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N550 Pharm > Endocrine 1, 2 > Flashcards

Endocrine 1, 2 Flashcards

1
Q

Insulin MOA

A

Insulin binds to plasma membrane receptors initiating an intracellular cascade of enzymatic events: Glucose diffusion into cells, glucose storage mode, uptake of AA/phos/K/mg, protein synthesis, inhibition of proteolysis, fatty acid/TG synthesis, dec lipolysis, regulate DNA/ gene expression (via insulin regulatory elements)

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2
Q

___ units of physiologic insulin is the average daily requirement

A

40 units

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3
Q

In what way does ANS control insulin release?

A

Alpha decreases insulin secretion

Beta and PSNS increases insulin secretion

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4
Q

Which insulins are mixed commonly?

A

R/NPH or rapid/NPH

Before breakfast, R covers breakfast, NPH covers lunch (or R dinner; NPH night)

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5
Q

Which types of insulin are ultra-rapid acting? Onset, peak, DOA?

A

Lispro (humalog)
Aspart (novolog)
Glulisine (apidra)
Onset 15-30 min, peak 30-60 min, DOA 3-5h

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6
Q

Which types of insulin are short acting? Onset? Peak? DOA?

A

Regular (humulin R, novolin R)
Onset 30 min (slight peak of glucose before insulin starts working)
Peak 1-5h, DOA 5-8h

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7
Q

Which types of insulin are intermediate acting? Onset? Peak? DOA?

A

NPH (humulin N, novolin N)
P=protamine (this is what we use to reverse heparin), they may develop protamine allergy over time
Onset 1-2h, peak 6-10h, DOA 16-20h

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8
Q

Which types of insulin are long-acting? Onset, peak, DOA?

A 
Glargine (lantus)- no peak, not mixed with other insulins
Detemir (levemir)
Ultralente
Stimulate basal release (no peak)
Onset 2-6h, DOA 24h
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9
Q

IV regular insulin pharmacokinetics? E1/2t, DOA, metabolism

A

E1/2t 5-10 min
DOA 30-60 min
Proteolytic enzyme metabolizes insulin in the liver and kidneys

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10
Q

Insulin adverse reactions?

A 
HYPOGLYCEMIA
Injection site reaction
Lipodystrophy at site
Protamine allergy (only NPH)
Weight gain
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11
Q

Hypoglycemia symptoms?

A

Diaphoresis, tachycardia, hypertension (epi response to raise BG), CNS agitation, seizures, coma

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12
Q

Drug interactions with insulin?

A

ACTH, glucagon, estrogens- oppose hypoglycemic effects
Epi decreases release of insulin (raises BG)
Tetracycline, chloramphenicol, salicylates- prolong DOA
MAOIs increase hypoglycemic effects

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13
Q

In type 1 DM, 1 unit insulin decreases BG by ____

In type 2 DM 1 unit insulin decreases BG by ____

A

Type 1: 40-50 mg/dL
Type 2: 30-40 mg/dL
Although it varies with individuals

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14
Q

Benefits of tight controlled BG vs. non-tight control?

A

Tight control: reduces risk of chronic complications in type 1 DM, also inc wound healing, dec infection, dec osmotic diuresis, dec DKA incidence
Non-tight control: when controlled to tightly, we risk hypotension, plus its annoying and more work

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15
Q

Hyperkalemia treatment

A

10u Reg insulin IV

25g glucose, 1 amp 50% dextrose in 5 min

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16
Q

Hypoglycemia treatment

A

OJ, soda, honey, sugar tablet/cube

25-50 mL 50% dextrose solution

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17
Q

Which of these oral antidiabetic medications cause hypoglycemia?
Sulfonylureas, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, melitinides, GLP-1 mimetics/gliptons

A

Can cause hypoglycemia: Sulfonylureas, gliptons, and meglitinides all increase insulin secretion from B cells
Don’t cause hypoglycemia: biguanides and TZDs increase insulin sensitivity at target tissues, alpha-glucosidase inhibitors slow absorption from the gut

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18
Q

Sulfonylureas MOA?

A

Stimulate release of insulin from pancreatic beta cells
Binds to ATP sensitive K channes in the cell membrane resultinmg in depolarization, Ca influx, and insulin release (tricks the beta cell into thinking it is in a glucose-rich state)
Secondary MOA: enhance beta cell sensitivity to glucose, enhance tissue sensitivity to insulin, lower BG

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19
Q

Sulfonylureas effect on FBG and Hbg A1C?

