Anti Diabetics Flashcards
Insulin secretion mechanism
Glucose in blood increases –> cell depolarizes –> Ca+ triggers insulin secretion
Insulin receptor
a subunit for recognition
b subunit tyrosine kinase and phosphorylates tyrosine
Insulin inhibits
gluconeogenesis
Insulin causes
- glucose entry in muscle and adipose tissue
- glycogen synthesis in liver and muscle
- fatty acid synthesis and storage
- amino acid uptake
- glycolysis
Rapid acting insulin is
fast onset, short duration
Short acting insulin is
rapid onset
Long acting insulin is
slow onset, long duration
Rapid acting insulin analogs
Insulin Lispro
Insulin Aspart
Insulin Glulisine
Rapid acting insulin analogs mimic ___
prandial release of insulin
usually given with long acting insulin
given 15 min before meal
Short acting insulin __
soluble crystalline zinc insulin
given 30 minutes before meal
Intermediate acting insulin ___
Neutral protamine Hagedorn (NPH)
aka. Isophane insulin
Crystalline zinc + protamine
used for basal control
Long acting insulin analogs
Insulin Glargine
Insulin Degludec
Insulin Detemir
Rapid and long acting insulin do?
- improve HbA1C levels
- reduce hypoglycemia
Standard mode of insulin therapy is
SC injection
IV insulin is used in
- pt with ketoacidosis
- perioperative period
- labor and delivery
- ICU
Inhaled insulin AE and CI
- cough, throat pain, hypoglycemia
CI:
- copd
- asthma
- smokers
Insulin regimen goals?
replace basal insulin and pradnsial insulin
2 methods of insulin release
- basal bolus insulin regimens
2. insulin pump therapy
Basal bolus insulin regime
- one shot of long acting insulin when fasting
- doses of rapid acting around mealtimes
Insulin pump therapy
best way to mimic normal insulin secretion
- glulisine, lispro, or insulin aspart is used in the insulin pump
The biggest AE of insulin
hypoglycemia
- less risk with rapid than regular
- less risk with long than NPH
If you have mild hypoglycemia?
drink OJ, or have sugar
If you have severe hypoglycemia?
IV glucose infusion
Drugs that cause hypoglycemia
Ethanol
B blockers
Salicylates
Drugs that cause hyperglycemia
- Epinephrine
- Glucocorticoids
- Atypical antipsychotics
- HIV protease inhibitors
- Phenytoin
- Clonidine
- Ca2+-channel blockers
- Diuretics
NON- insulin antidiabetic agents
- Insulin secretagogues
- Biguanides
- Thiazolidinediones
- A glucosidase inhibitors
- Incretin analogues
- Inhibitors of DPP-IV
- Amylin analogs
- Bile-acid sequestrants
- SGLT2 inhibitiors
Insulin secretagogues
Sulfonyureas
Meglitinides
Sulfonyureas
1st gen and 2nd gen
reduce fasting plasma glucose and HBA1C
- stimulate insulin release from B cells by binding to SUR1 subunit and blocking K channels
AE:
- hypoglycemia
- weight gain
First gen sulfonylureas
Chlorpropamide
AE:
- hypoglycemia
- hyperemic flush when alcohol ingested due to inhibitiono f aldehyde dehydrogenase
- SIADH
CI:
- old ppl
Second gen sulfonylureas
Glyburide
Glipizide
Glimepiride
- more potent than 1st gen
AE: - hypoglycemia
- weight gain
Meglitinides
Repaglinide
Nateglinide
- not as effective as sulfonylureas
- rapid onset, short duration
- postprandial glucose regulators
- take before each meal
AE:
- weight gain
CI:
- pt with sulfur allergy
Biguanides
Metformin
Metformin
AE:
- GI
- impaired B12 absorption
- lactic acidosis
CI:
- renal, hepatic disease
- hypoxia
- alcoholism
first line of therapy in type 2 diabetes
TZDs
promote glucose uptake in adipose tissue
➢ Pioglitazone
➢ Rosiglitazone
slow onset
MOA: gene regulation AE: - fluid retention, edema - weight gain - CHF
CI:
- heart failure
liver function monitoring required
a-Glucosidase Inhibitors
Acarbose
Acarbose
MOA:
- reduces postprandial digestion of starch
- reduces absorption
- drop HBA1C and FPG lvl
AE:
- GI effects
- hepatic. enzyme elevation
CI:
- IBS
liver function monitoring required
Incretin analogs
Exenatide (injectable)
Exenatide
analog of Glucagon like polypeptide 1
agonist of GLP-1 receptor
resistant to dipeptidyl peptidase IV (DPP-IV)
MOA:
• Enhances glucose-dependent insulin secretion.
• Suppresses postprandial glucagon release.
• Slows gastric emptying.
• Decreases appetite.
• May stimulate β-cell proliferation
AE:
- nausea, vomiting
- acute pancreatitis
CI:
- pt with gasteroparesis
Inhibitors of DPP-IV
Sitagliptin
Sitagliptin
MOA:
- inhibitor of DPP-IV
- increase GLP1 and insulin
AE:
- pancreatitis
- hypersensitivity reactions
Amylin analogs
Pramlintide
Pramlintide
MOA:
- analog of amylin
- inhibits food intake, gastric emptying and glucagon secretion
BIle acid sequestrants
Colesevelam
Colesevelam
MOA: lower LDL cholesterol used for type 2 DM
SGL2 inhibitors
Canagliflozin
Canagliflozin
MOA:
- blocks glucose reabsorption
- increased glucose excretion and decreased blood glucose lvls
AE:
- UTI
- hyperkalemia, hypermagnesmia
CI:
- pt with GFR < 45
type 2 DM inital drug therapy
metformin
monotherapy reduce HBA1C by 1%
Dual combination therapy
after 3 months if monotherpay doesnt help add second oral agent
GLP1 agonist or insulin
Triple combination therapy
if 2 drug doesnt help add 3rd agent might need to get –> insulin if HBA1C > 8.5%
GLP1 receptor agonist vs. Insulin
GLP1 RA is better injectable option because minimize hypoglycemia and weight gain
When is insulin initial therapy for type 2 DM
- ongoing catabolism (weight loss)
- hyperglycemic syndromes
- ketonuria
- HbA1C > 10%
- random glucose > 300
Gestational DM (preganancy)
NPH insulin single dose and id postprandial glucose control needed then add insulin lispro or aspart
DM with CVD
- ACEI/ARB
- Statins
- Aspirin
DM with nephropathy
- ACEI/ARB
DM with gastroparesis
prokinetic agents: metoclopramide or erythromycin
DM with erectile dysfunction
phosphodiesterase type 5 inhibitors
Glucagon
secreated by pacreatic a cells
increases: glycogen degradation, gluconeogenesis, fatty acid oxiziation, insulin release
decreases: glycolysis
Glucagon uses:
- severe hypoglycemia
- radiology of bowel
- B blocker poisoning
- C peptide test
