Drugs and Labs, what needs
to be monitored?
Jennifer Rodgers, MSN, ARNP
Wichita State University
DRUGS & LABS
• We are a testing society
• Over 1100 tests to pick from
• RIGHT TEST RIGHT PATIENT
• Don’t get a test you don’t want the
answer too
• Is the patient willing to participate?
DRUGS & LABS
• Insurance companies demand we have a
code for every test
• Be cost effective- What test will give me
the most information with the least
amount of $$$?
• Understand lab values & also validity and
sensitivity of the tests you are ordering
DRUGS & LABS
• Let the guidelines, patient clinical picture,
& your experiences guide you
• Remember NO test takes the place of a
thorough history and physical exam
• If you do it in the right order History & PE
will guide you
DRUGS & LABS
• 84 Year Old Male Severe COPD, Weight
Loss, Chronic Hypoxemia, HTN, History of
Afib & Pulm. Embolism on Coumadin
• HPI: Over past 2 months has been slowly
declining several hospitalizations for COPD
Exac. weakness, 20 # weight loss, fatigue
• Presented to the office with hemoptysis &
weakness
84 YEAR OLD MALE
• PE: Pale, Ill appearing increased dyspnea
from baseline
• Lab Hgb 8.0 INR>80 seconds
• VS Afebrile 110/60 110 SpO2 90% on 4
Liters
84 YEAR OLD MALE
• Obviously Admit, Reverse Coumadin with
FFP & Vitamin K
• Coumadin needs careful monitoring &
patient education
• So often the elderly are the ones taking
this unpredictable medicine
PROTIME w/INR
• International Normalized Ratio System
• Factors that can alter: Heparin/LMH/
Coumadin, Liver Failure/Tumor, DIC, Vit K
deficiency, ETOH intake, Malabsorption
Disorders, Diet, Other medications
THERAPEUTIC INR WITH
COUMADIN TREATMENT
• DVT prophylaxis
1.5-2.0
• ORTHO. SURGERY2.0-3.0
• DVT
2.0-3.0
• A-FIB prophylaxis
2.0-3.0
• PE
2.0-3.0
• Prosthetic Valve
2.5-3.5
Adapted from: Mosby’s Manual of Diagnostic & Laboratory
Tests. (2nd Ed.). (2002). 112.
HOW TO MONITOR?
• ½ Life is 20-60 hours
• Peak time 5-7 days
• Bridge with LWH or SQ Heparin
• Timing of Lab Test has to match half life
of drug
• Have a system for adjusting or reversing
otherwise you will chase your tail!
Coumadin with Hypercoagulation
• How to reverse or adjust?
• > 7 OR symptomatic FFP/Vit. K 5-10 mg
• 4-7 Hold X 1 day decrease by 20%
• 3.6-4 Hold X 1 day decrease by 15%
• 3-3.5 decrease by 10%
• 3 day ½ life
• Follow protimes closely, Patient Education
COUMADIN OTHER THOUGHTS
• If you can’t regulate someone think about
why?
• Where metabolized? > Liver
• Problem in the Liver?
• 84 year old male
• ? Why so hypercoagulable
COUMADIN OTHER THOUGHTS
• 84 Year old male- Remember unintentional
weight loss, then developed persistent
nausea to the point could not eat or drink,
even water bothered
• +RUQ pain
• What tests do we want? GB Sono>stones
• HIDA Scan> normal GB
• CT Abd Pelvis>Large Hepatic Lesion
COUMADIN OTHER THOUGHTS
• So….Liver Bx + for Cancer with Mets
• Sad outcome>however after being stable
on Coumadin therapy for 5 years, that
explains hypercoagulation, wt. loss,
general decline in condition
• Remember to always put the puzzle
together, look at whole patient not just
abnormal lab test!
COUMADIN OTHER THOUGHTS
• 92 year old female on Coumadin for Afib
• INR remains 1.0 seconds even after
adjusting dose
• Nursing Home confirms she is getting the
medication daily
• On 10 Mg Coumadin/daily still normal
INR???
COUMADIN OTHER THOUGHTS
• Look further….she was getting the
medication daily, but on further
investigation she was pocketing pills and
not swallowing anything!!!
