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Diabetes Mellitus & Pancreatic Hormones Flashcards

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1
Q

Pancreatic Enzymes: Uses & Pharmacodynamics

A

Uses: cystic fibrosis and pancreatitis
- some bariatric procedures require supplements

Pharmacodynamics

  • inactivated by pH values less than 4; do not crush or chew
  • – sprinkled on food if powdered form
  • Taken immediately before or with a meal
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2
Q

Pancreatic Enzymes: Pharmacokinetics & Precautions

A

Absorption: none, because it acts locally in GI tract
Excretion: feces
Pancrelipase made form pork; pancreatin made from pork, beef, or vegetable sources

Precautions: antacids decrease effectiveness; decreases absorption of oral iron

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3
Q

Pancreatic Enzymes: ADRs & Rational Drug Selection

A

ADRs: skin- irritation, rashes; GI- stomatitis, nausea; high doses- hyperuricosuria, hyperuricemia

Rational Drug selection: watch products because they are NOT bioequivalent; most old formulas are no longer FDA approved

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4
Q

Pancreatic Enzymes: Monitoring

A

Pancreatitis: contraindicated during acute exacerbations of chronic illness
Hypersensitivities: may need products from vegetable sources
Growth charts, albumin, cholesterol, glucose, CBC, iron levels. serum uric acid
Steatorrhea: rates and intensity help monitor dosing

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5
Q

Pancreatic Enzymes: Info

A

Info:

  • Each drug is specified in lipase, protease, and amylase units
  • Drugs are prescribed in units of lipase
  • Many older formulations are not available in FDA-approved source, so finding the right dosing is more complex; this is improving over time
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6
Q

Pancreatic Enzymes: Patient Education

A
  • Do not chew, crush, or drink with water
  • Avoid leaving in mouth
  • Enteric-coated formulations should not be mixed with alkaline foods prior to ingestion
  • If powder spills, wash off skin immediately
  • With infants/toddlers: watch for aspiration, inhalation
  • Lifestyle management: follow dietary guidelines
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7
Q

Endocrine Pancreatic Hormones- Insulin: Pharmacodynamics

A

Binds at insulin receptor sites on cell membrane allowing glucose to enter cells
Acts on liver to increase storage of glucose as glycogen
Promotes protein synthesis on muscle cells
Reduces circulation of free fatty acids and promotes storage of triglycerides in adipose tissue

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8
Q

Endocrine Pancreatic Hormones- Insulin: Rapid Acting

A

Lispro (Humalog), aspart (Novolog), or glulisine (Apidra)

Onset about 5 minutes, peaks in 1 hour, duration about 4-5 hours

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9
Q

Endocrine Pancreatic Hormones- Insulin: Short-acting

A

“Regular” (Humulin) insulin

Sometimes used around mealtime

Taken about 30-45 minutes before eating, peaks in 3-4 hours, duration 4-10 hours

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10
Q

Endocrine Pancreatic Hormones- Insulin: intermediate-acting

A

Normal pressure hydrocephalus mixed with protamine, delaying absorption

Insulin looks cloudy and has to be mixed before it is injected

Onset one-half to 1 hour, peaks 4-10 hours, and duration 12-24 hours

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11
Q

Endocrine Pancreatic Hormones- Insulin: Long-acting

A

Glargine (Lantus), detemir (Levemir), degludec (Tresiba)

Onset 2-4 hours, duration 24 hours with little or no peak

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12
Q

Endocrine Pancreatic Hormones- Insulin: Pharmacokinetics

A

Absorption determined by type of insulin, injection site, and volume injected

Abdominal site absorbs 50% more than other sites

Metabolism: induced CYP1A2

Excretion: urine

Watch for standardized U 100/mL, needs U100 needles

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13
Q

Endocrine Pancreatic Hormones- Insulin: ADRs

A

Hypoglycemia, diabetic ketoacidosis
- watch alcohol use, increases hypoglycemia
- beta blockers mask hypoglycemia symptoms
Pregnant women can use rapid- or short-acting insulin- does not cross placenta
- Insulin aspart, insulin lispro, and insulin glulisine
Hypothydroidism
- Delays insulin breakdown; therefore, may require less insulin units
Hyperthyroidism
- Increases renal clearance, requiring more insulin than baseline

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14
Q

Endocrine Pancreatic Hormones- Insulin: Monitoring

A

Glycohemoglobin, renal function, CBC

  • A1c test twice a year in patients who are meeting treatment goals and have stable glycemic control
  • A1c test quarterly in patients whose treatment has changed/not meeting goals
  • Point-of-care testing for A1c allows for timely decisions on treatment changes
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15
Q

