Diabetes Mellitus Flashcards
List drugs causing diabetes
- Glucocorticoids, OCP
- Thiazide diuretics (dec insulin release), BBs (glucose intolerance)
Mention properties of regular insulin
Short-acting, rapid onset, short duration, given 30-45 min before meals
Used IV/IM in emergencies: DKA
Mention properties of insulin lispro (& mention other preparations)
Very rapid onset, very short duration, given SC 15 min before meals
Rapid absorption & rapid onset, better postprandial glycemic control
Very short duration of action, less risk of late PP hypoglycemia
Available as premixed fixed conc with protaminated lispro/aspart
……
Aspart, glulisine
Mention properties of lispro-aabc (& mention other preparations)
Could be injected at mealtime 0-2 min before meal (better effect on 1& 2-hr PP glucose), upto 20 min after starting meal.
…..
Fast acting insulin aspart
Mention properties of NPH
Intermediate onset & duration, given SC 2-4 times/d in DM1 or once in DM2
Variable absorption >50%
Can be mixed with regular insulin. Also with lispro/aspart but immediately before administration
Not used in DKA
Premixed fixed conc are availabe with regular inuslin.
Mention properties of glargine 100U (& mention other preparations)
Long acting. Slow onset, long acting upto 24 hrs (better compliance than NPH)
Injected SC once/twice daily
Broad conc plateau, less risk of hypoglycemia
Should not be mixed with other types in same syringe
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Detemir
Mention properties of degludec (& mention other preparations)
Ultra-long acting. Does not peak & lasts for 36hrs, can be mixed with rapid-acting insulin with no effect on kinetics.
…..
Glargine U-300
Mention properties of Afrezza
Only covers prandial insulin requirements, thus DM1 patients also require SC long-acting insulin
Dis:
1. Fine dose adjustments are not possible
2. Not recommended in smokers & CI in chronic lung disease
List indications of insulin therapy
- Type 1 DM & DKA
- Type 2 DM (failure of diet regulation & exercise + metformin or other oral AB)
- DM with pregnancy & lactation
- DM with stress & emergency (inc insulin requirements)
- Treatment of hyoerkalemia
- DM with severe liver/renal disease
Causes 3-5 are temporary
List adverse effects of Insulin
- Hypoglycemia (most frequent & most serious)
- Inc body weight
- Immune reactions: A. Insulin resistance B. Allergy
- Lipodystrophy: lipohyoertrophy (change injection site to avoid), lipoatrophy
- Hypokalemia (high doses)
Treatment of hypoglycemia
Rapid administration of glucose (sugar or candy)
IV glucose or glucagon 1 mg IM/SC
Describe insulin therapy in DKA
IV approach: regular insulin (low dose IV infusion) until blood acetone disappears, IV dose: dec by half if blood glucose falls to 250 mg/dl, once patient is stable switch to SC 4times/d
SC approach: in mild to moderate uncomplicated DKA SC rapid-acting insulin analogs with aggressive fluid management
Mention subcutaneous antidiabetic drugs (other than inuslin)
Incretin mimetics
Amylin analogues
Describe MOA of metformin
Insulin sensitizer (biguanide)
Not fully understood
1. Dec hepatic gluconeogenesis (main)
2. Direct stimulation of glycolysis in skm & adipose t, remove glucose & inc lactate in blood
3. Dec intestinal glucose absorption with mild anorectic effect
Describe adv & indications of metformin
Adv: no inc in body weight, no hypoglycemia
Ind:
1. initial therapy of DM2 with diet & exercise
2. Off-label uses: DM1 adult with high BMI & desiring to improve control while minimizing effective use of insulin, PCO, Prediabetes, anti-psychotic induced weight gain
Side effects of metformin
Preparations are availabe combined with…..
- GIT: metalic taste, dyspepsia, diarrhea (common, start with small dose & inc)
- Lactic acidosis (uncommon but serious) thus CI in liver/renal failure, severe hypoxia
- Dec absorption of vit B12
…..