• Then you discuss with DPOA, patients
wishes risk/benefit of the meds
DRUGS & LABS
• 78 year old female 2 months S/P CABG
presents with lethargy, bradycardia, has
been in nursing home since surgery, prior
to that leaving independently at home
• She has been getting progressively weak,
less interactive with staff, decreased
appetite
DRUGS & LABS
• What drug might be the cause?
• What do you know about
Amiodarone?
AMIODARONE
• Very effective Anti-arrhythmic that slowly
loads into multiple tissues in the body it is
slow to “load” & slow to clear
• Not excreted by liver or kidneys but
through body tissue containing
Amiodarone cells i.e. skin, GI etc.
• So even when stopped remains in the
body weeks to months
AMIODARONE
• This 78 year female developed Afib post
CABG & was started on Amiodarone
• ? Cause of symptoms
• 1-3 % of patients can develop thyroid
dysfunction after starting on Amiodarone
(hyper or hypo)
• So…look at whole patient
AMIODARONE
• Check TSH Sensitivity 89-95% Specificity 90•
•
•
•
•
96%
78 year old female TSH 30.6 (2-10)
Confirm with Free T4
This patients symptoms & decline were from
Amiodarone induced hypothyroidism
Start levothyroxine, slow to load recheck 6-8
weeks, not sooner
Stop Amiodarone!!
AMIODARONE OTHER THOUGHTS
• 78 year old female 1 month later, much
improved ambulating, eating, alert, nearly
back to baseline
• It can also Cause Pulmonary
Toxicity/Fibrosis 4-9%
• Review side effects!!
DRUGS & LABS
• TSH-Used to differentiate between primary
•
•
•
•
hypothyroidism & secondary (pituitary)
hypothyroidism
2-10 nml range
Goal in suppression (HYPER) therapy <2
If screening & TSH abnormal check free T4
REMEMBER INVERSE TSH < = hyper
TSH> = hypo
DRUGS & LABS
• Free T4-unbound T4 that enters the cell &
is metabolically active >true reflection
hormonal status
• If < FT4=hypothyroid <0.8 ng/dl
• >FT4=hyperthyroid >2.4 ng/dl
DRUGS & LABS
• If can’t keep euthyroid on levothyroxine
• TSH too high- Adherence? Dose too low?
Drug Interaction?
• TSH too low- Dose too high? Taking more
than prescribed?
WHAT ABOUT STATINS?
• Work by inhibiting HMG Co-A reductase
>reduces the livers ability to make
cholesterol
• In addition, reduce plaque size in the
artery, decrease clot formation, &
decrease CRP levels
• Impact LDL, Triglyercides, & to a small
degree HDL
WHAT ABOUT STATINS?
• Causes LFT elevation 1 in 100 patients
• Causes myopathy in 1 in 1000 patients
• Most serious avoid rhabdomyolysis
• In patient with normal liver (no fatty liver,
cholestatic or obstructive jaundice, chronic
hepatitis, alcoholic hepatitis, or inflammatory
disease of the heart or skeletal muscle) should
have normal LFT’s
WHAT ABOUT STATINS?
• In patients with asymptomatic
hepatocellular dysfunction, an elevation of
ALT or AST 2-3 times normal therapy
should not be started or if taking statin
discontinued.
• Pre-treatment baseline LFT’s CK
• Recommendations are to obtain LFT’s
within 6 weeks of initiating therapy
WHAT ABOUT STATINS?
• aspartate aminotransferase (AST) test is
the most sensitive marker of the impact of
statins and other dyslipidemic agents.
• AST should not be elevated more than 2-3
times the ULN.
WHAT ABOUT STATINS?
• Avoid concomitant use of clarithromycin,
fluconazole, erythromycin, ketoconazole,
rifampin, itraconazole, terbinafine,
verapamil, and amiodarone.
• The combination of these medications and
lipid-lowering agents will significantly
increase the possibility of Statin Induced
Myopathy.
INCREASED RISK FOR STATIN
INDUCED MYOPATHY
•
•
•
•
•
•
> 80 years old (women>men)
Small Frame & Fragility
CKD, Diabetes
Polypharmacy
Perioperative Periods
Alcohol Abuse (independent predisposing factor)
• Follow ATP III guidelines & don’t exceed recommended
doses & treat cautiously in pts at increased risk
http://www.nhlbi.nih.gov/guidelines/cholesterol/statins.pdf retrieved 05/21/10
WHAT ABOUT THE STATINS?
