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PHARMACOLOGY SEMMELWEIS > DM drugs (A13-14) > Flashcards

DM drugs (A13-14) Flashcards

1
Q

How are insulin drugs classified?

A
  • Rapid-acting - Short-acting - Intermediate acting - Long-acting
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2
Q

3 Rapid-acting insulin drugs (1 in the list)

A

Rapid-acting - Insulin Lispro (A13) - Insulin Aspart (not in the list) - Insulin Glulisine (not in the list)

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3
Q

1 Short-acting insulin (in the list)

A
  • Regular insulin (A13)
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4
Q

1 Short-acting insulin (in the list)

A
  • NPH insulin (A13)
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5
Q

3 Long-acting insulin drugs (1 in the list)

A
  • Insulin Glargine (A13) - Insulin Detemir (not in the list) - Insulin Degludec (not in the list)
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6
Q
  • Insulin Lispro (A13) - Insulin Aspart (not in the list) - Insulin Glulisine (not in the list)
A

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

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7
Q
  • Regular insulin (A13)
A

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

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8
Q
  • NPH insulin (A13)
A

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)

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9
Q
  • Insulin Glargine (A13) - Insulin Detemir (not in the list) - Insulin Degludec (not in the list)
A

Analogue insulin

onset : 2 h (long) peak : flat Duration of action : 12-24 h Clinical application - Provide basal insulin levels in ordinary maintenance regimens

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10
Q

WHAT IS THE SIDE EFFECTS OF INSULING DRUGS?

A
  • 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
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11
Q

What is the Modes of insulin administration ?

A
  • 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
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12
Q

Therapeutic goals of glycemic control in diabetic patient?

A
  • HbA1c < 7%
  • Pre-prandial plasma glucose < 7.2 mmol/L
  • 2 h’ post-prandial plasma glucose < 10.0 mmol/L
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13
Q

How can we classify the non-insulin antidiabetic drugs?

A

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

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14
Q

about Insulinotropic drugs : sulfonyl ureas

A

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
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15
Q

About Insulinotropic drugs : Meglitinides

A

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
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16
Q

About Insulin effect enhancing drugs : biguanids

(non-insulinotropic)

A

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)
17
Q

About Insulin effect enhancing drugs : Glitazones

(non-insulinotropic)

A

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
18
Q

About incretin effect prolonging drugs : DPP4 inhibitors

(non-insulinotropic)

A

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​

19
Q

About incretin effect prolonging drugs : GLP-1 analogue

(non-insulinotropic)

A

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
20
Q

About insulin independent drugs : alpha glucosidase inhibitors

A

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)
21
Q

About insulin independent drugs : SGLT2 inhibitors

A

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
22
Q

Non-insulin type injectable : Amylin mimetics

A

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

PHARMACOLOGY SEMMELWEIS (54 decks)

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