ESSENTIALS OF PHARMACOLOGY CASE I

Ritu Chhabriya, PT, MS

T-DPT student, Fall 2010

MGH Institute of Health professions

Total number of slides: 45

Definitions

Pharmacology: “The study of how chemical substances affect living tissue , and it includes monitoring of how these agents bind to receptors to enhance or inhibit normal function.” (Gladson B, 2006)

Physical therapists: “Physical therapists (PTs) are highly-educated, licensed health care professionals who can help patients reduce pain and improve or restore mobility - in many cases without expensive surgery and often reducing the need for long-term use of prescription medications and their side effects.” (http://www.apta.org/AM/Template.cfm?Section=Home&TEMPLATE=/CM/ContentDisplay.cfm&CONTENTID=76051 Last updated 9/29/2010)

Why should PTs know about pharmacology?

Important to understand how does drugs affect our practice (positive & negative effects of medication) (Gladson B 2006)

For optimum scheduling purposes (Gladson B 2006)

To recognize drug therapy interactions (Gladson B 2006)

To recognize adverse reactions to medications (Gladson B 2006)

To be aware about over the counter (OTC) medications and its effects on body

Monitoring of patients during phase 3 and 4 of dug development

Goals of drug therapy(DT)

DT is ideally used to treat the cause of the problem, underlying condition/disease. Occasionally used to treat symptoms(eg., pain in Ca)

“Get the right drug to the right site at the right time, without the wrong consequences”.

There may be therapeutic failure, side-effects, adverse reactions and toxicity.

Medications must be approved by FDA(Food Drug Administration) to ensure safety.

Need to evaluate risks vs. benefits.

Adapted from Pharmacology lecture: Goals of drug therapy

Pharmacokinetics

“The rate at which drug concentrations accumulate in and are eliminated from various organs of the body” (Gladson B, 2006)

What body does to the drug: Absorption Distribution Metabolism Excretion

Pharmacokinetics (Absorption) Absorption: drug is transferred from site of

administration to systemic circulation Factors affecting Absorption:

Route of administration Drug formulation (dosage forms, drug water solubility,

drug lipid solubility, drug concentration , passive diffusion)

First pass elimination (liver) Environmental factors (surface area, type of surface,

blood supply, gastric emptying and presence of food in GI tract)

Exercise (intensity, mode, fitness of individual, drug properties, +/- of other medical conditions)Adapted from Gladson B, 2006: Pharmacology:Pharmacokinetics;

http://www.health.utah.edu/pt/facultystaff/materials/Pharmacology_for_Physical_Therapists_04-08.pdf Accessed Oct 14,2010

Pharmacokinetics (Distribution) “The rate at which drug may be

distributed to different parts of body, the interstitial, intracellular fluids, and extra-vascular tissues” (Gladson B 2006)

Factors affecting distribution: Organ blood flow Degree of drug ionization, binding to

plasma proteins, molecular weight, membranes and barriers, lipid and water solubility, local metabolism at the site

Adapted from Gladson B, 2006: Pharmacology Lecture: [Pharmacokinetics]

Pharmacokinetics (Metabolism) “Also known as biotransformation, is the

third phase of pharmacokinetics and refers to how the drug is inactivated and prepared for elimination” (Gladson B 2006)

Factors affecting metabolism of medications: Enzymes Site/processes Prodrug First pass effect (oral) Age and stress.

http://www.health.utah.edu/pt/facultystaff/materials/Pharmacology_for_Physical_Therapists_04-08.pdf Accessed Oct 14,2010

Pharmacokinetics (Excretion) “Eliminating the active chemical from the

body” (Pharmacology-pharmacokinetics)

Kidneys/urine; breast milk, saliva, tears and sweat; feces, lungs. Factors affecting elimination of drugs:

Renal excretion: polarity of the compound, lipid solubility, degree of drug ionization

Half life (amount of time taken for the amount of drug in body to be reduced by 50%)

