23) Diabetes Flashcards
(171 cards)
1
Q
The endocrine pancreas in the adult human consists of
A
- Approximately 1 million islets of Langerhans
2
Q
Within the islets, at least five hormone-producing cells are present. The hormone products related to diabetes include:
A
- Insulin
- Islet amyloid polypeptide (IAPP, or amylin)
- Glucagon
3
Q
Insulin
A
- Storage and anabolic hormone of the body
4
Q
Islet amyloid polypeptide (IAPP, or amylin)
A
- Also secreted by β-cells
- Modulates appetite, gastric emptying, and glucagon/insulin secretion
5
Q
Glucagon
A
- Hyperglycemic factor that mobilizes glycogen stores
6
Q
Diabetes mellitus
A
- Elevated blood glucose associated with absent or inadequate pancreatic insulin secretion
- With or without concurrent impairment of insulin action
7
Q
The disease states underlying the diagnosis of diabetes mellitus are now classified into four categories
A
- Type 1
- Type 2
- Other
- Gestational
8
Q
Pre-diabetes glucose test values
A
- A1C = 5.7-6.4%
- Fasting = 100-125 mg/dL
- 2 hour OGTT 140-199 mg/dL
9
Q
Confirmation diagnostic glucose test values
A
- A1C = >6.5%
- Fasting = >126 mg/dL
- 2 hour OGTT = >200 mg/dL (or random > 200 with classic symptoms)
10
Q
GDM (1-step strategy) glucose values
A
- A1C = N/A
- Fasting = ≥92 mg/dL
- 1 hr: ≥180 mg/dL
- 2 hr: ≥153 mg/dL
11
Q
OGTT
A
- Oral glucose tolerance test (75g glucose)
12
Q
Types of drugs used in diabetes mellitus
A
- Insulins
- Non-insulin drugs
13
Q
Types of insulin used in diabetes
A
- Rapid, short acting
- Intermediate acting
- Slow, long-acting
14
Q
Rapid, short acting insulin drugs
A
- Lispro, regular
15
Q
Intermediate acting insulin drugs
A
- NPH
- Lente
16
Q
Slow, long acting insulin drugs
A
- Glargine
17
Q
Types of non-insulin drugs used in diabetes
A
- Insulin secretagogues
- Biguanides
- Alpha-glucosidase inhibitors
- Thiazodinediones
- Amylin analogs
- Incretin modulators
- SGLT2 inhibitors
18
Q
Insulin secretagogues
A
- Glipizide
19
Q
Biguanides
A
- Merformin
20
Q
Alpha-glucosidase inhibitors
A
- Acarbose
21
Q
Thiazolidinediones
A
- Pioglitazone
22
Q
Amylin analogs
A
- Pramlintide
23
Q
Incretin modulators
A
- GLP-1 analog (exenatide)
- DPP-4 inhibitor (sitagliptin)
24
Q
SGLT2 inhibitors
A
- Canalgiflozin
25
Insulin is a small protein or peptide i.e. it cannot be taken orally because
- Digestive enzymes will break the peptide or protein into basic unit amino acids
- Therefore insulin is given as an injection (except for the new Afrezza®)
26
Insulin is secreted in response to
- All insulin secretagogues
27
Insulin is classified based on
- How quickly they take effect (onset of action)
| - How long they work for (duration of action)
28
Basal-bolus strategy
- Taking a longer acting form of insulin to keep blood glucose levels stable through periods of fasting
- Take separate injections of shorter acting insulin to prevent rises in blood glucose levels resulting from meals
29
The goal of subcutaneous insulin therapy
- Replicate normal physiologic insulin secretion
| - Replace the background or basal (overnight, fasting, and between-meal) as well as bolus or prandial (mealtime) insulin
30
_____ % of the exogenous insulin is cleared by the _____ and ____ % is removed by the _____
- 60% by kidneys
| - 30-40% by liver
31
Four principle types of injected insulin
- Rapid
- Short
- Intermediate
- Long
32
Rapid acting has a very fast onset and short duration of action, and also contains
- Small amount of zinc to improve the stability
33
Short acting has a fast onset of action, and also contains
- Small amount of zinc to improve the stability
34
Intermediate acting insulin
- Neutral protamine Hagedorn [NPH] insulin
35
Rapid acting insulin injection schedule
- Should be taken immediately before the meal
| - Insulin lispro, aspart and glulisine DOA: 4-5 h i.e. decrease the risk of post-meal hypoglycemia
36
Rapid acting insulin brand/generic names (LAAG)
- Humalog (insulin lispro)
- Novolog (insulin aspart)
- Apidra (insulin glulisine)
- Afrezza (oral inhalation)
37
