MSK_Pharm Flashcards
Function of calcium in the body
- bone - structure, storage
- contraction - VSM, heart
- coagulation
Is bone static?
No
Remodelling occurs with osteoclasts (reabsorption), osteoblasts (deposition), and osteocytes (homeostasis)
Takes 3-4 months
trabecular bone > cortical bone
Drugs that decrease calcium in body
Glucocorticoids
furosemide diuretics
sodium
calcitonin
SSRI
PPI
blood thinners
bisphosphonates
denosumab
SERMs (raloxifene)
estrogen
teriperatide
Drugs that increase calcium in the body
thiazide diuretics
calcium salts
PTH
vitamin D
Effect of PTH
*released from parathyroid gland when serum calcium level is too low
increase bone reabsorption - release calcium
increase GI absorption of calcium
decrease kidney excretion of calcium
increase level of calcium in the blood
decrease phosphate in blood
Effect of Vitamin D
*made by liver and kidney
1, 25 dihydroxyvitamin D
increase bone reabsorption
increase GI absorpiton calcium
decrease renal excretion calcium
increase phosphate level in blood
increase level calcium in the blood
Calcitonin
*Released from thyroid gland when serum calcium is too high
decrease bone reabsorption
increase renal excretion
decrease serum calcium
no effect on intestine
no effect on phosphate
Hypercalcemia
too much calcium in the blood
cardiovascular damage
kidney damage (kidney stones)
fatigue, lethargy, depression, muscle weakness, constipation, abdominal cramping, nausea, vomiting, anorexia
Causes:
cancer
vitamin D toxicity
sarcoidosis
thiazide diuretics
Hypocalcemia
too little calcium in the body
spasms, tetany, muscle cramping
Causes:
low PTH
low vitamin D
diet
thyroidectomy
furosemide diuretic
Drugs involved with calcium and bone mineralization
bisphosphonates
denosumab
SERMs (estrogen, raloxifene)
calcium salts, cinacalcet
Furosemide/thiazide
glucocorticoids
teriparatide, PTH
vitamin D
List of Calcium salts
calcium carbonate
calcium gluconate
calcium citrate
calcium acetate
calcium lactate
Indication Calcium salts
hypocalcemia
pre-menstrual cramps
colorectal adenoma
AE Calcium salts
hypercalcemia
cramping, constipation, anorexia
kidney stones
lethargy, fatigue, depression
dysrhythmias
Drug interactions Calcium salts
glucocorticoids - decrease GI absorption calcium, incrase bone reabsorption, increase kidney excretion calcium
PPI, SSRIs, furosemide, blood thinners, glucocorticoids decrease calcium
thiazide diuretics - hypercalcemia
chelation of other drugs - don’t take at the same time, decrease drug absorption
RDA of calcium
600-900mg/day
only use supplements to top up diet
Baseline data required before calcium salt prescription
ECG - heart, dysrhythmias
Serum calcium, phsophate, magnesium
Albumin - Kidney
Vitamin D
Scientific forms
Vitamin D2 - ergocalciferol (plants, inactive form)
Vitamin D3 - cholecalciferol (partially active, sunlight)
1,25 dihydroxyvitamin D - Calcitriol (fully active)
Contraindication Calcium salts
hypophosphatemia
hypercalcemia
kidney stones
Indication
Vitamin D supplements
Low vitamin D
Rickets
osteomalacia
hypoparathyroidis
MOA
Vitamin D
- Bone - increase bone reabsorption
- GI - increase SI absorption of calcium
- Renal - decrease excretion calcium and phosphate, reabsorption
Target level of Vitamin D for bone health
30-60ng/mL
Deficiency treatment
infants 2000IU
children 4000IU
adults 10,000IU
Baseline labs for Vitamin D
serum vitamin D
serum calcium, phsophate, magnesium
ALP (bone reabsorption)
24 hour urine calcium
Contraindication
Vitamin D
hypercalcemia
hypervitaminosis D
digoxin
malabsorption
AE
Vitamin D
Hypervitamin D
- fatigue, lethargy, depression
- supression growth, reabsorption bones
- constipation, nausea/vomiting, decreased appetite
deposition calcium in vasculature, heart, kidney
Antedote Vitamin D
furosemide
fluids
glucocorticoids
low calcium diet
Bisphosphonates
List of drugs
alenDRONATE (PO)
riseDRONATE (IV)
ZoleDRONic acid (IV)
Bisphosphonate
MOA
structural analog of pyrophosphate
deposition into bone structure
- Ingested by osteoclasts; decrease activity, recruitment