A

Reduce FBG 60-70 mg/dL

Reduce Hgb A1C 2%

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20
Q

List 1st and 2nd generation sulfonylreas and their DOA

A

1st: Tolbutamine (orinase) DOA 6-12h; chlorpropamide (diabinese) DOA 36-72h
2nd: glipizide (glucotrol) DOA 12-24h; glymuride (micronase, diabeta) DOA 18-24h; glimepiride (amaryl)
1st gen has more drug interactions and SE than 2nd bc 2nd gen is 100x more potent

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21
Q

Sulfonylureas pharmacokinetics?

A

90-98% protein bound
Metabolized hepatically (avoid in liver dz), some active metabolizes
If renal impairment, use glipizide or tolbutamide

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22
Q

Sulfonylureas adverse effects?

A

HYPOGLYCEMIA (hold 1-2 days preop)
GI: N/V, fullness, heartburn, cholestasis, altered LFTs, appetite stimulant (exacerbate obesity)
GU: ADH effect- Na and H2O retention
Pruritis, rash

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23
Q

Biguanides: MOA

metformin

A

Dec hepatic and renal glucose production (decreased gluconeogenesis/glycogenolysis), inhibits aerobic metabolism

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24
Q

Biguanides benefits

A

No weight gain, possible weight loss
May increase HDL, decrease LDLs and TGs
Hypoglycemia rare when used alone

