Week 2 Endocrine Flashcards
1
Q
A1C reduction with glucose
What is the gold standard?
A
Insulin
reduces A1C by about 2.5
Everything else about 1.5
2
Q
What drugs to use when compelling need to minimize hypoglycemia? (4)
A
DPP4
GLP1
SGLT2
TZD
3
Q
Thiazolidinediones (2)*
A
Rosiglitazone (Avandia)
Pioglitazone (Actos)
4
Q
Beta-Adrenergic Antagonists
MOA
Common agents
AE
A
Acts by decreasing symptoms of adrenergic stimulation caused by T4 concentrations
Inhibits peripheral conversion of T4 to T3
Propanolol (non selective BB)
Decreased BP, bradycardia, cardiac arrest
CHF, Asthma
5
Q
Insulin Preparations
A
Rapid
Short
Intermediate
Long
6
Q
Biguanides Old Contraindications*
A
Male Creatinine >/- 1.5mg/dL
Female Creatinine >/- 1.4mg/dL
7
Q
What drug?
Direct acting (categorized based on duration after injection)
Major SE: Hypoglycemia
A
Insulin
8
Q
Causes/Diagnoses of Hypothyroidism (3)
T4 concentrations
TSH concentrations
A
Hashimoto’s thyroiditis
Surgery
Meds (Lithium, RAI, Amiodarone)
Decreased total and free T4
Elevated TSH
9
Q
What insulin cannot be mixed with others?*
A
Long Acting*
10
Q
Basal Insulin
Adults secrete about __ unit of insulin per ___ regardless of food intake
A
Secreted in small amounts throughout the day 50%
1 unit per hour
11
Q
DPP-4 Inhibitors
Adverse Effects
A
Well tolerated
Pancreatitis (rare)
Heart disease?
12
Q
What drug?
Activates PPAR (steroid hormon) -> insulin sensitivity
Major SE: Peripheral edema, heart failure, bone loss, weight gain
A
Thiazolidinediones
13
Q
Thioureas*
AE(3)
A
Rash
Fluid Retention
Decreased WBC** reverses on discontinuation if caught early
14
Q
Types of Therapy for Hyperthyroidism (3)
A
Surgery
Meds
Radioactive iodine
15
Q
GLP-1 Agonists*
What is it?
A
Recombinant peptide that shares 53% of amino acid sequence w human GLP-1
16
Q
SGLT 2 Inhibitors
Administration
A
Oral daily dosing
Dose must be adjusted for renal dysfunction
17
Q
Canagliflozin (Invokana)
Dosing Admin Renal Dose Adjustment Cost Patient Assistance
A
100-300mg daily Before first meal of the day Yes 350$ for 30 tablets Available
18
Q
DPP-4 Inhibitors CV Safety
A
Overall they were neutral
19
Q
Dapagliflozin (Farxiga)
Dosing Admin Renal Dose Adjustments Cost Patient Assistance
A
5-10mg daily In the morning with or without food Yes $350 for 30 tablets Available
20
Q
Oral Combination Products a lot are combined with what drug?
A
Metformin
ie) Pioglitazone + Metformin, Glyburide + Metformin, etc
21
Q
Thiazolidediones
AE (2)
____ Risk
Pioglitazone recommended against use if you have
A
Hepatotoxicity, Edema
Fracture (reduces osteoblastic activity and increases urinary calcium excretion)
Bladder Ca or hx
22
Q
Hypoglycemia Picture of Sx
What do you do?
A
Shaky Fast Heartbeat Sweating Dizzy Anxious Hungry Blurry Vision Weakness of Fatigue Headache Irritable
Check -> Tx -> Check
23
Q
Thyroid Hormones effect (2)
A
Growth and Development
Maintain metabolic stability
24
Q
Short Acting Insulin (1)
A
Regular Humulin R
25
Biguanides New Contraindications*
GFR <30 = Contraindicated
GFR 30-45 = Do not start
GFR dips < 45 = Re-evaluate vs cut dose in half
GFR 30-60 with iodinated contrast = hold for 48 hrs
26
Adverse Effects of Insulin* (4)
Hypoglycemia
Insulin Allergy
Immune Insulin Resistance
Lipohypertrophy (rotate injection sites)
27
SGLT -2 CV Safety*
Significant CV reduction of residual CV risk!
28
GLP-1 Agonists (4)*
Exenatide (Byetta)
Liraglutide (Victoza)
Albiglutide (Tanzeum)
Duglaglutide (Trulicity)
29
*Rapid Acting Insulin* (3)
```
Insulin Lispro (Humalog)
Insulin Aspart (Novalog)
Insulin Glulisine (Aventis)
```
30
Levothyroxine*
Considered a "____"
Produces physiologic levels of?
