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Advanced Pharm COPY COPY > Endocrine- DM > Flashcards

Endocrine- DM Flashcards

1
Q

How is Insulin released?

What is the structure of insulin?

A
  • Insulin is released as proinsulin, a precursor molecule
  • Insulin is a small protein consisting of a chain of 21 amino acids linked by two disulfide (s-s) bridges to a Beta chain of 30 amino acids
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2
Q

What is the MOA of insulin?

A
  • Insulin binds to plasma membrane receptors initiating an intracellular cascade of enzymatic events
    • glucose diffusion into cell
    • glucose storage mode (glycogen synthetase)
    • uptake of amino acids, phosphate, K, and Mg
    • protein syntheisis and inhibition of proteolysis
    • increased fatty acid and triglyceride synthesis; decreased lipolysis
    • regulate DNA/gene expression via insulin regulatory elements
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3
Q

What is normal endogenous insulin physiology?

A
  • Portal circulation receives basal rate of 1 U per hour
  • With meals this rate of insulin secretion increases 5-10x
  • 40U is average daily requirement
  • “units” is a term used to quantify potency
    • i.e. ability to decrease serum BS
  • ANS does influence insulin secretion
    • alpha decreases insulin secretion
    • beta and PSNS increase insulin secretion
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4
Q

Who needs insulin therapy?

A
  • Type 1 diabetics
    • insulin dependent b/c their body produces NO insulin
  • Type 2 diabetics
    • do not always produce enough insulin
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5
Q

What are the three different ways insulin has been made over time?

A
  • Stage 1: insulin was extracted from the glands of cows and pigs
  • Stage 2: Pig insulin was converted into human insulin by removing the one amino acid that was different and replacing it with human kind
  • Stage 3: Insert human insulin into E.coli and culture the recombinant E.coli to produce insulin. (Humulin)
    • Yeast can also be used (Novolin)
    • recombinant method has also made it possible to have insulins that work faster or slower than regular
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6
Q

What are the different types of insulin?

A
  • Ultrarapid acting
    • Lispro (humalog)
    • Aspart (Novolog)
    • Glulisine (apidra)
  • Short acting
    • Regular (humulin R, novolin R)
  • Intermediate acting
    • NPH (humulin N, Novolin N)
  • Long acting
    • Glargine (lantus)- has no peak
    • Detemir (levemir)
    • ultralente
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7
Q

How do the peak effects of the different SQ insulins vary?

(graph)

A
  • short duration, fast acting (lispro)- 1-2 hours
  • short duration , slow acting (regular)- 3-4 hours
  • intermediate duration, slow acting (NPH)- 6-7 hours
  • long duration, slowest acting (glargine)- no peak
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8
Q

Random insulin considerations:

HOw can insulin be administered?

What are the benefits of all the different options?

Which insulin can you not mix with any others?

A
  • Insulin can be administered parenterally and nasally
    • SQ is most common
  • Benefits of different onsets/durations:
    • rapid- convenient, can inject minutes before a meal
    • mixtures (rapid/NPH)- R covers breakfast, NPH covers lunch; R covers dinner, NPH covers o/n
    • Long acting- mimics basal insulin
  • Do not mix Glargine with any other insulins
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9
Q

What are the pharmacokinetics of IV regular insulin?

E1/2t

DOA

metabolism

formulation?

A
  • E1/2t- 5-10 minutes
  • DOA- 30-60 minuts
    • longer than you would expect with short 1/2t b/c insulin tightly binds to receptors
  • Metabolized in liver and kidney by proteolytic enzymes
  • Only the U100 formulation should be used
    • there is a U500 formulation that should never be administered IV
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10
Q

Onset, peak, duration, and Use for: (table)

Rapid acting (lispro)

short acting (regular)

intermed (NPH)

Long acting (glargine)

ultralong ancting (dugludec)

A
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11
Q

What are some of the convenient ways to administer insulin?

A

insulin pens

jet injectors

insulin pumps (be sure to disable/remove)

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12
Q

What are the adverse effects of insulin?

A
  • Injection site rxns
  • lipodystrophy at injection site
  • protamine allergy
  • weight gain
  • HYPOGLYCEMIA
    • diaphoresis, tachycardia, HTN, CNS agitation, sz, coma
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13
Q

What drugs interact with insulin?

