Transcript DM, GI, Vitamins

NAPLEX
Drugs for
Diabetes Mellitus
Drugs for Diabetes Mellitus
Type 1
• Typically occurs in children
• Usually no family incidence
• Immune mediated
• Ketosis prone
• Usually diagnosed in an acute situation
• Patients require insulin
PG 92
Drugs for Diabetes Mellitus
Type 2
• Typically occurs in adults, however, children may
also develop
• Family incidence common
• About 90% of all diabetes patients
• Obesity frequently a factor
• Symptoms present gradually
• May have some pancreatic function
• Dietary modification, weight loss, and oral
hypoglycemic drugs are useful
PG 92
Type 1 vs. Type 2 Diabetes
Type 1
Type 2
Associated obesity
No
Yes
Propensity to ketoacidosis
Yes
No
Very low
Significant
No
Yes
Endogenous insulin
secretion
Hyperglycemia responds to
sulfonylureas
PG 273
Which of the following medications for diabetes
require monitoring of liver function?
I. pioglitazone (Actos)
II. rosiglitazone (Avandia)
III. acarbose (Precose)
a. I only
b. III only
c. I and II only
d. II and III only
e. I, II, and III
Which of the following medications for diabetes
require monitoring of liver function?
I. pioglitazone (Actos)
II. rosiglitazone (Avandia)
III. acarbose (Precose)
a. I only
b. III only
c. I and II only
d. II and III only
e. I, II, and III
Drugs for Diabetes Mellitus
Signs/Symptoms (POLYs)
• Hyperglycemia
• Ketonemia and ketonuria
• Polydipsia
• Glycosuria
• Polyphagia
• Polyuria
Complications (OPATHIES) Concomitant Conditions
• Nephropathy
• CHD
• Retinopathy
• Dyslipidemia
• Neuropathy
• Hypertension
• Gastropathy
• MI and Stroke
• Peripheral vascular disease/foot ulcers
PG 93
Diabetes Mellitus
Diagnostic tests
• Oral glucose tolerance test (OGTT)
• Fasting plasma glucose (FPG)
• Two-hours postprandial (2HPP)
PG 93
Diabetes Mellitus - laboratory monitoring
• Fasting glucose (FPG)
• Home self-blood glucose
• Glycosylated hemoglobin (HbA1C) normal 3-5%;
diabetic often above 8%, ADA goal is <7% - not for
diagnosis
• Microalbumin
• Lipid profile
PG 93
Natural History of Type 2
Diabetes
Thiazolidinediones, AGIs, Metformin
Glucose
Relative
function
Insulin
SFU, Meglitinides
Lifestyle
350
300
250
200
150
100
50
Postmeal glucose
Fasting glucose
300
250
200
150
100
50
0
Insulin resistance
At risk for
diabetes
-10
-5
Insulin level
-cell failure
0
5
10
15
20
25
30
Years of diabetes
D Kendall, R Bergenstal. © International Diabetes Center (used with permission).
Drugs for Diabetes Mellitus
Insulin
Insulin
Expiration
at Room
Temp.
Sources
Novolog
28
Animal - bovine, porcine, fish, etc.
Novolog
70/30
14
Humalog
28
Humalog
75/25
10
Humulin N
14
Humulin
70/30
10
Lantus
28
Detemir
42
Human - semisynthetic, recombinant DNA
Storage
Current - 28 days maximum at room temperature
Stored - keep refrigerated; do not freeze.
Prefilled syringes - generally, 28 days in refrigerator; store vertically
with needle point up.
Insulin pens – pen in use may be kept at room temp (see chart p.94
for ranges)
PG 94
Drugs for Diabetes Mellitus
Mixing Insulins
Always draw clear regular insulin into syringe first.
Be consistent with mixing method (i.e., same order, brand,
strength)
Glargine & Detemir cannot be mixed with other insulins
Lipodystrophy: Lipoatrophy or lipohypertrophy
Self-association (hexameric)
Fatty acid side chains bind to albumin in injection depot
Albumin binding in circulation
PG 94
Drugs for Diabetes Mellitus
Insulin Resistance – inability of body to use endogenous
insulin due to receptor defects