- increase osteoblast inhibition of osteoclasts
bisphosphonate
AE
Esophagitis, ulcers, cancer
- sit up for 60 minutes
- take with full glass of water
Osteonecrosis of the jaw (IV)
- Dentist prior to Rx
Hip and long bone fractures
- decreases remodeling of bone
Musculoskeletal pain
- after first dose or months after
- requiring opioids
- D/C if pain recurrent
Occular inflammation
- uveitis, conjunctivitis, sceleritis
Hyperparathyroidism
- low serum sodium results in PTH release
Atrial fibrillation
Flu like symptoms (IV)
Renal damage (IV)
Bisphosphonate
administration instructions
- take with full glass of water
- do not lie down for 60 minutes
- take on an empty stomach
- dental work prior to prescription
- report GI, vision, hip pain
Bisphosphonate
Monitoring
BASELINE:
DXA scan
every 1-2 years
Serum calcium, magnesium, phosphate, Vitamin D (25 hydroxy vitamin D)
Serum creatinine, GFR (>30mL/min)
Contraindications
Bisphosphonates
- esophagitis, ulcers, cancer
- osteoporosis hip and fractures
- necrosis jaw
- severe MSK pain
- GFR < 30mL/min, kidney damage
Serum Estrogen Receptor Modulators (SERMs)
raloxifene
extrogen
MOA
Raloxifene
Estrogen agonist in bone, lipid metabolism, clotting
Increase bone mineral density
Reduction spinal fractures
Estrogen increases OPG (osteoprotegrin) which binds to RANKL on osteoblast and prevents it from activating the osteoclast RANK
AE
Raloxifene
DVT/PE/CVD
- must D/C if bedrest or sedentary
- D/C 72 hours in advance
(plane travel)
hot flashes
abortive agent - teratogenic
Benefits of
Raloxifene
decrease risk of breast and endometrial cancer
lowers LDL and cholesterol
increase bone mineral density and decrease fractures
Monitoring
Raloxifene
HCG test
Serum calcium, vitamin D
DXA scan, height, 1-2 years
AE
Estrogen
increase risk of breast cancer and endometrial cancer
Denosumab
MOA
monoclonal antibody
binds to RANKL
prevents interaction between RANKL-RANK and osteoclast reabsorption
increases bone mineral density and prevents fractures
AE
Denosumab
hypersensitivity reactions
Flu like symptoms
serious infection
ONJ - osteonecrosis of the jaw
Hypocalcemia
hyperparathyroidism
Monitoring
Denosumab
Serum calcium, vitamin D, magnesium, phsophate, creatinine
HCG
DXA, height
Administration instructions
Rx. Vitamin D, Calcium
Avoid infections
Dentist prior to prescription
Anti-Gout Drugs
- NSAIDS (First line therapy)
- indomethacin
- naproxen
- diclofenac - Anti-Gout Anti-inflammatory drugs
- Colchicine - Glucocorticoids
- prednisone - Xanthine Oxidase Inhibitors
- Allopurinol
- Febuxostat - Uricosuric agent
-probenecid - Combination drugs
- probenecid / colchicine
NSAIDs for anti-gout
MOA
Ex. naproxen, indomethacin, diclofenac
Block COX1 and COX2
prevention formation prostaglandins (inflammatory cytokines)
Decrease vasodilaiton, vascular premability, WBC migration - decrease inflammation and pain
SE
NSAIDS
GI: ulceration, perforation, bleeding
Kidney: AKI
Cardio: MI, stroke, HTN, hemorrhage
Tinnitus/salicylism
Reye’s syndrome children
premature closure ductus artereosus/cleft lip and palate
*shortest duration possible
Drug therapy
< 3 gouty attacks per year
Drugs for symptom management (inflammation)
- NSAID
- Colchicine
- glucocorticoids
Drug therapy > 3 gouty attacks per year
Drugs for hyperuricemia (increase secretion, decrease production)
- Xanthine Oxidase Inhibitors (allopurinol, febuxostat)
- prevention uric acid formation - Uricosuric agents
Probenecid
- uric acid secretion by kidney - uric acid oxidase
- Pegloticase
- convert uric acid to allantoin
Glucocorticoid for anti-gout
MOA
Prednisone
second line therapy (after NSAID)
NSAID intolerance/contraindication/unresponsive
Decrease WBC recruitment, migration
SE
Glucocorticoids
hypokalemia
hypernatremia
water retention, FVO, edema
striation skin
poor healing wounds, wound infections
hyperglycemia
muscular weakness/atrophy
truncal deposition of fat
moon face
osteoporosis
cataracts, glaucoma
adrenal insufficiency
aggitation, depression, insomnia, hallucinations etc.