Sulfonylureas, SGLT-2-I, DPP-4-I, TZDs
Describe MOA of Pioglitazone
TZD, euglycemic, but delayed effect as its mechanism involves gene regulation
PPARG-agonists:
1. Enhanced adipocyte differentiation, dec circulating FFA through inc uptake of circulating FFA into fat cells, dec intracellular lipolysis thus dec FFA mobilization
2. This effect causes dec inuslin resistance, inc glucose uptake & dec hepatic glucose production, dec BG
Mention indications, adverse effects & precautions of TZDs
Ind: used as monotherapy or combined in DM2
AE: weight gain, fluid retention & edema thus may precipitate HF
PREC: avoid in HF & liver dysfunction, monitor signs of liver injury, consider risk of fractures
Describe MOA of canagliflozin
Inhibit SGLT-2 in proximal tubules in kidney, prevents reabsorption of filtered glucose in kidney, remove excess glucose
Reduce HbA1c, weight & BP
Indications, adv, AE, & pecautions of SGLT-2-I
Ind: DM2 monotherapy/combined with TZDs/metformin
Adv: orally once daily, beneficial in DKD
AE: genitourinary infections, mild hypoglycemia with inuslin, inc risk of fractures
PREC: adequate renal function needed
Describe MOA of sitagliptin
DPP-4 inhibitors, which degrades incretins secreted from GIT following meals thus cause inc glucose-dependent insulin rise & dec glucagon secretion thus dec PP hyperglycemia
Indications & AEs of DPP-4 inhibitors
Ind: DM2 monotherpay of combined with metormin of TZDs (given orally once daily)
AE: Nasopharyngitis, URTI, joint pain (well-tolerated)
Describe MOA of liraglutide
GLP-1 R agonist
1. Inc glucose-dependent insulin secretion thus inc acute responsiveness of b-cells
2. Suppress inappropriate pp glucagon
3. Slow gastric emptying & reduce food intake (used in obesity)
Describe AEs of GLP-1-R agonists
- Nausea (most common)
- Possibly pancreatitis
- Avoid in patients with family history of medullary carcinoma
GR: Combination of basal insulin & GLP-1RA is favorable
Has potent glucose-lowering actions & less weight gain & hypoglycemia compared with intensified insulin regimens
Describe MOA of glimepride & ind
- Inc insulin secretion by binding with specific receptor in b-cells linked to ATP sensitive K+ channels, it blocks them, causes depolarization & Ca++ influx & insulin release from granules (main)
- Dec glucagon on chronic use
Ind: DM2 if initial therapy with lifestyle + metformin failed or if the latter is CI or not well-tolerated
CIs of sulfonylureas
- Allergy to sulfa
- Type 1 DM
- DM with pregnancy & lactation crosses placenta & execreted in milk (fetal/newborn hypoglycemia)
- DM with stress (ineffective)
- DM with liver/renal disease prolonged action & more risk of hypoglycemia (metabolised in liver, execreted in urine)
AEs of sulfonylureas
- Hypolycemia: more in long t1/2 as glibenclamide
- Hypersensitivity
- Heavy weight
List adv, disadv & precautions of repaglinide
Nonsulfonylrea insukin secretagogue
Adv: very rapid onset & shorter duration than sufonylurea thus less pp hyperglycemia & less late pp hypoglycemia. May be given in sulfa allergy
Dis: frequent dosing (3/d pradial), weight gain & hypoglycemia (less than sulfonylurea)
PREC: used cautiously in liver impairment
Describe MOA of acarbose
a-glucosidase inhibitors, as normal brush border of intestine contains this enzyme which converts oligosaccharides into disaccharides thus this drug causes glucose absorption.
List adv, ind & AEs of acarbose
Adv: limits postprandial rise in BG (insulin sparing effect), no hypoglycemia
Ind: adjuvants to sulfonylureas in DM2 or metformin intolerance
AEs: GIT upset, flatulence, abdominal pain diarrhea due to sugar fermentation in colon
Describe MOA of premalintide & its ind & AEs
Analogue of amylin (hormone co-secreted with insulin following food intake)
1. Dec pp glucagon secretion
2. Delays gastric emptying & improves satiety
Ind: type 1 & 2 DM prior to meal adjunct to insulin (but no in same syringe)
AEs: hypoglycemia (reduce inslin by 50%), NV, anorexia
In DM-2, Consider intiating dual/triple therapy if……, & insulin therapy if……..
A1c more or e 9%
A1c more or e 10% esp w/ catabolic features
Classify antidiabetic drugs according to cardiac safety into
1. Neutral
2. Unfavourable
3. Beneficial
- Metformin (PREC: lactic acidosis), gliptins (ex, saxagliptin- >HF)
- SGLT-2-I, GLP-1-RA
- Glitazones
