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Pharmacology > Diabetes > Flashcards

Diabetes Flashcards

1
Q

PRAMLINTIDE

Use

A

It is an synthetic amylin. Used in non insulin dependent type 2 diabetes. Allows insulin-dosage to be reduced.
Amylin is secreted along insulin by the beta cells, It delays gastric emptying , decreases post meal glucagon secretion and improves satiety
While giving amylin insulin should be reduced 50% to avoid hypoglycaemia

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2
Q

PRAMLINTIDE

Administration

A

Subcutaneously before a meal

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3
Q

Pramlintide MOA

A

Amylin analogue, downregulates hepatic prod. of glucose, slows gastric emptying.

Binds to K-channel, thereby stimulating the release of insulin from the pancreas → ↓glucose

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4
Q

PRAMLINTIDE

SIDE EFFECTS

A 
Nausea 
Vomiting 
Hypoglycemia
● GI disturbances
● hypoglycemia
● Anorexia
● Vomiting
● Headache
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5
Q

PRAMLINTIDE

Contraindication

A

● Diabetic gastroparesis
● Hypersensitivity
● Hypoglycemic unaware patients

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6
Q

Incretin based drugs/ GLP-1 Receptor agonist examples

A

LIRAGLUTIDE
EXENATIDE
DULAGLUTIDE
ALBIGLUTIDE

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7
Q

LIRAGLUTIDE
EXENATIDE
DULAGLUTIDE
ALBIGLUTIDE

USE

A

Non-insulin dependent type 2 diabetes.

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8
Q

WHEN IS EXENATIDE C/I

A

In severe renal impairment

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9
Q

LIRAGLUTIDE EXENATIDE DULAGLUTIDE ALBIGLUTIDE

Mechanism of Action

A

Agonists on incretin GLP-1 receptor → cause insulin secretion to be upregulated and glucagon secretion to be downregulated.

May suppress hunger.

They are analogs of GLP-1 receptors
● Slows gastric emptying, reduces food intake by increasing satiety, promotes beta cell
proliferation
● Occurs due to incretin hormone
● Incretin hormones are responsible for 60-70% of post meal insulin secretion.
● Given subcutaneously

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10
Q

LIRAGLUTIDE EXENATIDE DULAGLUTIDE ALBIGLUTIDE
Incretin based drugs:

Adverse Effects

A

Nausea
● Vomiting
● Diarrhea
● Constipation
● More expensive than metformin (but have no negative effect on heart)
Pancreatitis
Hypoglycemia when used w/other anti-dia agent

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11
Q

LIRAGLUTIDE EXENATIDE DULAGLUTIDE ALBIGLUTIDE

C/I

A

Chronic pancreatitis
Medullary thyroid carcinoma
Multiple endocrine neoplasia syndrome- type 2

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12
Q

DPP-4 inhibitors: EXAMPLES

A

ALOGLIPTIN
LINAGLIPTIN
SAXAGLIPTIN
SITAGLIPTIN

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13
Q

DPP4 s MOA

A

● Inhibitor of DPP-4 that degrades GLP-1 and other incretins
● Blocking DDP-4 GLP-1 & GIP are increased → ↑insulin secretion
● Can be used for monotherapy and combination therapy
● These drugs do not cause satiety and are weight neutral

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14
Q

DPP4s SE

A 
Mild hypoglycemia
● Rhinitis
● Upper respiratory infection
● Allergic reaction
● Headache
● disabling joint pain
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15
Q

DPP4s C/Is

A 
● GLP-1 receptor agonist
● Heart failure
Chronic HF
Acute inflammation of the pancreas Kidney disease (moderate to failure)
Rhinitis
● Upper respiratory infection
● Allergic reaction
● Headache
● disabling joint pain
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16
Q

When is the DPP4 Linagliptin especially used

A

It is good for renal dysfunction

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17
Q

How is linagliptin excreted

A

Excreted via enterohepatic system

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18
Q

What is the C/I of Alogliptin

A

Increased heart failure

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19
Q

How are Sulfonylureas divided?

A

1st. gen: CHLORPROPAMIDE TOLBUTAMIDE TOLAZAMIDE
2nd. gen:GLYBURIDE GLIPIZIDE
3. rd. gen: GLIMEPIRIDE

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20
Q

Sulfonylureas MOA

A
  1. Stimulate insulin release by inhibiting K-channels on β-cells
  2. Increase insulin action on prolonging binding of insulin to target tissue receptors
  3. reduce serum glucagon levels through indirect inhibition

Stimulate insulin release from beta cells of the pancreas
● Block ATP sensitive K channels, resulting in depolarisation
● Calcium influx is seen
● Insulin exocytosis
● It reduces hepatic glucose production and increases peripheral insulin sensitivity
● Duration of action is 12 to 24hrs.

