Anti-Diabetic Agents Flashcards
alpha secretes:
glucagon
beta secretes:
insulin and amylin
delta secretes:
somatostatin
G-cell secretes:
gastrin
F-cell secretes:
pancreatic polypeptide
Insulin
- type of hormone?
- process to make?
- peptide hormone
- made as pre-pro-inslin –> cleaved to pro-insulin –> maturation that cleaves C-peptide leaving just insulin
*positive regulation of insulin release:
- glucose (substrate)
- amino acids (substrate)
- incretins (hormones)
- Epi/Beta2 stim (hormone)
- vagus stim (neuronal)
*Negative regulation of insulin release:
- NE/alpha2 stim (neuronal)
- amylin (hormone feedback)
Insulin secretion is dependent on? Process?
- Calcium - vesicles and docking and stuff
- ATP sensitive K channel closes when ratio of ATP/ADP is high bc of high glucose levels=making ATP –> depolarization –> CA influx)
Insulin receptor and effect on cell upon binding:
bunch of stuff but upreg of GLUT4 transporter on membrane (MUSCLE AND ADIPOSE TISSUE)
GLUT4 is on what tissue? regulated by what?
Muscle and adipose - insulin mediated uptake of glucose
Insulin effects on Liver, muscle and adipose.
1) liver = mediates storage of glucose as glycogen (NOT HEPATIC UPTAKE OF GLUCOSE)
2) adipose= stimulates uptake of glucose (GLUT4)
- uptake and conversion of fatty acids into storage triglycerides
3) Muscle=stimulates uptake of glucose (GLUT4)
- uptake and storage of amino acids into proteins
Type 1 Diabetes
- insulin-dependent diabetes mellitus
- juvenile-onset
- 1a=immune mediated (most)
- 1b=idiopathic
-beta cell destruction = absolute deficiency
Type 2 diabetes
- adult-onset
- non-insulin dependent diabetes
- resistance to insulin and then get insulin secretory deficiency (body tries to inc insulin production to keep up with sugar levels)
-obesity/genetics/nutrition/physical activity
Gestational diabetes
- glucose intolerance in 2nd or 3rd trimester
- 4% get this
- return to normal immediately post delivery
- 40% who get will develop diabetes in next 10 years
type 1 diabetes - signs and symptoms:
1) polyuria/nocturnal enuresis- osmotic diuresis:loss of glucose, electrolytes and water
2) Thirst- hyperosmolar state
3) blurred vision-hyperosmolar state
4) WL/polyphagia
- acute=depletion of water, glycogen, triglyc stores
- chronic=loss of muscle mass as amino acids are used for gucose and ketone bodies
5) Weakness/Dizziness-postural hypertension, potassium loss and muscle catabolism
6) Paresthesias - temporary Periph sensory nerve dysf
7) level of consciousness - depends on level of hyperosmolarity
- slow insulin def = minimal signs but fast deficiency shows fruity breath, ketoacidosis, dehydration, coma,…
Type 2 diabetes- signs and symptoms
1) asymptomatic initially
2) infections - glucose available as E source for microorganisms - skin and candidal vag
3) neuropathy - retinopathy and peripheral neuropathy
4) classic severe insulin deficiency signs - polyuria,thrirst, blurred vision, fatigue, weakness
5) obesity & metabolic syndrome - dyslipidemia, HTN, CAD
Fasting blood glucose levels should be around?
100mg/dL
insulin therapy is required for whcih diabetes?
- type 1
- also used for type2 with declining insulin production/secretion
Whats the point of synthetic insulins pharmakokinetics wise?
We change around a few amino acids of the sequence = different kinetics = how much the insulin sticks to itself (determines length of action)
Rapid acting insulin drugs & duration*
- insulin lispro
- insulin aspart
- insulin glulisine
- inhaled insulin
-3-5 hrs
short acting insulin drugs & duration*
- regular insulin
- 4-12 hrs
Intermediate acting insulin drugs & duration*
- NPH
- 10-20hrs
Long acting insulin drugs & duration*
- insulin Glargine 12-20 hrs
- insulin detemir 22-24hrs
Rapid acting insulin-
- key feature
- peak period?
