Download Spring 2015 Exam 2 OMSI CLIs [3-14

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Test 2 OMS I spring 2014
MOSBYS
Acetylcholine Receptor Antibody
(AChR Ab)
• For diagnosis of myasthenia gravis (MG) and monitoring of patient response to
immunosuppressive therapy
• Presence of AChR Ab is diagnostic for MG, but levels do not correspond to disease
severity. Monitoring of levels is useful for measuring progress of immunosuppressive
therapy.
• Cannot diagnose congenital MG (b/c non-immune pathology)
• 3 different types of AChR Ab test for MG:
• AChR – binding Ab - most commonly used
• AChR – modulating Ab – most sensitive
• AChR – blocking Ab – least sensitive ; best for quantifying
Before 1 year of MG illness , these tests often are not positive and
radioimmunoassay should be used instead
Increased levels: MG , ocular MG , thymoma
Interfering factors: ALS therapies and muscle relaxant drugs can cause false postives;
immunosuppressive drugs treating subclinical MG can suppress AChR Ab formation
Complement Assay
• Indication: Used to diagnose angioedema or (in PBL case) to
diagnose systemic lupus erythematosus (SLE), also used to
diagnose various nephritis conditions
• Test measures amount of C3 and C4 complement present in units /
mL after a blood sample is exposed to antigen and 50% of RBCs are
lysed
• Increased levels:
rheumatic fever, acute MI, ulcerative colitis, inflammatory
illness, cancer
Decreased levels:
Hereditary angioedema (congenital lack of C1 inhibitor causes
overuse of complement protein and exhaustion), severe liver
disease (synthesis site of complement), autoimmune disease
(SLE in particular), serum sickness, renal transplant rejection ,
protein malnutrition, anemia, infection, glomerulonephritis
Blood Cortisol
• Performed on pts who are suspected to have hyper or hypo-functioning
adrenal glands
Test Explanation
• CRH is made in the hypothalamus-> stimulates ACTH in the anterior
pituitary-> stimulates the adrenal cortex to produce cortisol
• Cortisol, a glucocorticoid, produces negative feedback on CRH/ACTH
• Affects fat, protein, and carbohydrate metabolism and has a profound effect
on blood glucose levels
• Stimulates gluconeogenesis
• Inhibits insulin’s effects (aka reduces glucose transport into cells)
Cortisol levels vary during the day (diurnal variation) and are highest between
6-8 am**
Blood collected at 8am and 4pm (levels at 4pm=1/3-2/3 of 8am value)
• Sometimes the earliest sign of adrenal hyperfunction (Cushing’s syndrome) is
the loss of diurnal variation, even when cortisol levels are not elevated
• High lvls of cortisol=Cushing’s syndrome; Low levels=Addison’s dz
Blood Cortisol
• Increased levels: pregnancy, stress
• Drugs causing increased levels: amphetamines, cortisone,
estrogen, OCPs, spironolactone
• Drugs causing decreased levels: Androgens,
aminoglutethimide, betamethasone/exogenous steroids,
danazol, lithium, levodopa, metyrapone, phenytoin
Blood glucose
• Direct measure of blood glucose used mainly for diabetic patients
• Test explanation:
• Glucose levels are low in the fasting state which causes glucagon release by pancreatic alpha
islet cells
• Glucagon breaks glycogen down to glucose in the liver
• If fasting persists, proteins and fatty acids are broken down under glucagon stimulation
• Glucose levels are elevated after a meal causing a release of insulin from pancreatic beta cells
• Insulin causes upregulation of insulin receptors and glucose uptake into mainly muscle, liver
and adipose tissue. [Note: Glucose uptake into the brain is not regulated by insulin]
• ACTH, adrenocorticosteroids, epinephrine, growth, and thyroxine affect glucose
• Must be evaluated for the time of day
• True glucose elevation is usually DM
• Hypoglycemia is inadvertent insulin overdose in patients with brittle diabetes
• Must monitor frequently in diabetes patients
• Finger stick blood glucose are performed before meals and at bedtime
• Interfering factors:
• Increased levels: Stress (trauma, general anesthesia, infection, burns, MI), caffeine,
pregnancy, IV dextrose, antidepressants, beta blockers, corticosteroids, dextrothyroxine,
diazoxide, diuretics, epinephrine, estrogens, glucagon, isoniazid, lithium, phenothiazines,
phenytoin, salicylate, and triameterene
• Decreased levels: acetaminophen, alcohol, alpha glucosidase inhibitors, anabolic steroids,
biguanides, clofibrate, disopyramide, gemfibrozil, incretin mimetics, insulin, MAOi,
meglitinides, pentamidine, propanolol, sulfonylurea, and thiazolidinediones
Glucose, postprandial
• The 2 hour test is a measurement of the amount of glucose in the
patient’s blood 2 hours after a meal is ingested (postprandial)
• Test explanation:
• The meal acts as a glucose challenge to the body’s metabolism
• Insulin is normally secreted after a meal in response to the high blood
glucose, in diabetes patients the glucose is usually still elevated 2 hours
later
• If the levels are between 140-200 then a glucose tolerance test must be
obtained
• If the levels are greater than 200 then a diagnosis of DM is made
• 1 hour test detects gestational diabetes
• The detection of gestational diabetes prevents excessive fetal growth and
birth trauma, fetal death, neonatal morbidity, called O’Sullivan test
• O’ Sullivan test gives a 50 g oral glucose dose and tests 1 hour later 24-28
weeks gestation; a 3 hour test is ordered for levels above 140
• Interfering factors
• Increasing factors: smoking during testing, stress (via catecholamine
secretion), eating a snack or candy
• Falsely decreased if the person cannot eat the entire test meal or vomits
Glucose, Postprandial – Increased and Decreased
Levels
• Increased:
• Diabetes mellitus, gestational DM, malnutrition (b/c of
decreased glucose tolerance), hyperthyroidism, acute stress,
Cushing syndrome (b/c of increased cortisol),
pheochromocytoma, chronic renal failure (b/c kidney fails to
metabolize glucagon), glucagonoma, diuretic therapy,
acromegaly (b/c GH stimulates glucagon release), liver
disease (b/c liver metabolizes most glucose)
• Decreased:
• Insulinoma , hypothyroidism , hypopituitarism , Addison disease
(b/c diminished cortisol) , insulin overdose ,
malabsorbtion/maldigestion (b/c glucose is not absorbed)
Glucose tolerance test
• Assists in the diagnosis of DM and the evaluation of patients with hyperglycemia
• Test explanation:
• Criteria to diagnose diabetes: [KNOW]
• Sufficient clinical symptoms ( polydipsia, polyuria, ketonuria, weight loss) plus random
blood glucose > 200
• Elevated Fasting Blood Glucose on more than one occasion
• 2 hours after meal glucose > 200
• Used when diabetes is expected (retinopathy, neuropathy, renal disease) but
criteria for diagnosis can’t be met without GT
• May be used for the following
•
•
•
•
•
•
Family history of diabetes
Patients who are massively obese
History of recurrent infections
Delayed healing of wounds
Women who have stillbirths or large babies
Transient glycosuria or hyperglycemia during pregnancy, or following MI, surgery or
stress
• The ability to tolerate glucose load is evaluated through serum and urine glucose
levels at 30 minutes, 1, 2, 3, and 4 hours
• Normally there is a rapid insulin response that peaks in 30- 60 minutes and
returns to normal in 3 hours, glucose shouldn’t spill into urine
Glucose tolerance test
• Indication: diagnosis of DM or gestational diabetes or evaluation of hypoglycemia
• Test explanation:
•
For diabetes mellitus:
•
•
Used when diabetes is suspected because of diabetes spectrum symptoms (e.g. retinopathy) but confirmation is
required
75g glucose load is administered with serum glucose readings at .5 , 1 , 2 , 3 , or even more hours
• Glucose exceeding 200 at two hours is sufficient for diagnosis of DM, indicative of a lack of
insulin response. Glucose will spill over into the urine of diabetic patients.
•
For gestational Diabetes:
•
A 50 g dose administered between 24 and 28 weeks gestation. (O’Sullivan Test).