A
  • Appose the hypoglycemic effects of insulin:
    • ACTH, glucagon, estrogens
  • Decrease release of insulin and stimulates mobilization of glucose:
    • epinephrine
  • prolongs DOA:
    • tetracycline, chloramphenicol, salicylates
  • Increase hypoglycemic effects
    • MAOIs
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14
Q

Pacito a pacito,

suave suavecito…

A

…..Des-pa-cito!!

¡Vamos a una playa en Puerto Rico!!

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15
Q

How much does 1U insulin decrease BS in a pt with type 1 DM?

Type 2 DM?

A
  • Type 1- 1U decreases BS by 40-50 mg/dl
  • Type 2- 1U decreases BS by 30-40 mg/dl
  • **individual sensitivity is highly variable!
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16
Q

What are the benefits of tight control of BS?

A
  • tight control reduces the risk of chronic complications in type 1 diabetics
  • may affect surgical morbidity and mortality
    • increased wound healing
    • decreased infection
    • decreased osmotic diuresis
    • decreased incidence of diabetic ketoacidosis
17
Q

What are the drawbacks of tight control of BS?

A
  • risk of hypoglycemia
    • can cause permanent neurological damage
    • signs and symptoms are masked by anesthesia
  • tight control is labor intensive
  • requires BS monitoring q30 min
18
Q

How do you treat hyperkalemia with insulin?

A
  • 10 U RegularIV and 25 g of glucose (1 amp of 50% dextrose solution over 5 minutes)
19
Q

How do you treat hypoglycemia?

A
  • Critical to avoid brain damage and death!
  • If conscious, give fast acting oral sugar
  • If under anesthesia/impaired, 25-50 ml of 50% dextrose
20
Q

What are the different types of oral antidiabetic medications?

How do they work?

*bolded answers are the ones that have risk of hypoglycemia

A
  • Sulfonylureas- increase insulin secretion from Beta cells
  • Biguanides- increase insulin sensitivity at target tissue
  • Thiazolidinediones- increase insulin sensitivity at target tissues
  • Alpha-glucosidase inhibitors- slows absorption from the gut
  • Meglitinides- increase insulin secretion from B cells
  • GLP-1 Mimetics/Gliptins (DPP-4 inhibitors)- increase insulin from B cells
21
Q

Sulfonylureas

MOA

A
  • MOA- stimulate release of insulin from pancreatic beta cells
    • binds to ATP sensitive K channels in the cell membrane resulting in depolarization, Ca influc and insulin release
22
Q

What are the Sulfonylureas that we use?

What are each of their DOA?

A
  • second generation- 100x more potent with less SE than first generation
    • glipizide- DOA 12-24 hours
    • Glyburide (Micronase, Diabeta)- DOA 18-24 hours
    • Glimepiride (Amaryl)
  • first generation (don’t use)
    • Tolbutamide (Orinase)- DOA 6-12 hours
    • Chlorpropamide (Diabinese)- DOA 36-72 hours
23
Q

Pharmacokinetics of Sulfonylureas:

PB

metab

What should you use with renal impairment?

SE

How long should it be held pre-op?

A
  • 90-98% PB (albumin)
  • All metabolized hepatically, some have active metabolites; avoid in hepatic disease
  • If renally impaired, use glipizide or tolbutamide- completely metabolized to inactive or weakly active states
  • SE
    • GI- nauesea, fullness, heartburn, cholestasis, appetite stimulant
    • GU- ADH like effect, Na and H2O retention
    • Derm- pruritis, rash
    • Hypoglycemia
  • Hold 24-48 hours pre-op
24
Q

Biguanides

only drug

MOA

excretion

clinical effects

A
  • Metformin (Glucophage)
  • MOA
    • decreases hepatic and renal glucose producition (gluconeogenesis and glycogenolysis)
    • enhances insulin receptor binding
    • increases glucose utilization and decreases insulin resistance
  • Excreted by kidneys
  • Clinical effects:
    • decreases FPG 60 mg/dl
    • additive effect with sulfonylureas
25
Q

Biguanides (Metformin)

benefits

adverse effects

contraindications

A
  • Benefits
    • no wt gain, even modest wt loss
    • may increase HDL, decrease LDL and TG
    • Hypoglycemia rare when used alone
  • Adverse effects
    • GI distress- diarrhea/nausea
    • lactic acidosis
    • rash
  • Contraindications
    • ESRD (CR>1.4)
    • hepatic dysfunction
    • CHF, shock, hypoxic pulmonary disease
26
Q

