What is the MoA of Statin-Induced Myopathy?
Block the conversion of HMG-CoA to mevalonic acid which an
important early step in cholesterol synthesis as well as being a
precursor to ubiquinone Statins also
decrease the synthesis of ubiquinone (or coenzyme
Q10) which plays a role in the muscle cell energy production
Ubiquinone deficiency may lead to disturbances in myocyte
cellular respiration and adverse effects including myopathies and
rhabdomyolysis Onset usually occurs within first few weeks to
four months after the initiation of statin therapy or increase in
dose (or increase due to drug interaction) May occur though
anytime during therapy
Statin-Induced Myopathy is generally (uncommon/common) with statin
therapy alone.
Uncommon
2-11% for myalgias 0.5 % for myositis 0.1 %
rhabdomyolysis
What are risk factors for Statin-induced Myopathy
Advanced age > 80 Women > men Small
body frame Pre-existing neuromusclar disorders
Comorbid conditions (diabetes, chronic renal
insufficiency, hypothyroidism) Perioperative periods
Dose related Genetic factors
What are some comorbid conditions that can induce Statin-induced Myopathy?
diabetes chronic renal insufficiency
hypothyroidism
Regarding Pharmacogenomics of Statin-induced Myopathy, deficient
inSLCO1B1 gene can increase risk of myopathy. The gene is associated
with___ but NOT___
simvastatin; also seen with
cerivistatin Not associated with
atorvastatin or rosuvastatin
What are 2 drugs that associated with myopathy due to defect in
SLCO1B1 gene?
Simvastatin (Zocor)
cerivistatin (baycol) - pulled from
market
What's the statin you should alarm when see in the case due to myopathy?
Simvastatin 80 mg daily
Should NOT be start on this ONLY be continued for
patients who have been stabilized on 80 mg/daily for > one
year. Patients on lower doses SHOULD NOT be titrated up to 80
mg
What medications are contraindicated
with Simvastatin/ Lovastatin?
will have to pick them on case
Azole: itraconazole, ketoconazole, voriconazole
macrolides (erythromycin, clarithromycin)
cobicistat HIV protease inhibitors Red Yeast
Rice Letermovir (used for CMV)
What is the max dose of Simvastatin when coadminister with
verapamil, diltiazem, dronedarone?
Simvastatin 10 mg
What is the max dose of Simvastatin when coadminister with amiodarone,
amlodipine, ranolazine
; niacin when dosed at > 1 gram daily?
Simvastatin 20 mg
What is the max dose of Simvastatin when coadminister with ticagrelor
Simvastatin 40 mg
If the patient is already Amiodarone 40 mg already and have to use a
statin, what would u do?
Pick a different statin than Simvastatin 20 mg
Which population should not take more than 20 mg of Simvastatin po
daily with concomitant niacin?
Chinese descent.
___ actually is the only FDA approved statin for combination therapy
with cyclosporine
Pravastatin (Pravachol)
What is the maximum dose for Rosuvastatin
(Crestor) patients on cyclosporine, gemfibrozil, severe renal impairment
10 mg
Gemfibrozil is used to control Triglycerides.
Which statins have the increased risk of muscle toxicity 1-5% when
coadminister with it?
L.A.S
lovastatin (Altoprev) atorvastatin (Lipitor)
simvastatin (Zocor)=
=> Theya are LIPOPHILIC statins = renal excreted after
glucoronidation
and this is inhibited by gemfibrozil
T/F. The risk when coadminister Gemfibrozil (Lopid) and statins is
also seen in Fenofibrate?
FALSE.
Not seen
How often should we do CPK monitoring for Statin?
Routine CPK monitoring is not recommended
Is coenzyme Q10 supplementation good for statin myopathy?
NO.
Steroid-induced Myopathy is most often associated with?
High dose > 40-60 mg
for a long time
In steroid-induced myopathy, what happens to urinary creatinine when
decrease or stop steroid?
Creatinine will decrease
Steroids and NMBAs can cause acute necrotizing myopathy. What are the
physical and lab values for this?
they report they feel nothing whereas you would feel weak
instead Marked elevations in CPK, muscle biopsy reveals
diffuse necrosis, vacuolization and atrophy with selective loss of
thick myosin filaments
CPK - should be a
monitoring parameter for these patients?
What are the patients at most risk for steroid induced myopathy?
What's the recommended monitoring for them?