Cushing’s , pheocromocytoma, acromegaly, aldosteronism, or hyperthyroidism may all also cause
glucose intolerance
• Chronic renal failure, acute pancreatitis, myxedema, type IV lipoproteinemia, infection or cirrhosis
cause abnormal GT test
• Contraindications
•
•
Serious concurrent infections or endocrine disorders (glucose intolerance)
Patients who vomit all or part of the meal
• Interfering factors
•
•
•
Increasing factors: smoking, eating, stress, exercise
Fasting or reduced caloric intake before test can cause intolerance
Drugs that cause intolerance: antihypertensives, antiinflammatories, aspirin, beta blockers,
furosemide, nicotine, oral contraceptives, phenothiazines, psychiatric drugs, steroids, and thiazides
GT – increased and decreased
factors
• Increased:
• DM , acute stress , cushing syndrome , pheochromocytoma ,
chronic renal failure , glucagonoma , acute pancreatitis , diuretic
therapy , corticosteroid therapy , acromegaly , myxedema ,
gastrectomy
Glycosylated hemoglobin
• Used to monitor diabetes treatment because it provides accurate
long-term index of patient’s average blood glucose level
• Normal non-diabetic: 4-6%
• ADA target for diabetic: 7%
• Test explanation:
• HbA1C is a hemoglobin subtype that combines strongly with glucose
via a glycosylation reaction
• The amount of GHb (glycohemoglobin) depends on the most of
glucose available in the bloodstream over the 120 day life an RBC,
• Provides a 100-120 day approximation of blood glucose levels (b/c
normal RBC lifespan is 120days) and is not effected by short term
spikes or timing of blood draw
• Serum glycalated protein tests shows provide evaluation of more
recently elevated blood glucose because the are degraded faster
than RBC (e.g. glycated albumin or fructosamine)
Glycosylated hemoglobin
Good for determining:
•
•
•
•
•
•
•
Evaluation of the success of diabetic treatment and patient compliance
Comparing and contrasting the success of past and new forms of diabetic therapy
Determining duration of hyperglycemia
Providing sensitive estimate of glucose imbalance in patients with mild diabetes
Individualizing diabetic control
Providing a sense of reward for many patients
Evaluating the diabetic patient whose glucose levels change significantly from day
to day (brittle diabetes)
• Mean plasma glucose = (35.6 x GHb) – 77.3
• Interfering factors
• Hemoglobinopathies affect results because quantity of hemoglobin A varies
• False elevation: when RBC life span is lengthened because the HBA1 has
longer period for glycosylation
• Abnormal low levels of proteins may falsely indicate normal glycalated
fructosamine levels despite reality of high glucose
• Ascorbic acid may cause false lows of glycated fructosamine
• Also elevated in: splenectomy (b/c RBC survival is prolonged) and pregnancy
(indicating gestational diabetes or prediabetes)
Growth Hormone pp.
• Indication:
• identify adolescent GH deficiency or document patients with gigantism or acromegaly. Can
also be used to evaluate pituitary hypofunction.
• Explanation:
• Secreted by acidophils of anterior pituitary to mediate somatomedin release. In childhood,
insufficiency results in non-growth while excess results in gigantism.
• GH should be drawn 60-90 minutes after deep sleep to attempt to draw when GH
levels are at maximum. Exercise also stimulates GH release.
• Increased levels:
• Gigantism, acromegaly, anorexia nervosa (b/c starvation stimulates GH secretion), stress,
surgery, hypoglycemia, starvation, deep sleep, exercise
• Decreased levels:
• GH deficiency, pituitary insufficiency, dwarfism, hyperglycemia, failure to thrive, delayed
sexual maturity
Somatomedin C (aka insulin like
growth factor-1, IGF-1)
• Used to screen:
• Patients with growth hormone deficiency, Pituitary insufficiency,
acromegaly.
• Levels depend on GH levels
• Somatomedins stimulate somatostatin and should feedback to decrease
pituitary.
• Test explanation:
• GHRH (from hypothalamus) -> GH (from anterior pituitary) ->
Somatomedin C/IGF-1 (mostly from liver)
• GH secretion varies widely throughout the day.
• Insulin-like growth factor-1 (IGF-1) provides a more accurate
reflection for the mean plasma concentration of GH for acromegaly.
