Drugs used in die-beetus Flashcards
What are the rapid acting insulins
Aspart
Lispro
Glulisine
What is the clinical use of rapid acting insulin
– Postprandial hyperglycemia – taken before the meal (as sc injections only
What is the short acting insulin
Regular insulin
What are the clinical uses of regular insulin
– Basal insulin maintenance
– Overnight coverage
– If for postprandial hyperglycemia – inject 45 min before the meal
– Can be injected intravenously in urgent situations
What is the intermediate acting insulin
NPH insulin
Composition of NPH insulin
Complex of protamine with zinc insulin
Clinical use of NPH insulin
-Basal insulin maintenance and/or overnight
coverage
– Use is declining – is being replaced by long-acting insulins
What are the long acting insulins
Detemir
Glargine
Clinical use of long acting insulins
Basal insulin maintenance (1‐2 sc injections daily)
What is the importance of tight glycemic control with insulin in diabetes
- Improves survival
- Reduces diabetic complications
- Has been shown to be effective in multiple clinical trials, especially in patients with type 1 diabetes
What is the use of insulin in the treatment of severe hyperkalemia
– Insulin + glucose (to prevent hypoglycemic shock) + furosemide
– Insulin (i.v.) rapidly activates Na+/K+-ATPase to shift K+ from extracellular fluid into cells
– Effect is transient (several hours)
– K+ is eliminated from the body using loop diuretics in the meantime
Insulin delivery systems
Standard- subq injection
Portable pen injectors
Insulin pumps
What is the most common complication of insulin therapy
hypoglycemia
Common causes of hypoglycemia
– Delay of a meal or a missed meal
– Exercise
– Overdose of insulin
signs of hypoglycemia
– CNS/Behavioral Manifestations: confusion, bizarre behavior, seizures, coma
– Sympathetic hyperactivity: tachycardia, palpitations, sweating, tremor
– Parasympathetic hyperactivity: hunger, nausea
– Patients on tight glycemic control – “hypoglycemic unawareness”
Treatment of hypoglycemia
– Glucose or sucrose (juice, candy, etc. if conscious; I.V. glucose if unconscious)
– Glucagon (1 mg, sc)
MOA of amylin
Enhances the action of insulin via the following:
- Inhibition of glucagon secretion
- Decreased gastric emptying (slows the rate of intestinal glucose absorption)
- Causes a feeling of satiety
What is the amylin analog drug
Pramlintide
Clinical use of Pramlintide
– Type 1 diabetes
– Type 2 diabetes patients who takes mealtime insulin therapy
– Injected sc before meals as an adjunct to insulin therapy to control postprandial hyperglycemia
Adverse effects of pramlintide
– GI: nausea, vomiting, diarrhea, anorexia
– Severe hypoglycemia – if used together with insulin
Drug interactions of pramlintide
Enhances effects of anticholinergic drugs on GI tract (i.e. constipation)
What are incretins
group of gastrointestinal hormones that cause a decrease in blood glucose levels
What is GLP-1 synthesized by?
intestinal L cells
What does GLP-1 promote
- β‐cell proliferation
- Insulin gene expression
- Glucose‐dependent insulin secretion
What does GLP-1 inhibit
glucagon secretion
gastric emptying
not an effective drug bc short half life
What are the long acting GLP1 receptor agonists
What are their half lives?
