Chapter 13: Diabetes Flashcards
Type 1 DM
2-5% of all cases
induced by auto-immune destruction of pacnreatic cells
Type 2 DM
90-95% of cases
prevalence varies by ethnicity
strong genetic predisposistion
plasma insulin levels drop as the body develops resistance
oral hypoglycemics
sulfonylureas
biquanides
alpha-glucosidase inhibitors
thiazolidines
meglitinides
DPP-4 inhibitors
glucosuria
glucose in urine d/t kidney excreting too much
polyuria
increased urination
polyphasia
increased appetitie
polydipsia
increased thirst
poor glycemic control places at a high risk for
retinopathy
neuropathy
MI
what is treatment for T2DM based on
HGBA1C results
what medications are obese patients more likely to benefit from and why
metformin because it acts more on glucose utilization and hepatic glucose storage and production
which medication do non-obese diabetic patients respond better to
sulfonylureas
patients who are at risk for hypoglycemia benefit more from which drug and why
metformin because it is less likely to produce it
what do patients with a high postprsndial glucose level beneit most from
addition of a glucosidase inhibitor or a meglinitidine
steps for treatment of T2DM
- lifestyle intervention and metformin (titrated to maximum effective dose over 1-2 months)
- additional medications
- glycemic control (start insulin)
sulfonylureas
mechanism of action
- lowers blood glucose by increasing insulin secretion from pancreatic Bcell
- decreases glycogenolysis
- decreases glyconeogenesis
- increase cell sensitivity to insulin
sulfonylureas clinical uses
monotherapy an in combination with other drug classes as well as insulin
sulfonylureas should not be used in combination with what
meglitinides
why is there controversy ove whether sulfonylureas should be as first line therapy for T2DM
only lowers A1C levels by 1-2%
1st class of drugs used to treat T2DM
conscientious prescribing of sulfonylureas
start low, go slow, watch for toxicity
mild-mod T2DM responds best
combination therapy is popular
the only sulfonylureas that doe not cause weight gain
metformin
patient education for sulfonylureas
take 30-40 minutes before eating and never on an empty stomach
watch for weight gain, GI upset, gas
avoid alcohol and ASA
accu-checks
what medications increase the effects of sulfonylureas
CYP450 inhibitors
(azoles, NSAIDs, sulfonamides, antidepressants, MAOIs, and digitalis)
what medications may decrease the effects of sulfonylureas
CYP450 inducers
(phenobarbital, beta blockers, and hydantoins)
sulfonylureas contraindications
cross-sensitivy to sulfonamides (including thiazide diuretics)
severe renal, hepatic, thyroid, or other endocrine disorders
uncontrolled infection, burns, and trauma
biguanides: Metformin (Glucophage)
first line therapy
lowers A1C 1-2%
metformin mechanism of action
reduces hepatic production of glucose and inhibits intestinal absorption of glucose
metformin clinical uses
monotherapy and in combination with other agents
conscientious considerations for metformin
- decreases LDL, trigs, plasminogen, B12
- combinations are more effective than monotherapy
- monitor renal function for ketoacidosis
- dc if hypoxic or surgery
- assess for HF, septicemia metabolic acidosis, pregnancy
- many drug interactions
patient education for metformin
take missed dose within an hour of scheduled dose or waite until next scheduled dose
healthy diet, avoid alcohol
regular follow-up is necessary
test for blood glucose and urine ketones
what medications may increase metformin levels
lasix, nifedipine, cimetidine, cationic drugs (digoxin, amiloride, procainamide, quinidine, ranitidine, trimethoprim, vancomycin, triamterene, morphine)
what medications increase hyperglycemia risk when taken with metformin
thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, CCBs, and isoniazid
what can cause hypoglycemia when taken with metformin
alcohol
excess alcohol can increase risk for lactic acidosis
metformin contraindications
those at increased risk for lactic acidosis d/t renal impairment
hepatic dysfunction, HF, metabolic acidosis, dehydration, alcoholism
Meglitinides: secretagogues
mechanism of action
close ATP-dependent potassium channels in the beta cell membrane by binding at specific receptor sites causing insulin release
lowers A1C by 0.6-1%
examples of meglitinides
repaglinide (Prandin)
nateglinide (Starlix)
why must meglitinides be adminstered more often than sulfonylureas
they have a shorter half-life
meglitinides clinical usage
postprandial hyperglycemia
which meglitinide is almost as effective as metformin
repaglinide
meglitinide dosages are based on
A1C levels
meglitinide therapy
monotherapy has better long term effects
may need adjunct insulin in times of stress
what medications may lead to increased serum concentrations of meglitinides resulting in hypoglycemia