Hypoglycemia. Sudden onset, fatigues, confusion, pallor,
headache, loss of consciousness. Treat with glucose, glucagon
(SC, IM, IV), diazoxide oral (Proglycem) - a potassium channel activator
Ketoacidosis. Gradual onset, positive glycosuria and ketonuria,
thirst, “Juicy Fruit” breath, rapid pulse, drowsiness, loss of appetite
PG 94
Patients should be warned about the
possibility of lactic acidosis if they are
taking which of the following
medications?
a. glimiperide (Amaryl)
b. repaglinide (Prandin)
c. glyburide (Diabeta)
d. metformin (Glucophage)
e. insulin lispro (Humalog)
Patients should be warned about the
possibility of lactic acidosis if they are
taking which of the following
medications?
a. glimiperide (Amaryl)
b. repaglinide (Prandin)
c. glyburide (Diabeta)
d. metformin (Glucophage)
e. insulin lispro (Humalog)
Comparison of Insulin Preparations
Type
Onset (h)
Peak (h)
Duration (h)
Aspart (Novolog)
0.25
0.5-1.5
3-5
Lispro (Humalog)
0.25
0.5-1.5
3-5
0.5-1.0
2.5-5
6-8
NPH (Humulin N, Novolin N)
1-1.25
4-12
10-16
Lente (Humulin L, Novolin L)
1-2.5
7-15
24
4-6
10-30
36+
Glargine (Lantus)
4
-
24
Detemir (Levemir)
1
-
6-24
Rapid Acting
Short Acting
Regular (Humulin R, Novolin
R)
Intermediate Acting
Long Acting
Ultralente (Humulin U)
PG 95
Glargine Compared to NPH
Inhaled Insulin
1-1-08
voluntary
discontinuation
4-6-08
Cancer Warning
Drug
Starting Dose
Duration (h)
Comments
1-2 grams daily in 1-2
doses
6-12
Short half-life; good in renal
disease
250 mg daily
12-18
Significant uricosuric effect
100-250 mg daily
12-24
Excreted renally
Chlorpropamide
(Diabinese)
250 mg daily
24-72
Caution in elderly and
patients with renal or
hepatic insufficiency
Glyburide (Diabeta,
Micronase)
2.5 mg daily
18-24
Hypoglycemia; take 30
minutes before meal
1.5-3 mg daily
18-24
Hypoglycemia; take 30
minutes before meal
Glipizide (Glucotrol)
5 mg daily
10-24
Hypoglycemia; take 30
minutes before meal
Glimepiride (Amaryl)
1-2 mg daily
18-28
Hypoglycemia; take 30
minutes before meal
Sulfonyureas
Tolbutamide (Orinase)
Acetohexamide (Dymelor)
Tolazamide (Tolinase)
Glyburide, micronized
(Glynase)
PG 97
Short-acting insulin secretagogues
Nateglinide (Starlix)
120 mg tid ac
4
Hypoglycemia; take
1-30 min ac
Repaglinide (Prandin)
0.5-1 mg with
meals
4
Hypoglycemia; take
1-30 min ac
500 mg tid
4-6
May cause lactic
acidosis (Scr
men <1.5,
women <1.4)
Biguanides
Metformin (Glucophage)
PG 96
Alpha glucosidase inhibitors
Acarbose (Precose)
25 mg tid
4-6
Eliminated in bile;
take with first bite
of meal
Miglitol (Glyset)
25 mg tid
4-6
Eliminated renally;
take with first bite
of meal
Pioglitazone (Actos)
15-30 mg daily
24
Avoid use in liver
disease;
beneficial effects
on lipid profile
Rosiglitazone (Avandia)
2-4 mg daily or
divided bid
12-24
Avoid use in liver
disease
100mg daily
24
Renal adjustment
Thiazolidinediones
DPP- IV Inhibitors
Sitagliptin (Januvia)
PG 96
DPP- IV Inhibitors - dipeptidyl peptidase IV
Mixed
Meal
Intestinal GLP-1
release
DPP-4 inhibitors work by enhancing the incretin
system in the body. When the body senses
hyperglycemia in response to a glucose load (like
a meal), incretins stimulate the alpha and beta
cells in the pancreas to release insulin and signal
the liver to cease glucose production. The DPP-4
enzyme breaks down endogenous incretins.
DPP-4 inhibitors block this enzyme, thereby
increasing the active levels of incretin hormones in
the body.
GLP-1 active
DPP-IV
inhibitor
Adapted from Deacon et al. Diabetes 1995;44:1126
GLP-1
inactive
Exenatide-Overview



