Endocrine DM Flashcards
MOA -Flozin
SGLT2 Inhibition
Define Impaired fasting glucose
> or equal to 6.1 but< 7.0 mmol/l
offered an oral glucose tolerance test
Define impaired glucose tolerance (IGT)
fasting plasma glucose > 7.0 mmol/l
OGTT 2-hour : > or = to 7.8 mmol/l but < 11.1 mmol/l
Rx DM1 and a BMI > 25
Metformin
In pregnancy what is fasting glucose & 2-hour glucose cut off?
fasting glucose is >= 5.6 mmol/L
2-hour glucose is >= 7.8 mmol/L
Increase levels of incretins such as GLP-1 and GIP
DPP-4 inhibitors
-Gliptan
bind to an ATP-dependent K+ channel on the cell membrane of pancreatic beta cells; blking channel = stimulation of insulin release
Sulfonylurea
average plasma glucose using HbA1c
average plasma glucose = (2 * HbA1c) - 4.5
HNF-1 alpha is ass w/
MODY
drug & class= increasing urinary glucose excretion
Gliflozins - SGLT2 inhibitors
To be given w/ risk of CVD or chronic heart failure
In patients with T2DM, SGLT-2 should be introduced at any point
Insulin in DKA
started at a rate of 0.1 units/kg/hour.
If falls below 15mmol/L but the pt is still acidotic w/ ketones then an infusion of 5% dextrose & and cont 0.9% sodium chloride, and insulin.
Fluids in DKA
1L 0.9% sodium chloride over an hour, followed but 2x 1L 0.9% sodium chloride over 2 hours etc
Insulin in hyperglycaemic hyperosmolar state (HHS)
0.05 units/kg/hour
AntiDms that Stimulate the secretion of insulin from pancreatic
β cells (Insulinotropic agents )
-Glucose-dependent 2
-Glucose-independent (2)
- Glucose-dependent (GLP-1 agonists, DPP-4 inhibitors): Insulin secretion is stimulated by elevated bl glucose levels (postprandially).
- Glucose-independent (sulfonylurea, meglitinides): Insulin is secreted regardless of the blood glucose level, → risk of hypoglycemia
Depend on residual β-cell function
Sulfonylureas MOA
-ide
Trigger the closure/ blockage of ATP-sensitive K+ channels,= stim insulin exocytosis
Increase insulin secretion from pancreatic β cells
SE Sulfonylureas (4)
- Risk of hypoglycemia (2nd gen)
- Weight gain
- Disulfiram-like reaction
(first generation) - Hematological changes: agranulocytosis, hemolysis
Contraindications of Sulfonylureas (4)
- Severe cardiovascular comorbidity
- Obesity
- Severe renal or liver failure
- Sulfonamide allergy (particularly long-acting substances)
MOA Meglitinides
Increase insulin secretion from pancreatic β cells
SE Meglitinides
Nateglinide
Repaglinide
Risk of hypoglycemia
Weight gain
MOA DPP4 - gliptin
-gliptin
Inhibit GLP-1 degradation → ↑ glucose-dependent insulin secretion
↓ glucagon secretion,
slow gastric emptying (↑ feeling of satiety, ↓ weight)
SE DPP4 - gliptin(6)
- GI symptoms
- Pancreatitis
- Nasopharyngitis URTI
- Headache, dizziness
- Arthralgia
- Edema
MOA: Glucagon-like peptide-1
(GLP-1) agonists (incretin mimetic drugs) - tide- ( gulptide)
tide-
Stimulate the GLP-1receptor directly
SE: GLP-1 agonists
tide-(gulptide)
- ↑ Risk of pancreatitis and possibly 2. pancreatic cancer
- Nausea
Contraindications GLP-1 agonists
tide-(gulptide)
Preexisting, symptomatic gastrointestinal motility disorders
MOA Biguanides
acts by activation of the AMP-activated protein kinase (AMPK)
Enhances the effect of insulin
1. Increase glucose up take
2. Increase glucose sensitivity
3. decrease glycogenesis
SE Biguanides (4)
- Lactic acidosis
- Weight loss
- GI (diarrhea, abdominal cramps)
- ↓ Vitamin B12 absorption
Contraindications Biguanides
- CKD
- paused before administration of iodinated contrast medium and major surgery.
