Diabetes Flashcards
PRAMLINTIDE
Use
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
PRAMLINTIDE
Administration
Subcutaneously before a meal
Pramlintide MOA
Amylin analogue, downregulates hepatic prod. of glucose, slows gastric emptying.
Binds to K-channel, thereby stimulating the release of insulin from the pancreas → ↓glucose
PRAMLINTIDE
SIDE EFFECTS
Nausea Vomiting Hypoglycemia ● GI disturbances ● hypoglycemia ● Anorexia ● Vomiting ● Headache
PRAMLINTIDE
Contraindication
● Diabetic gastroparesis
● Hypersensitivity
● Hypoglycemic unaware patients
Incretin based drugs/ GLP-1 Receptor agonist examples
LIRAGLUTIDE
EXENATIDE
DULAGLUTIDE
ALBIGLUTIDE
LIRAGLUTIDE
EXENATIDE
DULAGLUTIDE
ALBIGLUTIDE
USE
Non-insulin dependent type 2 diabetes.
WHEN IS EXENATIDE C/I
In severe renal impairment
LIRAGLUTIDE EXENATIDE DULAGLUTIDE ALBIGLUTIDE
Mechanism of Action
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
LIRAGLUTIDE EXENATIDE DULAGLUTIDE ALBIGLUTIDE
Incretin based drugs:
Adverse Effects
Nausea
● Vomiting
● Diarrhea
● Constipation
● More expensive than metformin (but have no negative effect on heart)
Pancreatitis
Hypoglycemia when used w/other anti-dia agent
LIRAGLUTIDE EXENATIDE DULAGLUTIDE ALBIGLUTIDE
C/I
Chronic pancreatitis
Medullary thyroid carcinoma
Multiple endocrine neoplasia syndrome- type 2
DPP-4 inhibitors: EXAMPLES
ALOGLIPTIN
LINAGLIPTIN
SAXAGLIPTIN
SITAGLIPTIN
DPP4 s MOA
● 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
DPP4s SE
Mild hypoglycemia ● Rhinitis ● Upper respiratory infection ● Allergic reaction ● Headache ● disabling joint pain
DPP4s C/Is
● 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
When is the DPP4 Linagliptin especially used
It is good for renal dysfunction
How is linagliptin excreted
Excreted via enterohepatic system
What is the C/I of Alogliptin
Increased heart failure
How are Sulfonylureas divided?
1st. gen: CHLORPROPAMIDE TOLBUTAMIDE TOLAZAMIDE
2nd. gen:GLYBURIDE GLIPIZIDE
3. rd. gen: GLIMEPIRIDE
Sulfonylureas MOA
- Stimulate insulin release by inhibiting K-channels on β-cells
- Increase insulin action on prolonging binding of insulin to target tissue receptors
- 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.
Sulfonylureas SE
Hypoglycemia + weight gain
Hyperinsulinemia
Sulfonylureas C/I
Interact w/many other drugs
Pregnancy
● Hepatic insufficiency
● Renal insufficiency
What group does metformin belong to
Biguanides
Use of Metformin
Non-insulin dependent type 2 diabetes. PCOS Insulin sensitizer ● Increase glucose uptake ● Reduces glucose resistance ● Very decreased risk of hypoglycemia
Metformin MOA
● 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.