• Not used to ddx GH deficiency (additional testing needed)
• A person with normal IGF-1 almost never has acromegaly.
IGF-1
• Increased:
•
•
•
•
•
•
•
•
Gigantism
Acromegaly
Stress
Major surgery
Hypoglycemia
Starvation
Deep-sleep state
Exercise
• Decreased:
• GH deficiency (but
more tests to ddx)
• Pituitary insufficiency
• Dwarfism
• Laron type dwarfism
(GH receptor
insensitivity)
• Hyperglycemia
• Hypothryoidism
• Liver disease
Magnesium
• Most magnesium is intracellular; about ½ is in bone
• Most magnesium is bound to an ATP molecule and is
important in phosphorylation of ATP
• Important in enzymatic and metabolic processes as well as
organ function (neuromuscular and cardiac tissue in
particular)
• Low magnesium levels may increase cardiac irritability and
aggravate cardiac arrhythmias
• Hypermagnesemia slows neuromuscular conduction and is
demonstrated by cardiac conduction slowing (widened PR and
QT intervals, wide QRS), diminished DTR and respiratory
depression
Magnesium
• Intracellular levels of ions, in order: K> Mg> Ca
• Because charges must be maintained, a total body reduction in any one of these
causes extracellular ions to shift into the cell, creating a comparable blood
reduction in all 3
Mg increases intestinal absorption of calcium (hypocalcemia can respond to Mg
replacement)
• Magnesium deficiency occurs in the malnourished, like in postop pts
• Alcohol use increases Mg loss in urine
• Mild hypomagnesemia is found in DM, hypoparathyroidism, hyperthyroidism,
hyperaldosteronism
• Toxemia of pregnancy is associated w/ reduced magnesium levels
• Signs of magnesium depletion: neuromuscular (weakness, irritability, tetany), EKG
changes, delirium, convulsions
• Signs of increased Mg levels: lethargy, N/V, slurred speech
• Increased Mg levels assoc w/ ingestion of Mg-containing antacids
• Because Mg is excreted by the kidney, chronic renal dz causes increased Mg levels
• Because Mg is intracellular, hemolysis of the blood sample will cause falsely
elevated values
• Drug interactions can cause changes in Mg levels**
Vitamin B12 (540-541)
• Identify the cause of megaloblastic anemia and evaluate malnourished patients
• Test explanation:
•
B12 needed for the conversion of folate to its active form
•
•
•
•
•
Necessary for synthesis of nucleic acids and amino acids
RBC are megoblastic in B12 deficiency so they cannot conform to the size of small capillaries,
consequently fracture and hemolyse causing shortened RBC life span and anemia
Giant, hypersegmented neutrophils and large nucleated platelets are also seen
May take 6-18 months to be seen (Large liver store)
Meat, eggs, and dairy are main source of B12
• Causes:
• No Intrinsic factor (needed for B12 absorption (results in pernicious
anemia))
• Lack of gastric acid to separate B12 from its binding protein
• Diseases of ileum (where B12 is absorbed)
•
•
•
•
•
Serum B12 measures recent B12 ingestion
Prolonged deficiency is best measured by MMA (urinary methylmalonic acid)
Elevated serum MMA and urinary excretion of MMA directly measure B12 activity
The active form of B12 converts L-methylmalonyl CoA to succinyl CoA so without active B 12 larger quantities of MMA is
seen in urine
• Urine MMA test is more accurate. uMMA : creatinine test is more accurate because it indicates tissue - cellular B12
deficiency
Interfering factors
• Chloral hydrate increases B12
• Drugs that decrease: alcohol, aminoglycosidesm aminosalicylic acid, anticonvulsants, colchicine, oral contraceptives
Increased and Decreased B12
• Increased:
•
•
•
•
Leukemia
polycythemia vera
liver dysfunction
