Week 12 Flashcards
1
Q
What are the characteristics of diabetes mellitus?
A
hyperglycemia
impaired metabolism of carbs, fats and protein
impaired insulin secretion, insulin resistance
2
Q
What type of DM is 5-10% of cases?
A
Type I
3
Q
What is the typical age of onset for type 2 DM?
A
> 30 years
4
Q
What type of DM has a strong genetic link?
A
type 2
5
Q
What type of DM is absolute deficiency of insulin production?
A
type 1
6
Q
What type of DM is insulin resistance, defective insulin release?
A
Type 2
7
Q
How is DM diagnosed by repeat?
A
HBA1C of 6.5% or more
FPG of 126 or more
symptoms + RPG >200
PG greater than 200 2 hour post GTT
8
Q
What type of DM is typically an autoimmune medicated destruction of pancreatic beta cells?
A
Type 1
9
Q
What are the 4 main features of type I DM?
A
- long pre-clinical period
- hyperglycemia when 80-90% of beta cells are destroyed
- transient remission (honeymoon period)
- established disease
10
Q
What is the goal of insulin therapy in T1DM Treatment?
A
mimic normal physiologic levels
basal (long acting)
bolus (short acting)
11
Q
What is recombinant or the first “biologic” insulin?
A
human insulin, regular, short acting
100units/mL or 500units/mL
12
Q
What are the insulin analogs?
A
rapid “ultra short” acting
long-acting
13
Q
What is NPH insulin?
A
intermediate acting
14
Q
What are the mixture insulins?
A
regular/intermediate
15
Q
What is insulin not given orally?
A
oral administration destroys protein
must be given parenterally
16
Q
What is the advantage of rapid (ultra short) acting analogs?
A
may inject closer to mealtime
17
Q
What is the advantage of long acting insulin analogs?
A
continuous coverage without injections
reduced solubility, slowing absorption
18
Q
What are the long acting insulin analogs?
A
glargine (lantus and toujeo)
Detemir (levemir)
Degludec (tresiba)
19
Q
What is the duration of glargine?
A
22-36 hours
20
Q
What is the duration of detemir?
A
12-20 hours
21
Q
What is the duration of degludec?
A
greater than 42 hours
22
Q
What long acting insulin causes less nocturnal hypoglycemia?
A
Toujeo and Degludec
23
Q
NPH insulin (Isophane) Intermediate- Acting Insulin is a suspension of what? (2)
A
crystalline zinc insulin
positively charged polypeptide, protamine
24
Q
What is significant about NPH insulin (Isophane) Intermediate- Acting Insulin?
A
absorbed slower after subQ injection
duration of action is longer than regular (or analog) insulin
duration is shorter than glargine, detemir or degludec (long acting insulins)
25
Who is Humulin manufactured by?
Eli Lilly
26
Who manufactures Novolin Novo Nordisk Human Insulin?
Novo Nordisk
27
What is the total daily dose of insulin requires in T1DM?
0.4 to 1 units/kg/day of actual body weight
28
What is the total daily dose of insulin in T1DM of the honeymoon period?
0.2 to 0.5 units/kg/daily
29
What is the requirement for basal insulin in T1DM?
approximately half totally daily insulin dose
may use any intermediate or long acting inslin
NPH usually preferred as it can be mixed
30
What are the requirements for meal time insulin?
other 50% of the total daily dose
divided between meals based on type of meal, patient characteristics
*use rapid-acting or regular insulin
31
What is non-intensive insulin therapy- 2 injections?
"split mixed" dosing
2 daily injections (basal insulin if NPH)
2/3 TDD in morning
1/3 TDD in evening
32
What is non-intensive insulin therapy-3 injections?
same dosing as "split-mixed" but moves NPH to bedtime
decreases nocturnal hypoglycemia
increase effect at darn
33
What is involved with intensive insulin therapy?
multiple self monitoring of blood glucose checks daily
| greater than 3 insulin injections daily
34
What is a glycosylated hemoglobin (HBA1C) in non diabetics?
4-6%
35
What is the AACE recommended guideline for HBA1C?