FDA approved:
 April 28, 2005
Class:
 Glugagon like peptide-1 analog (GLP-1)
Indication:
 Adjunct therapy of T2DM in patients taking
• Metformin (MET)
• Sulfonylurea (SFU)
• Combination MET & SFU

Dosage:


PG 95
5 mcg subcutaneously twice daily
10 mcg twice daily after 1 month
Byetta has which of the following
mechanisms of action?
I. Simulates GLP-1
II. Promotes satiety
III. Inhibits glucagon production
a. I only
b. III only
c. I and II only
d. II and III only
e. I, II, and III
Byetta has which of the following
mechanisms of action?
I. Simulates GLP-1
II. Promotes satiety
III. Inhibits glucagon production
a. I only
b. III only
c. I and II only
d. II and III only
e. I, II, and III
ExenatideMechanism of Action
GLP-1 secreted upon
the ingestion of food
Courtesy of Eli Lilly & Amylin
Pramlintide

FDA approved:
 March 17, 2005

Class:
 Amylinomimetic

Indication:
 Adjunct therapy of T1DM and T2DM in patients
taking
• Mealtime insulin
• With or without SFU and/or MET
PramlintideMechanism of Action
Slows gastric
emptying
Promotes
satiety
Inhibits glucagon
release
Which of the following medications
for
diabetes is least likely to cause
hypoglycemia?
a. Amaryl
b. repaglinide
c. Glucovance
d. insulin lispro (Humalog)
e. sitagliptin
Which of the following medications
for
diabetes is least likely to cause
hypoglycemia?
a. Amaryl
b. repaglinide
c. Glucovance
d. insulin lispro (Humalog)
e. sitagliptin
Which of the following strengths is/are
available for Glucophage tablets?
I. 500 mg
II. 850 mg
III. 2,000 mg
a. I only
b. III only
c. I and II only
d. II and III only
e. I, II, and III
Which of the following strengths is/are
available for Glucophage tablets?
I. 500 mg
II. 850 mg
III. 2,000 mg
a. I only
b. III only
c. I and II only
d. II and III only
e. I, II, and III
NAPLEX
Drugs Used to Treat
Peptic Ulcer Disease
PG 140
A patient is unable to take a proton pump inhibitor
orally. Which of the following drug(s) is/are
available in an injectable dosage form?
I. Aciphex (rabeprazole)
II. Prilosec (omeprazole)
III. Protonix (pantoprozole)
a. I only
b. III only
c. I and II only
d. II and III only
e. I, II, and III
A patient is unable to take a proton pump inhibitor
orally. Which of the following drug(s) is/are
available in an injectable dosage form?
I. Aciphex (rabeprazole)
II. Prilosec (omeprazole)
III. Protonix (pantoprozole)
a. I only
b. III only
c. I and II only
d. II and III only
e. I, II, and III
Drugs Used to Treat Peptic Ulcer Disease
Antacids
Magnesium hydroxide - diarrhea, possible renal toxicity
Aluminum hydroxide - constipation, caution in renal patients
Calcium carbonate - constipation, gas, milk-alkali syndrome
Sodium bicarbonate - sodium overload, gas
H2-receptor antagonists
Cimetidine (Tagamet) – drug interactions**, enzyme inhibitor
Ranitidine (Zantac)
Nizatidine (Axid)
Famotidine (Pepcid)
PG 140
Phosphate
binding
Drugs Used to Treat Peptic Ulcer Disease
Proton pump inhibitors
Omeprazole (Prilosec, Losec) – drug interactions (weak inducer or
inhibitor 1A2 / 3A4)
Lansoprazole (Prevacid) - powder for injection available
Rabeprazole (Aciphex)
Pantoprazole (Protonix) - powder for injection available
Esomeprazole (Nexium) - powder for injection available
- decrease absorption or atazanavir, indinavir, iron salts, -azoles,
GI stimulants
Metoclopramide (Reglan, Maxolon)----higher doses cause CNS side
effects
Cisapride (Propulsid) - removed from market
PG 140
Drugs Used to Treat Peptic Ulcer Disease
Ulcer-adherent complex
Sucralfate (Carafate)---contains an Al+++ compound; caution in renal pts.
can alter absorption of many drugs
Anticholinergics
Atropine, L-hyoscyamine, propantheline, etc.----think dry eyes, dry mouth
Prostaglandins
Misoprostol (Cytotec)---Category X; diarrhea—titrate dose, renal dose
adjustment
PG 140
Helicobacter Pylori Therapy