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25
Biguanides adverse effects
GI distress (diarrhea, metallic taste, nausea) Lactic Acidosis Rash Hold 1-2 days before surgery
26
Biguanides contraindications
Women with ESRD, creatinine over 1.4 Med with ESRD, creatinine over 1.5 Hepatic dysfunction CHF, shock, hypoxic pulmonary disease
27
Thiazolidinediones (TZDs): MOA, and name a couple?
Improves insulin sensitivity/decreases insulin resistance peripherally Pioglitazone (Actos) Rosiglitazone (Avandia)
28
TZDs clinical effect and pharmacokinetics?
Effect: decreases FPG up to 50 mg/dL, decreases Hgb A1C 1-2%, resumes ovulation in premenopausal women who have insulin resistance PO, hepatic metabolism
29
Alpha-gucosidase inhibitors MOA and name a couple of them
MOA: competitively and reversibly antagonizes enzymes in the intestinal brush border responsible for digesting complex carbohydrates (when in the GI tract, it doesn't get reabsorbed to the blood) delays glucose absorption, lowers post-prandial hyperglycemia (after a meal) Acarbose (precose) Miglitol (glyset)
30
TZD side effects and black box warning?
SE: edema, weight gain, hepatotoxicity (monitor LFTs, look for jaundice) Black ox warning: CHF (can cause or exacerbate), MI (from rosiglitazone)
31
Alpha-glucosidase inhibitors clinical effect and pharmacokinetics?
Decreases PPG 60-70 Decreases FBG 25-30 only Decreases Hbg A1C 0.7-0.9% Not absorbed after oral administration, excreted in stool
32
Alpha-glucosidase inhibitors adverse effects? Cautions?
Abdominal pain/distention, diarrhea, flatulence Caution in patients with IBD, ulcers, intestinal obstruction Tak with first bite of meal, if you skip a meal, skip the dose
33
Meglitinides MOA, how do they compare to sulfonylureas?
MOA: stimulates insulin secretion from pancreatic beta cells, quick onset and peak (1h), short DOA (4h), reduces PPH (postprandial hyperglycemia) Compared to sulfonylureas, less hypoglycemia, shorter DOA, quicker onset
34
Name a couple meglitinides, what are adverse effects?
Repaglinide (prandin), nateglinide (starlix) AE similar to sulfonylureas, hypoglycemia, n/v/c/d, heartburn, headache Take it 15-30 min before meals, if a meal is skipped, skip the dose
35
GLP-1 Agonisits (gliptins) MOA
Inhibits DPP4 (an enzyme that inactivates uncertain hormones, GLP1), enhances glucose-dependent insulin secretion, reduces glucagon secretion, slows gastric emptying
36
Sitagliptan (januvia)- what are the beneficial effects and adverse effects? E1/2t?
E1/2t 12h Reduces postprandial and fasting BG AE: rare fatal pancreatitis and anaphylaxis
37
What is exenatide (byetta)?
Synthetic GLP1, mimics GLP1 (an incretin), similar to gliptin, used as an adjunct to metformin or sulfonylureas
38
Exenatide (byetta) adverse effects?
N/V, delayed gastric emptying Renal failure, pancreatitis Antibodies developed against the drug Hypersensitivity
39
Pramlintide- what is it?
Amylin mimetics | Amylin is a pancreatic hormone released with insulin
40
Pramlintide (amylin mimetic): effects? Uses?
Reduces postprandial blood glucose | Used in both DM 1 and 2 who fail to attain control with insulin
41
Pramlintide pharmacokinetics? AE? Interactions?
Peaks in 20 min, E1/2t 50 min Metabolized in the kidney (NOT liver) AE: high risk for hypoglycemia, nausea, injection site reaction Interactions: decreased absorption of ABX an oral contraceptives
42
What does the thyroid do?
Responsible for growth and development of nervous system in infants Regulates metabolism and body temp Synthesizes and secretes thyroid hormones and calcitonin
43
Thyroid hormones are made up of two tyrosine molecules that are ____ and linked by an _____
They are IODINATED. Iodine is an essential component of thyroid hormones. Linked by an ether
44
_____ releases thyrotropin-releasing hormone (TRH). THR causes release of TSH from the ____
Hypothalamus releases TRH | Anterior pituitary releases TSH
45
Does the thyroid secrete more T3 or T4?
T4, which is then converted into T3 in the periphery
46
What do anti-thyroid drugs do? Name a couple.
Tx hyperthyroidism/ Graves Ex: propylthiouracil (PTU), methimazole Blocks organification process by competing with thyroglobulin for oxidized iodide Reduces synthesis of thyroid hormones
47
Antithyroid drugs onset of action? | PTU, methimazole
1-2 weeks
48
Is methimazole or PTU more potent, causing less side effects?
Methimazole is more potent, only requires daily dosing, less side effects
49
Antithyroid drugs adverse effects?
Goiter formation (inhibition of thyroid hormone up regulates TSH, leading to thyroid gland hypertrophy) PTU only- dec prothrombin, causes bleeding Pruritic rash Arthralgias Rare: agranulocytosis, hepatotoxicity, vasculitis
50
Other things that PTU does
Inhibits conversion of T4 to T3 in the periphery Increased bleeding tendency Preferred in pregnancy, doesn't cross placenta Preferred in thyroid storm (acute hyperthyroidism)
51
What other meds treat hyperthyroid?
B-blocker: blocks hyperadrenergic effects (tachycardia, tremor, nervousness), use esmolol for thyroid storm Corticosteroids: suppresses thyroid receptor Ab and inflammation Iodide: blocks conversion of T4 to T3, decreases vascularity of thyroid gland, blocks thyroid hormone release (this is only temporary treatment)
52
What other treatments besides meds for hyperthyroid?
Radioactive iodine, thyroid gland ablation Surgical removal of thyroid gland These options usually require thyroid replacement
53
Levothyroxine (synthroid): what is it?
Tx hypothyroid | Chemically synthesized T4
54
Levothyroxine half-life? What needs to be monitored?
LONG half-life of 7 days Easy to titrate Monitor TSH, T4, and s/s of hyperthyroid if dose is too high Monitor for adverse reaction: rash
55
When would you give T3 liothyronine (cytomel) instead of T4?
