DM drugs (A13-14) Flashcards
How are insulin drugs classified?
- Rapid-acting - Short-acting - Intermediate acting - Long-acting
3 Rapid-acting insulin drugs (1 in the list)
Rapid-acting - Insulin Lispro (A13) - Insulin Aspart (not in the list) - Insulin Glulisine (not in the list)
1 Short-acting insulin (in the list)
- Regular insulin (A13)
1 Short-acting insulin (in the list)
- NPH insulin (A13)
3 Long-acting insulin drugs (1 in the list)
- Insulin Glargine (A13) - Insulin Detemir (not in the list) - Insulin Degludec (not in the list)
- Insulin Lispro (A13) - Insulin Aspart (not in the list) - Insulin Glulisine (not in the list)
Analogue insulin (amino acid sequence modified to speed-up entry into the circulation, without affecting its interaction with insulin receptor) onset : 5-15 min (rapid) peak : 1h Duration of action : 3-4 h Clinical application - Pre-prandial injections in ordinary maintenance regimens - Preferred insulin for continuous subcutaneous insulin infusion devices - Emergency treatment of diabetic ketoacidosis
- Regular insulin (A13)
Human insulin
onset : 30-60 min (short) peak : 1-3h Duration of action : 4-8 h Clinical application - Pre-prandial injections in ordinary maintenance regimens
- Emergency treatment of diabetic ketoacidosis
- NPH insulin (A13)
Human insulin
onset : 1-2 h (intermediate) peak : 4-6h Duration of action : 8-12 h Clinical application - Combined with short-/rapid-acting insulin preparations
(regular insulin and protamine)
- Insulin Glargine (A13) - Insulin Detemir (not in the list) - Insulin Degludec (not in the list)
Analogue insulin
onset : 2 h (long) peak : flat Duration of action : 12-24 h Clinical application - Provide basal insulin levels in ordinary maintenance regimens
WHAT IS THE SIDE EFFECTS OF INSULING DRUGS?
- Hypoglycemia
- Risk of neurological damage in case of severe hypoglycemia (high-risk groups → advanced renal disease, elderly, children < 7 years old)
- Hypokalemia
- Insulin-induced immunologic complications (very rare with modern preparations)
- Injection site reaction
What is the Modes of insulin administration ?
- Subcutaneous injections with conventional disposable needles and syringes
- Portable pen-sized injectors to facilitate subcutaneous injections
- Continuous subcutaneous insulin infusion devices (avoid the need for multiple daily injections
Therapeutic goals of glycemic control in diabetic patient?
- HbA1c < 7%
- Pre-prandial plasma glucose < 7.2 mmol/L
- 2 h’ post-prandial plasma glucose < 10.0 mmol/L
How can we classify the non-insulin antidiabetic drugs?
1. Insulinotropic
a. Sulfonyl ureas
b. meglitinides
2. Insulin effect enhancing drugs
(non-insulinotropic)
a. biguanids
b. glitazones
3. incretin effect prolonging drugs
(non-insulinotropic)
a. DPP4 inhibitors
4. insulin independent drugs
a: alpha glucosidase inhibitors
b. SGLT2 inhibitors
5. Non-insulin type injectable
a : GLP1 agonist
b. Amylin mimetics
about Insulinotropic drugs : sulfonyl ureas
Sulfonyl ureas (1st gen is toxic and 2nd is more potent)
1st gen (dont need to know)
2nd gen : Glimepiride (A14), Glipizide (A14)
Mode of actions
- Closure of K+-channels in pancreatic β-cells → membrane depolarization → Ca2+ influx triggers insulin release, glucagon release from α-cells ↓
- Continuous use of sulfonylureas enhances tissue response to insulin (especially muscle and liver) via changes in receptor function
- Oral
- Short onset of action
- Type 2 D.M
- Side effects: weight gain, hypoglycemia, rash, sulfonamide hypersensitivity reaction, increased cardiovascular risk, hematological abnormalities (rare)
- Drug interactions (mainly 1st gen’ agents) → hypoglycemia with cimetidine, insulin, salicylates, sulfonamides
About Insulinotropic drugs : Meglitinides
meglitinides
Repaglinide (A14), Nateglinide (not in the list)
- Weaker binding affinity and faster dissociation from the SUR1 subunit of the ATP-sensitive K+-channel
- Oral
- Rapid onset of action, duration of action 5-8 h’
- Type 2 D.M
- Side effects: hypoglycemia
- No sulfonamide hypersensitivity
About Insulin effect enhancing drugs : biguanids
(non-insulinotropic)
Metformin (A14)