Adapted from Gladson B, 2006: Pharmacology lecture-[Pharmacokinetics]http://www.health.utah.edu/pt/facultystaff/materials/Pharmacology_for_Physical_Therapists_04-08.pdf Accessed Oct 14,2010

Pharamcodynamics

What does the drug do to the body? Factors influencing pharmacodyanamics:

Receptor sites and drug-receptor interactions Agonists and Antagonists Dose response curves Therapeutic index Potency Variables: Age, gender, disease, genetic

factors, compliance, pharmacological drug interactions

Adapted from Gladson B, 2006: Pharmacology-[Pharmacokinetics]; http://www.health.utah.edu/pt/facultystaff/materials/Pharmacology_for_Physical_Therapists_04-08.pdf Accessed Oct 14,2010

Overview of thyroid hormone secretion

Adapted from http://ucsdlabmed.wikidot.com/chapter-11 October 13, 2010

List of serum tests used in the diagnosis of thyroid diseaseList of Tests used in diagnosis Adult Reference Range

Total thyroid hormonesThyroxine - T4 (rarely used)

Triiodothyronine - T3

4.5-10.5 μg/dL60-181 ng/dL

Free thyroid hormonesFree T4

Free T3

0.9-2.1 ng/dL0.1-0.3 ng/dL

Thyroid stimulating hormone (TSH)EuthyroidHyperthyroidHypothyroid

0.35-5.5 mU/L*0-0.35 mU/L< 5.5 mU/L

Anti-thyroid antibodiesAnti-thyroglobulinAnti-microsomal antibodyTSH-receptor antibodyThyroid stimulating immunoglobulins (TSI)Anti-thyroperoxidase antibodies

negativenegativenone detectednegativenegative

Reverse T3 20-80 ng/dL

Thyroglobulin < 60 ng/mL

Adapted from http://ucsdlabmed.wikidot.com/chapter-11 October 13, 2010

Factors affecting TSH levels:

Diurnal variation: TSH secretion ↑just before sleep and then ↓ through the day. (Surks MI, 2006)

Sleep: Sleep deprivation & vigorous exercise have a delayed peak in TSH secretion & a slower decline toward baseline. (Surks MI, 2006)

Obesity: Serum TSH ↑ in obese individuals and is correlated with serum leptin. (Surks MI, 2006)

In comparison to lean individuals (mean body mass index BMI, 23 kg/m2), obese subjects (mean BMI, 34 kg/m2) had an almost 2-fold increase in serum TSH at all times during the day 8 and many values were in the 2.5 to 4.5 mU/L range. (Kok P et al 2005, Surks MI, 2006)

Overview of management of hypothyroidism

Pittas AG, Lee SL. Evaluation of Thyroid Function. Handbook of diagnostic endocrinology. 2003:107

Case of Ms. M

A 35 y/o female was referred to outpatient PT clinic with low back and hip pain by her PCP.

Subjective examination revealed that she has been having LBP since 3 years, unsure of MOI, gradual onset. She reported to have frequent headaches and fatigue. She had not been exercising secondary to fatigue and LBP and had gained 30 lbs in past 6 months.

Aggravating factors: standing > 20 min, cleaning>15 min , washing dishes>20 min, walking > 20 min.

Easing factors: Rest, medications (OTC). Never had “relief as such”

Case of Ms. M

Past medical history: K/c/o hypothyroidism since past 6 months (monitored

by medications); occasional undiagnosed dizziness (does not take any medications)

No previous treatment taken for LBP Reports no other medical illness.

Personal history: Married, lives with husband and two children: 9 year

old, and 5 year old. She did not drive and used public transport for commute.

Does not drink/smoke. Is a housewife by occupation.

Case of Ms. M

Medications: Ms. M reported that she does not remember the exact name of medication she was taking for thyroid, “was not sure why would the physical therapist be interested in medications?”