Humalog, novolog, apidra OAA/peak/DOA
- OAA = 5-15 min
- Peaks = 1 h
- DOA = 4-5 h
38
Afrezza OAA/peak/DOA
- OAA = 15 min
- Peaks = 1 h
- DOA = 3 h
39
Short acting insulin injection schedule
- Administered 30-45 min before mealtime
| - Only type that should be administered IV
40
Short acting insulin is useful for
- Management of diabetic ketoacidosis
| - Insulin requirement after a surgery
41
Short acting insulin brand/generic names
- Humulin R U500 (regular)
| - Novolin R (regular)
42
Short acting insulin (Humulin R U500 and Novolin R) OAA/peak/DOA
- OAA = 30 min
- Peak = 2 h
- DOA = 5-8 h
43
Long acting insulins characteristics
- Soluble, peakless, long acting insulin analogue
| - Usually given once a day
44
Intermediate acting insulins brand/generic names
- Humulin N (NPH)
| - Novolin N (NPH)
45
Intermediate acting insulins OAA/DOA
- OAA = 1-3 h
| - DOA = 4-12 h
46
Long acting insulins brand/generic names
- Levemir (Insulin detemir)
- Lantus, Toujeo, Basalgar (Insulin glargine)
- Tresiba U200 (Insulin degludec)
47
Levemir (long acting insulin) OAA/DOA
- OAA = 3 h
| - DOA = 24 h
48
Lantus, Toujeo, Basalgar (long acting insulin) OAA/DOA
- OAA = 3 h
| - DOA = 24 h
49
Tresiba U200 (long acting insulin) OAA/DOA
- OAA = 1 h
| - DOA = 24 h
50
Hypoglycemia signs/symptoms
- Sympathetic: tachycardia, palpitations, sweating
- Parasympathetic: nausea and hunger
- Severe hypoglycemia may lead to coma
51
Treatment for hypoglycemia
- Glucose administration
52
Side effects of insulin
- Hypoglycemia
- Insulin allergy
- Atrophy of subcutaneous tissue at injection site, redness, itching, edema
- Hunger and nausea
- Potassium shift
53
Insulin allergy is usually reduced with
- Human analogue insulin
54
Potassium shift from insulin administration
- Extra to intracellular space
| - Decreasing serum potassium concentration
55
Afrezza side effects
- Cough, pulmonary function should be monitored
| - Caution in smokers and patients with COPD
56
Drugs that primarily stimulate insulin release by binding to the sulfonylurea (SU) receptor
- First generation SU
- Second generation SU
- Meglitinide analogues
- Drugs that mimic incretin and amylin
57
Drugs that primarily lower glucose levels by their actions on the liver, muscle and adipose tissue
- Biguanides
| - Thiazolidinediones
58
Drugs that affect absorption of glucose
- α-glucosidase inhibitors
59
Drugs that mimic incretin effect or prolong incretin action
- Glucagon-like peptide 1 (GLP-1)
| - Dipeptidyl peptidase-4 (DPP-4) inhibitors
60
Other hypoglycemic drugs
- Amylin mimetic
- Bile acid sequestrant
- Dopamine-2 agonist
61
Oral anti-diabetic drug options/actions
- Drugs that primarily stimulate insulin release by binding to the sulfonylurea (SU) receptor
- Drugs that primarily lower glucose levels by their actions on the liver, muscle and adipose tissue
- Drugs that affect absorption of glucose
- Drugs that mimic incretin effect or prolong incretin action
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors
- Other hypoglycemic drugs
62
Sulfonylureas (SU) MOA
- SU binds to SU receptor that is associated with a beta-cell inward rectifier ATP-sensitive potassium channel
- Binding of a SU inhibits the efflux of potassium ions through the channel
- Results in depolarization which opens a voltage-gated calcium channel
- Results in calcium influx and the release of preformed insulin
63
SU metabolism
- Metabolized in the liver to inactive metabolites
- Metabolites are excreted in the kidney
- 2nd generation has metabolites partly excreted in the bile
64
Advantages of 2nd generation SU
- Greater affinity to receptor which lower effective doses and plasma levels
- 100 times more potent
- Have shown less hypoglycemic side effects
65
2nd generation SU generic names
- Glyburide
- Glipizide
- Glimepiried
66
Glyburide (2nd generation SU) brand names/DOA
- Diabeta
- Miconase
- Glynase
- DOA = 10-24 h
67
Glipizide (2nd generation SU) brand names/DOA
- Glucotrol
- Glucotrol XL
- DOA = 10-24 h
68
Glimepiride (2nd generation SU) brand names/DOA