Endocrine Pancreatic Hormones- Insulin: Patient Education

A

Goal A1c less than 7% for most nonpregnant adults

  • Individualized goals for older adults with long-time diagnoses
  • Administration, understanding types of insulin
  • Glucose monitoring, frequency and recording
  • Emergency plan for glucose readings and “flu”
  • Lifestyle management, diet, exercise
  • Injection site selection
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16
Q

Oral Diabetic Agents: Mechanisms

A

Type 2 DM more than just insulin resistance

  • Insufficient production of endogenous insulin
  • – Sulfonylureas: cause an increase in insulin production
  • Tissue insensitivity to insulin
  • – Thiazolidinediones: improve insulin sensitivity
  • – Biguanides: do the same
  • Impaired response of beta cells
  • – Meglitinides: increase secretion of insulin
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17
Q

Oral DM Medications: For excessive production of glucose by liver

A

Metformin- improves hepatic response to elevated blood gas, decreases glucose production, and decreases GI absorption

Alpha-glucosidase inhibitors: inhibit absorption of carbohydrate in GI tract

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18
Q

Oral DM Medications: For impaired glucagon-like peptide-1 (GLP-1) activity

A

(Rapid Intestinal Dumping)

Use of dipeptidyl peptidase 4 (DPP-4) medications to slow inactivation
- may stop weight gain or be weight neutral as well

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19
Q

Sulfonylureas

A

Glipizides (Glucotrol), glyburide (diabeta), glimepiride (Amaryl)

All stimulate insulin release from beta cells

All potentiate effects of antidiuretic hormone

Hypoglycemia is a major side effect

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20
Q

Sulfonylureas: Precautions and Contraindications

A

Cross-sensitivity with sulfonamides or thiazide diuretics

Avoid in pregnant women

Old adults more sensitive to hypoglycemia events

Pediatric: Use in children 10-18 years, but it is unlabeled

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21
Q

Sulfonylureas: ADRs and Drug Interactions

A

ADRs: hypoglycemia, GI, dermatological rashes, syndrome of inappropriate antidiuretic hormone secretion, hemolytic anemia, leukopenia, thrombocytopenia, weight gain

Drugs interactions: many
- may increase or decrease hypoglycemia effect

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22
Q

Sulfonylureas: Clinical Use and Dosing for DM

A
  • Use second-generation agents most of the time
  • Individualized dose progression is based on response
  • Start with lowest dose and increase every 4-7 days
  • Neurogenic diabetes insipidus
  • – Chlorpropamide is used off-label
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23
Q

Sulfonylureas: Rational Drug Selection/Dosing

A

Age: Chlorpropamide and glyburide used in older adults (use short-acting glipizide)

Cost: many generics available

Concurrent renal disease
- Glipizide or tolbutamide, or glyburide

Concurrent insulin: only glimepiride FDA labeled for co-administration, but most second-generation agents used

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24
Q

Sulfonylureas: Monitoring & Patient Education

A

Monitoring

  • HgA1c: baseline, then every 3 months while adjusting, then every 6 months
  • CBC at onset, then annual, more if symptoms

