1)Osteoporosis:  __% of Americans over 50 are at risk.

2)  3Ca3(PO4)2(OH)2 is  known as ______.

3)  Our Bones contain 99% of our bodies calcium and 85% of it's phosphorous?

1)  55%

2)  hydroxyapatite 

3) True

1)  A type of arthritis marked by progressive cartilage deterioration in the synovial joints and vertebrae?

2)  Idiopathic OA is also called?

3)  What are known causes of OA (3)  

1)  Ostearthritis (approximately 21 million AMericans have it)

2)  Primary OA

3)  Trauma, underlying joint disorder, systemic metabolic/endocrine disorders

1)  What are some risk factors for OA?

2)  T/F..Amost all people over 75 have OA

3)  Describe differences in Localized, Generalized and Erosive OA

1)  OBESITY and AGE are biggest ones

2)  True

3)  •    Localized OA: involving one or two sites
•    Generalized OA: affecting 3 or more sites
•    Erosive OA: indicated presence of erosion and marked proliferation in PIP and DIP hand joints
 

1) OA usually begins with damage to articular cartilage through injury, obesity etc o    Damage to cartilage increases metabolic activity of ______, leading to increased synthesis of matrix constituents with cartilage swelling

2)  T/F....this hypertrophic reparative response to damage does not restore cartilage to normal but instead is the first step in the process leading to further cartilage loss

1)  Chondrocytes

2)  True

o    Predominant symptom is localized deep, aching pain associated with affected joint

Radiographic Evidence

Early: No change

Mod: joint space narrowing, osteophytes "lipping"

Late:  Deformity

OA

1)  PTS that lose 10 lbs…decrease OA in knees by __%

2)  What are teh ACR's criteria for an OA dx?

1)  50%

2)  Pain
Bony changes upon exam
Normal ESR…in other words, no inflammation
Characteristic radiographs
 

1)  T/F Wrist Involvement is less common than MP Joint Involvement with OA. (DIP >  PIP most involved)

2)  T/F...Joint Involvement in OA is usually Symmetrical?

1)  It is more common...MP very uncommonly affected in OA.

2)   False usually assymmetrical.

1)  With OA what is considered to be the "best thing to do"

2)  What other non-pharm techniques may help?

1)  Educate the pt...(weight loss)

2)  Physical/Occupational Therapy

What is the main goal of treating OA with pharmaceuticals?

 2)  What is the 1st line Pharm for OA

3)  At what dosage?..What are maximums?

4)  How does it work?

1)  Pain Relief

2)  Acetaminophen (APAP)

3)  325 -650 mg PO q6h...

(don't excede 4gm a day for healthy or 2-3gm daily for KIDNEY/HEPATIC DZed)

4)  Inhibits synthesis of Prostaglandin in CNS blocking generation of pain impulses.

Advantages of Acetaaminophen?

Disadvantages?

What is the Topical 1st line for OA?

How does it work?

Capsaicin (0.025% to 0.075%)Topical analgesic

INHIBITS the release of substance P from peripheral sensory neurons.... (i know this contradicts the notes but it makes sense from what I found online) ...substance P actually CAUSES PAIN...

How do NSAIDs fct?

Why aren't they 1st line?

1)  Inihibtion of prostaglandin synthesis through inhibition of COX-1 and COX-2 Enzymes

2)  MAJOR PROB GI Bleeding due to inhibition of COX-1 (Gastroprotection via platelet aggregation..stop this and you bleed out into theses areas)

RENAL:  Acute renal insufficiency...HYPERKALEMIA

HEPATIC-can causce Drug-induced hepatitis

1)  T/F...With NSAIDS anti-inflammatory effects are quicker to come than analgesic effects?

2)  If your first NSAID fails...try another

1)  False, the reverse...anti-inflammatory effects can take 2-3 weeks

2)  True

What are all of these?

Salsalate

 Diflunisal

Choline salicylate

Choline magnesium salicylate

What are all of these?

Etodolac

Diclofenac

Indomethacin

Ketorolac

Nabumetone

Which NSAIDS are these? 

 Fenoprofen

Ibuprofen

Flubiprofen

Ketoprofen

Naproxen

Naproxen Sodium

Oxaprozin

Priopionic Acids

NSAIDs

Meclofenamate

Mefenamic acid

Fenamates

NSAIDs

Piroxicam

Meloxicam

Are the max doses typically high or low for these

Oxicams

very low (Piroxicam max=20mg/day...Meloxicam 15mg/day)

What is unique about Celebrix vs. NSAIDs

Who is it 1st line for?

Celecoxib (Celebrex) only blocks the COX-2 pathway...meaning it doesn't cause the GI problems

Pts over 65 with comorbid medconditions including glucocorticoid use, peptic ulcer dz, GI bleeds or anticoagulants

Drug interactions of Celecoxib include?