Onset
Prodrug
T4 and T3
2-3 wks
31
What drugs to use when ASCVD predominates
1) SGLT2i*
| 2) GLP 1
32
Bolus Insulin
Also called
Larger amounts secreted in response to food to
In response to food 50%
Premeal, mealtime, prandial, nutritional insulin
Decrease postprandial hyperglycemia
33
Duration of action of Insulin is ______ in pts with (2) failure
Prolonged
| Hepatic and Renal
34
*Intermediate Acting Insulin*
```
Onset
Peak
Duration
___ used for ____ IV use
Usually administered
Appearance*
```
```
2-4 hr
4-8 hr
8-12 hr
NOT for emergency
1-2 times/day
CLOUDY
```
35
Glucagon
Secreted by a cells
Increases hepatic glucose output -> increases blood glucose concentration
36
Thioureas*
MOA
Inhibits iodination of tyrosine
Coupling of iodotryrosines
PTU also inhibits peripheral conversion of T4 to T3
DOES NOT effect release of preformed T4 and T3
37
Glipizide (2)*
Duration
Active Metabolite
Elimination
Glucotrol, Glucotrol XL
12-16 hrs
Inactive
90% Hepatic
38
GLP 1 Agonists*
AE (3)
N/V
HA
Pancreatitis
39
Storage of Insulin*
Refrigerate if not in use
Room Temperature if in use/limit to 28 days
Away from direct heat or light
Check for clumps, frosting, failure to stay in suspension when mixed
Never use cloudy or discolored insulin except for NPH
40
Meglitinides Potential Advantages
_____ onset and ____ duration of action
May be used in pts with ____ insufficiency
May be useful in pts who ___ meals
AE (2)
Rapid, short
Renal
Skip
Hypoglycemia
Weight Gain
41
Diabetes Mellitus
A syndrome that develops when insulin secretion or activity are not sufficient to maintain blood glucose levels
42
*Intermediate Acting Insulin* (2)
NPH Humulin N
| NPH Novolin N
43
*Insulin Dose based on:
Type 2:
Type 1:
Observe for
Total Body Weight
0.2 u/kg/day
Depends
Trends in hypoglycemia and hyperglycemia
44
Comparison of Common Agents
Equvalent Glucocorticoid dose, Mineralcorticoid potency
1) Hydrocortisone
2) Cortisone
3) Prednisone
4) Methylprednisolone
5) Dexamethasone
1) 20, +2
2) 25, +2
3) 5, +1
4) 4, +1
5) 0.75, 0
45
Levothyroxine Adverse Effects (4)*
HF
Angina (painful constriction of tightness)
MI
Hyperthyroidism
46
*Short Acting Insulin*
```
Onset
Peak
Duration
Administered
May be given
Appearance
```
```
30 min
2-3 hr
4-6 hr
30-45 min before a meal*
IV
Clear
```
47
Intermediate/Long Uses (2)
Basal insulin needs
| Not to cover meals
48
Thioureas (2)*
Propylthiouracil (PTU)
| Methimazole (Tapazole)
49
DM Type II
NIDDM
- results from insulin secretory defect and insulin resistance
RELATIVE lack of insulin
50
Thyroid Hormone Synthesis and Release
Iodine + Tyrosine
Organification into T1 and T2
Coupling into T3 and T4
Secretion of T3 and T4 into circulation
T4 is solely secreted from thyroid gland
51
Gestational Diabetes
Onset or discovery of glucose intolerance during pregnancy
52
Natural Thyroid Hormones
(____ Thyroid)
Dessicated (3) thyroid
Contains a ____ quanitity of T4 and T3
Bioavailability is ______
Allergies
Armour
Hog, Beef, Sheep
Standardized
Unpredictable
53
Meglitinides
MOA
Onset
Peak
Duration
Metabolized
Same as sulfonylureas
15 min
60-90 min
< 4 hrs
CYP3A4
54
DPP-4 Inhibitors (4)*
Sitagliptin (Januvia)
Saxagliptin (Ongylza)