What are the Thiazolidinediones (TZDs)

MOA

A
  • Pioglitazone (Actos)
  • Rosiglitazone (Avandia)
  • MOA
    • Improves insulin sensitivity/decreases resistance
      • especially in skeletal muscle and adipose tissue
    • Reduces hepatic glucose production
    • requires the presence of insulin for effect
27
Q

Thiazolidinediones

Clinical effect

pharmacokinetics

other effects

A
  • Clinical effects:
    • decreases FPG up to 50 mg/dl
    • decreases Hgb A1c 1-2%
  • Pharmacokinetics
    • PO
    • hepatic metabolism
  • Other effects- resumption of ovulation in premenopausal women who were experiencing anovulation from insulin resistance
28
Q

Thiazolidinediones

Major adverse effects

A
  • Adverse effects:
    • edema
    • weight gain
    • hepatoxicity- monitor LFTs, counsel pts about symptoms of jaundice
  • BLACK BOX
    • CHF- can cause or exacerbate
    • MI
29
Q

What are the Alpha-glucosidase inhibitors?

MOA?

A
  • Acarbose (Precose)
  • Miglitol (Glyset)
  • MOA
    • Competitively and reversibly antagonizes enzymes in the intestinal brush border responsible for digesting complex carbs
    • delays glucose absorption
    • lowers post-prandial hyperglycemia
30
Q

Alpha-glucosidase inhibitors

clinical effect

pharmacokinetics

adverse effects

A
  • clinical effect
    • Only decreases FBG 25-30 mg/dl
    • decreases PPG 60-70 mg/dl (post prandial)
    • decreases HghA1c 0.7-0.9%
  • Pharmacokinetics
    • Taken with first bit of food
    • not absorbed after oral administaration
    • excreted in stool
  • Adverse effects
    • GI- distension, pain, diarrhea, flatulence
    • Caution in pts with IBD, UC, obstruction
31
Q

What are the Meglitinides?

MOA?

A
  • Repaglinide (prandin)
  • Nateglinide (Starlix)
  • MOA
    • stimulates insulin secretion from the B cells
    • quick onset and peak effect (1 hour)
    • short DOA (4 hours)
    • reduces PPG
32
Q

How are Meglitinides administered?

SE?

A
  • Dosing PO
    • 15-30 minutes before a meal
    • skip a meal, skip a dose
  • SE
    • similar to sulfonylureas
    • hypoglycemia
    • GI- N/V/C/D, heartburn
    • HA
33
Q

How do the GLP-1 Agonists and Mimetics “Gliptins” work?

A
  • Inhibit DPP-4 (dipeptidyl peptidase), an enzyme that inactivates incretin hormones (GLP-1)
    • Enhances glucose-dependent insulin secretion
    • reduces glucagon secretion
    • exhibits other anti-hypoglycemic actions once released from the gut including decreased appetite and slowing gastric emptying
34
Q

What GLP-1 agonist do you especially have to worry about risk of aspiration with?

A
  • Sitagliptan (Januvia)
    • E1/2t 12 hours
    • modestly reduces PPG and FPG
  • SE comparable to placebo
35
Q

What type of drug is Exenatide (Byetta)?

A
  • Injectable (SQ) Synthetic GLP-1 analog that mimics GLP-1
    • nearly identical affects as gliptins
    • adjuct to metformin or sulfonylureas
      • no wt gain
  • Adverse effects:
    • N/V
    • some pts develop antibody agains the drug
    • pancreatitis- potentially fatal
    • renal failure- 1:13,000 (transplant required)
    • hypersensitivity
    • delayed gastric emptying
36
Q

What are the Amylin Mimetics?

A
  • Pramlintide SQ- synthetic analog of amylin, a pancreatic hormone released with insulin, that decreases gastric emptying, decreases glucagon secretion, and increases sensation of satiety
  • Reduces PPG
  • peakse 20 min after injection, 49 min 1/2 life
  • metabolized in kidneys
  • enhances insulin effects
  • SE- hypoglycemia, decreased absorption of drugs (ABX, oral contraceptives 1 hr before or 2 hr after injection)

Advanced Pharm COPY COPY (27 decks)

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