Methotrexate

Lithium

Aspirin

How might Glucosamine help OA pts?

Stimulates proteoglycan synthesis...max dosage is 1500 mg as it may cause HYPERGLYCEMIA..or upset GI. 

For whom do we recommend Corticosteroid injectionsin OA?

What dosage for large joints?

For small joints?

How many to be given a year?

Severe pain with little relief from analgesics/NSAIDS

5-15mg

2.5-5mg

Limit to 3-4/year for ENTIRE BODY

Which joint are Corticosteroids proven to be effective in OA?

How do Hyaluronate  Injections help relieve pain?

What are some disadvantages

Knee Joint

Provide joint lubricant via visoelastic solution it forms in water (6 mo of relief)

Expensive..can cause acute joint swelling and local skin reactions

What are some of teh Drug Interactions of NSAIDs

What do we worry about for Celecoxib pts?

Sulfa Allergies

OA (RA can strike any age)

RA

RA

OA

RA

OA

T/F  RA results in Swollen Joints...along with bone/cartilage loss

ARA Criteria? (7 items)

True

1) Morning stiffness >1hr

2) Arhtiritis in 3 joint areas

3) 1 of which is hand joint

4) Symmetrical

5) Rheumatoid Nodules over bony prominences

6)  Positive serum Rheumatoid factor

7)  Radiography shoing soft-tissue swelling, bony decalcifications, or erosions

What is 1st line RA Treatment?

How long should we wait before we evaluate its effectiveness?

NMARD (disease Modifying Antirheumatic Drugs)..Methotrexate or MTX, in particular.

3 months

T/F NSAIDs should be used as a monotherapy for RA

False NSAIDs not recommended for MONOTHERAPY

What is Typical MTX dosing schedule

What must also be taken with MTX?

7.5-10mg PO once WEEKLY

Folic Acid 1mg PO DAILY (MTX somehow inhibits Folic Acid activation...and you may become depleted)

What are 3)  Adverse Effects of MTX and what labs should we get for each of these

How does MTX work?

1)  Myelosuppression: get baseline CBC...then every 1-2 months

2)   Hepatic fibrosis/cirrhosis...baseline AST, ALT, then eveyr 1-2 months

3) Pulmonary fibrosis/infiltrates

WE DON"T KNOW HOW IT WORKS YET

Pregnancy/nursing

Chronic Liver Dz

Immunodificiency

Pleural/peritoneal Effusions

Leukopenia

Thrombocytopenia

CrCl<40ml/min

What mechanism is this?

Inhibits pyrimidine synthesis, resulting in antiproliferative and anti-inflammatory effects

Leflunomide

How do we dose Leflunomide?

Load with 100 mg PO daily x 3 days

Then 10-20 mg PO daily

Adverse Effects of Leflunomide include?

what group of RA pts might Plaquenil or Hydroxychloroquine be good for?

What do we need to watch out for?

First line for early/mild dz (No myelosupression)

Macular damage/gi toxicities

T/F Sulfasalazine is a DMARD that inhibits pyrimidine synthesis for late/proliferative dz

It has Drug Interactions with: ANTIBIOTICS, Fe Supplements, and WARFARIN

It is often used as it has very little side effects?

False...it inhibits prostaglandin synthesis for mild/early dz.

True

False...it is often avoided due to its adverse effects including (anorexia, vomiting, diarrhea, rash, leukopenia and hepatic damage

What are advantages of Biologics for RA

What are some disadvantages?

(genetically modified proteins)

Adv:They antagonize proinflammatory cytokines without requiring LAB MONITORING

Dis:You will have an overall increase of infections as you are inducing immunosuppresion of sorts

 Which Biologic RA drug am I?

-used in conjunction with a DMARD

-Binds tumor necrosis factor (TNF) and blocks its interaction with the cell surface
 

Etanercept (SubQ injection once or twice a week...50mcg,..25mcg,) 

Who is Etanercept (Enbrel) Contraindicative for?

CHF Pts..(can exacerbate heart failure)

Those with active infection

YOU MAY SEE injection site reaction

Etanercept , Infliximab, and Adalimumab have pretty much the same Contraindications and Adverse Effects?

 How does Infliximab (Remicade) work?

It must be used in conjunction with MTX?

Dosing Schedule is?

  True

Binds TNF-alpha

True, prevents formation of Ab to the drug as it contains foreign IgG₁ bound to anti-TNF.

 3mg/kg IV INFUSION at 0,2,6 WKS...then every 8 Weeks

How does Adalimumab work?

Which Biological RA drug inhibits T-cell Activity?

What are this drugs adverse effects/contraindications?