Patient Education
- Administration, ADRs, Lifestyle management

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25
Biguanides: Meformin (Glucophage, Glucophage XR)
Decreases glucose production in liver, decreases GI glucose absorption, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization Does not stimulate insulin release for beta cells Inhibits platelet aggregation and reduces blood viscosity Patients may lose weight: not labeled use, mostly weight neutral
26
Biguanides: Pharmacokinetics
- Absorption: 50% to 60% after oral dosing; food decreases and delays absorption - Metabolism: no hepatic metabolism - Excreted by kidneys - Alcohol potentiates drug's effect on lactate metabolism
27
Biguanides: Precautions and Contraindications
- Renal or hepatic disease is contraindicated - Withhold drug 48 hours before and after procedures involving iodine-based contrast mediums - Watch patients with vitamin B12 anemia/deficiency - Biguanides are not recommended for children younger than 10 years of age
28
Biguanides: ADRs
Metabolic (lactic acid) acidosis risk! - Lactic acidosis is rare, except in dehydration episodes - Renal disease: watch patients at risk for metabolic acidosis - Liver disease: risk for lactic acidosis is increased GI ADRs usually resolve in 2 weeks after starting dose
29
Biguanides: Rational Drug Selection/Dosing & Monitoring
Rational Drug Selection: - Type 2 DM: start with 500 mg twice/day and titrate up - -- If patients have not responded to 4 weeks of high dosing, considering adding oral sulfonylurea or other medication Monitoring: assess renal function, ketones, HbA1c before starting dosing; check every 6 months
30
Biguanides: Patient Education
Administration ADRs: report diarrhea lasting more than 2 days, dehydration Lifestyle management Usually not the source of any hypoglycemia Alert imagining staff about drug presence
31
Alpha-Glucosidase Inhibitors: Pharmacodynamics
Acarbose (Precose), miglitol (Glyset) - Inhibit the absorption of carbohydrate from GI tract, lowering the BG levels after meals - These are not monotherapy drugs - Hypoglycemia treated with milk; lactose not sucrose
32
Alpha-Glucosidase Inhibitors: Pharmacokinetics
Absorption: less than 2% of acarbose absorbed as active drug Metabolized by intestinal bacteria and digestive enzymes (lots of gas production) Excreted by kidneys
33
Alpha-Glucosidase Inhibitors: Precautions, Contraindications, and ADRs
Precautions and Contraindications - Should not be used in patients with IBD, or those at risk for bowel obstruction or renal impairment - Should not be used during pregnancy - Not to be used in pediatric population ADRs - GI symptoms: flatulence, diarrhea, abdominal pain - Do not cause hypoglycemia
34
Alpha-Glucosidase Inhibitors: Drug Interactions & Clinical Use/Dosing
Drug Interactions - Acarbose: digoxin - Miglitol: propranolol, ranitidine Clinical Use and Dosing - Initial dose is 25 mg TID - Increase dose in 4-8 week intervals
35
Alpha-Glucosidase Inhibitors: Patient Education
Administration: should be taken with first bite of meal ADRs: GI Lifestyle: type 2 DM care
36
Thiazolidinediones: Pharmacodynamics
Pioglitazone (Actos), rosiglitazone (Avandia) - Improve target cell response to insulin by activating receptor cell protein that improve insulin action - Increase utilization of insulin by liver and muscle cells and reduce liver glucose production
37
Thiazolidinediones: Pharmacokinetics
- Absorption: Rapid after oral dosing - Metabolism: liver via CYP2C8, 3A4 to both active and inactive metabolites; substrate inhibits CYP2C8, CYP2D6, induces weakly CYP3A4 - Greater than 99% protein bound - Excretion: in urine (15% to 30%) and feces as metabolites
38
Thiazolidinediones: Precautions and Contraindications
- Chronic liver disease (heavy liver processing) - Fluid retention: exacerbations heart failure (HF) - FDA loosening restrictions, but still dangerous drug Not approved for children younger than age 18 years
39
Thiazolidinediones: ADRs & Drug Interactions
Cardiovascular (CV)- edema, upper respiratory infection, HA, fatigue - Watch for signs of CHF, use with caution with patients with elevated liver enzymes - Increased risk of bladder cancer with pioglitazone use Drug Interactions - Birth control requiring higher dosing of oral contraceptives - Watch for drugs metabolized by CYP3A4: Coricidin, corticosteroids, ketaconazole
40
Thiazolidinediones: Monitoring, Rational Drug Selection, & Patient Education
Monitoring- Liver enzymes at start of therapy, A1c Rational Drug Selection: - Careful selection of patient population - Monotherapy or combination with sulfonylureas, insulin - Initial dosing: 15-30 mg/day; max dosing: 45 mg/day - Strong recommendation for endocrine co-management Patient education: once-daily dosing - Administration, ADRs, lifestyle management
41
Meglitinides: Pharmacodynamics
Nateglinide (Starlix), repaglinide (Prandin) - Meglitinides increase insulin release from beta cells by closing potassium channels, which leads to the opening of calcium channels, and it is the influx of calcium that releases the insulin - Time in plasma is short, less than 2 hours, so these agents only lower postprandial BG levels
42
Meglitinides: Precautions, Contraindications, & ADRs
Precautions & Contraindications - Liver impairment - Not approved in pediatric population ADRs - Hypoglycemia in vulnerable populations
43