< 6.5%
36
What is the ADA recommended guideline for HBA1C?
<7%
37
How long does a HBA1C last?
process is irreversible and lasts the life of the RBC (120 days)
reflects average glucose over 3 months
38
Type II DM is a disorder of: (4)
insulin secretion
insulin resistance
excess glucose production
or all of the above
39
What is the glycemic goal and HBA1C based on for type 2 treatment?
individualize based on age and comorbidities
40
What is the recommended treatment for type 2 DM at diagnosis?
therapeutic lifestyle changes AND mono therapy with metformin
41
When should dual therapy be started in type 2?
if not at target A1C after 3 months of mono therapy OR is baseline A1C is greater than 9%
42
When should triple therapy be started?
if not at target A1C after 3 months of dual therapy
43
When should combo therapy be started?
if not at target after 3 months of triple therapy?
| blood glucose is 300-350 and/or HBA1C is greater than 10-12%
44
What are highly effective hypoglycemic agents?
insulin
biguanides (metformin)
sulfonyureas (SUs)
rapid-acting secretagogues (Glinides)
45
Why is insulin now being used earlier in pharmacotherapy for type 2?
minimizes micro and microvascular complications
multiple drugs are being used earlier
46
When should insulin be started in Type 2?
not an HAB1C goal after 2 or more non-insulin hypoglycemics
those with FBG greater than 250
those with A1C levels greater than 10%
hyperglycemia symptoms
DO NOT use as a threat for reaching HBA1C goals
47
What insulin should you start with for Type 2 and why?
Basal (long acting)
causes less hypoglycemia
NPH & LA analogs are equally effective
48
What long acting insulin is available OTC and cheaper?
NPH
49
What are the steps when prescribing long acting insulin in type 2?
1. 10 units or 0.1-0.2 units/kg/daily
2. adjust once or twice weekly
3. if not at goal or dose greater than 0.5 units/kg/d start prandial insulin
4. if still not controlled, begin "basal-bolus" insulins
50
When should rapid insulin analogs be given?
0-15 minutes before meals
51
When should regular insulin be given?
30 minutes before meals
52
What is considered first line for oral Type 2 treatment?
biguanides- metformin
53
What is the mechanism of action for Biguanides-metformin (glucophage)?
1. reduces hepatic glucose production
2. reduces intestinal glucose absorption
3. increase insulin sensitivity
4. improves peripheral glucose uptake and utilization
54
What are the benefits of metformin?
```
promotes modest weight loss or weight neutral
lowers fasting BG 20% and A1C 1-2%
synergistic effect with SUs
minimal hypoglycemia
minimal side effect profile
```
55
What are the adverse reactions of metformin?
```
GI effects: N/V, diarrhea, flatulence
lactic acidosis (death)
```
56
What are the contraindications of metformin?
males : SCr > 1.5
| females: SCr >1.4
57
What was the first biguanide that was recalled due to numerous fatalities and lactic acidosis?
phenformin
58
When should metformin not be used?
when CrCl is less than 30mL/min (CKD stage 4 and 5)
59
When should metformin be monitored closely?
when CrCl of 30-59 mL/min (CKD stage 3)
60
What is important to monitor when taking metformin?
renal
dehydration
infection/sepsis
metformin overdose (lactic acidosis)
61
What oral hypoglycemic agent is second line for oral therapy?
Sulfonylureas (SUs)
62
Why is glimepiride (Amaryl) the most popular of the Sulfonylureas?
once a day dosing but has greater risk of hypoglycemia
63
Why are sulfonylureas moderately effective as a class?
efficacy decreases over time (around 5 years, beta cell "burn out")
64
Why are first generation sulfonylureas rarely used?
due to potent second generation agents with fewer side effects
65
What are the 3 main second generation sulfonylureas?
Glimepiride (amaryl)
Glipizide
Glyburide
66
What sulfonylureas results in the most hypoglycemia?
glipizide (glucotrol) not preferred
67
What is the MOA of sulfonylureas ?
stimulate the release of insulin
requires presence of insulin (functioning pancreas)
not effective in type 1
68
What are the rapid secreting secretagogues?