Binds to human TNF-alpha (just like Infliximab)

Abatacept (orencia)

Ad Efx:headaches, COPD exacerbation, 

Contra: Use with any TNF-blocker 

Which Biologic RA drug inhibits B-cell activity?

It's Adverse Effects?

Rituximab

Tumor Lysis Syndrome

Cytopenia

Heb B REACTIVATION

For RA Corticosteroids are used as a 1st line defense

False...they are used for bridging therapy to get pt. by while other drugs are getting to work (3 mo periods)

Abnormal Loss of bony tissue resulting in fragile porous bones attributable to a lack of calcium

What % if Americans > 50 yo are at risk?

Effects men/women equally?

Osteoporosis

55%

No 8 million Women, 2 million Men effected

We replace teh majority of our skeleton every _____ years?

Decreased Ca+…leads to high levels of ___

T/F ...PTH acts to Decrease blood calcium?

What Vit. Helps absorb Ca?

7-10 Years

PTH

False...PTH increases...Calcitonin acts to decrease (reabsorb to bone)

Vit D. (sunlight and diet)

What is a Normal T-Score?

What is Osteoporosis T-score?

What is Osteopenia T-score?

How are these scores derived?

Anything larger than -1

Anything smaller than -2.5

-1 to -2.5

based on standard deviations from Mean (an average grown woman's bone density)

Why does Menopause cause Osteoporosis?

Less Estrogen being produced...Estrogen is responsible for Apoptosis of Osteoclasts (bone destroyers...) Without it these Osteoclasts live longer and are more proliferative....hence faster bonebreakdown...

Did your skull just explode? maybe you have a estrogen deficiency.

What is best Tx for Osteoporosis?

What is highest pk bone mass AGE for women?

Prevention "an ounce of prevention is worth a lb of Tx of symptoms"...This is because there is no gaining back what you lose through osteoporosis. 

30yo

Name some drugs that may Induce Osteoporosis

Glucosteroids 

Anticonfulsants (phenytoin, phenobarbital)

HEPARIN

Loop Diuretics

Immunosuppresants

Thyroid Supplements

What are some Lifestyle changes that decrease risk of Osteoporosis

How much Calcium should be taken by adults?

not smoking

exercising

don't drink

Intake of Vit. D and Calcium

Fall Prevention

1500mg/day in divided doses

Calcium Citrate has more Calcium available than Calcium Carbonate?

Any adverse effects to taking Calcium?

False...Calcium Carbonate (tums) does...but is less tolerable to the stomach

Possible Kidney stone, gas, upset stomach,CONSTIPATION

Interactions with Calcium?

Proton Pump Inhibitors (PPI)

Iron, Tetracycline, fluoroquinolones, bisphosphonates, phenytoin

Verapamil

Thiazide Diuretics

Fiber Laxitives

1)  What Groups may need extra Vit D?

2)  What is a healthy Adult Vit. D. intake?

African-Americans

Northerners

Amish peeps

Seniors

Depressed cavemen

200 mg..for elderly pts...maybe 600mg

What are some adverse affects of Vit. D?

What is a  dosing for Vit.  D deficiency pts?

What is the pharm name for Vit. D₂

What is the pharm name for Vit. D₃

Hypercalcemia (weakness, headache, somnolence, nausea, cardiac rhythm disturbance)

 Hypercalciuria (kidney stones)

50,000 units weekly or monthyly

Ergocalciferol (PO, injection or liquid)

Cholecalciferol

How do Thiazide Diuretics aid in Osteoporosis?

Do they intereact with Vit. D?

THey help with calcium reabsorption

Yes

Name the 3 Bisphosphonates

Who are they indicated for?

Aldedronate (Fosamax)

Risedronate (Actonel)

Ibandronate (Boniva)

Prevention of osteoporosis in postmenopausal

treatment of dudes with osteoporosis

treatment of glucocorticoid-induced osteoporosis

Treatment of Paget's dz

Inhibit bone resoprtion by acting on Osteoclasts or osteoclast precursors DIRECTLY..

This LEADS to an indirect increase IN BMD

T/F It is okay to take other meds with Bisphosphonates?

Contraindications for Bisphosphonates?

ABSOLUTELY NOT...

Hypocalcemic Pts

Severe renal impairment (less than 30ml/min Cr Clearance)

Those who cannot stand or sit upright for 30 min

What does SERM stand for? 

How do they work?

What is the SERM we looked at?

Selective estrogen receptor modulator

Extrogen-mimicking drug that is selective...prevents bone lose and improves lipid profiles....ALSO BLOCKS ESTROGEN IN THE BREAST AND UTERUS.

Raloxifene (Evista)

What other positive effect does Evista have other than help prevent osteoporosis?

What is it's usual dosage?

Reduces risk of invasive breast cancer in postmenopausal women with osteoporosis...and women at high risk for breast cancer.