Alogliptin (Nesina)
Lingagliptin (Tradjenta)
55
What drugs to use when HF/CKD predominates
1) SGLT2i if eGFR is adequate
| 2) GLP-1
56
Biguanides* (1)
Metformin (Glucophage)
57
Medication-Induced Hyperglycemia
```
Thiazide diuretics
Protease inhibitors
Atypical antipsychotics
Glucocorticoids
Calcineurin inhibitors
Nicotinic acid
Oral Contraceptives
Phenytoin
```
58
Biguanides Contraindications*
Impairments (2)
Contraindications (4)
Renal Impairment*
Hepatic Impairment = may decrease ability to eliminate lactic acid*
Hypoxic states
Acute or chronic alcohol abuse
Elderly
CHF on drug therapy
59
*Long Acting Insulin* (5)
```
Insulin Glargine (Lantus) 100n/mL
Insulin Glargine (Basaglar) 100u/mL
Insulin Glargine (Toujeo) 300u/mL
Insuline Detemir (Levemir)
Insulin Degludec (Tresiba)
```
60
DPP-4 Inhibitors
Administration
Once daily oral admin
| Adjustment necessary for pts with renal dysfunction
61
Combination Products* (3)
```
Novolin or Humulin 70/30
- NPH 70% Regular 30%
Novolog 70/50
- Aspart protamine 70% Aspart 30%
Humalog 50/50 75/25
- Lispro protamine 50% 75% Lispro 50% 25%
```
62
Adverse Effects of Insulin*
```
Hypoglycemia*
Signs of autonomic ______
- Sympathetic (4)
- Parasympathetic (2)
- May progress to (2) if untreated
```
Hyperactivity
- Tachycardia, Palpitations, Sweating, Tremulousness
- Nausea, Hunger
- Seizures, Coma
63
SGLT 2 Inhibitors*
Potential Advantages (4)*
Weight Loss (75g urine glucose = 300kcal/day)
Decrease risk of hypoglycemia
Lowers BP
Renal Protection
64
Liothyronine* T3 Cytomel*
Higher incidence of?
Why is not really used?
Cardiac events
Difficulty monitoring w conventional lab tests
$$
65
Biguanides*
Caution with: *
Advantages (3)
AE(2)
Iodinated Contrast*
No hypoglycemia when used as monotherapy
Weight loss
Decrease triglycerides
N/V/D
Metallic taste
66
*Insuline Detemir*
Onset
Peak
Duration
Appearance
2 hr
3-9 hr
14-24 hr
Clear
67
SGLT2 Inhibitors (3)*
Canagliflozin (Invokana)
Dapagliflozin (Farxiga)
Empagliflozin (Jardiance)
68
Pharmacologic Agents (10)
```
Insulin
Sulfonylureas
Meglitinides
Biguanides
a Glucosidase Inhibitors
Thiazolidinediones
GLP-1 Agonists
DDP 4 Inhibitors
SGLT 2 Inhibitors
Amylin Agonists
```
69
SGLT- The Bad
May 2016: All
June 2016: Canagliflozin
June 2016: Canag and Dapag
November 2016: All
Increased risk for DKA
Boxed warning for leg/foot amputations
Increased risk for acute kidney injury
Increased risk for bone loss
70
Animal Insulin (2)
Human Insulin is produced through
Insulin is a ____ hormone that cannot be given ___
Circulating insulin has half life of only a few ___ dt rapid removal by (2)
Beef, Pork
Recombinant DNA Techniques
Peptide, PO
Minutes, Liver and Kidneys
71
GLP 1 CV Safety
WE literally just wanted to prove it didn't have cardiotoxic effects (thia)
But we found the opposite happened, not even just safety but they improved CV risk!
72
Thyroid Hormones
T3 Triiodothyronine
| T4 Thyroxine
73
DPP Inhibitors*
MOA
Inhibits DPP-4 enzyme that is responsible for the breakdown on incretin hormones GLP-1
74
*Insulin Glargine*
Onset
Peak
Duration
Appearance
4-5 hr
No peak
22-24 hr
Clear
75
Tx of Adrenal Insufficiency
For Adrenal Crisis, Addisonian Crisis what do you use?