- Amaryl
| - DOA = 12-24 h
69
2nd generation SU side effects
- Hypoglycemia (unknown MOA)
- At higher doses, block K+ channels (might increase cardiovascular events)
- Sulfate allergy (contains sulfonamide moiety)
- Nausea, headaches, weight gain
- Hepatitis
70
Hematologic side effects associated with 2nd generation SU
- Thrombocytopenia
- Leukopenia
- Aplastic anemia
- Hemolytic anemia
71
Glipizide and glimepiride are substrates of
- CYP2C8/9
72
MOA of meglitinide analogues
- Modulate β-cell insulin release by inhibiting the efflux of K+
- Overlap with the SU in their molecular sites of action (two binding sites in common with the SU and one unique)
73
Meglitinide analogues generic/brand names
- Repaglinide (Prandin)
| - Nateglinide (Starlix)
74
Repaglinide (Prandin) T1/2, DOA, metabolism
- T1/2 = 1 h
- DOA = 4-7 h
- Metabolism = hepatic CYP3A4
75
Nateglinide (Starlix) T1/2, DOA, metabolism
- T1/2 = 1 h
- DOA = 4 h
- Metabolism = hepatic CYP3A4 and CYP2C9
76
Because of its rapid onset, meglitinide analogues are used in controlling
- Postprandial glucose excursions
77
Meglitinide analogues can be used in patients with
- Renal impairment
| - Elderly
78
Meglitinite analogues do NOT contain
- Sulfure moiety
| - Can be used in sulfur allergy patients that cannot take SU
79
Meglitinide analogue side effects
- Hypersensitivity to the molecule
- Diabetic ketoacidosis
- Patients with hepatic impairment
- Causes hypoglycemia
- Headaches
- Upper respiratory tract infections
- Urinary tract infections
- Heartburn
- Weight gain
80
Biguanides
Generic
- Metformin
Brands
- Glucophage
- Glumetza
- Glucophage XR
- Fortamet
- Riomet
81
Metformin MOA
- Full explanation remains elusive
| - Primary effect is reduction of hepatic glucose production
82
Biguanides (metformin) are called
- Euglycemic agents
| - Rarely cause hypoglycemia
83
Metformin T1/2
- 1.5-3 h
84
Metformin is not bound to
- Plasma protein
85
Metformin metabolism/excretion
- Not metabolized
| - Excreted by kidneys as the active compound
86
Biguanide GI toxicities
- Dose related
- Occur in up to 20%
- Anorexia, nausea, vomiting, abdominal pain, and diarrhea (discontinue if persistent diarrhea)
87
Biguanide interferes with
- Calcium dependent absorption of vitamin B12
| - Can lead to deficiency (especially for patients with peripheral neuropathy and macrocytic anemia)
88
Biguanides in patients with renal insufficiency
- Accumulate
| - Cause lactic acidosis
89
Cautions when taking biguanides
- Hypersensitivity
- Renal dysfunction
- Acute or chronic metabolic acidosis
- Congestive heart failure patients
- GI: nausea, vomiting, and diarrhea
- Chest discomfort, abdominal discomfort
- Upper respiratory tract infection
90
Thiazolidinediones act to
- Decrease insulin resistance
91
Thiazolidinediones are ligands of
- Peroxisome proliferator-activated receptor gamma (PPAR-Ɣ), part of the steroid and thyroid superfamily of nuclear receptors
92
PPAR-Ɣ receptors are found in
- Muscle
- Fat
- Liver
93
Thiazolidinedinones modulate the expression of genes involved in
- Lipid and glucose metabolism
- Insulin signal transduction
- Adipocyte and other tissue differentiation
94
Effects of thiazolidinediones
- Increase glucose transporter expression (GLUT 1 and 4)
- Decrease free fatty acid levels
- Decrease hepatic glucose output
- Increase differentiation of preadipocytes to adipocytes
95
Thiazolidinediones generic/brand names
- Pioglitazone (Actos)
| - Rosiglitazone (Avandia)
96
Pioglitazone (Actos) metabolism
- Hepatic
| - Substrate and inhibitor of CYP2C8 and CYP3A4
97
Rosiglitazone (Avandia) metabolsim
- Hepatic
| - Substrate and inhibitor of CYP2C8
98
Other effects of Pioglitazone (Actos)
- Decrease TG
| - Increase HDL
99
Other effects of Rosiglitazone (Avandia)
- Increase HDL
- Increase LDL
- Increase total cholesterol
100
Pioglitazone (Actos) peak, T1/2, binding
- Peak = 2 h
- T1/2 = 7 h
- 99% protein bound
101
Rosiglitazone (Avandia) peak, T1/2, binding
- Peak = 1 h
- T1/2 = 4 h
- 99% protein bound