Bacteria associated with causing duodenal ulcers




patients with symptoms should be tested
eradication helps reduce recurrence
Duodenal ulcers can lead to Zollinger-Ellison
Syndrome
Therapy generally includes two antibiotics and one
acid suppressing agent

Bismuth subsalicylate + metronidazole + tetracycline
(Helidac) + H2 antagonist x 14 days
Clarithromycin + amoxicillin + lansoprazole (Prevpac)

Alternative antibiotics x 10 to 14 days

– Tetracycline, metronidazole, rifampin
PG 140
NAPLEX
Vitamins / Nutritionals
Water Soluble Vitamins
Vitamin
Deficiency Symptoms
Therapuetic Uses
Other Comments
Vitamin C
(ascorbic Acid)
Scurvy
-Enhances
wound healing
-prevents deficiency
-Increase Absorption of
Iron
1.
Deficiency disease,
Wernicke-Korsakoff
syndrome
1.
Deficiency disease
1.
Thiamine (B1)
Riboflavin (B2)
Polyneuropathy, beriberi
Lesions of the mouth (cheilosis),
lips,tongue and eyes
2.
3.
4.
2.
2.
Niacin (B3)
(Nicotinic acid)
Niacinamide
(nicotinamide)
PG 99
Dermatitis, diarrhea, dementia,
pellagra
Deficiency disease,
peripheral vascular
disease, reduction or
serum lipids
1.
2.
Antioxidant
Urinary Acidifier
Same data
Assist in prevention of colds - ?
Responsible for typical “vitamin”
odor
Necessary for normal
carbohydrate metabolism
Will impart a red-green-orange
fluorescence to urine
May cause false elevations in
fluorescent determinations of
urinary catecholamines
Niacinamide does not have
hypolipidemic or vasodilating
effect.
Possible drug interactions with
vasodilator antihypertensive
agents. May cause postural
hypotention
Water Soluble Vitamins (cont’d)
Vitamin
Deficiency
Symptoms
Therapeutic
Uses
Other Comments
Pyridoxine (B6)
Convulsions, skin
lesions
Deficiency disease
1.
2.
Folic acid (folate)
Megaloblastic anemia,
CNS damage, mouth
sores
Deficiency disease
1.
2.
3.
Cyanocobalamin
(B12)
Pernicious anemia,
macrocytic anemia,
glosssitis
Deficiency disease
1.
2.
PG 98
Aids in decarboxylation
of amino acids
Higher requirements for
patients on isoniazid
(INH), oral
contraceptives, or
hydralazine therapy
Phenytoin and other
anticonvulsant may
inhibit folic acid
absorption
Folic acid administration
may decrease serum
levels of phenytoin
Products contatining
more than 0.8 mg of folic
acid are Rx only.
Oral neomycin or
aminosalicylic acid may
significantly reduce B12
absorption.
Hydroxycobalamin is a
longer-acting form of
vitamin B12.
Fat Soluble Vitamins
Vitamin
Deficiency
Symptoms
Toxicty
Therapeutic
Uses
Other Comments
Vitamin A
Retinoids
Retinol
Retinoic acid
Carotenoids
Beta carotene
Dry eye
(xerophthalmia), night
blindess
(nyctalopia), increased
respiratory infection
Hypervitaminosis
A: Fatigue,
Lethargy,
Abdominal Upset,
Rough skin,
Brittle nails
Deficiency
disease, acne
treatment,
cancer
prevention?
1.
Vitamin D
Cholecalciferol (D3)
Ergocalciferol
Rickets, osteomalacia
Hypervitaminosis
D:
Hypercalcemia,
Hypercalciuria,
Kidney stones,
Anorexia,
Nausea,
Weakness
Deficiency
disease
PG 99
2.
3.
1.
2.
3.
USRDA for vitamin A is 5,000
IU = 1,000 retinol equivalents
(RE)
Higher Fat malabsorption may
decrease vitamin A absorption
Neomycin, mineral oil, and/or
cholestryamine administration
may also cause vitamin A
malabsorption
Cholestyramine and mineral oil
may reduce the absorption of
vitamin D.
Phenytoin and barbiturates
decrease vitamin D half-life
Consumption of five times the
RDA of vitamin D may result in
adverse effects
Fat Soluble Vitamins (cont’d)
Vitamin
Deficiency
Symptoms
Toxicty
Therapuetic
Uses
Other Comments
Vitamin E
Tocopherols
Alpha-tocopherol
Tocotrienol
Reproductive failure,
neurologic
abnormalities, red
blood cell hemolysis
None reported
Deficiency