Image Adapted from http://ameglegal.files.wordpress.com/2008/02/confused.jpg Accessed Oct 13 2010

Ms. M: “I was not aware that I am suppose to get my medication list for PT. How does that impact PT?”PT: “That’s a good question! Medications have a hidden impact on your functional outcomes. Especially, as you have hypothyroidism, it is crucial for me to know which medication you are taking, along with dosage details. This will enable me to consider “the changes” medications can cause in your body and then we can change our exercise options to maximally benefit from PT .”

Ms. M: “Interesting! I shall surely let you know about my medications once I reach home or may be come back for follow up visit”

PT: “Thank you for your co-operation. Sounds good. Apart from your thyroid medication, are you taking any other medication for your LBP?”

Ms. M: “Oh yes! I do take some Ibuprofen when I am in a lot of pain, along with some antacids, calcium, and iron supplements.”

PT: “Since how long are you taking Ibuprofen? Does your PCP knows that you are taking Ibuprofen, antacids, calcium and

iron supplements?”

Ms. M: “I am taking Ibuprofen since past 7-8 months when needed. I get stomach pain when I taken too many of these, so I try to take antacids. My PCP should be aware as his RN told me take some Ibuprofen whenever it hurts! The rest of medications I started as I read in a magazine, it is good to

take iron and calcium supplements for fatigue”

PT: “For your information, Ibuprofen is known to cause gastric irritation. I strongly recommend you should speak to your PCP about stomach pain, as you can develop ulcer if

you ignore. Also, please be aware that there could be multiple drug interactions which can alter the effectiveness of therapeutic dosage of medication prescribed leading t a

therapeutic failure”

Ms. M: “Sure I will.”

PT: “Alright, lets begin our PT evaluation!”

Patient-PT interaction

Ms. M: “I was not aware that I am suppose to get my medication list for PT. How does that impact PT?”

PT: “That’s a good question! Medications have a hidden impact on your functional outcomes. Especially, as you have hypothyroidism, it is crucial for me to know which medication you are taking, along with dosage details. This will enable me to consider “the changes” medications can cause in your body and then we can change our exercise options to maximally benefit from PT .”

Picture adapted from http://www.newamerica.net/blog/files/doctor_patient.jpg Accessed Oct 14, 2010

Patient-PT interaction Contd. Ms. M: “Interesting! I shall surely let you know about

my medications once I reach home or may be come back for follow up visit”

PT: “Thank you for your co-operation. Sounds good. Apart from your thyroid medication, are you taking any other medication for your LBP?”

Ms. M: “Oh yes! I do take some Ibuprofen when I am in a lot of pain, along with some antacids, calcium, and iron supplements.”

PT: “Since how long are you taking Ibuprofen? Does your PCP knows that you are taking Ibuprofen, antacids, calcium and iron supplements?”

Picture adapted from http://www.newamerica.net/blog/files/doctor_patient.jpg Accessed Oct 14, 2010

Patient-PT interaction Contd. Ms. M: “I am taking Ibuprofen since past 7-8 months when

needed. I get stomach pain when I taken too many of these, so I try to take antacids. My PCP should be aware as his RN told me take some Ibuprofen whenever it hurts! The rest of medications I started as I read in a magazine, it is good to take iron and calcium supplements for fatigue”

PT: “For your information, Ibuprofen is known to cause gastric irritation. I strongly recommend you should speak to your PCP about stomach pain, as you can develop ulcer if you ignore. Also, please be aware that there could be multiple drug interactions which can alter the effectiveness of therapeutic dosage of medication prescribed leading t a therapeutic failure”

Ms. M: “Sure I will.” PT: “Alright, lets begin our PT evaluation!”