myeloproloferative disease
Decreased Levels:
• pernicious anemia
• malabsorbtive syndromes (Chron’s dz)
• intestinal worms (D. Latum)
• atrophic gastritis,
• Zollinger-Ellison (tumor secreting gastrin)
• gastrectomy
• ileum resection
• Achlorydia (lack of stomach acid)
• pregnancy,
• vit C deficiency
• folic acid deficiency
Nerve Conduction Studies
(Electroneurography)
• Identifies peripheral nerve injury in patients with localized or
diffuse weakness, to differentiate primary peripheral nerve
disease from muscular injury, and to document the severity
of injury in legal cases
• Normal findings: show no peripheral nerve injury or disease
• Monitors nerve injury and response to treatment
Nerve Conduction Studies
• Test explanation:
• Allows the detection and location of peripheral nerve injury or disease
• Initiate an electrical impulse at one site (proximal) of a nerve and record the time required
for that impulse to travel to a second site (distal) of the same nerve
• The conduction velocity can be determined
• Done in conjunction with EMG
• Normal values vary from nerve to nerve and among individuals
• Compare conduction velocity of the suspected side with the contralateral nerve conduction
velocity
• Normal conduction velocity is 50-60 m/sec
• Greater than normal values are not pathologic
• Muscular factor can be evaluated by measuring latency (time required for stimulation of distal
end to cause muscular contraction)
• Conduction velocity = (distance (m))/ (total latency – distal latency)
• Distal latency = time from distal nerve stimulation to muscle contraction
• Pathologies (slowing):
• Traumatic transection or contusion of a nerve will usually cause maximal slowing of
conduction
• Neuropathies, both local and general, cause slowing
• Primary muscle disorders can cause a slow conduction because conduction may require
muscle contraction
• Interfering factors
• Patients in severe pain
Urine glucose
• Monitors the effectiveness of therapy for DM; if present, reflects degree
of glucose elevation in blood
• Test explanation
• May indicate DM or other glucose intolerance disorders
• Normally blood glucose is filtered from blood by glomeruli and all the
glucose is reabsorbed in proximal tubules
• Blood glucose exceeds capability of renal threshold to reabsorb and it spills
into the urine. Occurs at about 180 mg / dL .
• Glucosuria may occur immediately after a high carb meal or in patients on IV
dextrose or due to stress or injury
• Glucosuria can indicate diseases that affect renal tubule or genetic defects in
metabolism and excretion of glucose
• In these disorders renal threshold for glucose is low so normal blood glucose
cannot be reabsorbed
• GT test in these patients are usually normal
• Interfering factors
•
•
•
•
Sugars can cause false positive b/c they reduce copper in test strip
Drugs that cause false positive: ASA, aminosalicylic acid, ascorbic acid, cephalothin, chloral hydrate,
nitrofurantoin, streptomycin, and sulfonamides
False negative: ascorbic acid (clinistix test), levodopa, and phenazopyridine
Drugs that increase urine glucose: ASA, cephalosporins, chloral hydrate, chloramphenicol,
dextrothyroxine, diazoxide, diuretics, estrogen, glucose infusions, isoniazid, levedopa, lithium,
nafcillin, nalidixic acid, and nicotinic acid
DRUGS TO KNOW
Drug
Uses
Side effects
Contraindications
Therapeutic considerations
levothyroxine
Hormone,
T4, for hypothyroidism,
myxedema coma
Replaces missing hormone
Hyperthyroidism,
osteopenia, pseudotumor
cerebri, seizure, myocardial
infarction
Acute MI, uncorrected
adrenal cortical
insufficiency