Meglitinides: Drug Interactions
CYP3A4 & CYP2C9 inducers increase meglitinide metabolism Antifungals (ketoconazole) and antimicrobials (erythromycin) inhibit metabolism, increasing risk for hypoglycemia
44
Meglitinides: Rational Drug Selection- Repaglinid (Prandin)
For patients with postprandial hyperglycemia Patients with HbA1c less than 8: start with 0.5 mg before each meal Patients with HbA1c greater than 8: start with 1 mg before each meal Increase slowly: may double every 2 weeks for max 16mg/24 hours
45
Meglitinides: Monitoring and Patient Education
Monitoring: get baseline HbA1c and recheck in 3 months Patient Education - Administration: no more than 30 minutes before a meal; hold if not eating - ADRs - Lifestyle management
46
DPP-4 Inhibitors: Pharmacodynamics
"Gliptins" Sitagliptin (Januvia) and Saxagliptin (Onglyza) - Inhibits DPP-4 - Breaks down GLP-1 and gastric inhibitory polypeptide, which are released in response to a meal - Leads to increase in secretion of insulin and suppresses the release of glucagon by the pancreas - Promotes pre- and postprandial glucose levels - Promotes mild weight loss in obese patients with diabetes
47
DDP-4 Inhibitors: Precautions, Contraindications, & ADRs
Precautions and Contraindications: - Renal dysfunction - Pregnancy (Check with OB for necessity) - Not approved in children ADRs: GI, HA
48
DDP-4 Inhibitors: Drug Interactions, Clinical Use and Dosing
Drug Interactions - Angiotensin-converting enzyme inhibitors: increased risk of angioedema Clinical Use and Dosing - Monotherapy or in combination with other antidiabetic drugs
49
DDP-4 Inhibitors: Rational Drug Selection & Monitoring
Rational Drug Selection - Age: well-tolerated by older adults - Weight/Obesity: patients may lose weight - Cost: more expensive than older drug families Monitoring - Renal function at baseline and annually - HbA1c every 3 months - Monitor for potential thyroid medullary cancer concerns, especially in those with previous nodules
50
DDP-4 Inhibitors: Patient Education
Administration- taken once daily in the morning ADRs- well tolerated Lifestyle- changes still needed
51
GLP-1 Agonists: Pharmacodynamics
Exenatide (Byette) and others - Promote insulin release from pancreatic beta cells in the presence of elevated glucose - Mimic natural incretins - --slow glucose absorption from gut, promote satiety - -- Slow postprandial spikes
52
GLP-1 Agonists: Precautions, Contraindications, & Drug Interactions
Precautions & Contraindications - Acute pancreatitis noted in post-marketing surveillance - Severe GI disease (Colitis, Crohn's disease) - Pregnancy (check with specialists) Drug Interactions - Increased international normalized ratio (INR) if administered with warfarin - Digoxin
53
GLP-1 Agonists: Clinical Use and Monitoring
Clinical use only for type 2 DM - Add-on therapy is typical - Combine with: metformin, sulfonylureas, others Monitoring - Glycemic control and GI distress - Potential site reactions
54
GLP-1 Agonists: Patient Education & ADRs
Administration of SC injection for rapid release - 60 minutes before meals - Dosed 6 hours apart - If dose is missed, wait for next scheduled time ADRs- Gi upset/nausea (major cause of noncompliance); Lifestyle
55
SGLT-2 Inhibitors: Pharmacodynamics
the "Flozin" meds - Canaglilozin, dapagliflozin - Reduce BG by blocking reabsorption of glucose in kidney - Also reduce BP and cal lead to mild weight loss - First choice to add if HbA1c is not at goal with metformin due to significant reduction of CV risk and progression of renal functional loss - Sometimes linked with increased K+, bladder cancer, and increased lipid levels
56
Glucagon: Pharmacodynamics
Considered an insulin antidote: used in patients with diabetes who experience hypoglycemia or insulin overdose - Stimulates hepatic gluconeogenesis and glycogenolysis, raising BG levels - BG concentration rises within 10 minutes of injection, and maximal concentrations are attained at approximately a half hour after injection - Hepatic stores of glycogen are necessary for glucagon to produce an anti-hypoglycemic effect
57
Glucagon: Pharmacokinetics & Precautions and Contraindications
Pharmacokinetics - Well absorbed after parenteral administration - Extensively metabolized by liver and kidneys Precautions and Contraindications - may be used with pregnant women and children - administered cautiously to patients suspected of having pheochromocytoma or insulinoma
58
Glucagon: ADRs and Drug Interactions
ADRs: N/V, allergic reaction Drug Interaction: increased anticoagulant effects of oral anticoagulants
59
Glucagon: Clinical Use and Dosing
Reversal of hypoglycemia; prevention of low sugars for colonoscopy after 3- day preparations In primary care setting: IM dosing - Less than 20 kg weight: 0.5 mg or 20-30 mcg/kg/dose, repeat every 20 minutes - Less than 20 kg weight: adult dosing 1 mg IM, may repeat in 20 minutes
60
Glucagon: Monitoring and Patient Education
Monitoring: BG levels immediately prior to and after injection Patient Education: - Administration: educate family members and roommates on how to test BG and how to administer IM glucagon - Glucagon depletes glycogen stores; patient should be given supplemental carbohydrates as soon as he or she awakens and is able to swallow, especially in children or adolescents - ADRs - Lifestyle Management

Pharmacology (25 decks)

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