Dr. Rabadaba: Pharm Diabetes

Question 1

Diabetes: 2 forms

Answer 1

• Diabetes Insipidus
  
  • rare
  • kidneys excrete to much water
  • due to vasopressin deficiency or resistance
• Diabetes Mellitus
  
  • common
  • Kidney excretes to much water
  • due to insulin dificiency or resistance

Question 2

Diabetes Mellitus

Answer 2

• common: 10-15% of people
• Kidneys excrete to much water
• due to insulin deficiency or resistance
• Mellitus means sweet
  
  • urine smells sweet
    
    • glucose not absorbed by kidney
• 3 forms:
  
  • Type 1 Diabetes mellitus (T1DM)
    
    • autoimmune disease
    • rapid decrease in insulin secretion
      
      • decrease beta cells
  • Type 2 Diabetes Mellitus (T2DM)
    
    • Slow Decrease of insulin action
  • Gestational Diabetes (GD)
    
    • Pregnant
    • insulin Resistance

Question 3

Oral Manifestations of Diabetes

Answer 3

• Dehydration–> Dehydration in 70% of patients
• State of hyperglycemia(sugar)=Microbial growth
  
  • can’t stop microbial growth or fight viral infecitons
• Increased incidence:
  
  • bacterial, fungal, viral infections
  • plaque
  • gingivitis
  • periodontal disease
  • mucosal lesions and abcesses
  • caries

Question 4

T1DM:

Answer 4

• Autoimmune disease
• rapid decrease in insulin secretion
  
  • Decrease in beta cells
• Tx: Insulin Replacement

Question 5

Insulin Metabolic Effects

Answer 5

• Muscle:
  
  • increase uptake of Glucose and a.a.
  • prevent degradation & release of amino acids
• Liver:
  
  • Increase uptake of glucose
    
    • CO2
    • Glycogen
  • Decrease uptake of amino acids, FA, ketopacids
• Adipose Tissue
  
  • Increase:
    
    • uptake of Glucose and FA
    • formation of TAG
• Plasma:
  
  • Decrease:
    
    • Glucose
    • Free Fatty Acids
    • Ketoacids
    • Amino Acids

Question 6

Insulin effects on Skeletal muscle, Adipose tissue, liver

Answer 6

• increases glucose uptake through :
  
  • GLUT-4 translocation in adipose tissue and Skeletal muscle
  • Hexokinase IV (Glucokinase) in the liver
    
    • GLUT2 always on membrane
• Increases glycogen synthesis in liver and muscle via GSK3-P (inactive)
• Increases cellular uptake of potassium through Na/K-ATPase translocation

Question 7

Dextrose & Insulin Tx

Answer 7

Treatment of moderate hyperkalemia (5.5-6.5)

Question 8

Fast acting, Long Acting, Very-Long acting Insulin

Answer 8

• Created through mutations
  
  • Fast Acting/Short Acting
    
    • decreased self association and dimerization
    • Onset: <15-30mins
    • Peak: 1-3 hours
    • Duration: 3-5 hours
      
      • Insulin Lispro
      • Insulin Aspart
      • Insulin Glulisine
      • Sanofi-Aventis
  • Long Acting
    
    • Favors oligomerization and precipitate
    • Drugs:
      
      • Insulin Detemir
      • Insulin Glargine
    • Duration: 12-24 hours
    • no peak
    • onset: 30mins-4 hours
  • Very Long Acting
    
    • onset: 30 mins-4 hours
    • no peak
    • Duration: 1-2 days
    • Drugs:
      
      • Insulin Degludec

Question 9

Optimal Insulin replacement therapy involves

Answer 9

• short and long acting insulins to mimic the normal daily fluctuations
  
  • Short acting insulin
    
    • before every meal
  • Long acting (basal coverage)
    
    • Wake up and before bed

Question 10

Alternative treatment to Type 1 Diabetes

Answer 10

• Insulin Pump
  
  • “Artificial Pancreas”
  • closed loop system
  • main issues when pump dysfunctions
    
    • skin infections
    • ketoacidosis

Question 11

Therapy for Patients with Type 1 diabetes

Answer 11

• Use for stringent glycemic control
  
  • Multiple-dose insulin (MDI) injections:
    
    • (one basal=long acting and 3 prandial injections=short acting)
  • OR continuous subcutaneous infusion (CSII)
• Educate on matching prandial injections to carb intake for tighter control
• Parents, friends, significant other should be educatd on how to inject glucagon if they are unconscious or refuse food in accidental insulin overdose
• Pramlintide

Question 12

Type 1 Diabetes therapy: A1c Goal

Answer 12

• Children: <7.5%
• Adult:
  
  • newly diagnosed young adults: <6.5%
  • history of hypoglycemia, advance vascular comorbidities, lmitied life expectancy: <8%

Question 13

Hazards of insulin use

Answer 13

• Hypoglycemia-main complication
  
  • glycemic control should not be as stringent in at risk patients
  • untreated=convulsion, loss of consciousness, coma’

Question 14

Signs of Hypoglycemia

Answer 14

• Sympathetic
  
  • tachycardia
  • palpitation
  • sweating
• Parasympathetic
  
  • Nausea
  • hunger

Question 15

Glucagon: Generic Name

Answer 15

• G-Pen
• G-pump

Question 16

Glucagon MOA

Answer 16

• binds to glucagon receptor in liver
• promotes glycogenolysis and gluconeogenesis
• inhibits glycogen synthesis

Question 17

Glucagon: Advantages vs Disadvanatages

Answer 17

• Advantage:
  
  • Increase hepatic glucose production
  • Restores consciousness
• Disadvantage:
  
  • No added inconvenience bc same as hypoglycemia
    
    • Nausea and vomiting
    • Increased Heart Rate
  • Must be injected IV, IM or SC

Question 18

Amylin

Answer 18

• secreted wtih insulin from B-cells
• Insoluble
• Self aggregate–>difficult to use therapeutically
• Promote satiety
• Slows gastric emptying
• reduces glucagon secretion from alpha cells

Question 19

Pramlintide

Answer 19

• Soluble, non-aggregating analog of amylin
• aproved in 2005 as adjunctive tx for Type 1 and type 2 diabetes

Question 20

Pramlintide: MOA

Answer 20

• synthetic analogue of amylin
• binds to AMY receptors
• delays gastric emptyiing
  
  • aviud ub gastrioaresis patients
• Inhibits glucagon release
• induces satiety

Question 21

Pramlintide: Advantages vs Disadvantages

Answer 21

• Advantages:
  
  • Slows appearance of nutrients in circultion
  • Decreases hepatic glucose production
  • reduces postprandial hyperglycemia
  • Reduces A1c by:
    
    • 0.4% in T1DM
    • 0.5% in T2DM
  • marginal weight loss
• Disadvantages:
  
  • severe hypoglycemia (20-50%_
    
    • reduce insulin by 50%
  • Nausea (30-60%)
  • Loss of appetite (20%)