gemfibrozil, macrolide antibiotics, many herbals (St. John’s wort, ethanol, garlic), any drug affected by the CYP450 system
meglitinides contraindications
hepatic impairment
meglitinide patient education
take with meals 2-4 times a day
watch for weight gain and hypoglycemia
thiazolidinediones (TZDs) mechanism of action
increase sensitivity of muscle, fat, and liver to endogenous and exogenous insulin
improves cellular response to insulin without increasing output of insulin from the pancreas
benefits of TZDs
do not produce hypoglycemia in diabetic or nondiabetic patients
most common adverse effects of TZDs
weight gain, fluid retention
clinical use of TZD
indicated as monotherapy and in combination with metformin, sulfonylureas, and insulin
TZD patient education
increased risk for HF
what should be monitored when on TZDs
LFTs (closely for 1st year d/t risk of hepatotoxicity)
edema, cytopenia HDL, trigs
TZDs with oral contraceptives
ovulation may resume
TZD medication interactions
phenobarbital, amiodarone, rifampim, fluconazole, medications metabolized by CYP450 system (carbamazepine, cyclosporine, felodipine, and some oral contraceptives)
TZD contraindications
CHF
hepatic impairment
alpha-glucosidase inhibitors
mechanism of action
reduce rate of digestion of polysaccharides in the proximal small intestine by lowering postpradnial glucose levels without causing hypoglycemia
(reduces A1C by approx 1%)
common side effects of alpha-glucosidase inhibitors
increased gas and GI symptoms
examples of alpha-glucosidase inhibitors
acarbose
miglitol
alpha-glucosidase inhibitors as monotherapy
seldom gives satisfactory results
conscientious prescribing for alpha-glucosidase inhibitors
start low, go slow
increase dose slowly over several weeks in increments of 2.5mg to minimize GI upset
Patients who show signs of hypoglycemia while being treated with alph-glucosidase inhibitors
treat with glucose not sucrose
why is periodic LFTs indicated with acarbose
has been associated with raised liver enzymes
what should be monitored for with alpha-glucosidase inhibitor therapy
GI/GU
diabetic ketoacidosis, IBD, colonic ulceration, partial intestinal obstruction, chronic intestinal disease, renal function, pregnancy statius
is insulin needed with alpha-glucosidase inhibitor therapy
occasionally adjunct in time of stress
alpha-glucosidase inhibitor patient education
diet/exercise
side effects
follow-up
dosage may need adjustment during stress
miglitol interactions
may decrease absorption of digoxin, propranolol, and ranitidine
acarbose interactions
may decrease effects of digoxin, thiazide diuretics, thyroids, estrogens, oral contraceptives, and CCBs
alpha-glucosidase inhibitor contraindications
IBD
GI obstruction
colonic ulceration
cirrhosis
malabsorption syndrome
what is the only drug in the amylin analogue class and what is its make-up
pramlintide (Symlin)
synthetic analogue of human amylin
amylin analogue mechanism of action
neuroendocrine action that regulates glucose influx, including glucagon suppression, slowing of gastric emptying, and a potential effect on feeding behavior and weight control
clinical uses for amylin analogue
adjunct treatment in patient with either type DM who have not achieved desired insulin control despite optimal insulin therapy
with or without sulfonylureas and/or metformin in T2DM
amylin analogue conscientious prescribing
adjust dose after owering insulin dose
what tests are used to assess health in patients taking amylin analogues
FPG, HGBA1C, renal function, LFT, CBC
what should be adusted prior to begining therapy with amylin analogues
reduce insulin dose by 50% and monitor BG frequently
amylin analogue patient education
carry fast-acting sugar at all times
DO NOT mix with insulin (sepatate injections)
administer immediately prior to major meals
should be able to reduce insulin dose by 1/2
will need to frequently monitor BG
black box warning for amylin analogue
use with insulin
insulin induced severe hypoglycemia can occur within 3 hours of injection
amylin analogue interactions
do not administer with medications that alter GI motility or slow intestinal absorption
(anticholinergic agents like atropine or alpha-glucosidase inhibitors)
amylin analogue and analgesics
administer analgesics and other oral agents that require rapid onset 1 hour before or 2 hours after injection
amylin analogue contraindications
hypoglycemia unawareness
gastroparesis
glucagon-like peptide-1 (GLP-1) agonists
drug namess
exenatide (Byetta)
GLP-1 agonists
mechanism of action
analogue of the hormone incretin, which increases insulin secretion
high frequency of GI side effects
clinical uses of GLP-1 agonists
combination therapy only
for patients with T2DM that have not achieved glycemic control using metformin, a sulfonylurea, or both
byetta conscientious prescribing