Metformin Adverse effects
● Weight loss ● GI disturbances ● Metabolic acidosis ● Lactic acidosis ● Hypoglycemia (when combined with insulin or secretagogues) ● Diarrhea ● Nausea ● Vomiting ● Vit B12 deficiency
Metformin C/I
● Alcohol abuse ● MI ● Exacerbation of heart ● Sepsis ● Renal dysfunction (Met should be stopped if GFR < 40) ● Heart failure ● 80 years Acute/chronic metabolic acidosis
SGLT-2 INHIBITORS examples
CANAGLIFLOZIN
DAPAGLIFLOZIN
EMPAGLIFLOZIN
CANAGLIFLOZIN
DAPAGLIFLOZIN
EMPAGLIFLOZIN
MOA
● 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
CANAGLIFLOZIN
DAPAGLIFLOZIN
EMPAGLIFLOZIN
SIDE EFFECTS
Genital yeast infection Polyuria Genital pruritus Thirst ● Osmotic diuresis ● Genital and urinary tract infection ● Urination frequency changes ● Hypotension ● Ketoacidosis
CANAGLIFLOZIN
DAPAGLIFLOZIN
EMPAGLIFLOZIN
Contraindications
Renal insufficiency
Ketoacidotic patients
Alcohol abuse
Glucagon MOA
Activates glucagon receptor
Glucagon Indications
● Severe hypoglycemia
● Clinical beta blocker overdose
Glucagon S/E
● GI disturbances
● Hypotension
Alpha glucosidase inhibitors:
Acarbose
● Poorly absorbed and excreted by urine
Miglitol
Alpha glucosidase inhibitors:
ACARBOSE & MIGLITOL
MOA
● 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
ACARBOSE & MIGLITOL
S/E
● Flatulence
● Diarrhea
● Abdominal cramps
● GI disturbances
Acarbose
Miglitol
CONTRAINDICATIONS
● Inflammatory bowel disease
● Colonic ulcer
● Intestinal obstruction
Thiazolidinediones(TZDs):
Rosiglitazone
● Adverse effect: cardiovascular issues
Pioglitazone
Thiazolidinediones(TZDs): MOA
Rosiglitazone
Pioglitazone
● 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
Thiazolidinediones(TZDs):
Rosiglitazone
Pioglitazone
CONTRAINDICATIONS
● Heart failure
Thiazolidinediones(TZDs):
Rosiglitazone
Pioglitazone
ADVERSE EFFECTS
● Liver toxicity ● Weight gain ● Osteopenia ● Increased risk of fracture for women ● Fluid retention ● Edema ● Risk of MI
Glinides:
Repaglinide
Nateglinide
Glinides MOA
● Rapid onset ● Short duration of action ● They are postmeal glucose regulators ● Metabolised in liver ● Excreted by bile
Glinides S/E
Hypoglycemia
Weight gain
Type 1 diabetes
● 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
INSULIN
● 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
Rapid/Short acting insulin:
● Should be given 15 mins before or 15-20mins after starting food
● They are crystalline zinc structure
Insulin Lispro
● Peak levels (30-90mins)
Insulin Aspart
● Peak levels (10-20mins)
Insulin Glulisine
● Peak level (20-30mins)
Inhaled Insulin
● Peak level (50-120mins)
● Should be given 30-60mins before meal
Intermediate acting insulin:
They are regular insulin + zinc + protamine
Neutral protamine hagedorn (NPH)
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
Rapid/Short acting insulin: EXAMPLES
Insulin Lispro
Insulin Aspart
Insulin Glulisine
Inhaled Insulin
Intermediate acting insulin: EXAMPLE
Neutral protamine hagedorn (NPH)
Long acting insulin: EXAMPLES
Insulin Glargine
Insulin Degludec
Insulin Detemir
Long acting insulin:
● Should only be given subcutaneously.
● They shouldn’t be mixed with another long lasting insulin
Insulin Glargine
● Has a slower onset than NPH insulin and a flat and prolonged effect
Insulin Degludec
● Has longest half life and lasts for more than 24hrs
Insulin Detemir
● Has a fatty acid chain which attaches to albumin which results in slow and long lasting activity
INSULIN MOA
● 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
INSULIN USE
● Type 1 and 2 diabetes
INSULIN S/E
● Hypoglycemia ● Weight gain ● Local site reaction ● Lipodystrophy ● Headache ● Anxiety ● Blurred vision ● Vertigo
INSULIN CONTRAINDICATIONS
● Renal insufficiency
● Old patients
● Patients younger than 7 years
