Flashcards in Drugs for Fibromyalgia and Spasticity Deck (65):
What is the suspected cause of fibromyalgia?
Elevated levels of neurotransmitter function in the
ascending pathways of the spinal cord and diminished levels in the descending, modulatory pathways of people with fibromyalgia. This
would lead to amplification of all nociceptive signals arriving in the brain
from peripheral tissues.
What are some of the symptoms of fibromyalgia?
-irritable bowel or bladder
What are some of the currently most commonly used drugs for fibromyalgia (not just symptom relief)?
What are the serotonin-Nor repute inhibitors used in fibromyalgia treatment?
both labeled for use
Which does Doloxetine prevent uptake of more, serotonin or Nor?
Which does Milnacipran prevent uptake of more, serotonin or Nor?
NE 3x more
T or F. Neither Sero/NE Reuptake Inhibitor acts on a receptor
T. and neither affects Dopamine
How is Doloxetine metabolized?
CYP 2D6 and eliminated in urine
How is Milnacipran metabolized?
Does not involve CYP activity; eliminated in the urine as a mix of parental drug and metabolites.
Contraindications of Doloxetine or Milnacipran?
-pre-existing CV conditions
Why cant Doloxetine or Milnacipran be given to patients with underlying CV problems?
they increase heart rate and BP
BBW of Sero/NE reuptake inhibitors?
T or F. Both Sero/NE reuptake inhibitors can cause hyponatremia
T. Via SIADH potential
How does Pregabalin (Lyrica) work?
Fibromyalgia drug that is an analog of gabapentin (anti-seizure drug) that acts by inhibiting presynaptic alpha-2-delta subunits of L-type Ca2+ channels, thus, inhibiting the excitatory transmission of glutamate
What is the clinical of Lyrica?
Glutamate inhibition seems to alleviate
neuropathic pain, anxiety and pain syndromes
How is Lyrica eliminated?
it is rapidly absorbed and eliminated in urine mostly unchanged with some tubular reabsorption (no known DD interactions)
Contraindications of Pregabalin (Lyrica)?
Rebound worsening of symptoms upon drug withdrawal. May cause dependence with continued use.
Additive sedation may occur with other agents that affect the CNS in this manner. Patients should be monitored for worsening depression or suicidal thoughts /behavior.
AEs of Pregabalin?
Dizziness, sedation, blurred vision and xerostomia may occur; these are especially problematic in the elderly.
What should be monitored when giving Pregabalin (Lyrica)?
What are the off-label drugs for Fibromyalgia?
What is Fluoxetine (Prozac)?
selective serotonin reuptake inhibitor (SSRI)
What are some skeletal muscle relaxers?
How does Methocarbamol (Relaxin) work?
No direct effect on muscle or excitation-contraction coupling.
Effects thought to be due to generalized sedative action. Pain relief due to altered pain perception.
What are the FDA indications for Relaxin?
How is Methocarbamol metabolized?
Hepatic dealkylation and hydroxylation with urinary elimination.
NOTE: Significant hepatic and/or renal
dysfunction has the potential to increase drug toxicity.
AEs of Relaxin?
Additive CNS depression with other depressant drugs, and alcohol.
Common side effects include drowsiness, dizziness, lightheadedness, blurred vision, N/V, headache and irritability.
How does Tizanidine (Zanaflex) work?
PO agent that acts as an agonist on pre-synaptic α-2 receptors leading to decreased activation of polysynaptic spinal cord motor neurons with concomitant reduction in muscle tone but NOT muscle strength.
Can Tizanidine (Zanaflex) be used as an anti-HTN?
No, weak in that area compared to other a2 agonists
What is Zanaflex approved for?
-spinal cord trauma
How is Zanaflex eliminated?
Extensive first-pass metabolism, short half-life with extensive renal excretion of long-lasting
When is elimination of Tizanidine hindered?
with advancing age and in renal dysfunction (CrCl less than 25 ml/min)
AEs of Zanaflex?
-rebound hypertonicity, tachycardia, and HTN if not tapered off high doses
-xerostomia, dizziness, sedation, hypotension (via a2 action)
DD interactions of Tizanidine?
-additive CNS depression with CNS depressants
-Additive hypotensive effects with a2 agonists
What are some 2 agonists that would be contraindicated with Zanaflex?
What should be monitored if giving Zanaflex?
What is Carisoprodol (Soma)?
PO drug that has CNS action in reticular activating system and spinal cord leading to sedation and altered perception of pain. It is believed (but not proven) that generalized sedation is the basis for the muscle relaxation.