"glinides"
nateglinide (starlix)
rapaglinide (prandin)
69
What is the MOA of secretagogues?
stimulates insulin release from the pancreas
similar to SUs but shorter half life
faster onset than SUs, hence rapid acting
70
Which secretagogues is slightly more effective at A1C reduction?
repaglinide (Prandin)
71
What are the adverse side effects of secretagogues?
hypoglycemia (less than sulfonylureas)
| weight gain
72
What are the adrenergic manifestations of hypoglycemia?
shakiness, nervous, anxiety
| palpitations, tachycardia, sweating (absent or diminished if on beta blockers)
73
What are the glucagon manifestations of hypoglycemia?
hunger
nausea
vomiting
headache
74
What are the neuroglycopenic manifestations of hypoglycemia?
impaired judgement, mentation
fatigue, lethargy, ataxia
stupor, coma, seizures
75
What is the treatment for mild hypoglycemia (glucose less than 50)
3 glucose tablets
1/2 cup fruit juice
5-6 pieces of hard candy (no artificial sweeteners)
glucose gel
76
What is the treatment for severe hypoglycemia? (glucose less than 40)
glucagon injection
| 50% dextrose IV push
77
What are the moderately effective hypoglycemic agents?
TZDas
DPP4Is
SGLT2Is
78
What are the thiazolidinediones (TZDs)?
Rosiglitazone (Amanda)
| Pioglitazone (Actos)
79
thiazolidinediones (TZDs) have a synergistic effect when combined with what?
sulfonylureas
| metformin or insulin
80
What is the MOA of thiazolidinediones (TZDs)?
increase insulin sensitivity in the liver fat and skeletal muscle by increasing glucose utilization and decreasing hepatic glucose production
81
What mediation is an "insulin sensitizer" and requires its presence?
thiazolidinediones (TZDs)
82
What are the adverse effects of thiazolidinediones (TZDs)?
weight gain (9 lbs)
increased total cholesterol, LDL, and HDL
edema
hepatic metabolism (avoid if LFTs greater than 2.5 ULN)
83
What thiazolidinediones (TZDs) had an FDA warning in 2007 for increased risk of MI?
rosiglitazone (Avandia)
84
What is the MOA of Dipeptidyl Peptidase-4 Inhibitors (DPP4Is)?
inhibits DPP-4, an enzyme that degrades intestinal incretin hormones (GLP-1, GIP)
85
How do incretin hormones work?
increase insulin secretion in response to meals
86
What is the effect of prolonging incretin levels by Dipeptidyl Peptidase-4 Inhibitors (DPP4Is?
stimulate insulin synthesis and release and decrease glucagon secretion from pancreatic alpha cells
87
What medications are considered the "incretin enhancers"?
Dipeptidyl Peptidase-4 Inhibitors (DPP4Is
88
What is the net result of Dipeptidyl Peptidase-4 Inhibitors (DPP4Is?
prolonged basal insulin secretion
89
What Dipeptidyl Peptidase-4 Inhibitors (DPP4Is) does not have a renal adjustment?
Linagliptin (trajenta)
90
What is a concern of Dipeptidyl Peptidase-4 Inhibitors (DPP4Is?
increased risk of heart failure
| however in 2016, NEJM found no increased risk of hospitalization for HF
91
What is the new, novel class of oral anti diabetics that are moderately effective?
Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2Is)
92
What is the MOA of Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2Is)?
inhibition of Na-glucose co transporter 2
SGLT2 recovers filtered glucose from the urine
inhibition increases urinary glucose loss
93
What medication increases urinary Na loss and therefore lowers BP and decreases weight?
Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2Is)
94
What are the adverse effects of Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2Is)?
increases risk of genital fungal infections
dehydration
recent FDA safety communication (ketosis and UTIs and pyelonephritis)
95
What are the minimally effective hypoglycemic agents?
alpha glucosidase inhibitors (AGIs)
Pramlintide
Glucagon- like peptide 1 receptor agonists (GLP-1-RAgs)
96
What is the cost of alpha glucosidase inhibitors (AGIs)?
