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Nursing - Bloomberg > 💊370: Diabetes Pharmacology > Flashcards

💊370: Diabetes Pharmacology Flashcards

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1
Q

What are the metabolic defects of Diabetes Mellitus?

A
  1. Insulin deficiency
    And/Or
  2. Defective insulin action (insulin resistance)
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2
Q

What is insulin?

A

Protein with 2 linked amino acid chains.

Synthesized in the pancreas by Beta cells in islets of Langerhans.

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3
Q

Where is insulin synthesized?

A

pancreas by Beta cells in islets of Langerhans.

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4
Q

What are triggers for insulin secretion?

A
  1. Blood glucose

2. Amino acids, fatty acids

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5
Q

What are normal blood glucose levels?

A

4.0 - 7.7 mmol/L

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6
Q

What are dangerous hypoglycaemic levels?

A

Brain requires > 2.5 mmol/L

Seizures and coma at < 2.0 mmol/L

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7
Q

What are the levels of hyperglycaemia and what occurs?

A

Glucose in urine > 10 mmol/L

  • Osmotic diuresis, dehydration, thirst

Type 1: Diabetic ketoacidosis (DKA)
Type 2: hyperglycaemic Hyperosmolar State (HHS)

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8
Q

What are abnormal results for FPG test?

A

No caloric intake for at least 8 hours

IFG: 6.1 - 6.9
Diabetes >= 7.0

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9
Q

What are abnormal results for the 2hPG in a 75g OGTT test?

A

IFG: 7.8 - 11.0
Diabetes: >= 11.1

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10
Q

What are abnormal results for the A1C test?

A

Prediabetes: 6.0 - 6.4

Diabetes >= 6.5

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11
Q

What are abnormal results for the Random PG test?

A

Diabetes >= 11.1

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12
Q

What is the mechanism of normal Prandial Glucose metabolism?

A
  1. ⬆️ BG stimulates pancreatic insulin release
  2. Insulin allows glucose uptake by muscle and fat
  3. Insulin inhibits glucose production by liver
  4. Insulin’s inhibits breakdown of TG to fatty acids and proteins to amino acids

Result: BG < 7.8 mmol/L

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13
Q

What is the normal mechanism of Fasting glucose metabolism?

A
  1. Low insulin secretion, little glucose uptake by peripheral tissues
  2. Counter-regulating hormones (CRH) stimulate glucose production in liver
  3. Hepatic glucose production:
    A) Glycogenolysis
    B) Gluconeogenesis

Result: BG > 4.0 mmol/L

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14
Q

What is Glucogenolysis?

A

Breakdown of glycogen into glucose in the liver

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15
Q

What is Gluconeogenesis?

A

Synthesis of glucose from breakdown of proteins or TG in the liver

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16
Q

What are macro vascular complications with DM?

A
  1. Stroke
  2. CAD, Hypertension
  3. Peripheral Vascular Disease
  4. Diabetes Foot
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17
Q

What are microvascular complications of DM?

A
  1. Retinopathy and Cataracts
  2. Nephropathy
  3. Neuropathy
  4. Diabetic Foot
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18
Q

What are therapeutic goals for patients with diabetes?

A
  1. Normalize blood sugars
  2. Percent/resolve symptoms
  3. Prevent acute and chronic complications
  4. Avoid negative sequels if therapy (ie. hypoglycaemia)
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19
Q

What are the ABCDES for all patients with diabetes?

A 
A = A1C  =<7%
B = BP <130/80
C = Cholesterol LDL-C =< 2.0 mmol/L
D = Drugs to protect the heart 
E = Exercise / Eating 
S = Smoking cessation
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20
Q

What are therapeutic interventions for glycemic control?

A
  1. Diet
  2. Exercise
  3. Oral hypoglycaemic agents
  4. Insulin
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21
Q

Why is exercise important for diabetic patients?

A
  1. Exercise ⬆️ insulin sensitivity and glucose tolerance

2. Promotes weight loss

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22
Q

What are the glycemic target lab values?