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21
Q

Sulfonylureas SE

A

Hypoglycemia + weight gain

Hyperinsulinemia

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22
Q

Sulfonylureas C/I

A

Interact w/many other drugs
Pregnancy

● Hepatic insufficiency
● Renal insufficiency

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23
Q

What group does metformin belong to

A

Biguanides

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24
Q

Use of Metformin

A 
Non-insulin dependent type 2 diabetes. 
PCOS
 Insulin sensitizer
● Increase glucose uptake
● Reduces glucose resistance
● Very decreased risk of hypoglycemia
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25
Q

Metformin MOA

A

● Reduction of hepatic gluconeogenesis
● Slows intestinal absorption of sugar and improves peripheral glucose uptake and
utilization
● Can be used alone or in combination
( can metfor. be used with insulin? = yes - due to lower risk of hyperinsulinemia and hypoglycemia with metfo. )

Reduce serum glucose levels by inhibiting hepatic gluconeogenesis, decreasing absorption of glucose from the GI, and increasing peripheral utilization of glucose by adipose tissue and skeletal muscle.

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26
Q

Metformin Adverse effects

A 
● Weight loss
● GI disturbances
● Metabolic acidosis
● Lactic acidosis
● Hypoglycemia (when combined with insulin or secretagogues)
● Diarrhea
● Nausea
● Vomiting
● Vit B12 deficiency
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27
Q

Metformin C/I

A 
● Alcohol abuse
● MI
● Exacerbation of heart
● Sepsis
● Renal dysfunction (Met should be stopped if GFR < 40)
● Heart failure
● 80 years
Acute/chronic metabolic acidosis
28
Q

SGLT-2 INHIBITORS examples

A

CANAGLIFLOZIN
DAPAGLIFLOZIN
EMPAGLIFLOZIN

29
Q

CANAGLIFLOZIN
DAPAGLIFLOZIN
EMPAGLIFLOZIN

MOA

A

● Inhibits renal glucose absorption via SGLT2
● By inhibiting SGLT2, these agents decrease reabsorption of glucose, increase urinary
glucose excretion and lower blood glucose
● It also causes decreased reabsorption of sodium
● Causes osmotic diuresis
● It may reduce systolic BP

Inhibits SGLT-2 (which is responsible for glucose reuptake) → decreased renal glucose reabsorption → Glycosuria & ↓blood glucose

30
Q

CANAGLIFLOZIN
DAPAGLIFLOZIN
EMPAGLIFLOZIN

SIDE EFFECTS

A 
Genital yeast infection 
Polyuria 
Genital pruritus 
Thirst
● Osmotic diuresis
● Genital and urinary tract infection
● Urination frequency changes
● Hypotension
● Ketoacidosis
31
Q

CANAGLIFLOZIN
DAPAGLIFLOZIN
EMPAGLIFLOZIN

Contraindications

A

Renal insufficiency
Ketoacidotic patients
Alcohol abuse

32
Q

Glucagon MOA

A

Activates glucagon receptor

33
Q

Glucagon Indications

A

● Severe hypoglycemia

● Clinical beta blocker overdose

34
Q

Glucagon S/E

A

● GI disturbances

● Hypotension

35
Q

Alpha glucosidase inhibitors:

A

Acarbose
● Poorly absorbed and excreted by urine

Miglitol

36
Q

Alpha glucosidase inhibitors:
ACARBOSE & MIGLITOL

MOA

A

● Blocks alpha glucosidase enzyme in the intestine, which is responsible to break down glucose and delays absorption
● Results in low post prandial level
● No hypoglycemia when given by monotherapy
● Hypoglycemia is seen when given by combination therapy

37
Q

ACARBOSE & MIGLITOL

S/E

A

● Flatulence
● Diarrhea
● Abdominal cramps
● GI disturbances

38
Q

Acarbose
Miglitol

CONTRAINDICATIONS

A

● Inflammatory bowel disease
● Colonic ulcer
● Intestinal obstruction

39
Q

Thiazolidinediones(TZDs):

A

Rosiglitazone
● Adverse effect: cardiovascular issues

Pioglitazone

40
Q

Thiazolidinediones(TZDs): MOA

Rosiglitazone
Pioglitazone

A

● Reduces resistance by being agonist to PPAR(gama)
● Activating PPAR(gama) regulates insulin responsive genes and makes it more sensitive
● Can be used for monotherapy or combination
● They are extensively bound to serum albumin
● Metabolised by CYP450 isozymes
● Excreted by bile and feces