60mg PO daily

What are teh adverse effects of Evista?

Any important drug interactions?

VTE ...Hot flashes...Leg cramps

Bile acid resins, WARFARIN, THYROID hormones

Who is Evista contraindicated for?

Pregnancy (CAT X) or those Nursing

Those with past VTE events

How does Calcitonin work?

Commonly found?

Mechanism of Action
Directly inhibits osteoclastic bone resorption

 Yes...naturally occuring hormone..we use a version of Salmon Calcitonin

 How is Calcitonin administered?

What are its adverse effects?

Name some of Calcitonin's drug interactions

 Intranasal: 200 units (1 spray) once daily
Alternate nostrils each day
IM, SubQ: 100 units every other day
 

nasal probs (bleeds, dryness, irritation)

Back pain

Arthralgia

Headache

There are none

What is the name of the only Drug approved for Bone regrowth therapy.

How does it work?

How must it be administered?

Adverse Effects?

Teripatide (Forteo)

Stimulates osteoblast function
Increases renal tubular reabsorption of calcium

Injection pen...(make sure done while sitting as it may cause hypotension) 20mcg subQ daily

Pain at Inj. Site...Cramps...Dizziness

What drug directly inhibits Teripetide (forteo)

What is it contraindicated for?

What are they BLACK LABEL for?

Any Bisphosphonate

Paget's Dz..those with unexplained elevations of alkaline phosphatase

ANYBODY with a past hx of "skeletal radiations" as they are at risk for developing Osteosarcomas on this drug

A HEREDITARY metabolic dz caused by hyperuricemia that is a form of acute arthritits and is marked by joint inflammation

What are teh two enzymes that play a huge role in Gout manifestation

What is metabolic rout is gout due to?  

Which  causes gout if there is too much of it

Which  causes hyperuricemia if there is too little of it.

PRPP (phophoribosyl pyrophosphate )

and

HGPRTase (hypoxanthine-guanine phosphoribosyl transferase )

Nucleic Acid

PRPP

HGPRTase

What is a normal Uric output for a Man?

For a woman?

What 2 organs eliminate Uric acid from the body?

1200mg

600mg

Kidneys (urine...2/3 of elim)...GI tract (by enteric bacteria) (1/3 of elim)

Attacks generally occur where 1st?

When do these usually occur?

How long can a attack last before it resolves?

•    Attack typically first metotarsophalangeal joint (podagra), then, in order of frequency, the insteps, ankles, heels, knees, wrists, fingers, and elbows

Attacks generally occur in the middle of teh night...and are VERY PAINFUL (wake up pt.)

3-14 days if untreated before spontaneous resolution

 What are some precipitating factors for GOUT?

 What is our 1st line Tx of Gout?

If these don't bring relief use?

 Stress,trauma, ALCOHOL, Infection Surgery, MEdications (those that lower uric acid or increase uric acid concentrations)

 NSAIDs (INDOMETHACIN)

Colchicine (1st line if NSAID contraindicated)

How does Colchicine work?

How do we dose it?

Contraindicated for?

Reduces the deposition of Urate Crystals

0.6 mg to 1.2 PO followed by 0.6 mg every hour until a Max of 6mg total given....or diarrhea..whichever comes first :)...dont exceed 7 days of use

renal impared, Pregnant (IV),

Adverse Effects of Colchicine?

GI..nausea, vomitting, diarrhea, abdominal pain

Bone marrow Toxicity....DON't EXCEED 7 days of dosing.

When do we use corticosteroids to Tx Gout?

How do we Tx Uric Acid Nephrolithiasis

Hydration (due to concentrated urinary excretions that are ACIDIC)

Alkanalize the Urine

Use Allopurinol (only drug that inhibits uric acid synthesis)

What is the word for Urate deposists

What is a cause of ACUTE GOUTY NEPHROPATHY?

Tophi...Tophaceous Gout (uncommon and a late complication)

Chemotherapy

What do Uricosuric meds do?

Name 2 and explain how they work

Any adverse effects of these meds?

Decrease serume urate concentrations (prophylactic therapy for gout)

Probenecid (inhibits the resorption of uric acid at PCC)

 Sulfinpyrazone  (increases urinary excretion of uric acid)

GI irritation, rash, precipitation of acute gouty attack, Stone formation...contraindicated for those with kidney stones..and low Cr clearance (anything lower  than 50 ml/min)

How does Allopurinol work?

Who is it the drug of choice for?

Adverse Effects?

Xanthine oxidase inhibitor...(one of final steps before Xanthine becomes Uric Acid)

Those with a hx of Renal stones/impairment..those on chemotherapy...those that overproduce uric acid.  

LEUCOPENIA..GI upset..acute gouty attacks, skin rash