A

A1C =< 7.0%
Preprandial PG: 4.0 - 7.0 mmol/L
2hPG: 5.0 -10.0 mmol/L (5-8 if not at target)

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23
Q

What drugs cause Hyperglycaemia?

A
  1. Corticosteroids
  2. Diuretics (ex. Thiazides)
  3. Protease inhibitors
  4. Sympathomimetics (ex. Epinephrine)
  5. Clycosporine, tacrolimus
  6. Phenytoin
  7. Sudafed??

⬇️ insulin secretion, ⬆️ insulin resistance, or ⬆️ hepatic glucose output

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24
Q

What drugs cause hypoglycaemia?

A
  1. Alcohol (hepatic output)
  2. Beta blockers (hepatic output)
    (Can mask hypoglycaemia symptoms such as tachycardia, tremors)
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25
What are prototypes of Short Acting (“Regular”) insulin’s?
Humulin R | Novolin ge Toronto
26
What are Short Acting (“Regular”) insulins?
Unmodified human insulin - Used to control prandial glucose - SC, IM, IV DOSE 30-60 min before meals
27
What are prototypes of Rapid Acting Insulin Analogs?
Slightly modified human insulin - Very fast onset and short duration - Control prandial glucose - SC or IV DOSE immediately before/during meals
28
What are prototypes of Rapid Acting Insulin Analogs?
Lispro (Humalog) Aspart (NovoRapid) Glulisine (Apidra)
29
What are Intermediate Acting Insulin?
Neutral Protamine Hagedorn (NPH) - Insulin conjugated with protamine to ⬇️ solubility and slow absorption - Delayed inset, extended duration - SUSPENSION for SC (never IV!!!) DOSE twice a day
30
What are common prototypes of Intermediate Acting Insulin?
Humulin N | Novolin ge NPH
31
What are Long Acting Insulin Analogs?
Modified human insulin Low solubility at physiologic pH Act as DEPOT when injected SC (slowly release over 24hrs) Lacks peak effect => ideal Nadal insulin
32
What are prototypes of Long Acting Insulin Analogs?
1. Glargine (Lantus, Basaglar) | 2. Detener (Levemir)
33
What are advantages of Long Acting Insulin?
1. No peak activity, consistent insulin levels 2. Less risk of hypoglycaemia (esp nocturnal) 3. Longer duration of action allows for daily dosing
34
What are Ultra Long Acting Insulin Analogs?
Modified human insulin with duration of action of 42 hours | Can give missed dose as late as 16 hours after
35
What is a prototype of Ultra Long Acting Insulin?
Degludec (Tresiba)
36
What are two prototypes of Pre-Mixed Insulin’s?
1. Humulin 30/70 (30% regular, 70% NOH) | 2. Humalog Mix25 (25% lispro, 75% NPL)
37
What some advantages and disadvantages of Pre-Mixed insulin’s?
Advantage: Convenient, less chance for error or cross-contamination Disadvantage: No flexibility to change doses, so cannot achieve optimal BG control
38
What are side effects of insulin?
1. HYPOGLYCAEMIA 2. Weight gain 3. Hypokalemia 4. Local allergic rxns (rare) 5. Injection site rxns (rotate sites)
39
What are symptoms of Hypoglycemia?
1. BG < 4.0 mmol/L 2. Tremor, weakness 3. Palpitations 4. Tachycardia 5. Sweating 6. Tingling lips 7. Hunger 8. Blurred vision 9. Agitation 10. Restless sleep, nightmares 11. Morning HA “hangover”
40
What are risk factors for Hypoglycemia?
1. Elderly (⬇️ CRH response) 2. Renal/hepatic dysfunction 3. Intensive insulin therapy 4. Drugs (SFU, alcohol) 5. Beta-Blockers can mask symptoms **
41
What is the usual management of Hypoglycemia?
15-20g CHO orally
42
What is the general onset, peak, and duration of Rapid-Acting insulin analogues?
Onset: 10-15 min Peak: 1 - 2 hours Duration: 3-5 hours