$30-60/30 days of treatment
97
What is the MOA of alpha glucosidase inhibitors (AGIs)?
inhibits pancreatic alpha amylase and GI brush border alpha glucosides
delays hydrolysis of ingested carbohydrates
reduced postprandial insulin & glucose peaks
98
What is alpha glucosidase inhibitors (AGIs) effective for both Type 1 and 2?
does not stimulate insulin secretion
DOES NOT cause hypoglycemia
99
What are the adverse GI effects of alpha glucosidase inhibitors (AGIs)?
flatulence (73%)
| diarrhea (31%)
100
What medication is a synthetic analog of human amylin that decrease post-prandial glucose levels?
Pramlintide (Symlin)
101
Why is Pramlintide (Symlin) effective for type 1 and 2?
it does not act on beta cells
102
What is the effect of Pramlintide (Symlin) on weight?
LOSS
103
What is the risk of hypoglycemia with Pramlintide (Symlin)?
neutral
104
What medication is an additional SQ injection separate from insulin injection prior to each meal
Pramlintide (Symlin)
105
What is the cost of Pramlintide (Symlin)?
$1,500 per month
106
What are the side effects of Pramlintide (Symlin)?
nausea in 28-48%
107
What is the MOA of Glucagon- like peptide 1 receptor agonists (GLP-1-RAgs)?
incretin mimetic
enhances glucose dependent insulin secretion of beta cells in pancreas
inhibits the release of glucagon after meals
slows the rate of gastric emptying
increase satiety (weight loss)
108
Why were Glucagon- like peptide 1 receptor agonists (GLP-1-RAgs) recently discontinued?
increased risk of heart failure
109
What other factors are important when starting pharmacotherapy in type 2?
```
patient preference
route of administration
ability to lower A1C
risk of hypoglycemia (esp elderly)
cost
```
110
What type is DKA most seen?
type 1
111
What is DKA most often precipitated by?
omission of treatment (medication non adherence)
infection (if present usually hyperthermic)
alcohol abuse
112
What is the presentation of DKA?
polyuria, polydipsia, polyphagia and weakness
"fruity odor" to breath
N&V
Dehydration (dry mucus membranes, tachycardia, hypotension)
113
What is the treatment for DKA?
```
fluids
insulin
potassium
bicarbonate
sodium
```
114
What are the two active thyroid hormones?
T4-thyroxine
| T3- tri-iodothyronine
115
What % of T3 is produced in the thyroid gland?
20%
116
How is 80% of T3 produced?
produced peripherally by the breakdown of T4
117
What is the steady state of thyroid hormone?
4-5 half lives
118
What regulates the hormone production of the thyroid gland?
hypothalamic-pituitary-thyroid axis
119
Where is TSH secreted?
by the anterior pituitary
120
What is the most common type of primary hypothyroidism?
Hashimoto's thyroiditis
121
What is the cause of secondary hypothyroidism?
pituitary or hypothalamic disorder
122
What is the clinical presentation of hypothyroidism
weight gain
| depression
123
When working up a patient for depression, what is essential?
thyroid function tests
124
hypothyroid treatment that is desiccated beef or pro thyroid gland, measured in mg, potential for allergy and considered obsolete?
armor thyroid USP
125
What medication is a T3 and T4 mixture that is expensive and lacks therapeutic rationale?
Liotrix
126
What is the classic triad of symptoms of Grave's disease?
hyperthyroidism
opthalmopathy
dermopathy
127
What are the antithyroid medications for hyperthyroidism?
Propylthiouracil (PTU)
| Methimazole (Tapazole)
128
What medication inhibits peripheral conversion of T3 to T4?
Propylthiouracil (PTU)
129
How often should patients on Propylthiouracil (PTU) be evaluated?
every 3 months for recurrence of hyperthyroidism
130
What medication is 10x more potent than PTU
Methimazole (Tapazole)
131
What mediation blocks oxidation of iodine in thyroid?
Methimazole (Tapazole)
No effect on circulating T3 or T4
132
What are the major side effects of antithyroid medication?
agranulocytosis
aplastic anemia
thrombocytopenia