- amino acid alteration in C-terminal tail of the B peptide preventing insulin complex formation
- peak=30min-3hrs
- insulin lispro
- insulin aspart
- insulin glulisine
- inhaled insulin
Short-acting insulin-
- key feature
- peak period?
- identical to human insulin
- peak=2.5-5hrs
Intermediate acting insulin
- key feature
- peak period?
- protamine-insulin complex
- peak=4-8hrs
Long acting insulin
- key feature
- peak period?
-amino acid subs that result in PPT formation at neutral pH
- insulin Glargine 12-20 hrs PEAK=flat
- insulin detemir 22-24hrs PEAK=NONE
insulin pumps use which insulin?
short acting - the pump is constantly infusing some insulin
Adverse effect of insulin therapy:
- hypoglycemia**
- hypersensitiviy-rare-immune response to non-insulin protein contaminants
- resistance-rare - antiinsulin antibodies
- lipohypertrophy-fat deposition at injection site
- lipoatrophy-fat loss at injection site
If diabetic get hypoglycemia and is conscious vs unconscious?
conscious=food, sugar tablet unconscious=glucose or glucagon
symptoms of hypoglycemia
- tachycardia
- sweating
- tremors
- nausea
- hungry
- neurologic symptoms (irritability, confusion, headache, speech difficulty…)
Glucagon
- type?
- MOA?
- administration?
- AE?
- peptide
- catabolism of stored glycogen
- subcu injection
- safe- nausea, vomit
Metformin
- type?
- MOA
- AE?
- benefit to use?
1) biguanides
2) -decrease hepatic glucose output
- inc peripheral glucose use
- activation of hepatic enzyme AMP-activated protein kinase (AMPK)
3) GI issues
- Vit b12 deficiency
4) no hypoglycemia
first line oral antidiabetic agent for type 2 diabetic
metformin
Which oral anti-diabetic drug is not dependent on beta cell fucntion
metformin
Sulfonylureas - name the drugs?
oral antidiabetic drugs
- glimepiride
- glipizide
- glyburide
Meglitinide-name the drugs?
oral antidiabetic drugs
- repaglinide
- nateglinide
Sulfonylureas and meglitinides
- MOA?
- AE?
- oral antidiabetic drug
- inh ATP-sensitive potassium channel of beta cell=insulin release
- weight gain
- hypoglycemia
Glucosidase inh -
- name the drugs?
- MOA?
- AE?
- oral antidiabetic drug
- acarbose and miglitol
- inh brush border glucosidase enzyme = no absorptio of glucose
- abdominal pain, diarrhea, flatulence bc unabs carbs
COntraindications for glucosides inh?
acarbose and miglitol
-not ok for people with GI disease
Thiazolidinediones (TZDs)
- drugs?
- MOA?
- AE?
-oral antidiabetic drug
-pioglitazone - rosiglitazone
-dec perpheral resistance by activating peroxisome proliferator activated receptor gamme
-effect on glucose metabolism and insulin signaling
AE=periph edema; weight gain; hep tox; bone fractures; hypoglycemia; cardiovascular
Thiazolidineddones - contracindications?
people with heart problems
Prmlintide
- type?
- MOA?
- admin?
- AE?
-amylinomimetic - oral antidiabetic
-inh glucagon release
-inh gastric emptying
-anorectic effect
-synthetic pepetide=injection
-AE=N, V,anorexia, hypoglycemia
delayed drug absorption
Exenatide & Liraglutide
- type?
- MOA?
- admin?
- AE?
- incretins-oral anti-diabetic drugs
- potentiate insulin secretion
- inh glucagon release
- inh gastric emptyng
- anorectic effect
- INJECTION-peptide
- N
- V
- diarrhea
- -acute pancreatitis*
- delayed drug absorption
- hypoglycemia
Sitagliptin, Saxagliptin, Linagliptin
- type?
- MOA?
- admin?
- AE?
- dipeptidyl peptidase (DPP) inhibitors
- inh integrin degredation
- oral admin
- acute/hemorrhagic/necrotizing pancreatitis
- upper respiratory inf