43
What is the general onset, peak, and duration of Short-Acting insulins?
Onset: 30 min Peak: 2 -3 hours Duration: 6.5 hours
44
What is the general onset, peak, and duration of Intermediate-Acting insulins?
Onset: 1-3 hours Peak: 5-8 hours Duration: Up to 18 hours
45
What is the general onset, peak, and duration of Long-Acting insulin analogues?
Onset: 90 min Peak: N/A Duration: Up to 24 hours
46
What are components of a Basal-Bolus insulin regimen?
1. BASAL insulin = (usually long-Acting) controls BG between meals 2. BOLUS insulin = (usually rapid-acting) controls prandial BG 3. Insulin correction = additional PRN rapid-Acting 4. Titrate = BG monitoring at least 4 times daily with dose adjustments
47
What are components of Conventional insulin regimen?
1. Rapid or Short-Acting 2. Intermediate-Acting Insulin Both take in Morning and Evening
48
What are advantages of Basal-Bolus insulin regimens?
1. Better prandial and fasting BG control 2. More flexibility with meals and timing 3. ⬇️ in micro vascular complications 4. ⬇️ macro vascular complications 5. Best for Type 1 patients
49
What are disadvantages of Basal-Bolus insulin regimens?
1. ⬆️ risk of hypoglycemia 2. Weight gain 3. ⬆️ injections and BG monitoring 4. Patient must be motivated and educated
50
What is a Sliding Scale?
Regular or rapid-Acting insulin given in response to regular BG measurements 1. Reactive approach 2. Short-term use only 3. Not proactive
51
How do colds/illness impact diabetic patients?
Stress ➡️ release CRH ➡️ Hyperglycemia
52
How does exercise impact diabetes?
Exercise (esp aerobic) ⬆️ insulin sensitivity during and after ➡️ Risk of Hypoglycaemia (esp Type 1)
53
How do insulin pumps work?
1. “Reservoir” 2. “Cannula” 3. “Infusion set” holds needle in place 4. Rapid-Acting Insulin only
54
What are advantages of insulin pumps?
1. More consistent and better BG control 2. Fewer episodes of Hypoglycaemia 3. Flexibility (adjust rate PRN) 4. No injections
55
What are disadvantages of insulin pumps?
1. Risk of Sever hyperglycaemia/DKA if pump fails 2. Cost (pump+supplies) 3. Education and training
56
What is the site of action for Metformin?
⬇️ hepatic glucose production ⬆️ insulin action Lowers fasting (FPG) and post-prandial glucose (PPG)
57
What are advantages of Metformin?
1. No Hypoglycaemia (does not stimulate insulin release) 2. No weight gain 3. ⬇️ risk diabetic complications
58
What are side effects of Metformin?
1. GI intolerance 2. Lactic acidosis (rare but potentially fatal) 3. Accumulation in kidneys ➡️ renal dysfunction (avoid if GFR <30) 4. Dosed 2-3 times daily with meals
59
What are Thiazolidinediones?
⬇️ hepatic glucose production ⬆️ insulin action Lowers FPG and PPG
60
What is a prototype of Thiazolidinediones?
Pioglitazone (Actos) “-glitazone”
61
What are side effects of Glitazones?
1. No Hypoglycaemia 2. Heart failure due to fluid retention (avoid in CHF) 3. ⬆️ risk MI 4. Hepatotoxicity (monitor LFTs) 5. CYP450 levels
62
What is the dosing and administration of of Glitazones?
Once to twice daily without regard to meals
63
What is the site of action for Sulfonylureas?
⬇️ pancreatic insulin secretion Lower FPG and PPG
64
What is a prototype of Sulfonylureas?
Glyburide (Diabeta)
65
What are side effects of Sulfonylureas?
1. Hypoglycaemia (take with meals) 2. Weight gain 3. Sulfa allergy 4. Accumulation + renal dysfunction (⬆️risk hypoglycaemia)
66
What is the site/mechanism of action for Meglitinides?