____ protein bound
Formulations (3)
Parenteral glucocorticoids
Highly
Oral: exhibits 100% absorption
IV: succinate
IM: acetate
76
DM Complications
```
Blindness
Heart Attack
Kidney Failure
Stroke
Dental Problems
Amputation
Pregnancy Complication
Nerve Damage
Sexual Dysfunction
Insulin Injection
```
77
Insulin
Secreted by B cells
Promote uptake utilization and storage of glucose -> lowers plasma glucose concentration
78
Glyburide (3)*
Duration
Active Metabolite
Elimination
Diabeta, Glynase, Prestab
12-24 hrs
Inactive
50% Hepatic/50% Renal (the only one w renal excretion)
79
DM Type I
IDDM
- results from B cell destruction
- ABSOLUTE lack of insulin
80
What is an essential component of both T3 and T4
Iodine
81
SGLT 2 Inhibitors*
Concerns
```
Limp amputation
Electrolyte disturbances
Decreased BP
Bacterial urinary infections
Fungal genital infections
Malignancy
```
82
Causes/Diagnosis of Hyperthyroidism (3)
T4 concentrations
TSH concentrations
Graves Disease
Thyroid stimulating antibodies
Meds (Amiodarone)
Elevated total and free T4
Suppressed TSH
83
Empagliflozin (Jardiance)
```
Dosing
Administration
Renal Dose Adjustments
Cost
Patient Assistance
```
```
10-25mg daily
In the morning with or without food
Yes
TBD
TBD
```
84
Administration*
1)
sites (3)
accelerates absorption (3)
types (3)
2)
What insulins are given by this route (2)
1) SubQ
Abdomen, Butt, Arms/Legs
Exercise, Rubbing, Heat
Vial and Syringe, Pens, Pumps
2) IV
Rapid and Short
85
Sulfonylureas*
Metabolism and Excretion
Hepatically metabolized
- caution w hepatic impairment
Renally excreted
- Glyburide may accumlate in pts w CrCL < 30ml/min
86
Portable Pen Injectors
Vials of insulin + replaceable needles
More accurate dosing mechanisms
Faster and Easier than conventional syringes
Increased patient compliance
87
Incretin Mimetics
Food -> GLP 1 ->
Stimulates insulin release
Delays gastric emptying
Suppression of postpradial glucagon release
DPP-4 inhibits GLP 1
88
Thiazolidinediones Contraindication*
May cause or exacerbate CHF*
Contraindicated in NYHA Class III or IV HF*
After initiation of dose, observe pts for s/s of HF
89
Pancreatic Hormones (2)
Glucagon
| Insulin
90
Thioureas*
Well absorbed by the
___ is highly protein bound unlike ___ which is not significantly bound to protein
Both agents have ____ lives, however they
Patient becomes _____ over a 1-2 month period
GI
PTU, Methimazole
Short, accumulates in thyroid gland to exert longer effects
Euthyroid
91
Sulfonylureas Adverse Effects*
Hypoglycemia (most common)*
Rash, Photosensitivity, Hypersensitivity
N/V, abnormal LFT's
Weight Gain
92
What drugs to use when compelling need to minimize weight gain or promote weight loss?
GLP 1
| SGLT 2
93
Secondary causes of DM (4)
Pancreatic Disease
Cystic Fibrosis
Endocrinopathies
Drugs and Chemicals
94
Infusion Pump
Connected to subc catheter to deliver short acting insulin
Decreases glycemic variability
Does have logistical issues and is more expensive
95
What drugs?
Promotes production of insulin when stimulated by food
Major SE: Pancreatitis
Incretins (GLP1 & DPP4 Inhibitors)
96
Sulfonylureas
MOA
Secondary effects (2)
Therapeutic Use:
Increase secretion of preformed insulin by B cells by closing K+ channels
Increase insulin receptor sensitivity
Decrease hepatic glucose output
Type 2
97
Biguanides*
MOA
Secondary effects
Therapeutic use
Decrease hepatic glucose output
Increases peripheral glucose uptake and utilization
Type 2 DM
98
Thiazolidediones*
MOA + (3)
Binds to nuclear steroid hormone receptor and promotes glucose uptake into skeletal, muscle, and adipose tissue
- Increases insulin sensitivity
- Decreases insulin resistance
- NO EFFECT ON INSULIN SECRETION*
99
Iodine-Containing Compounds
MOA
Common Agents (2)
AE
Immediately inhibits release of T4 and T3
Lugols solution, Potassium iodide solutions (SSKI)
Rash, metallic taste, sore gums, GI discomfort, hypothyroidism
100
Glimiperide (1)*
Duration
Active Metabolite
Elimination
Amaryl
24 hr
Weakly active
100% Hepatic
101
*Goals for Glycemic Control*
1) A1C
2) Fasting Glucose
3) Peak postprandial glucose (1-2 hrs after meal)
1) <6.5-7.0%
2) 80-130
3) <180
102
What drugs? (2)
Closes K+ channels -> insulin release
Major SE
Hypoglycemia, Weight Gain
Sulfonylureas
| Meglitinides
103
Liotrix (T4:T3 4:1) Thyrolar*
Why is not really used? (2)
No advantage over T4 alone
| $$$$
104
Drug of choice for thyroid replacement?*
Chemically ____
Expensive?