NO DIRECT EFFECT on neuronal conduction, neuromuscular
transmission or muscle excitability.
How is Soma metabolized?
Extensive hepatic metabolism (CYP2C19) to several (less) active compounds with ultimate elimination in the urine.
Renal or hepatic dysfunction increases the potential for retention of drug
and/or metabolites, thereby increasing toxicity.
AEs of Carisoprodol (Soma)?
Drowziness and dizziness are most common, together with other CNS manifestations like
agitation, insomnia, vertigo, ataxia;
systemic effects of sedation include asthenia, temporary vision loss, mydriasis, orthostatic hypotension.
What should be monitored if giving Soma?
What is Soma indicated for?
How does Cyclobenzaprine (Flexeril) work?
central action possible at the level of the brain stem to induce muscle relaxation
What is Flexeril indicated for?
muscle spasm or fibromyalgia (off-label), NOT for relief of cerebral or spinal cord disease
How is Cyclobenzamine eliminated?
Undergoes enterohepatic recirculation and extensive hepatic metabolism (CYP3A4, 1A2, 2D6) with reduced clearance in elderly and with hepatic impairment.
AEs of Flexeril?
significant antimuscarinic activity can produce drowsiness, xerostomia, and dizziness, constipation, etc.
Falls are common in elderly
Contraindications of Flexeril?
-other anticholinergics, TCA, and 1st gen antihistamines
-drugs also prolonging QT
What are the drugs for spasticity?
Note about drugs for spasticity
Although these drugs
can indeed produce muscle relaxation, they do so at drug doses that produce significant
sedation and so are not commonly employed
for this purpose.
How does Baclofen (Lioresal) act?
complex; acts as GABAb agonist at multiple levels in spinal cord, producing
either inhibitory signals or hyperpolarizing and
thereby reducing the excitatory (aspartate and glutamate) polysynaptic pathways.
How does Baclofen cause pain relief in the spinal cord?
inhibition of substance P action.
NOTE: In high doses, baclofen produces
sedation, although not as effectively as diazepam [Valium], therefore some drug activity is doubtless derived from supraspinal actions.
FDA Indications of Lioresal:
multiple sclerosis, muscle spasm, spasticity, spinal cord trauma
How is Lioresal eliminated?
renal (caution with renal failure)
What can happen with high doses of Baclofen in patients with renal dysfunction?
drug accumulation can lead to encephalopathy, abdominal pain,
seizures and respiratory depression.
AEs of Baclofen?
Abrupt discontinuance of therapy should be avoided (Black Box warning) as “rebound” neural activity can result in seizures, confusion, hallucinations, psychiatric disturbances (especially in those with preexisting CNS conditions!) and increased spasticity (perhaps advancing to
rhabdomyolysis, multisystem failure and death). Tapered dosing should occur over 2 or more weeks
Other AEs of Baclofen?
-can increase blood glucose
-renal failure with abrupt withdrawal
Contraindications of Baclofen?
-other anti-HTN and MAOIs
-other CNS depressants
How does Dantrolene (Dantrium) work?
dantrolene decreases muscle contraction by directly interfering (ryanodine receptor) with calcium ion release from the SR within skeletal muscle cells.
Effectively it "uncouples" the excitation-contraction process
Dantrolene does not work like a calcium channel blocker, e.g.,
verapamil, nor does it block Ach release from the endplate.
FDA uses of Dantrium?
-neuroleptic malignant syndrome
T or F. Dantrolene has little or no effect on
cardiac or smooth muscle at doses used for skeletal muscle relaxation.
T. The extent of its CNS
effect is not known.
How is Dantrolene given?
oral or IV (solubilized with surfactant + water - very alkaline, produces
thrombophlebitis; administered into fast running infusion or large vein).
Need for reconstitution
delays immediate administration!
How is Dantrolene eliminated?
Hepatic metabolism with inactive metabolites renally eliminated.
May cause hepatic toxicity when employed chronically.
What patient population is especially at risk for hepatic toxicity with Dantrolene?
Females >35 yrs, MS patients, and those with concurrent multiple drug therapy (especially
Regular liver function tests are recommended
What can Dantrolene do if given during caesarean section?
can cross placenta and cause 'floppy' child syndrome
AEs of Dantrolene?
-muscle weakness leading to drooling, enuresis, myalgia, dysarthria and backache
Contraindications of Dantrolene?
-other depressants, - IV with CCBs in the Tx of malignant hyperthermia