not a substitute for insulin
monitor for pancreatitis
assess for T1DM, renal function, GI-paresis, HGBA1C
GLP-1 agonists patient education
take within 60 of morning and evening meal
if dose missed resume treatment at next dose
report side effects
keep drug away from light
discard pen after 30 days of first use
GLP-1 agonists and warfarin
may increase INR and cause bleeding
GLP-1 agonists interactions
drugs dependant on threshold concentrations for efficacy (contraceptives, antibiotics) should be taken 1 hour before
caution with drugs that require rapid GI absorption
GLP-1 agonists contraindications
T1DM
treatment of diabetic ketoacidosis
severe renal impairment
severe GI disease
dipeptidyl-peptidase-4 inhibitors (DDP-IV)
mechanism of action
slows the inactivation of incretin hormones (GLP-1 and gluosce-dependent insulinotropic polypeptide)
intestinal concentrations of these are decreased in T2DM
DDP-IV clinical uses
approved as monotherapy or in combination with metformin or thiazolidinedione
DDP-IV (Januvia) conscientious prescribing
may experience weight loss
watch for skin conditions (Steven’s Johnson syndrome)
test for renal function, FPG, HGBA1C, hypoglycemia
DDP-IV patient education
adjunct to diet and exercise
counsel about adverse effects (nasopharyngitis, headache, URIs)
advise dosing may need adjusted during stress
examples of DDP-IV
sitagliptin (Januvia)
saxagliptin (Onglyza)
saxagliptin/metformin (Kombiglyze)
sitagliptin/metformin (Janumet)
DDP-IV interactions
may increase digoxin levels
may require lower dose of sulfonylurea to reduce risk of hypoglycemia
DDP-IV contraindications
anaphylaxis
angioedema
glucagon mechanism of action
increases BG levels
glucagon clinical uses
treat severe hypoglycemia
diagnstic aid for radiologic exam of the stomach, duodenum, small bowel, colon
when is glucagon not effective
states of starvation, adrenal insufficiency, chronic hypoglycemia, insufficient liver glycogen
glucagon contraindication
pheochromocytoma
what is the oldest available medication to treat T1DM
injectable insulins
what are injectable insulins ade from
derived from beef or prok or synthesized using recombinant DNA technology using strands of E. Coli
four categories of injectable insulins
regular
protamines
lentes
modifieds
insulin for special populations
used for gestational diabetes
less stringent glycemic control set for elderly
children should be referred to pediatric endocrinologist if multiple drugs are needed
why are glycemic controls less stringent for elderly
increased risk for hypotension and long-term microvascular complications
types of insulins
rapid acting
short acting
intermediate acting
long acting
examples of rapid acting insulins
aspart (Novolog)
lispro (Humalog)
examples of short acting insulins
regular insulin (Humalog-R, Humalin-R)
examples of intermediate acting insulins
NPH
insulin zinc (Humulin N) lente
isophane insulin suspension
examples of long acting insulins
insuline glargine (Lantus)
insulin detmir (Levimir)
extended zinc (UltraLente)
protomine zinc (PZ)
injectable insulins conscientious prescribing
have a plan for starting/maintainingg dosages
may need higher doses for T2DM
dosage adjustments should be step-wie
change regimen if goals not met in 2-3 days
can change from rapid to long acting at largest meal of the day
injectable insulin patient education
measure BG at least twice daily
effect of insulin on glucose cell membrane
acts on the membranes transporters that regulate insulin release and glucose homeostasis
why is it so hard to induce weight loss as part of a diabetes management regien
total number of insulin receptors acan be downregulated by obesity
insulin and liver
where glucose increases storage of glucose as glycogen and resets the liver;s catabolic activity after ingesting food
insulin and adipose tissue
where insulin reduces circulating free fatty acids and promotes storage of triglycerides in adipose tissue
insulin and muscle cell growth
where insulin promotes protein synthesis by increasing amino acid activity and glycogen synthesis to replace glycogen that has been depleted during work or exercise
general rule of insulin dosing
0.6-1 unit per kilogram of body weight
lente insulins
modified by a fish protein which prolongs insulin action
protamine insulin
modified by zinc moiety which prolongs insulin action
symptoms of diabetic ketoacidosis (DKA)
drowsiness, dim vision, and labored breathing preceded by a lengthy episode of polyuria, polydipsia, polyphagia, weight loss, vomiting, dehydration, and ketone odor to breath
what is DKA usually the result of
undue stress, illness, infection, missed insulin
treatment of DKA
requires hospitalization and correction of acid/base, fluid, and glucose imbalances
drugs that interact with insulin
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