102
Thiazolidinediones side effects
- Fluid retention, edema (may increase plasma volume/cardiac hypertrophy)
- Heart failure
- Anemia (mostly because of dilutional effect of increase plasma volume)
- Weight gain
- Headaches
103
Thiazolidinediones contraindications
- Contraindicated if hypersensitivity
| - Contraindicated if acute liver disease (transaminases more than 2.5 times the upper limits)
104
MOA of α-glucosidase inhibitors
- Competitively inhibit the intestinal α-glucosidase enzymes
| - Reduce post-meal glucose excursions by delaying the digestion and absorption of starch and disaccharides
105
Acarbose (Precose) and miglitol (Glyset) are potent inhibitors of
- Glucoamylase
- α-amylase inhibited by Acarbose
- Sucrase
- Less effect on isomaltase, hardly any on trehalase and lactase
106
α-glucosidase inhibitors binding site/type
- Reversibly, competitively, and in a dose-dependent manner
| - Oligosaccharide binding site of α-glucosidase enzymes in the brush border of the small intestinal mucosa
107
As a consequence of α-glucosidase inhibitors binding, hydrolysis is prevented
- Effect lasts for 4 to 6 hours if acarbose is present at the site of enzymatic action at the same time as the oligosaccharides
- Thus acarbose must be administered with the first bite of a main meal
108
α-glucosidase inhibitors metabolism
- Exclusively via GI tract principally by intestinal bacteria and digestive enzymes
- 35% is urine excreted (dose adjustment needed in case of renal impairment)
109
α-glucosidase inhibitors side effects
- GI: Flatulence, diarrhea and abdominal pain
- Increase in liver enzymes (AST and ALT)
- May increase the risk of hypoglycemia when administered with SU
110
Cause of GI side effects associated with α-glucosidase inhibitors
- Unabsorbed starches and sugars entering the large bowels are fermented by the bacteria there
- Causes flatulence and diarrhea as a commonly seen side effect in higher doses
111
α-glucosidase inhibitors contraindications
- Hypersensitivity
- Diabetic ketoacidosis or cirrhosis
- Inflammatory bowel disease
- Colonic ulceration
- Partial or predisposed intestinal obstruction
- Chronic intestinal diseases
112
An oral glucose load (glucagon-like-peptide-1) provokes
- Higher insulin response compared with an equivalent dose IV
- This is because the oral glucose causes a release of gut hormones
113
Release of gut hormones with oral glucose
- Incretins or glucagon-like peptide-1 (GLP-1)
| - Glucose-dependent insulinotropic peptide (GIP), that amplify the glucose-induced insulin secretion
114
Other biologic effects of GLP-1
- Suppresses glucagon secretion
- Delays gastric emptying
- Reduces apoptosis of human islets in culture
115
GLP-1 is rapidly degraded by
- Dipeptidyl peptidase-4 (DPP-4)
- Other enzymes such as endopeptidase
- Cleared by the kidney
116
Generic GLP-1 names
- Exenatide
- Liraglitude
- Lixisenatide
- Albiglutide
- Dulaglutide
117
Exenatide (GLP-1) brand names
- Byetta (IR): Twice a day
| - Bydureon (ER): Once a week
118
Liraglutide brand names
- Victoza
119
Lixisenatide brand names
- Adlyxin
| - If combined with insulin the brand is Soliqua
120
Albiglutide brand names
- Tanzeum
121
Dulaglutide brand names
- Trulicity
122
Exenatide, liraglutide, and lixisenatide dose, T/12, peak, DOA
- Once a day
- T1/2 = 12 h
- Peak = 2 h
- DOA = 10 h
123
Albiglutide and dulaglutide dose, T1/2, peak, DOA
- Once a week
- T1/2 = 5 d
- Peak = 1 d
- DOA = one week
124
GLP-1 side effects
- Nausea
- Erythema @ injection site
- Increase risk of pancreatitis (persistent abdominal pain)
- History of stomach or bowel problems (trouble digesting food, gallbladder problems as gallstones, pancreatitis, dialysis)
125
MOA of Dipeptidyl peptidase-4 (DPP-4) inhibitors
- Inhibit the degradation of the incretins/GLP-1 and GIP
126
Dipeptidyl peptidase-4 (DPP-4) inhibitors generic/brand names
- Sitagliptin (Januvia)
- Saxagliptin (Onglyza)
- Linagliptin (Tradienta)
- Alogliptin (Nesina)
127
Dipeptidyl peptidase-4 (DPP-4) inhibitors dose, T1/2, peak (ALL)
