of oral dose 99%Extenseivelly 98.5% bound to plasma protein
Metabolites have no significant activity
Plasma half life is 3-4 hours
Excreted in urine and stool
Use as single or divided to two doses per day
Con. Thiazlidenediones
![Page 57: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/57.jpg)
Pioglitazone:Execreted primarily in the stool
Half life 3-7 h
Extensively 99% bound to plasma proteins
Can be given in single dose
No evidence of drug induced hepato toxicity
Con. Thiazlidenediones
![Page 58: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/58.jpg)
Side effects :1- weight gain because of insulin like effects 2- fluid retention ( lower limb oedema )3- liver enzyme elivation ( the firstTZDs troglitazone was
withdrawn from market because of hepatotoxicity )4- most common sside effects : Headache , CHF , fatigue , slight decrease in
heamoglobin , hepatic cellular injury ( rare )
Con. Thiazlidenediones
![Page 59: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/59.jpg)
Contraindications 1- cardiac failure 2- impaired hepatic function 3- pregnancy and lactation
Drug interaction :Not recommended to be used with oral contraceptives )
Con. Thiazlidenediones
![Page 60: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/60.jpg)
![Page 61: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/61.jpg)
Alpha glucosidase inhibitors AGIs) :
Acts in the proximal small intestine They reduce the rate of digestion of
polysaccarides . They reduce intestinal absorption of starch , dextrin , and disaccharides by inhibiting action of alpha glucosidase enzyme , thereby primarily lowering postprandial glucose levels .
AGIs , donot prevent absorption of complex carbohydrates but delay it
3] drugs that delay glucose absoption
![Page 62: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/62.jpg)
There are 2 drugs :1- acarbose 2- miglitol Side effects :Gastric upset ( flatulanse , loose stool or diarrhae ,
abdominal paintolerability can be improved by slowly titrating the dose over
several days Drug interaction:Decrease metformin bioavailability when used concomitantly
Con. Alpha glucosidase inhibitors AGIs) :
![Page 63: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/63.jpg)
![Page 64: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/64.jpg)
![Page 65: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/65.jpg)
Con. Alpha glucosidase inhibitors AGIs) :
![Page 66: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/66.jpg)
Are naturally occurring hormones secreted by the intestine in response to meal when BG is elevated
Increased incretin levels signals : 1- incrase insulin secretion 2- stop hepatic glucose production
The levels of incretins increases significantly when food is ingested
4] incretins & DPP-4 inhibitors
![Page 67: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/67.jpg)
Endogenous hormones are : 1- GLP-1 ( glucagon like peptide 1) 2-,GIP ( glucose dependant insulinotropic peptide ) 1\ GIP : 42 amino acid peptide Secreted from dudenum & proximal jejenum ) 2] GLP_1: 30 amino acid peptide Secreted from the distal GI tract ( ielum & colon)
Con. Incretins & DPP-4 inhibitors
![Page 68: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/68.jpg)
Action : Increase insulin production from beta cells Decreas glucagon secretion )
The physiological activity of incretin is limited by the enzyme dipeptidyle peptidase-4 (DPP-4) .which rapidly degrades active incretin after its release
Consequently both GLP-1 & GIP are rapidly inactivated by the enzyme dipeptidyle peptidase-4 (DPP-4)
Con. Incretins & DPP-4 inhibitors
![Page 69: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/69.jpg)
DPP-4 inhibitors
![Page 70: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/70.jpg)
Mechanism of Action : Slow the inactivation of incretin hormones ( GLP-1
& GIP) Increased glucose stimulated insulin secretion Cause glucose stimulated glucagon suppression Primarily reduce postprandial glucose levels but
also has been shown to reduce fasting BG levels
DPP-4 inhibitors
![Page 71: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/71.jpg)
![Page 72: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/72.jpg)
![Page 73: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/73.jpg)
![Page 74: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/74.jpg)
![Page 75: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/75.jpg)
SGLT-2 inhibitors
![Page 76: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/76.jpg)
![Page 77: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/77.jpg)
Inhibit the reabsorption of glucose by kidneys so glucose levels in urine will be increased { this is an insulin independent mechanism to lower blood glucose levels
Advantages : Improve glycemic control Weight lloss Carry low risk of hypoglycemia
SGLT-2 inhibitors
![Page 78: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/78.jpg)
Examples : Dapagliflozin Canagliflozin
SGLT-2 inhibitors
![Page 79: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/79.jpg)
Life style :
![Page 80: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/80.jpg)
![Page 81: Oral hypoglycemic agents](https://reader035.fdocuments.us/reader035/viewer/2022062316/5886f73e1a28ab4e3a8b4b7f/html5/thumbnails/81.jpg)
Thank you