Picture adapted from http://www.newamerica.net/blog/files/doctor_patient.jpg Accessed Oct 14, 2010

Objective evaluation

Posture: Increased lumbar lordosis and Ant. Pelvic. Tilt Hip ROM- WNL; Lumbar ROM: All motions grossly

restricted to 50 % of ROM. SLR – B/L; Sensations and Reflexes :WNL Palpation: Lumbar hypomobility L4-L5 PA, L3-L4 PA, L5-

S1 PA, PSMS +, tenderness + B/L quadratus lumborum Trunk MMT deferred secondary to pain and fatigue Flexibility:

B/L Hamstring tightness -30 degrees B/L Ober’s test + B/L piriformis tightness +

PT assessment:

Patient is a 35 year old female, k/c/o hypothyroidism since past 6 months referred to PT with complaints of LBP and B/L hip pain suggestive of probable chronic lumbar strain. There is associated altered posture, decreased flexibility in LE muscles, para-spinal muscle spasm, lumbar hypo-mobility and ↓Lumbar ROM further leading aberrant stresses in lumbo-sacral complex. Further trunk and hip MMT will be performed in next follow up visits as patient was fatigued (VAS fatigue 8/10) during initial evaluation.

Practice pattern G: Impaired joint mobility, motor function, muscle performance, range of motion, or reflex integrity secondary to spinal disordersAdapted from Guide to Physical Therapist Practice.Phys Ther.

1997;77:1163-1650

Prognosis and treatment plan Prognosis: good, however needs to monitor serum

TSH levels on a regular basis to appropriately replace thyroid hormone with medication. This is crucial as patient has decreased tolerance and fatigues easily. Absence of neurological and radicular symptoms increases likelihood of good prognosis with pain relief within 4-6 weeks of treatment.

Treatment plan: Postural correction, core stability training, use of manual therapy and modalities to improve ROM and decrease pain along with lower extremity stretching regimen. Monitoring of symptoms of hypothyroidism, adverse reactions and drug interactions of medications that the patient consumes.

On Initial Evaluation day:

Patient was explained about her deficits, and was taught home exercise program as follows: Hamstring stretching Pirformis stretching Lumbar rotations without holds Cat and camel exerciseIdeally, PT would tell the patients to perform

stretching before the leave the clinic , however Ms. M was fatigued and was advised to learn it only.

Following this, she was applied Ice and TENS (modulated) for 15 minutes to lumbar spine

Follow up day 1

Subjective: “Felt better with exercises at home, but feels tired. Performed HEP as advised with Ice application. Was feeling cold today.” (weather 75 degree farhenite outside, 65 degree in thermostat). Patient was shivering when speaking to the therapist.

Objective: (Transferred to a warmer area where she was comfortable). On Exam: Lumbar ROM: 50 % restricted in all motions. Altered posture + Treatment provided:

Manual therapy including STM + MFR Lx paraspinal, quadratus lumborum, L1-L5 Gr II PA glides.

Therapeutic exercises: Transversus abdominus activation in supine, sitting, standing, continuation of previous HEP.

Postural education: Sleeping, sitting, standing, picking objects from floor, carrying groceries.

Assessment: After treatment, Lumbar ROM improved to 70% in all motions with reduction in pain. Patient was fatigued (VAS Fatigue 8/10) with limited therapeutic exercise program. Decreased tolerance to ther.ex. Patient was encourage to communicate about fatigue to MD

Plan: Stimulate communication with MD regarding complaints of fatigue and cold intolerance, continue PT and monitor symptoms.

Next day: Phone conversation with the patient

Patient reported that she has more than usual premenstrual LBP and is concerned if any exercise has caused it. She continues to have headaches and feels sleepy and is getting frustrated and worried.

PT: “I understand that you are having increased pain. Before I come to a conclusion, can you please let me know your medications?”

Ms. M: “Yes, I forgot about that. I take Levothyroxine 25 mcg/day as serum TSH levels were high (32 mU/L). Have been injected IV levothyroxine 6 months back when TSH levels were extremely high(150mU/L). I tied taking Ibuprofen 200 mg for pain relief, but my headache and LBP continues”

PT: “Oh ok! That’s a very high value of TSH as the normal should be around 4-5 mU/L. Are you being regularly monitored for TSH levels? When was you TSH last examined?”

Next day: Phone conversation with the patient contd.

Ms. M: “Yes, endocrinologist was quite surprised with TSH levels, so immediately injected me. I was examined for TSH 2 months back. How does all this information matter with my back pain?”