Untreated
thyrotoxicosis
Cholestyramine and sodium
polystyrene sulfonate
decrease absorption of
synthetic thyroid hormone
Rifampin and phenytoin
increase metabolism
T4 desirable because of its
longer half life
Hydrocortisone
• Corticosteroid
•
Replacement therapy
for primary and
secondary adrenal
insufficiency
•
Reduces inflammation
Cushing syndrome, reduces
bone density with chronic
use
Fungal infection
Cisplatin
Pg 696
Class: Directly modify DNA
structure
Mech: Platinum compound
that cross-links intrastrand
guanine bases
Indications:
• Genitourinary and lung
cancer
•
•
•
•
•
• Severe bone
marrow depression
• Renal or hearing
impairment
Nephrotoxicity
Myelosuppression
Peripheral neuropathy
Ototoxicity
Electrolyte imbalance
• Can be injected
intraperitoneally for
treatment of ovarian
cancer
• Co-administration of
amifostine can limit
nephrotoxicity
Drug
Uses
Side effects
Lomustine
Mech:
Alkylating agent
Myelosupression,
Nausea, toxic to
liver and kidney
Not in book
Contraindica
tions
Therapeutic
considerations
It is very lipid soluble; “mustiness”
are used for brain CA because
unlike many chemo drugs they
cross the blood-brain barrier easily
Class:
Mustard gas, nitrosurea
Indications:
Brain Cancer
Ezetimibe
Mech:
Decreases cholesterol transport
from micelles into enterocyte
inhibiting NPC1L1
Indications:
Primary hypercholesterolemia
Familial hypercholesterolemia
sitosterolemia
Vincristine
Mech:
Binds tubulin subunits and
prevents microtubule
polymerization
Indications:
Leukemia, hodgkin’s disease, nonhodgkins lymphoma,
rhadomyosarcoma,
Elevated liver
function tests,
myopathy,
dyspepsia,
arthralgia, myalgia,
headache
Active liver disease,
persistently
elevated liver
function tests when
co-administered
with statin
Modest LDL reduction, small effect
on HDL and Tgs
Inhibition of hepatic cholesterol
absorption causes compensatory
increases in synthesis partially off
setting; prevented by giving statin
Rapidly absorbed
Levels are increased by
cyclosporines and fibrates
Peripheral
neuropathy,
myopathy,
myelosuppression
Alopecia, GI
disturbancees,
diplopia
Charcot-Marie
Tooth syndrome
Intrathecal use
Peripheral neuropathy is dose
limiting
Drug
Uses
Side effects
Contraindications
Therapeutic
considerations
Octreotide
Pg 503
CLASS: somatostatin
analogue
Mech: inhibits GH release
Indications:
Acromegaly
Flushing and diarrhea from
carcinoid tumors
Carcinoid crisis
Diahrrea from vasoactive
intestinal peptide – secreting
tumors
TSH producing adenomas
•
•
•
Class: IMPDH inhibitor (rate
limiting step of guanosine
formation)
• Myelosuppresion ,
neutropenia , increased
risk of infection ,
lymphoma
Mycophenolate
mofetil
Pg 803
Indications:
• Solid organ transplant
• Lupus
• Rheumatoid arthritis
• pemphigus
Arrhythmias ,
bradycardia ,
hypoglycemia ,
gallstone formation
Hypersensitivity to drug
•
• Hypersensitivity to drug
Also used to control
GI bleeds
Available in monthly
formation
Useful for treatment of
autoimmune disorders
because highly selective
for lymphocytes
Administered in case 3
prior to surgical thymus
removal to reduce size of
thymus
Drug
Uses
Vasopressin
Class: ADH analogue
(analogues of
vasopressin):
Mech: Acts at collecting
ducts of kidneys on V2
receptors. Results in
concentration of urine and
decrease in thirst.
Desmopressin
Pg 474
Terlipressin
(investigational)
Pg 344
Indications:
Neurogenic DI
Aziathioprine
Pg 503
Class: inhibits IMPDH to
interfere with purine
metabolism
Indications:
• Lymphoblastic leukemia ,
acute myelogenous
leukemia , Crohn’s, RA,
and IBD
Side effects
Therapeutic
considerations
ADH is a
neurohypophysial
hormone.