disease, biliary
disease, cystic
fibrosis
1.
2.
3.
4.
Vitamin K
Phytonadione (K1)
Menaquinone (K2)
Menadione (K3)
Defective blood
coagulation,
hemorrhage
Menadione
excess may
cause
hemolytic
anemia and
hyperbilirubinemia in
newborn
infants
Deficiency
disease
1.
2.
3.
4.
PG 99
Vitamin E is an antioxidant
Vitamin E requirement is
dependent on intake of
polyunsaturated fatty acids
Avoid large vitamin E doses in
patients using oral anticoagulants
Avoid taking vitamin E at the
same time as iron supplements.
Vitamin K deficiency may be
caused by breast-feeding, severe
liver disease, malabsorption
syndromes, or chronic broadspectrum antibiotic use.
Phytonadione is routinely given to
neonates at birth (one dose of 1
mg) to prevent hemorrhage.
Microbiologic flora of gut
manufactures most of vitamin K
needed
Cholestryramine resin and
mineral oil consumption may
decrease vitamin K absorption.
NAPLEX
Iron Supplements
Iron Supplements
Use - treatment of microcytic, hypochromic anemia (iron
deficiency)
Dose based on elemental iron (usually 60 mg BID)
Monitor – Hct, Hgb, Ferritin, Transferrin, TIBC
Takes 4 weeks to see change
PG 101
Iron Supplements (cont’d)
Enhancing iron absorption—empty stomach, vit C, no milk,
eggs, antacids
Injectable iron products - generally used in end-stage renal
disease (ESRD)
• Iron dextran (INFeD) - Z-track method, test dose
• Sodium ferric gluconate complex in sucrose solution
(Ferrlecit)
• Iron sucrose injection (Venofer) – test dose
Iron toxicity
• Lethal dose
• Deferoxamine mesylate (Desferal mesylate) - IM, IV
- complexes with trivalent ions to form ferrioxamine - kidneys
PG 101
Other Agents Used to Treat Anemia-Related Diseases
Hematologic stimulants – colony stimulating factor
Epoetin alpha (erythropoietin, EPO, Epogen, Procrit)
- induces erythropoisis and the release of reticulocytes
- anemia related to HIV, CRF, allogeneic blood transfusions,
sickle cell, and many more investigational
- treatment doses (40,000units wkly) & maintenance doses \
(monthly) dose reduces as hemoglobin approaches 12g/dl or
hemoglobin increases 1g/dl in any 2 week period.
Darbepoetin Alfa (Aranesp) and
Filgrastim (granulocyte colony-stimulating factor [G-CSF], Neupogen)
- Chemotherapy induced neutropenia, and AML
Sargramostim (GM-CSF, Leukine) (neutrophils, eosinophils,monocytes, & macrogphages)
- (non)&Hodgkin’s lymphoma, acute lymphobastic leukemia (ALL)
Oprelvekin (interleukin-11, Neumega) - thrombopoietic growth factor
- prevention of severe thrombopenia
PG 101
A patient with osteomalacia would best be
given a nutritional supplement high in:
a. pyridoxine
b. ascorbic acid
c. beta carotene
d. nicotinic acid
e. cholecalciferol
A patient with osteomalacia would best be
given a nutritional supplement high in:
a. pyridoxine
b. ascorbic acid
c. beta carotene
d. nicotinic acid
e. cholecalciferol – (vitamin D analog)
A patient has been prescribed niacin for high
triglycerides. Which of the following adverse
effect are likely to occur as a result of niacin
use:
a. thrombus formation
b. dry mouth
c. peripheral vasodilation
d. cardiac palpitations
e. alopecia
A patient has been prescribed niacin for high
triglycerides. Which of the following adverse
effect are likely to occur as a result of niacin
use:
a. thrombus formation
b. dry mouth
c. peripheral vasodilation
d. cardiac palpitations
e. alopecia
A patient taking chronic doses of isoniazid
should be supplemented with:
a. beta carotene
b. ascorbic acid
c. cyanocobalamin
d. thiamine
e. pyridoxine
A patient taking chronic doses of isoniazid
should be supplemented with:
a. beta carotene
b. ascorbic acid
c. cyanocobalamin
d. thiamine
e. pyridoxine