PT: “Thank you for this question. I am not sure if you are aware that hypothyroidism may cause ↑ in premenstrual pain, fatigue and ↑sleep, along with intolerance to cold. This may be a potential cause of your symptoms. I would strongly recommend communication with the physician and checking your blood TSH levels.”

Ms. M: “Oh! I did not think from this point of view. I shall try calling the physician’s office, however not sure if I can get an appointment with him within 3weeks!”

PT: I shall try calling the physician’s office to inform him about your symptoms and may discuss treatment options. Will call you back to inform about our talk.

Ms. M: “Thank you! Appreciated”; PT: “My pleasure!”

Phone conversation PT and MD

PT: “Dear Dr.KM, Good morning. This is Ritu Chhabriya, PT of your patient Ms. M who was referred to our clinic for LBP. According to my evaluation, she probably has chronic lumbar strain with altered posture, altered flexibility of LE ms and ↓ROM. She is however experiencing 8/10 VAS fatigue, increased sleep, decreased tolerance to ther.ex, ↑PMS and a constant headache. Not sure but I am thinking these symptoms are systemic in nature may be due to hypothyroidism. Wanted to communicate with you regarding this, so that she can maximally benefit from PT.”

Dr. KM: “Thank you for informing me. Yes, you are correct, it can be thyroid related. Let me see if there is any cancellation and I can see her soon… Oh yes! Here it is. I have a opening today, I shall request my receptionist to block it so that she can schedule it.”

PT: “Dr. KM, Thank you for your response. She was indeed anxious about getting in your schedule. I shall call her and communicate to call your office back ASAP. Thank you once again!”

Dr.KM: “Sure! No problem. Bye!”

Communication to the patient PT: “Ms. M, how are you feeling now?” Ms. M: “Preety much same! Any news from MD?” PT: “Yes, I spoke to Dr. KM and he suggested that

he wants to see you at the earliest. He has a opening today evening to see you”

Ms. M: “ Oh great! At least I can go to him. Thank you! Really appreciate your help!”

PT: “Its my duty! Hope you feel better. Please keep me informed about your appointment with Dr.”

Ms. M: “Sure I will.”

Next follow up day: (2 days later) Ms. M: “I am feeling little better with ↓PMS and headache.

Surprisingly my TSH level was high(32uM/L) when I met the Dr. Not sure why?”

PT: “Ok! At least we were in the right direction to identify the symptoms. Did you mention about your other medications?

Ms. M: “Yes, but we ran out of time as I had to go for blood work and travel to pick my kids up from school. May be I can communicate after 3 weeks when I go see him again.”

PT: “Oh ok! I shall try talking to him about this as well. How is your HEP and LBP?”

Ms. M: “My back is better, however I get tired with exercises. “ PT: “Let us just do new exercises, please spread your workout throughout

the day so that you do not get worked up at 1 time of the day”

Third follow up visit

Ms. M continued with her symptoms of fatigue, muscle aches and pain, constant headache. Denies to participate in ther.ex as she has no energy at all.

PT advises the patient to rest in clinic, monitors her vitals and puts a cold pack on her back. Pt immediately called the doctor’s office and requested him to call back asap.

Dr. KM: “Hi Ritu, I am sorry I have taken time to get back to you as I was out of office. So how is Ms. M doing?”

PT: “Thank you for returning my call Dr. I am not sure if Ms. M communicated with you about other OTC medications that she was taking along with levothyroxine.”

Dr. KM: “Not actually! She was in a hurry to pick her kids from school” PT: “Yes, she did mention that. Well, she has reported that she is taking Calcium, Fe

supplements, along with antacids with ibuprofen that RN advised. I looked up drug information and read about potential drug interactions with these OTC. May be this is affecting the required levothyroxine level indicated for her to achieve better TSH levels? Overall, she is not able to participate in her therapeutic exercise program in physical therapy. Do you have any opinions on that?