Functions to retain water
and constrict blood
vessels
Only effective in
Neurogenic Diabetes
insipidus
• Myelosuppression,
hepatotoxicity,
pancretitis, infection,
gastritis
• pregnancy
• Metabolized by
xanthine oxidase, thus
Allopurinol increases
toxicity by limiting
degradation
• Also used for
immunosuppression
Drug
Uses
Side effects
Contraindications
Therapeutic
considerations
Dexamethasone
Pg 503
Class: Glucocorticoid
receptor agonist
Mech: Mimic cortisol
function by acting as
agonists at glucocorticoid
receptor
Indications:
•
Inflammatory
conditions in many
different organs
•
Autoimmune diseases
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Prednisone
Pg 503
Class: Glucocorticoid
receptor agonist
Mech: mimic cortisol
function function by acting
as agonists at glucocorticoid
receptor
Indications:
• Inflammatory conditions
• Autoimmune diseases
Immunosupression
Cataracts
Hyperglycemia
Hypercortisolism
Depression
Euphoria
Osteoporosis
Growth retardation in
kids
Muscle atrophy
Impaired wound
healing
Hypertension
Fluid retention
Inhaled may cause
oropharyngeal
candidiasis and
dysphonia
Topical causes skin
atrophy
• Same as above
Systemic fungal infection
•
•
•
• Same as above
Doesn’t correct
underlying etiology
just limits
inflammation
Should be tapered
when given
chronically to avoid
withdrawal and acute
adrenal insufficiency
Intranasal and
inhaled greatly
reduce systemic
adverse effects
18x more potent
than cortisol
• Same as above
• 4-5 x as potent as
cortisol
Drug
Uses
Side effects
Contraindicatio
ns
Therapeutic
considerations
Edrophonium
p. 128
AchEsterase
inhibitor
Seizure,
bronchospasm,
cardiac arrhythmia,
bradycardia, cardiac
arrest, hypotension,
salivation,
lacrimation,
diaphoresis,
vomiting, miosis
GI or GU obstruction
Short half life (2-10
minutes)
Same as above
Same as above
Diagnosis of
myasthenia gravis
Pyridostigmine
p. 128
AchEsterase
Inhibitor
Treatment of
myasthenia gravis
Another choline
ester or depolarizing
NM blocker therapy
Cardiovascular
therapy
For chronic
treatment of MG
because of its longer
half life
Drug
Uses
Side Effects
Contraindications
Therapeutic
Considerations
Glyburide (2nd generation
sulfonurea)
Type 2 DM
Hypoglycemia
DKA
Orally available,
metabolized by liver
Rash, diarrhea, nausea, dizziness
Mechanism-Sulfonylureas
and meglitinides inhibit the
B-cell K+ ATP channel at
the SURl subunit, thereby
stimulating insulin release
from pancreatic f3 -cells
and increasing circulating
insulin to levels sufficient
to overcome insulin
resistance
Major adverse
effect=hypoglycemia; use
cautiously in pts unable to
recognize or respond to
hypoglycemia (pts on Bblockers or
elderly/incapacitated)
Can cause wt gain –better
in non-obese pts
1st generation agents bind
w/ lower affinity to SUR 1
Channel and require higher
doses than second gen
Insulin
Prandial bolus: Regulal,
lispro, aspart, glulysine
Basal long-acting:
NPH, Glargine, Detemir
Mechanism-The classic
anabolic hormone, insulin
promotes carbohydrate
metabolism and facilitates
glucose, amino acid, and
triglyceride uptake and
storage in liver, cardiac and
skeletal muscle, and
adipose tissue
DM
Hypoglycemia
Injection site rxn, lipodystrophy
Hypoglycemia
Not orally available,
delivered parenterally,
subcutaneous route most
common.
Rapid Acting Insulins:
Lispro, Aspart, Glulysine:
injected minutes before a
meal
Regular Insulin: Short
acting, injected 30 minutes
before a meal
NPH: intermediate acting;
contains protamine,
prolonging time required
for absorption;
administered twice a day
Glargine and Detemir:
long, acting, steady release
without a peak, injected
1*/day
Drug
Uses
Side Effects
Contraindications
Therapeutic
Considerations
Metformin (insulin
sensitizer/biguanide)
Type 2 DM (drug
of choice)
Lactic Acidosis
GI distress is transient,
minimize w/ slow titration
Mechanism-Activates
AMP-dependent protein
kinase (AMPK) to block
synthesis of fatty acids and
to inhibit hepatic
gluconeogenesis and
glycogenolysis; increases
insulin receptor activity
and metabolic
responsiveness in liver and
skeletal muscle
PCOS (off-label)
Heart failure
Alcohol Abuse
Hepatic dz
Repiratory dz
Renal impairment
Metabolic Acidosis
Diarrhea, dyspepsia, flatulence,
N/V, cobalamin deficiency
Lactic Acidosis is not
common (but a very high
yield side effect!); typically
occurs in pts w/ conditions
that predispose to
metabolic acidosis
Does not induce
hypoglycemia
Lowers serum lipids and
decreases wt