41
Q

Thiazolidinediones(TZDs):
Rosiglitazone
Pioglitazone

CONTRAINDICATIONS

A

● Heart failure

42
Q

Thiazolidinediones(TZDs):
Rosiglitazone
Pioglitazone

ADVERSE EFFECTS

A 
● Liver toxicity
● Weight gain
● Osteopenia
● Increased risk of fracture for women
● Fluid retention
● Edema
● Risk of MI
43
Q

Glinides:

A

Repaglinide

Nateglinide

44
Q

Glinides MOA

A 
● Rapid onset
● Short duration of action
● They are postmeal glucose regulators
● Metabolised in liver
● Excreted by bile
45
Q

Glinides S/E

A

Hypoglycemia

Weight gain

46
Q

Type 1 diabetes

A

● Absolute destruction of beta cells
● Complete deficiency of insulin is observed
● Commonly seen children or puberty
● Insulin deficiency causes polydipsia, polyphagia, polyuria and weight loss
● 5 to 10% of cases only
● It maybe due to autoimmune process triggered by virus or environmental toxins
● Exogenous supply of insulin is needed
● Leads to hyperglycemia, avoid ketoacidosis, high level of HbA1c

47
Q

INSULIN

A

● Insulin is a polypeptide connected by disulphide bonds
● Proinsulin undergoes proteolytic cleavage to to form insulin and C peptide
● Insulin is presnet in chromosome 2 (short hand)
● Secretion of insulin is triggered by blood glucose
● Glucose is taken to the beta cells with the help of glucose transporter
● Glucose is then phosphorylated by glucokinase (glucose sensor)
● The end products enter mitochondrial respiratory chain
● Increased ATP causes blockage of potassium channels leading to deploarisation of
membrane and influx of calcium
● Increase in calcium causes steady release of insulin
● Insulin cannot be taken up by stomach cuz it will degrade
● Insulin can be take by subcutaneous injection, IV (IV pump) or inhalation

48
Q

Rapid/Short acting insulin:

A

● Should be given 15 mins before or 15-20mins after starting food
● They are crystalline zinc structure

49
Q

Insulin Lispro

A

● Peak levels (30-90mins)

50
Q

Insulin Aspart

A

● Peak levels (10-20mins)

51
Q

Insulin Glulisine

A

● Peak level (20-30mins)

52
Q

Inhaled Insulin

A

● Peak level (50-120mins)

● Should be given 30-60mins before meal

53
Q

Intermediate acting insulin:

A

They are regular insulin + zinc + protamine

54
Q

Neutral protamine hagedorn (NPH)

A

Aka insulin isophane
● The combination with protamine forms a less soluble complex resulting in delayed
absorption and longer duration of action.
● Should only be given subcutaneously (never IV)
● Can give from 1 to 3 doses per day

55
Q

Rapid/Short acting insulin: EXAMPLES

A

Insulin Lispro

Insulin Aspart

Insulin Glulisine

Inhaled Insulin

56
Q

Intermediate acting insulin: EXAMPLE

A

Neutral protamine hagedorn (NPH)

57
Q

Long acting insulin: EXAMPLES

A

Insulin Glargine

Insulin Degludec

Insulin Detemir

58
Q

Long acting insulin:

A

● Should only be given subcutaneously.

● They shouldn’t be mixed with another long lasting insulin

59
Q

Insulin Glargine

A

● Has a slower onset than NPH insulin and a flat and prolonged effect

60
Q

Insulin Degludec

A

● Has longest half life and lasts for more than 24hrs

61
Q

Insulin Detemir

A

● Has a fatty acid chain which attaches to albumin which results in slow and long lasting activity

62
Q

INSULIN MOA

A

● These activate insulin receptor.
● Modification to the sequence of amino acid of normal insulin produces rapid acting
insulin
● These kind of insulin are given to mimic the post meal insulin secretion.
● rapid/short acting insulin are given with long acting ones to maintain fasting blood
glucose as well

63
Q

INSULIN USE

A

● Type 1 and 2 diabetes

64
Q

INSULIN S/E

A 
● Hypoglycemia
● Weight gain
● Local site reaction
● Lipodystrophy
● Headache
● Anxiety
● Blurred vision
● Vertigo
65
Q

INSULIN CONTRAINDICATIONS

A

● Renal insufficiency
● Old patients
● Patients younger than 7 years

Pharmacology (22 decks)

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