Dr. KM: Yes, you are right and thank you for giving me a call regarding this. These OTC affects pharmacokinetics of the drug causing significant drug interactions. May be this could be a reason of her fatigue and decrease exercise tolerance. I shall send her a different list of mediations via our electornic medical record system. Please advise her to stop therapy for 2 weeks and adhere to new medications. Once she feels better she can resume.

PT: “Thank you Dr. KM. I shall do as you suggested. Appreciate your explanation!” Dr. KM: “Ritu, very few PTs are catching such obvious drug interactions. Good job! I am glad that

you were vigilant and quick in communication.”

PT: “MS. M, hope you are feeling alright. I have called your husband who is coming to pick you up. Please go home and rest. I have communicated with Dr.KM regarding your OTC medications where we discussed the potential drug interactions these medications can cause. Dr.KM has sent new list of medications to your pharmacy. We shall hold off of PT for 2 weeks, till you feel better and stronger.”

Patient returned to physical therapy after 2 weeks, had no headaches with localized pain in lumbar spine, tolerated therapeutic exercises well, was compliant with HEP, reported that TSH levels were 5uM/L now. She recovered with complete relief within 4 weeks of therapy.

Reflection from the case

Patients in outpatient clinic setting may not be aware about the importance of informing the PTs about medications.

Some patients do not remember the name of medications, exact dosage of the prescribed medications.

Some patients are not educated or are not aware of potential adverse reactions, side effects and drug interactions.

Patients are not aware about reliable resources on web about the medications they are taking.

Outpatient PT clinics are busy, we can easily miss this information. So is the MDs office, as they may patients scheduled every 10 minutes(busier than us) so easy break in communication can occur.

It is duty of each PT to communicate to patient and MDs along with educating the patients. When in doubt, always look up information form a reliable source.

Specific information about Levothyroxine

Brand names: Levothroid; Levoxyl; Synthroid

Unithroid; Tirosin Onset of action: Oral administration (3-

5 days); IV (6-8 hours) Levothyroxine has to be converted to T3 for its clinical effects.

Peak effect: IV(around 24 hours); Oral(1 to 3 weeks)

Adapted from http://www.globalrph.com/thyroid_related.htm#CLINICAL_PHARMACOLOGY accessed Oct 13, 2010

Levothyroxine: Pharmacokinetics

Absorption: Bioavailability: 40% to 80% With age absorption decreases, increases during fasting rates, decreased

in mal-absorption syndromes Distribution:

Protein binding more than 99% (decreased bioavailability, slower metabolic clearance, longer half-life)

Metabolism: Hepatic 80% deiodination; Active metabolite: L-triiodothyronine (T(3)) ; Renal: deiodination (Important to consider in patients with hepatic and renal dysfunctions)

Excretion: Fecal: approximately 20% unchanged Renal: primary excretion site, decreases with age.

Elimination: Half-life:            Euthyroid (6-7 days)           Hypothyroid (9-10 days)           Hyperthyroid (3-4 days)Adapted from (http://www.globalrph.com/thyroid_related.htm#Pharmacodynamics/Kinetics) Accessed Oct 13, 2010 ;

MICROMEDEX® 1.0 (Healthcare Series); DrugPoint® Summary Levothyroxine Sodium, Last Modified: June 04, 2010  

Levothyroxine: Pharmacodynamics

Mechanism of Action: Levothyroxine sodium is a synthetic

thyroid hormone that ↑ cellular metabolism and has a crucial role in growth, development, CNS functions, bone functions, food metabolism and body temperature.

Thyroid hormones, T(3) and T(4), are thought to act by binding to thyroid receptor proteins attached to DNA, thus activating gene transcription and protein synthesis.

The physiological effects of thyroid hormones are produced primarily by T(3), and approximately 80% of T(3) is derived from T4 by deiodination in peripheral tissues .