Mode of Actions
- Activates AMP kinase → reduces hepatic and renal gluconeogenesis → post-prandial and fasting glucose levels ↓
- Intestinal glucose absorption ↓
- Insulin sensitivity ↑
- Oral
- Maximal plasma concentration in 2-3 h’
- *Indications**
- Type 2 D.M (currently 1st line therapy)
- Restore fertility in women with PCOD and evidence of insulin resistance
- Weight reduction in non-diabetic individuals with obesity (‘off-label use’)
- Hyperinsulinemia (mostly in obese patients)
- *Side effects:**
- GI symptoms (nausea, diarrhea)
- Metformin-associated lactic acidosis (in susceptible patients → impaired renal/hepatic function, CHF, hypoxic/acidotic states, alcoholism)
- AKI in patients on metformin receiving IV iodine-containing contrast agent (stop metformin 1 day prior to examination)
About Insulin effect enhancing drugs : Glitazones
(non-insulinotropic)
Thiazolidinediones (Glitazones, not in the list)
Pioglitazone (need to know)
Mode of Actions
Activate PPAR-γ (nuclear receptor, signaling pathway in adipose tissue):
- GLUT-4 expression, glucose uptake by muscle and adipose tissue ↑ (reduce both fasting and post-prandial hyperglycemia)
- Hepatic gluconeogenesis ↓
- Positive effect on lipid metabolism and the distribution of body fat
- Adiponectin ↑ (increases insulin sensitivity and fatty acid oxidation)
- Oral
- Long duration of action (> 24 h’)
- Contraindicated in CHF and liver disease
Indication :
- Type 2 D.M (in combination)
- *- Side effects:** weight gain, edema, anemia, increased risk of bone fracture, potential hepatotoxicity
- Induce CYP450 activity
About incretin effect prolonging drugs : DPP4 inhibitors
(non-insulinotropic)
DPP4 inhibitors
: Liraglutide (not in the list)
Mode of Actions
Incretin is a family of peptide hormones, released from endocrine cells of the small intestine in response to food; DPP-4 is the endogenous inhibitor of these hormones.
- Insulin release ↑
- Glucagon release ↓
- Delayed gastric emptying
- Satiety
- Oral
- Duration of action 24 h’
- Expansive
Indications:
- Type 2 D.M (monotherapy or in combination with metformin or thiazolidinediones)
- Side effects: headache, nasopharyngitis, upper respiratory tract infections
About incretin effect prolonging drugs : GLP-1 analogue
(non-insulinotropic)
GLP-1 analogue
: Liraglutide (not in the list)
- Parenteral
- Expansive
Indications:
- Type 2 D.M (monotherapy or in combination with metformin or sulfonylurea)
- Weight-loss (liraglutide)
- *- Side effects:** GI symptoms, nausea, hypoglycemia, acute pancreatitis
About insulin independent drugs : alpha glucosidase inhibitors
Acarbose (A14)
Mode of Actions
Inhibit intestinal brush border α-glucosidases → disaccharides degradation ↓ → glucose absorption ↓ (reduce post-prandial glucose level, no effect on fasting level)
- Oral
- Rapid onset of action
- Contraindicated in impaired renal/hepatic function, intestinal disorders
Indications
- Type 2 D.M
- *- Side effects:** hypoglycemia, diarrhea and abdominal pain (GI symptoms due to increased fermentation of unabsorbed carbohydrates by gut bacteria)
About insulin independent drugs : SGLT2 inhibitors
Dapagliflozin (A14)
Mode of Actions
Inhibit sodium-glucose transporter (proximal convoluted tubule) → glucosuria → blood glucose level ↓ (reduce both fasting and post-prandial hyperglycemia)
- Oral
- Expansive
- Contraindicated in impaired renal function
Indications
- Type 2 D.M
- Potential use in CHF
- *- Side effects:** genitourinary infections (high glucose content of urine), osmotic diuresis may result in volume contraction and hypotension
Non-insulin type injectable : Amylin mimetics
Pramlintide (not in the list)
Mode of Actions
Amylin is a peptide hormone (IAPP – islet amyloid polypeptide); released from pancreatic β-cells in ratio of approx. 100:1 (insulin: amylin)
Functions as synergistic partner to insulin:
- Glucagon release ↓
- Delayed gastric emptying
- Suppress appetite
- Synthetic amylin agonist
- Parenteral
- Short duration of action
Indications
- Type 2 D.M
- Type 1 D.M (control post-prandial hyperglycemia)
- *- Side effects:** GI disturbances, hypoglycemia