MOA: Sodium-glucose cotransporter 2
(SGLT-2) inhibitors -gliflozin
-gliflozin
Increase glucose excretion with urine through the inhibition of SGLT-2 in the kidney
SE: SGLT-2 inhibitors -gliflozin
-gliflozin
1. Genital yeast infections and UTIs
Glucosuria
2. Polyuria & dehydration
4.DKA
2. Weight loss
3. ?breast cancer, bladder cancer
Contraindications: SGLT-2 inhibitors -gliflozin
-gliflozin
Recurrent urinary tract infections
CKD
Interactions with GLP-1 agonists
tide-(gulptide)
Warfarin: ↑ INR
MOA Thiazolidinediones
-glitazones
-glitazones
-Reduce insulin resistance through the stimulation of peroxisome proliferator-activated receptors
(PPARs)
- Increase transcription of adipokines
SE: Thiazolidinediones
-glitazones
1.Edema
2. Cardiac failure
3. Weight gain
4.↑ Risk of bone fractures (osteoporosis)
5.↑ LDL
MOA: Alpha-glucosidase inhibitors - Acarbose
Inhibit alpha-glucosidase (a brush border enzyme expressed by intestinal epithelial cells) → delayed - & ↓ intestinal glucose absorption
- & ↓ carbohydrate breakdown,
- resulting in ↓ hyperglycemia after food ingestion
SE: Acarbose
- GI sx (flatulence, bloating, abdominal discomfort, diarrhea)
Contraindications to Acarbose
- Severe renal failure
- IBD
- Conditions associated with malabsorption
Fx insulin
Stim uptake of glucose in Liver, Mscl & fat = decrease glucose in the blood
What is sugar stored as in the liver and how is it stored in cells
Liver Glycogen
Cells - ATP
What the Fx GLP
Stim b- cells to release insulin
What happens when there is not enough sugar in the blood
Glucagon is released by alpha cells
which breaks down stored glycogen
Most common form of Mody & genetics
MODY 3
60% of cases
due to a defect in the HNF-1 alpha gene
is associated with an increased risk of HCC
RX MODY
very sensitive to sulfonylureas, insulin is not usually necessary
2 drugs that increase insulin sensitivity & reduce production of glucose
Biguanies
Thiazolidinediones
MOA metfotmin
How does metformin increase insulin sensitivity
Ampk inhibits genes that promotes gluconeogenesis
Causes gult 4 to inbed in plasma membrane of skeletal & fat tissue =allow glucose to enter
How does meformin (3)
- Via ampk inhibits glconeogenesis
- Via AMPK increases insulin sensitivity of tissues by causing the Gult4 in mscl & fat to imbed Into plasma membranes =increase uptake of glucose
- decrease intestinal abs of glucose
MOA thiazolidinediones “glitazones” ?
Via ppar gamma receptor that regulates tanscription = increase of insulin sensitivity in mscl , fats, liver
- Increase syn. Of protein in lipid metabolism = decrease in triglycerides increase HDL & LDL
SE glitazones
Describe release of insulin
Sugar in blood cause glut2 receptors on cell to open & glucose to made into ATP
ATP closes k+ channels = build of of K which = open is ca2+ channel
Ca2+ = exocytosis of insulin
Effect of sulfonylureas on K channels
Closes k= build up of k=ca2+ channels open = release of insulin
SE sulfonylureas
Which is the drug that acts like sulphurias
Fx and example of incretins
Hormones like glp1 cause reduced bl glucose after a meal
by stim insulin release
Fx of glp 1 agonists
What is the fx of dpp4?
Breakdown of glp1
Se dpp4 inhibitor (4)
Explain the transportation of lipids (lipoprotein)
Chylomicrons - travel from gut to liver
VLDL- carrying triglycerides & cholesterol to body from liver
LDLcarry cholesterol to the body from liver
HDL is secreted from the liver to pick up excess cholesterol and bring them back to the liver
How do stains work?
Inhibit cholesterol synthesis via HMG-CoA reductase
No cholesterol will cause increased hepatocyte receptors for LDL, vLDL
MOA Fibrates
SE fibrates