Adapted from MICROMEDEX® 1.0 (Healthcare Series), DrugPoint® Summary Levothyroxine Sodium, Last Modified: June 04, 2010 ;

Gladson Barbara 2006)

Levothyroxine drug interactions Drug interactions:

Dopamine ↓ TSH secretion Drugs that may ↑/↓ thyroid hormone secretion may result in

hypothyroidism Antacids (K and Mg), calcium carbonate and ferrous sulfate ↓ T4

absorption Esterogen containing oral contraceptives may alter T4 serum transport Furosemide, anti-inflammatory drugs, salicylates may cause protein

binding site displacements Carbamezepin, Rifampin, Phenobarbitol ↑ hepatic metabolism Levothyroxine ↑ catabolism of anticoagulants Levothyroxine and anti-depressants may ↑toxic effects of both drugs Adding levothyroxine ↑ insulin requirement May ↑ the risk of coronary insufficiency when sympathomimetic agents

are administered to patients with CAD Raloxifen causes ↑ TSH levels.(Garwood CL et al. 2006)

Adapted from http://www.rxlist.com/synthroid-drug.htm Accessed on Oct 13, 2010

Levothyroxine: Drug-food interactions

Food that affect levothyroxine absorption such as Soybean flour (infant formula), cotton seed meal, walnuts, and dietary fiber (http://www.globalrph.com/thyroid_related.htm#Pharmacodynamics/Kinetics) Accessed Oct 13, 2010

Studies have shown that consumption of

expresso coffee interferes with T4 absorption in intestine. It is thus advised to consume coffee at least 4 hours apart from levothyroxine orally. Medication should not be consumed with coffee which is crucial for patient education stand point. .(Benvenga et al, 2008)

Levothyroxine: Adverse reactions Adverse reactions:

Possible therapeutic overdosage (symptoms of hyperthryoridism)

NMS (tremors, muscle weakness, fatigue, excessive sweating, anxiety, headache, irritability, insomnia)

CVS (palpitations, ↑ HR, ↑BP, Angina, MI, Arrest) RS:↑RR GI: diarrhea, vomiting, ↑LFT, abdominal cramps Endocrine: decreased BMD Hypersensitivity reactions (anthralgia)

Adapted from http://www.globalrph.com/thyroid_related.htm#Pharmacodynamics/Kinetics Accesed on Oct 13,2010

Effects of factors affecting levothyroxine activity within body

Age: Absorption decreases with increasing age. Iron deficiency (Fe saturation <25 or a ferritin <70) decreases T4 to T3 conversion,

therefore dosage needs to increase for these patients. Presence of an inflammatory condition will have diminished tissue levels of T3,

potentially severe enough to cause symptoms, therefore monitor ↑CRP levels in these patients.

Depression: patients with depression will have undiagnosed thyroid dysfunction. In this condition, there is reduced T4 to T3 conversion and reduced uptake of T4 into the cell, resulting in increased serum T4 levels with low intracellular T3 levels. This should be considered when interpreting standard thyroid tests

Stress: Stress induces reduced tissue T3 level and increased reverse T3 resulting in tissue hypothyroidism and potential weight gain, fatigue, and depression. This can be prevented with supplementation with timed-released T3 but not T4.

Leptin: If leptin >10, there is ↓ cellular T3 and a suppression of TSH, making the TSH an unreliable indicator of thyroid status, especially when combined with an elevated reverse T3. Thus, for anyone who has difficulty losing weight, a leptin level above 10 demonstrates that low intracellular thyroid levels is contributing to this difficulty, especially if combined with a high normal or elevated reverse T3 (above 150).

(http://www.globalrph.com/thyroid_related.htm#CLINICAL_PHARMACOLOGY accessed Oct 13, 2010)

Contra-indications of levothyroxine Acute MI Hypersensitivity to thyroid hormone or any

component of the product Nontoxic diffuse goiter/nodular thyroid

disease (with suppressed TSH); risk of precipitating overt thyrotoxicosis

Thyrotoxicosis; (subclinical or overt) Treatment of obesity or weight loss Uncorrected adrenal insufficiency; may

precipitate acute adrenal crisis Adapted from MICROMEDEX® 1.0 (Healthcare Series); DrugPoint® SummaryLevothyroxine Sodium, Last Modified: June 04, 2010  

Precautions with levothyroxine

Cardiac symptoms (↑HR, angina and arrhythmias), new or worsening; may develop with overtreatment ; reduce or stop therapy for one week, and then cautiously restart at a lower dose. Cardiovascular disease, underlying; initiate therapy at a lower dose.