- Once a day
- T1/2 = 12 h
- Peak = 2 h
128
Sitagliptin (Januvia) elimination
- Renal
129
Saxagliptin (Onglyza) elimination
- Hepatic by CYP3A4/5
| - Kidney
130
Linagliptin (Tradienta) elimination
- Unchanged in feces
131
Alogliptin (Nesina) elimination
- Renal
132
Dipeptidyl peptidase-4 (DPP-4) inhibitors side effects
- Nasopharynghitis
- Upper respiratory infections
- Headaches
- Hypoglycemia if in combo with insulin secretagogues
- Pancreatitis
133
Glucose is freely filtered by the renal glomeruli and is reabsorbed in the proximal tubules by the action of
- Sodium-glucose transporters (SGLTs)
134
SGLT2 in the proximal tubule
- Accounts for 90% of glucose reabsorption
| - Its inhibition causes glycosuria and lowers glucose levels in patients with type 2 diabetes
135
SGLT-2 inhibitors generic/brand names
- Canagliflozin (Invokana)
- Dapagliflozin (Farxiga)
- Empagliflozin (Jardiance)
136
SGLT-2 inhibitors dose, T1/2, metabolism (ALL)
- Once a day
- T1/2 = 12 h
- Hepatic metabolism
137
SGLT-2 inhibitors side effects
- Increase urination frequency, thirst
- Pelvic/rectal pain
- Decrease in amount of urine
Increase risk of genital infections and UTI
- Osmotic diuresis can cause intravascular volume contraction and hypotension
138
Pramlintide (Symlin)
- Islet amyloid polypeptide (IAPP, amylin) analogue
| - Analog/mimetic of human amylin
139
Amylin is co-located in _____ and co-secreted with insulin by _____
- Secretory granules
| - Pancreatic beta cells in response to food intake
140
Amylin and insulin show similar
- Fasting and postprandial patterns in healthy individuals
141
IAPP effects
- Reduces glucagon secretion
- Slows gastric emptying (vagally medicated mechanism)
- Centrally decreases appetite
142
Amylin absorption
- Rapidly absorbed after subcutaneous administration immediately before eating
143
Amylin DOA
- Not more than 150 minutes
144
Amylin metabolsim
- Metabolized and excreted by kidney
145
Amylin side effects
- Hypoglycemia
| - GI: Nausea, vomiting and anorexia
146
Glucagon brand names
- Glucagen
| - Glucagon
147
Glucagon synthesis/degradation
- Synthesized in the alpha cells of the pancreatic islets of Langerhans
- Degraded in the liver, kidney, plasma, and its tissue receptor sites
148
Glucagon half life in plasma
- 3-6 min
| - Similar to that of insulin
149
Glucagon binding
- Binds to specific Gs protein-coupled receptors on liver cells
- Leads to increased cAMP
- Facilitates catabolism of stored glycogen
- Increases gluconeogenesis and ketogenesis
150
Immediate pharmacologic result of glucagon infusion
- Raise blood glucose at the expense of stored hepatic glycogen
151
Cardiac effects of glucagon
- Potent inotropic and chronotropic effect on the heart, mediated by the cAMP
- Produces an effect very similar to that of β-adrenoceptor agonists
152
Glucagon indication
- Management of hypoglycemia
| - Must monitor blood pressure and blood glucose
153
Glucagon side effects
- Nausea
| - Vomiting
154
Glucagon onset and DOA
- Onset = 5-20 min
| - DOA = 60 min
155
Glucagon metabolism
- Hepatic
156
Glucagon administration routes
- IM
- IV
- SC
157
Kazano (oral combination)
- Alogliptin + metformin
158
Ivokamet (oral combination)
- Canagliflozin + metformin
159
Xigduo (oral combination)
- Dapagliflozin + metformin
160
Synjardy (oral combination)
- Empagliflozin + metformin
161
Glucovance (oral combination)
- Glyburide + metformin
162
Jentadueto (oral combination)
- Lingaliptin + metformin
163
Actoplus (oral combination)
- Pioglitazone + metformin
164
Prandimet (oral combination)
Repaglinide + metformin
165
Avandamet (oral combination)
- Rosiglitazone + metformin
166
Komboglyze (oral combination)
- Saxagliptin + metformin
167
Janumet (oral combination)
- Sitagliptin + metformin
168
Oseni (oral combination)
- Alogliptin + pioglitazone
169
Glyxambi (oral combination)
- Empagliflozin + linagliptin
170
Duetact (oral combination)
- Pioglitazone + glimepiride
171
Avandaryl (oral combination)
- Rosiglitazone + glimepiride