Exenatide (2.4 hr)
Liraglutide (11-15 hr)
Adverse effects of the GLP-1 receptor agonists
– GI: nausea, vomiting, diarrhea, anorexia
– Hypoglycemia (lower risk of hypoglycemia as
compared to insulin and sulfonylureas)
GLP-1 agonists are approved for which patients
Approved in type 2 diabetes patients who is not adequately controlled by metformin/sulfonylureas/thiazolidinediones
suffix for DPP-4 inhibitors
-gliptin
MOA of DPP-4 inhibitors
- Increase levels of GLP-1 to enhance its interactions with the cognate receptor
- Effects are similar to those of GLP-1 agonists
What is DPP-4
A serine protease that degrades GLP-1 and other incretins
Clinical use of the gliptins (DPP-1 inhibitors)
– Approved as adjunct therapy to diet and exercise
in patients with type 2 diabetes
– Used both as a monotherapy and in combination with metformin/sulfonylureas/TZDs
– Taken orally
Adverse effect of gliptins
Hypoglycemia (if combined with insulin secretagogues – their doses have to be adjusted)
Classes of K+ atp channel blockers
- 1st generation sulfonylureas
- 2nd generation sulfonylureas
- non-sulfonylureas (meglitinides)
first gen sulfonylureas
-mide
– Chlorpropamide
– Tolbutamide
– Tolazamide
second gen sulfonylureas
– Glipizide
– Glyburide
– Glimepiride
Meglitinides
-glinide
– Nateglinide
– Repaglinide
MOA of K+ atp channel blockers
- Binding to SUR1 – sulfonylurea receptor
* Blocking K+ current through Kir6.2 inwardly rectifying potassium channel
Clinical use of sulfonylureas
Type 2 diabetes as a monotherapy or in
combination with insulin or other anti-diabetic drugs
Adverse effects of sulfonylureas
– Hypoglycemia
– Weight gain (due to increased insulin release)
– Secondary failure – patients who respond initially later cease to respond to sulfonylureas and
develop unacceptable hyperglycemia
Sulfonylurea drug interactions that enhance their hypoglycemic effect
– Displacing from binding with plasma proteins: sulfonamides, clofibrate, salicylates and other NSAIDs
– Ethanol
– Inhibiting CYP enzymes: azole antifungals,
gemfibrozil, cimetidine, etc.
Sulfonylurea drug interactions that decrease their hypoglycemic effect
Inhibiting insulin secretion: beta-blockers, CCBs
– Inducing hepatic CYP enzymes: phenytoin,
griseofulvin, rifampin, etc.
Clinical use of meglitinides
– Control of postprandial hyperglycemia in patients with type 2 diabetes
– Taken orally before the meal
– Can be used either alone (to control isolated postprandial hyperglycemia) or in combination with other antidiabetic drugs
Adverse effects of meglitinides
– Hypoglycemia
– Weight gain
– Secondary failure
MOA of metformin
– Activation of AMP-activated protein kinase
What is the first line treatment for T2DM
Metformin
Advantages of metformin
• Superior or equivalent glucose-lowering efficacy compared to other oral medications
• Does not cause hypoglycemia
• Does not cause weight gain
• Taken orally
• Can be used either alone or in combination
with other oral agents
• In clinical trials decreased the risk of both macro- and microvascular complications in diabetic patients
Adverse effects of metformin
– Most common: GI complications – anorexia, vomiting, nausea, diarrhea, abdominal discomfort
– Lactic acidosis, especially under conditions of
hypoxia, renal and hepatic insufficiency
Contraindications of metformin
– Contraindicated in conditions predisposing to
tissue hypoxia (HF, COPD), renal failure, chronic
alcoholism and cirrhosis, etc.)
What are the thiazolidinediones
-glitazone
Pioglitazone
Rosiglitazone
MOA of glitazones
– Ligands of peroxisome proliferator-activated receptor-gamma (PPARγ)
– PPARγ is a nuclear receptor expressed primarily in fat, muscle, liver tissue, and endothelium
Adverse effects of glitazones
Weight gain
Edema
Exacerbation of heart failure
Osteoporosis
What is the suffix for SGLT2 inhibitors
-flozin
MOA of SGLT2 inhibitors
– Kidneys filter 160 to 180 g of glucose per day
– Glucose is reabsorbed in the proximal tubule primarily by SGLT2
– Gliflozins inhibit this transporter to increase glucose excretion and to reduce hyperglycemia
Adverse effects of SGLT2 inhibitors
hypotension
hypovolemia (fainting dizziness, syncopy)
Genital infections and UTIs
hypoglycemia
What are the α-glycosidase inhibitors
Acarbose
Miglitol
MOA of α-glycosidase inhibitors
– Competitive inhibition of α-glycosidases, a family of enzymes on the intestinal epithelium defer digestion and thus absorption of ingested starch and disaccharides
– Lower postprandial hyperglycemia to create an insulin-sparing effect
Adverse effects of α-GLYCOSIDASE INHIBITORS
– Most common: malabsorption, flatulence, diarrhea, and abdominal bloating
– Hypoglycemia has been described when
combined with insulin or insulin secretagogues