Concomitant adrenal insufficiency, treat with replacement glucocorticoids prior to initiation of levothyroxine to avoid acute adrenal crisis

Concomitant use with warfarin or coumadin-derivative anticoagulant therapy; PT/INR monitoring recommended

CAD & concomitant sympathomimetic agents; may precipitate coronary insufficiency ↓bone mineral density, especially in women with greater than replacement doses DM, adjustment of antidiabetic regimens may be necessary Elderly; increased risk of CVS effects; initiate therapy at a lower dose Narrow therapeutic index, careful dose titration is crucial to prevent consequences of

over/under-treatment Nontoxic diffuse goiter or nodular thyroid disease (without suppressed TSH),

especially elderly and those with cardiovascular disease; increased risk of thyrotoxicosis

Surgical procedures, preexisting coronary artery disease; increased risk of cardiac arrhythmias

report suspected adverse reactions to the US Food and Drug Administration at 1-800-FDA-1088 or www.fda.gov/medwatch

Adapted from MICROMEDEX® 1.0 (Healthcare Series); DrugPoint® Summary Levothyroxine Sodium, Last Modified: June 04, 2010  

Patient education

If you have heart disease or coronary artery disease, please notify a physician or dentist that yout take this drug, prior to surgical procedures.

This medication may cause hyperthyroidism (fatigue, heat intolerance, fever, sweating, hyperactivity, tremors, palpitations, myocardial infarction), pseudotumor cerebri in children (nausea, vomiting, headache, pulsating intracranial sounds), or seizures (rare).

If you have started taking this drug, you may not see an improvement of symptoms for several weeks.

If you want to stop taking this drug, do not suddenly discontinue. Please space a gap of 4 hours between taking this drug and

antacids, iron, and calcium supplements, if taking concomitantly. Please be aware that there are multiple significant drug-drug

interactions for this drug. Consult a doctor prior to starting any new drug (including over-the-counter and herbal drugs).

Adapted from MICROMEDEX® 1.0 (Healthcare Series); DrugPoint® Summary Levothyroxine Sodium, Last Modified: June 04, 2010

References:

MICROMEDEX 1.0 (Healthcare Series) DrugPoint Summary: Levothyroxine Sodium, Last Modified: June 04, 2010.Thomson Reuters.

Benvenga S, Bartolone L, Pappalardo MA, et al. Altered intestinal absorption of L-thyroxine caused by coffee. Thyroid. 2008;18(3):293-301.

Garwood CL, Van Schepen KA, McDonough RP, Sullivan AL. Increased thyroid-stimulating hormone levels associated with concomitant administration of levothyroxine and raloxifene. Pharmacotherapy. 2006;26(6):881-885.

http://www.apta.org/AM/Template.cfm?Section=Home&TEMPLATE=/CM/ContentDisplay.cfm&CONTENTID=76051 Accessed on Oct 13, 2010

Pharmacology Lecture: [Goals of drug therapy] Pharmacology Lecture: [Pharmacokinetics] http://ucsdlabmed.wikidot.com/chapter-11 Accessed on October 13, 2010 http://ameglegal.files.wordpress.com/2008/02/confused.jpg Accessed Oct 13 2010 Surks MI. Primary hypothyroidism: new issues and controversies. The Endocrinologist.

2006;16(4):203. Kok P, Roelfsema F, Frolich M, Meinders A, Pijl H. Spontaneous diurnal thyrotropin secretion is

enhanced in proportion to circulating leptin in obese premenopausal women. Journal of Clinical Endocrinology & Metabolism. 2005;90(11):6185.

Pittas AG, Lee SL. Evaluation of Thyroid Function. Handbook of diagnostic endocrinology. 2003:107

References continued.

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