⬆️ pancreatic insulin secretion Metabolized and secreted by liver in bile (short half-life, 1 hour) Mainly lower PPG, minimal effect on FPG Rapid onset
67
What are side effects of Meglitinides?
1. Hypoglycaemia 2. Weight gain 3. Liver dysfunction ➡️ accumulation ➡️ hypoglycaemia
68
What are incretin hormones?
1. Released in gut due to ⬆️ BG 2. Stimulate pancreatic insulin secretion 3. Inhibit release of glucagon 4. ⬇️ hepatic glucose production 5. Rapidly inactivated in body by enzyme DPP-4
69
What are DPP-4 inhibitors?
⬆️ levels and prolong activity of incretin hormones Lower PPG, minimal effect on FPG
70
What is a prototype of DDP-4 inhibitors?
Sitagliptin (Januvia) “-gliptin”
71
What are side effects of DDP-4 inhibitors?
1. HA 2. Infection (resp, UTI) 3. Pancreatitis risk 4. Gallstones 5. High Triglycerides 6. Renal dysfunction
72
What is the mechanism of action of Glucagon-Like Peptide-1 Agonists (GLP-1 Agonists)?
1. Stimulate pancreatic GLP-1 receptors 2. ⬆️ incretin activity 3. Glucose-dependent effects (insulin secretion stimulated, glucagon release suppressed) 4. Delays gastric emptying, suppressed appetite 5. Lower PPG, minimal effect on FPG
73
What are side effects of GLP-1 Agonists?
1. Weight loss (NO Hypoglycaemia) 2. GI side effects (n/v, diarrhea) 3. Pancreatitis 4. Renal dysfunction SC injection 1-2/day
74
What is the site/mechanism of action for Sodium-Glucosr Co-Transporter 2 (SGLT-2) inhibitors ?
1. Glucose reabsorption in kidney tubules occurs via SGLT-2 co-transporter 2. Blockade causes glucosuria 3. Improved glycemic control and weight loss Lower FPG and PPG
75
What are side effects and interactions for SGLT-2 inhibitors?
1. ⬆️ urination, 2. Genital yeast infection 3. UTI 4. Postural hypotension, dizziness 5. Diuretics (dehydration, volume depletion) 6. ⬇️ efficacy with rifampin, phenobarbital, and phenytoin
76
What is a prototype of SGLT-2 inhibitors?
Canagliflozin (Invokana) “-gliflozin”
77
What is the mechanism of action for Acarbose (Glucobay)?
Inhibit gut enzyme alpha-glucosidase which breaks down carbohydrates (CHO) Lowers PPG, no effect on FPG
78
What are side effects of Acarbose (Glucobay)?
No systemic side effects 1. GI side effects (bloating, gas, diarrhea)
79
What are benefits of Acarbose (Glucobay)?
Minimal systemic absorption
80
What are drug interactions with Acarbose (Glucobay)?
Decreases Metformin absorption | + ⬆️ GI side effects
81
How do you convert mg/L to mmol/L?
Divide by 18
82
What Non-Insulin agents decrease glucose production in the liver?
1. Metformin 2. Glitazones 3. DPP-4 inhibitors 4. GLP-1 agonists
83
Which non-insulin agents increase pancreatic insulin secretion?
1. Sulfonylureas 2. Meglitinides 3. DPP-4 inhibitors 4. GLP-1 agonists
84
Which non-insulin agents decrease pancreatic glucagon secretion?
1. DPP-4 inhibitors | 2. GLP-1 agonists
85
Which non-insulin agents increase insulin action/glucose uptake in muscles and fat?
1. Glitazones | 2. Metformin
86
Which non-insulin agents increase glucose secretion in the kidneys?
SGLT2 inhibitors
87
Which non-insulin agents decrease glucose absorption in the intestines?
1. Acarbose 2. Orlistat 3. DPP-4 inhibitors
88
Which drugs have potential cause weight gain?
1. Insulins 2. Sulfonylureas 3. Meglitinides 4. Thiazolidinediones
89
Which drugs may cause Hypoglycaemia?
1. Insulin’s 2. Sulfonylureas 3. Meglitinides

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