Free of ______
Levothyroxine
Stable
Inexpensive
Antigenicity
105
Combination Products
Advantages
Disadvantages
Less injections/day
Less calculations by pt
Dose adjustments alter both products
106
GLP 1 Agonists*
Precautions (2)
Not recommended in pts with CrCl <30 mL/min
Should not be used in pts with a personal or family hx of medullary thyroid cancer
107
Synthetic Thyroid Hormones (3)*
Levothyroxine (T4, L-thyroxine, Synthroid, Levoxyl)
Liothyronine (T3 (Cytomel))
Liotrix (T4:T3 4:1) (Thyrolar)
108
What drug?
Inhibits glucose reabsorption by kidneys, increase glycosuria
Major SE: Genitourinary infections, polyuria
SGLT 2 Inhibitors
109
Meds to treat Hyperthyroidism (4)
Thioureas
Iodine-containing compounds
B-adrenergic antagonists
Corticosteroids
110
Technosphere Insulin
Dry ___ of human ___ insulin formulated to absorb onto ____ microparticles for ____ admin
Peak ~ ___ min
Metabolism similar to ____ insulin
Administered when?
Black Box Warning:
First inhaled product the "Dreamboat"
Powder, rDNA, Technosphere, pulmonary
15
Regular human
Before or within 20 min of starting
Bronchoconstriction
NO USE w COPD, Asthma
Not recommended for patients who smoke
111
Insulin Administration
SQ or IV
112
What drug?
Decreases gluconeogenesis
Increases glyolysis
Major SE: Lactic acidosis, GI symptoms
Metformin
113
What drugs to use when cost is a major issue?
SU
| TZD
114
DPP-4 Inhibitors
FDA Warning 2015
Severe Joint Pain
115
Therapeutic Uses of Insulin
1) Type 1
2) Type 2
3) DM of ______
1) Therapy of choice
2) For those who cannot control with diet, exercise, oral meds OR newly diagnosed presenting with severe, symptomatic hyperglycemia
3) Pregnancy
116
Sulfonylureas (3)*
| 2nd gen
Glyburide (Diabeta, Glynase, Prestab)
Glipizide (Glucotrol, Glucotrol XL)
Glimepiride (Amaryl)
117
Tx of Hypoglycemia*
1) Mild Hypoglycemia + Conscious, Able to Swallow
2) Severe Hypoglycemia + Unconscious/Stupor
1) Simple sugar, glucose
(juice, hard candy, sugar packets/glucose gel, tablets)
2) 20-50ml Dextrose 50% IV or 1mg Glucagon SQ/IM
118
GLP 1 Agonists*
How is it administered?
How often?
Pre-filled pens for subcutaneous injection
Once or twice daily to once weekly
119
SGLT 2 Inhibitors
Drug interactions
No major interactions
120
*Rapid Acting Insulin*
```
Onset
Peak
Duration
Administered
Ideally added to ___ insulin regimen
May be given
Appearance
```
```
15-30 min
1-2 hr
3-4 hr
Immediately before a meal*
Basal
IV
Clear
```
121
____ channels determine resting membrane potential in __ cells
Glucose enters B cells via a membrane transporter __-__
KATP are blocked causing membrane _____ and opens ____ channels
Ca2+ signals ____ secretion
ATP Sensitive K+ (KATP)
B
Glut-2
Depolarization, Ca2+
Insulin
122
SGLT 2 Inhibitors*
MOA
Inhibits sodium glucose transporter 2 in the proximal renal tubules -> reduces reabsorption of filtered glucose and increased urinary excretion of glucose
Thereby reducing plasma glucose concentrations
123
Corticosteroids
MOA (2)
Decreases thyroid action
| Suppresses immune response in Grave's
124
Insulin Dosing Pearls*
1 unit of insulin decreases blood glucose by:
Start ___ then ___ to meet nutritional needs
Wait ___ before adjusting dose
Insulin should never be stopped in:
50mg/dL (30-100)
low, increase
24 hrs
Type 1*
125
The Role of the Adrenal Glands
| 3
Responsible for regulating stress response through synthesis of
1) Glucorticoids (cortisol)
2) Mineralcorticoids (Aldosterone)
3) Adrenal Androgens
126
Non-Glycemic Goals
1) BP
2) LDL
3) Triglycerides
1) <130/80
2) <100, <70 CV disease
3) <150
127
Rapid/Short Acting Uses (2)
Mealtime
| Elevated Glucose
