Antidiabetics Flashcards
Types of insulin
Human, Porcine, Bovine
Examples of Insulin
Neutral Protamine Hagedorn (NPH)
Regular
Lente
Ultralent
Common mixture of insulin
70% NPH + 30% Regular
Ultra-short acting insulin analogues
Aspart and Glulisine- 3-5
Lispro-2-5
Short Acting
Regular (soluble crystalline)-5-8
Intermediate
NPH (isophane)-18-24
Long acting
Detemir-20-22
Glargine-18-24
Ultra long acting
Degludec
>40
Administration of most insulin analouges
SUBCUTANEOUS
Analogs that increase in duration when dose is increased
NPH, Regular
Amino acid PROLINE at position 28 is replaced by Aspartic Acid
Aspart
Proline at B 28 interchanged with Lysine at B 29
Lispro
Glutamine for Proline
Glulisine
Quickly dissociates into monomers therefore faster absorption. Also the shortest acting of them all
Lispro
Difference long acting in terms of dissociation
It is bound together in the solution that’s why it is slowly dissociating
Instantl converted to monomers if given IV, short acting
Regular
Added to Regular insulin to improve stability and shelf life
Zinc
Delayed action so that insulin and protamine in an uncomplexed form
NPH
Long acting insulin are also called
Peakless- broad plasma concentration plateau
Responsible for controlling fasting blood sugar
Long acting
Responsible for controlling postprandial blood sugar
Short acting
Given a px whose on Glargine (taken before bedtime) and Lispro (taken before breakfast, lunch and dinner) who is complaining of palpitation, tremors and hunger pangs before lunch time. What is your management?
Reduce Lispro before breakfast
Common multi dose insulin regimen
- Short acting before meals and long acting at nighttime
- Short acting or regular and NPH before breakfast and supper
- Insulin in bolus
Insulin ADR
Hypoglycemia Lipodystrophy Allergy Insulin Resistance Weight gain
Normal RBS
140mg/dL
Insulin secretagogues
Sulfonylureas
Glibenclamide
2nd Generation Sulfonylurea
- 1st Gen- amides
- 2nd gen- ides
Secretagogues MOA
Closing of ATP-dependent K channel, thereby depolarizing the membrane to increase insulin release
Secretagogue with longest duration of action
Chlorpropamide (60 hrs)
2nd generation secretagogues DOA
10-24
Chlorpropamide ADR
Hypoglycemia
Hyponatremia (SIADH)
Disulfiram-like rxns
Meglitinides (Repa-, Nate-)
Less Hypoglycemic effects
WEIGHT GAIN
Biguanide
Metformin
Metformin does not cause hypoglycemia
Euglycemic
Metformin effects
Dec gluconeogenesis
Inc glucose uptake
Metformin MOA
Activates AMP PK for insulin signaling
First line drug for DM type 2
Metformin
Other indications of metformin
PCOS
Metformin ADR
GI disturbances
B12 Deficiency
Lactic acidosis
CI: RENAL INSUFFICIENCY
Oral agent that causes EDEMA and WEIGHT GAIN
a. Pioglitazone
b. Repaglinide
c. Insulin
Pioglitazone
- Repaglinide- weight gain only
- Insulin- causes both but not oral
Pioglitazone MOA
Increase peripheral glucose uptake
PPAR gamma agonists
LDL effects of TZDs
Pioglitazone- Dec
Rosiglitazone- Inc
TZDs ADR
Hepatotoxicity (Troglitazone)
WEight gain and Edema
MI risk (Rosi)
Acarbose MOA
Delay CHO absorption by inhibiting glucosidase actions
Acarbose is an
Alpha-glucosidase Inhibitor does not cause Weight Gain
Acarbose ADR
Flatulence
Incretins
Intestinal Secretion of Insulin
Secretes incretin
L cells
Incretin effect
Glucose-dependent- more potent release of insulin on ingested food than IV glucose
Disease where incretin effect is greatly reduced or absent
DM 2
First FDA approved Incretin mimetic
Exenatide
Exenatide MOA
GLP-1 agonist
Disadvantages of Exenatide
Injected
GI disturbances
Pancreatitis
advantages of Exenatide
lack of hypoglycemia Weight Loss (Laklak na ng Exenatide)
Why is GLP-1 limited thus requires continuous admnistration?
Rapid degradation by the ubiquitous enzyme dipeptidyl eptidase-IV (DPP IV)
DPP-IV inhibitors
-gliptins
gliptins
Oral
Euglycemic
Daily GFR of 180L/day, how much glucose is reabsorbed?
162g
N: plasma blood glucose concentration
5.6 mmol/L
SGLT 1
10%
Straight (S3)
SGLT 2
90%
Convoluted (S1)
SGLT 2 inhibitors
inhibits renal reabsorption of glucose. Favors glucose excretion
Advantages of SGLT 2 inhitors
May lower blood pressure
Amylin analog
Pramlintide
Pramlintide MOA
mimics amylin (secreted with insulin by B cells) and suppresses glucagon secretion, dec HGO and dec insulin demand
Glucagon other uses
Treatment of Beta blocker poisoning due to its chronotropic and inotropic effects
Hypoglycemia with reaction of two drugs
Glibenclamide and Repaglinide
Optimum treatment to a patient with elevated BS and will not result to weight gain
METFORMIN AND DAPAGLIPLOZIN