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Flashcards in Dr. Rabadaba: Pharm Diabetes Deck (21)
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1

Diabetes: 2 forms

  • 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

2

Diabetes Mellitus

  • 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

3

Oral Manifestations of Diabetes

  • 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

4

T1DM:

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

5

Insulin Metabolic Effects

  • 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

6

Insulin effects on Skeletal muscle, Adipose tissue, liver

  • 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

7

Dextrose & Insulin Tx

Treatment of moderate hyperkalemia (5.5-6.5)

8

Fast acting, Long Acting, Very-Long acting Insulin

  • 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

9

Optimal Insulin replacement therapy involves

  • 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

10

Alternative treatment to Type 1 Diabetes

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

11

Therapy for Patients with Type 1 diabetes

 

  • 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

12

Type 1 Diabetes therapy: A1c Goal

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

13

Hazards of insulin use

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

14

Signs of Hypoglycemia

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

15

Glucagon: Generic Name

  • G-Pen
  • G-pump

16

Glucagon MOA

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

17

Glucagon: Advantages vs Disadvanatages

  • 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

18

Amylin

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

19

Pramlintide

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

20

Pramlintide: MOA

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

21

Pramlintide: Advantages vs Disadvantages

  • 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%)