• If myopathy occurs, obtain CK level &
compare to pre-statin level
• If >10 times normal dc statin
• If 3-10 times normal < dose or give drug
holiday & follow until resolved
• Thyroid disease predisposing factor to
myopathy also check TSH
WHAT ABOUT RHABDO?
MOST COMMON SYMPTOMS
• Muscular: muscle pain, weakness, tenderness, and stiffness. These
•
•
symptoms occur 50% of the time with muscular symptoms and
signs occurring in the large muscles of the thighs, calves, and
lower back. The affected muscles become swollen and tender on
palpation.[2-4]
Urinary: The most significant diagnostic feature is the change in
color of the urine. Dark urine, typically brown, is often the first
clue to the diagnosis of rhabdomyolysis.[2-4]
Constitutional: These symptoms vary widely. The most common
symptoms are generalized malaise, fever, tachycardia, nausea, and
vomiting.[2-4]
Pasternak RC, Smith SC Jr, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C. ACC/AHA/NHLBI clinical advisory on
the use and safety of statins. J Am Coll Cardiol. 2002;40:568-572
WHAT ABOUT RHABDO?
•
•
•
•
If suspected, stop Lipid Lowering agents
STAT lab LFT’s CK, & CPK
CPK most important diagnostic criteria
If >10 times normal cause for concern
Phillips PS, Haas RH, Bannykh S, et al. Statin-associated myopathy with normal creatine kinase levels.
Ann Intern Med. 2002;137:581-585.
Pasternak RC, Smith SC Jr, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C. ACC/AHA/NHLBI
clinical advisory on the use and safety of statins. J Am Coll Cardiol. 2002;40:568-572
DRUGS & LABS
• alanine aminotransferase (ALT) less
sensitive to statin
• Excellent for evaluating “fatty liver” or
steatohepatitis
• Usually related to medication, obesity,
alcohol intake, starvation, diabetes, or
high blood triglycerides
DRUGS & LABS
• AST-Think statins
• ALT-Think diabetic meds like Avandia,
Actos
• Statins have best effect on lipids if taken
at night.
DRUGS & LABS
• 85 year old female over past week
increased fatigue, weakness, headache,
blurred vision & diplopia
• In addition, family has noticed increased
confusion
85 YEAR OLD FEMALE
• VS Afebrile 120/70 80 SR with Trigeminal
PVC’s, SpO2 92% 2 Liters
• PE Ill appearing elderly female, confused,
lethargic
• Patient then became unresponsive and the
cardiac monitor revealed…..
WHAT DRUG SHOULD WE BE
THINKING ABOUT AS WE CODE
THIS PATIENT?
85 YEAR OLD FEMALE
• DIGOXIN…patient had been taking for the past
•
•
•
10 years without incidence.
0.4% of all hospital admissions, 1.1% of
outpatients, & 10-18% of nursing home patients
on Digoxin develop toxicity.
2007 Annual Report of the American Association
of Poison Control Centers 2565 Digatalis
exposures reported with 10 deaths
http://emedicine.medscape.com/article/814404-overview Retrieved 5/25/10
Digoxin Toxicity
• Normal Range 0.5-2 ng/mL
• 50% mortality of Digoxin Level > 6ng/ml
• Usually caused by dehydration, electrolyte
imbalances, decreased renal function, or
drug interactions, new onset
hypothyroidism, & AMI
Drugs/supplements that can cause
Digoxin Toxicity
• Amiodarone, Amiloride, Beta Blockers,
Calcium Channel Blockers, Erythromycin,
Cyclosporine, HTCZ, Spironolactone,
Triameterene, Loop Diuretics,
Amphotericin B, Succinylcholine
• Ephedra (cardiac stimulation), natural
licorice (sodium retention & potassium
loss)
DIGOXIN TOXICITY REVERSAL
Treatment based on clinical course of
patient
Oxygen, cardiac monitoring, IV access
Digibind if Altered mental status,
arrhythmias with hemodynamic
instability, Potassium >5, or Serum Dig.