Colchicine
anti-gout anti-inflammatory
MOA
Disrupts WBC microtubules, preventing WBC infiltration/migration
anti-inflammatory
AE
Colchicine
Narrow therapeutic index
Cytotoxic to cells with high proliferation index (ex. GI, bone marrow)
GI: nausea, vomitting, diarrhea, pain (D/C)
WBC: agranulosis, thrombocytopenia, infections
MSK: Rhabdomyolysis (kidney and liver damage)
Teratogenic
Drug interactions
Colchicine
Statins: increase myopathy, liver damage, rhabdomyolysis
CYP3A4 inhibitors: toxicity
Indication
Colchicine
- management symptoms short term attack
- prevention gout attacks
Indication
Allopurinol
Chronic tophaceous gout
Chemotherapy/cancer therapy
MOA
Allopurinol
Xanthine Oxidase Inhibitor
- DNA breakdown forms hypoxanthine
- XOI blocks formation of Xanthine -> uric acid
SE
Allopurinol
GI: nausea, vomiting, diarrhea
WBC: bone marrow supression, infection risk
first dose can initiate gout attack
- administer with colchicine and NSAID for up to 6 months
AE
Allopurinol
WBC: agranulocytosis, thrombocytopenia
Fatal hypersensitivity syndrome
- liver, kidney failure, eosinophilia
SCAR - severe cutaneous adverse reaction
- HLA B5801 testing
- Asian heritage more common
SE
Febuxostat
Gout flare ups: prescribe with NSAID and colchicine for 6 months
CVE
Probenecid
indication
Hyperuremia
chronic gout
pregnancy
children < 2 years
Probenecid
MOA
Kidney
decrease reabsorption of uric acid
increase excretion of uric acid
results in decrease tophi
Probenecid
SE
GI: nausea, vomiting
skin: hypersensitivity
first dose: gouty flare up, administer with NSAID or colchicine
Kidney: renal injury, 3L per day fluid
Blood: hemolytic anemia, pancytopenia (G6PD deficiency African, mediteranian)
Probenecid
Drug interactions
Aspirin
antibiotics - penicillin, cephalosporins, sulfonamides
*reduction dosage required
Pegloticase
MOA
Urate oxidase
converts uric acid into allantoin
allantoin is water soluble and excreted by kdiney
Pegloticase
INdication
Last ressort therapy
Not responding to PO
IV
Pegloticase
AE
anaphylaxis infusion reaction
pre-treatment with prednisone and anti-histamines; close monitoring
- 2 hours, or delayed
hemolytic anemia - G6PD deficiency (screen)
Urate lowering drugs
Baseline data
Serum uric acid
LFT
CBC
Pain assessment
Allopurinol: HLA B 5801 (Korean, Thai, Chinese)
Febuxostat: LFT, CVRisk
Probenecid: G6PD deficiency
Urate Lowering Drugs
Monitoring data
SErum uric acid, CBC and diff
2-5 weeks
< 6mg/dL
then monitor every 6 months
LFTs, BUN, serum creatinine
improvement signs and symptoms of gout
Treatment pathway Gout
- establish diagnosis
- elimination diet, lifestyle, drugs
- assess gout burden and indication for urate lowering therapy (ULT)
- tophi
- frequency gout attacks > 2 per year
- presence CKD
- urolithiasis - first line therapy
- Xanthine oxidase inhibitors (febuxostat, allopurinol)
- alternative probenecid
XOI is prescribed with acute gout prophylaxis (NSAID, colchicine, glucocorticoid)
Long term maintenance gout
continue prophylaxis treatment if > 1 tophi on exam
6 month monitoring serum urate < 6mg/dL
refer out if not responsive
Treatment pathway acute gout attack
- continue prophylaxis therapy
- allopurinol, probenecid - initiation monotherapy or combination therapy
- NSAID
- glucocorticoid
- colchicine