Status asthmaticus
Recommended monitoring: serial CPKs and development of
weakness = TQ
What are the MoA of Colchicine to cause neuromyopathy?
Neuromyopathy most associated with overdose of colchicine
Affect microtubule function
What are the major risk factor for Colchicine to cause neuromyopathy?
chronic renal injury (CRI) or medication error
overdose
What are the findings for Colchicine to cause neuromyopathy?
proximal muscle weakness more prominent in lower than upper
extremities CPK elevation of > 10-20 x UNL EMG
studies document myopathic changes and diminished deep tendon
reflexes Vacuolation on muscle biopsy Resolution of
symptoms and normalization of CPK within a few days to several weeks
with discontinuation of the drug
What are population risk for Colchicine to cause neuromyopathy?
impaired renal or hepatic function who are also receiving a
strong CYP3A4 inhibitor.
=> Colchicine is contraindicated in patients with impaired renal
or hepatic function who are also receiving a p-glycoprotein inhibitor.
What is the MoA of Cocaine induced Rhabdomyolysis?
Direct muscle injury from marked increased sympathomimetic
activity Severe arterial vasoconstriction leads to skeletal
musche ischemia and infarction Also higher uptake of
catecholamines at alpha adrenergic receptors leads to higher
intracellular calcium levels in muscles cells and subsequent
rhabdomyolysis Higher with crack cocaine (IV or smoking) vs.
oral or intranasal Can occur with one time use also
What antimalarial drugs can cause toxic neuropathy?
chloroquine and
hydroxychloroquine
What is the moa of Alcohol-induced Myopathy?
Direct effect of alcohol/metabolites on muscle cell membrane
structure Chronic drinkers = increase risk as hypokalemia and
hypophosphatemia increase this muscle toxicity
What are 2 antibiotic class that induce myalgias?
Quinupristin /
dalfopristin
( Synercid
)
Fluoroquinolones
Describe Quinupristin /
dalfopristin
( Synercid
) induce myalgias?
First antibiotic for Vancomycin-resistant MRSA 40-50%
of patients complain of neuralgia or myalgia
CPK generally not elevated
Describe the Fluoroquinolones induce myalgias?
Chelation of magnesium in tendonous tissues=> inhibit
collagen formation BBW in patient > 65 or on concomitant
steroids
What kind of Fluoroquinolones have cause the most tendonapathies?
Levofloxacin
What are the BBB for 3 risk factors for Fluoroquinolone use?
Patients >
60
Solid organ
transplant
Concomitant steroid
therapy
Describe Daptomycin induce myopathy?
Phase 1: 4 mg/kg IV q12h => toxicity =>
change to q24h
Risk increases with
concomitant use of statin therapy and recommended that CPK is
check after a week of concomitant therapy
Looking for CPK elevations of > 5 x
UNL with or without association myopathy complaints
Increased risk with improper dose adjustment in patient�s with
renal disease (CRCL < 30 ml/min)
What is the MoA of
Zidovudine -
Mitochondrial myopathy
=> inhibiting ?-DNA polymerase and enzyme found exclusively in
the mitochondrial DNA
What are 3 electrolyte imbalances seen in myopathies?
Hypokalemia
Hypophosphatemia
Hypermagnesemia
What are other causes of Rhabdomyolysis (other causes)
Direct muscle injury (trauma, burns, prolonged immobility)
Muscle overuse (excessive exercise, seizure) Ischemia
(vascular occlusion)Infection (especially viral
illnesses) Metabolic disorders (hypophosphatemia,
hypokalemia) Inflammatory myopathies Drugs leading
to fever
What is the
drug can exacerbate Myasthenia Gravis ?
(Autoimmune
disorder characterized by weakness and fatigue of the skeletal muscle)
Pyridostigmine (
Regonol
)
Autoantibodies that attack the acetylcholine receptor and
eventually reducing the number of these receptors over time
Besides treatments with drugs such as oral acetycholinesterase
inhibitors there are DRUGS that should be AVOIDED in patients with
Myasthenia Gravis
What are drugs to avoid Myasthenia gravis?
Aminoglycosides
(MOST FOR MG)
-competitively restraining the release of ACh from presynaptic
membrane
Telithromycin - exacerbate
myasthenia gravis within the first two hours of the first dose:
black box warning Neuromuscular blockers Magnesium
sulfate as magnesium has a significant inhibitory effect on
acetylcholine release
High dose steroids: CAVEAT so risk vs benefit. Sometimes
have to use high dose steroid even you may exacerbate
MG