Level > 10 ng/ml
DIGOXIN TOXICITY REVERSAL
• Lidocaine & phenytoin in ventricular
arrhythmias >depress ventricular
automaticity without significantly slowing
AV conduction
• Quinidine, procainamide, and bretylium
are contraindicated
• Cardioversion is usually contraindicated, it
may precipitate Vfib or Asystole
DRUGS & LABS
• When you see neutropenia,
thrombocytopenia, leukopenia, or
leukocytosis, always ask yourself is there a
medication that is causing this?
• Use resources or clinical PharmD. to
research this if you don’t know the answer
NEUTROPENIA REVIEW
• An ANC of less than 1500 per microliter
(1500/microL) is the generally accepted
definition of neutropenia.
• Neutropenia is sometimes further classified as:
Mild if the ANC ranges from 1000-1500/microL
Moderate with an ANC of 500-1000/microL
Severe if the ANC is below 500/microL
(Agranulocytosis )
• ANC (Absolute Neutrophil Count)=WBC X (%
Neutrophils + % Bands)
DRUG INDUCED NEUTROPENIA
• Causative drug was given within 4 weeks
of the onset of neutropenia.
• Once drug discontinued, usually
neutropenia is corrected within 30 days.
DRUG CAUSES OF NEUTROPENIA
• Chemotherapy
• Immunosuppressive agents
• B-lactam antibiotics
• PTU
• Carbamazepine, Phenothiazines, Phenytoin
• Psychotropic Drugs
DRUG CAUSES OF
THROMBOCYTOPENIA
• Platelet count <150,000
• Early signs Bruising, petechiae, epitaxis
• Unfractionated Heparin, Thiazide diuretics,
Cimetidine, Sulfonamides, Quinine,
Phenytoin, Vancomycin, B-lactam
antibiotics, Levaquin, Digoxin, Valporic
acid
• Improvement within 3-7 days after dc
DRUG INDUCED
LEUKOPENIA
• Chemotherapy
• Anti-Psych Drugs such as Abilify,
Risperidol, Geodon, Seroquel & Zyprexa
• B-lactam induced leukopenia rare but
serious if not identified
DRUG INDUCED LEUKOCYTOSIS
• Granulocyte colony stimulating factor (GCSF) meds like Neupogen or Neulasta
• Recent or current steroids
• Certain Anti-seizure medications
• Antibiotics
DRUGS & LABS
• Remember to adjust to Renal dose if
increase in creatinine
• If patient presents with Acute Renal
Failure or a bump in their creatinine think
about meds
• Patients on nephrotoxic drugs remember
to follow creatinine
NEPHROTOXIC DRUGS
• NSAIDS, ACE Inhibitors, aminoglycosides,
Lithium
• Cephalosporins, Cimetidine, &
Trimethoprm-sulfa cause falsely elevate
serum creatinine
• Remember to look at antibiotics that need
to be renally dosed
• LMH Renal dosing
DRUGS & LABS
• Remember to monitor troughs in
Vancomycin, Gentamycin, & Tobramycin
• When admitting or working up patient
always review drug list and check levels
on meds that can be evaluated by a lab
test i.e. levothyroxine, Digoxin, Coumadin,
Lithium, Valproic acid, Theophylline, Antiseizure meds, etc.
DRUGS & LABS
• When starting new meds, think about
what organs & labs they will impact &
think about timing of labs and follow up
• Adding HCTZ to a 42 year female who has
HTN and is on ACE > will need follow up
Chem 7 in a week to 10 days
DRUGS & LABS
PEARLS
• With over 1100 lab tests and thousands of
medications, you can’t remember it all!
• Know your resources, don’t use a drug
that you don’t know mechanism of action
& side effects
• Good clinicians look things up often
DRUGS & LABS
PEARLS
• Look at the whole patient & clinical picture not
•
•
•
just the abnormal lab test
Right test, right patient, always think about cost,
cause & effect
Consider Drugs as a cause of abnormal labs
In this world of polypharmacy review drug list
What interacts? What can be toxic? What don’t
they need?
DRUGS & LABS
PUTTING IT ALL TOGETHER
• Look at whole person and how the drugs,
labs, and clinical picture add up; the light
bulb comes on and the puzzle is solved!