Life-threatening hypothyroidism, myxedema coma | Otherwise give T4- levothyroxine
56
Levothyroxine drug interactions?
Inc levothyroxine metabolism- penobarbital, phenytoin, rifampin, carbamazepine Dec T4-T3 conversion- PTU, b-blockers, amiodarone, glucocorticoids Dec absorption from gut- cholestyramine, FeSO4, AlOH3, sucralfate, kayexelate Inc thyroid binding- pregnancy, estrogen
57
Name 3 drugs that alter thyroid status
Amiodarone: structure resembles thyroid hormone, can cause hyper/hypo-thyroid Lithium: body thinks its iodine, leads to hypothyroidism Metoclopramide: increases TSH
58
Corticosteroids: what are mineralocorticoid effects vs. glucocorticoid effects?
Mineralocorticoid effects: reabsorption of Na and secretion of K in renal distal tubule (aldosterone effects) Glucocorticoid: antiinflammatory, augmentation of SNS activity
59
Corticosteroid MOA
Bind to steroid receptors in the cytoplasm Note: Mineralocorticoid receptors are found in organs of excretion, glucocorticoids wide-spread Steroid enters nucleus and influences DNA transcription (enhances/inhibits)
60
Corticosteroid effects
Raises BG, amino acid, TGs | Inflammatory response inhibited (arachidonic acid pathway)
61
Cortisol (solu-cortef) pharmacokinetics?
90% protein bound Metabolized mostly in liver, the rest is eliminated unchanged in the urine E1/2t 1.5-3h
62
How much endogenous cortisol do we secrete per day?
10-20mg | 50-150mg with extreme stress
63
Which steroid, when given with zofran before surgery, has a synergist long term effect on reducing post-op nausea?
Dexamethasone (decadron) | DOA is very long, 36-54 hours
64
Methylprednisolone, betamethasone, and prednisolone: do they have mineralocorticoid or glucocorticoid effects?
Methylprednisolone: glucocorticoid effects Betamethasone: lacks mineralocorticoid effects Prednisolone: both effects
65
Corticosteroids big clinical uses?
Adrenal insufficiency: cortisol Allergy/asthma: glucocorticoids, but takes 4-6h to see antiinflammatory effects Antiemetic: Decadron
66
If you swallow the inhaled glucocorticoid what are you risking?
Dysphonia- laryngeal muscle myopathy
67
Corticosteroids 3 big clinical uses?
Adrenal insufficiency: cortisol Allergy/asthma: glucocorticoids, but takes 4-6h to see antiinflammatory effects Antiemetic: Decadron 8-10mg, inhibits COX resulting in post-op analgesic effect
68
Other clinical uses for corticosteroids? (besides adrenal insufficiency, allergy, antiemetic)
Intracranial tumors Aspiration pneumonitis Immunosuppression (transplant) Lumbar disc herniation (triamcinolone/methylprednisolone epidural injection) RA, SLE, MG, sarcoidosis, ocular/cutanous inflammation UC, RDS prevention, leukemia
69
Corticosteroid side effects/interactions
``` HPA suppression (CV collapse) Fluid/electrolyte imbalance, CBC changes Infection, ulcers Osteoporosis, skeletal muscle weakness Psych disorders, growth retardation, dec anticoagulant effectiveness ```
70
Glucagon: what is it and what releases it?
Polypeptide hormone, produced by alpha cells in pancreas in response to hypoglycemia, an antagonist to insulin that raises BG
71
Glucagon MOA
``` Enhances cAMP (inc myocardial contractility, HR, gastric motility, renal flow, insulin secretion, gluconeogensis/glycogenolysis, relaxes smooth muscle, dec gastric motility) Vasodilates ```
72
Glucagon clinical uses
``` Increased CO (helps with b-blocker OD, improves CHF) Biliary dilation (helps with biliary stent placement) Enhance AV node conduction, diagnose pheo ```
73
Glucagon clinical uses? dose?
Increased CO (helps with b-blocker OD, improves CHF) Biliary dilation (helps with biliary stent placement) Enhance AV node conduction, diagnose pheo 1-5mg IV or 5 mcg/kg/min (20 mg/h)
74
Glucagon side effects
``` Hyperglycemia Hypoglycemia Hypokalemia N/V Inc HR (esp. with Afib pts) ```
75
Somatostatin is a GI regulatory peptide secreted by _____
pancreatic delta cells
76
Octreotide/ somatostatin
Octreotide is a SS analogue, both inhibit production and release of hormones from the GI tract and pancreas (inhibit growth hormone release, insulin secretion, and glucagon release)
77
E1/2t differences between SS and octreotide?
SS E1/2t 3 min | Octreotide E1/2t 2.5h
78
Octreotide uses?
``` Carcinoid crisis (dec release of amines like serotonin, but watch out for HB/bradycardia) Hepatorenal syndrome Control of esophageal variceal bleeding ```
79
Vasopressin/ADH: what happens at V1 and V2 receptors?
V1: arterial smooth muscle vasocontriction V2: inc water permeability/reabsorption at the collecting ducts in nephron back into circulation (reabsorbs more water)
80
Vasopressin uses? E1/2t?
``` Diabetes insipidus Esophageal varices r/t hemorrhage Hemorrhagic/septic shock Cardiac arrest resuscitation instead of epi E1/2t 10-20 min ```
81
Vasopressin side effects
Increased BP Coronary artery vasoconstriction: MI, angina GI hyperperistalsis: N/V, abd pain
82
Vasopressin/ADH: what happens at V1 and V2 receptors?
V1: arterial smooth muscle vasocontriction V2: inc water permeability/reabsorption at the collecting ducts in nephron back into circulation (antidiuretic!)
83
How does dosmopressin (DDAVP) compare to vasopressin?
DDAVP has a longer E1/2 of 2.5-4.4 hours More selective for V2 receptors (antidiuretic) Better choice for DI Stimulates secretion of vWF
84
Oxytocin (ptosin): what is it used for and what does it do?
Causes uterus contraction: induces labor, inc uterine tone after C-section, dec postpartum hemorrhage High doses dec BP
85
Oral contraceptives are a combo of what drugs to inhibit ovulation?
Estrogen | Progesterone
86
Estrogen prevents release of ____ | Progesterone prevents release of ____
Estrogen prevents release of FSH | Progesterone prevents release of LH
87
Oral contraceptive side effects?
Thromboembolism: DVT MI/stroke HTN

N550 Pharm (14 decks)

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