Fibromyalgia Flashcards
Duloxetine [Cymbalta] & Milnacipran [Savella]
Class
Serotonin-Norepinephrine Reuptake Inhibitor class of antidepressants
Duloxetine [Cymbalta] & Milnacipran [Savella]
MOA
inhibit reuptake of serotonin and NE
Duloxetine = SER>NE milnacipran = NE>SER by 3-fold
Neither has action on receptors themselves or upon reuptake of dopamine
Both parental agents are responsible for the
respective pharmacologic effects
Duloxetine [Cymbalta] & Milnacipran [Savella]
Elimination
Duloxetine undergoes extensive CYP metabolism, including CYP 2D6–> moderate inhibition (drug-drug interactions potential!)
Ultimate elimination occurs primarily as urinary metabolites.
Metabolism of milnacipran does not involve CYP activity; it too is eliminated in the urine as a mix of parental drug and metabolites
DON’T administer either when hepatic dysfunction/ chronic alcoholism
Duloxetine [Cymbalta] & Milnacipran [Savella]
Cautions
can be assoc w/ mild increase in HR and BP
(caution in pts w/ CV problems)
Contraindicated in closed-angle glaucoma pts
Don’t use w/ MAOIs
May produce hyponatremia due to SIADH
BBW: suicide ideation!!!!!
Pregabalin [Lyrica]
General
related to anti-seizure med gabapentin
Schedule-V drug
Pregabalin [Lyrica]
MOA
inhibits presynaptic alpha-2-delta subunits of Ltype calcium channels–> inhibits excitatory transmission by glutamate (neurotransmitter)–> alleviates neuropathic pain, anxiety and pain syndromes
Pregabalin [Lyrica]
Elimination
rapid absorption
renal elimination virtually unchanged
(w/ some renal tubular reabsorption)
Reduce dose in renal dysfunction/failure
Pregabalin [Lyrica]
Cautions
rebound worsening of symptoms upon drug withdrawal
can cause dependence w/ continued use
Additive CNS problems (i.e. sedation) when used w/ other drugs affecting CNS
Dizziness, sedation, blurred vision and xerostomia may occur; these are especially problematic
in the elderly
Monitor serum creatinine
Amitriptyline† [Elavil]
off-label for FM
tricyclic antidepressant
helps w/ imbalance b/w ascending and descending spinal pathway transmissions
Cyclobenzaprine† [Flexeril]
off-label for FM
{see NCs on muscle relaxers}
Fluoxetine† [Prozac]
off-label for FM
selective serotonin reuptake inhibitor (SSRI)
helps w/ imbalance b/w ascending and descending spinal pathway transmissions
Carisoprodol [Soma]
General
older drug for musculoskeletal pain
Monitor: serum creatinine/BUN
Carisoprodol [Soma]
MOA
CNS action in reticular activating system and spinal cord–> sedation and altered perception of pain
NO direct effect on neuronal conduction, neuromuscular transmission, or muscle excitability…it is believed therapeutic benefit is due to generalized sedation!
Carisoprodol [Soma]
Elimination
Extensive hepatic metabolism (CYP2C19) to several less active metabolites–> elimination in urine
Renal/hepatic dysfunction is a problem!
Carisoprodol [Soma]
Caution
Drowziness, dizziness, and other CNS effects (i.e. temporary vision loss, orthostatic hypotension, etc.)
CNS effects are additive if combined w/ other sedative agents
Cyclobenzaprine [Flexeril]
General
Oral
closely related to TCA amitriptyline
Not effective for relief secondary to cerebral or spinal cord disease.
Used for muscle spasms and off-label for FM
Cyclobenzaprine [Flexeril]
MOA
Central action (maybe at brain stem?)
Cyclobenzaprine [Flexeril]
Elimination
Undergoes enterohepatic recirculation and extensive hepatic metabolism (CYP3A4, 1A2, 2D6)
in elderly and pts w/ hepatic impairment–> problem!
significant anticholinergic action including:
drowsiness, xerostomia and dizziness; also fatigue, N/V, constipation, blurred vision; elderly pts at risk for confusion and cardiac effects leading to falling.
Cyclobenzaprine [Flexeril]
Cautions
Additive CNS depression with depressant drugs and alcohol.
Additive effects with other anticholinergics like amoxapine, atropine, dicyclomine, most tricyclics,
phenothiazines and 1st generation antihistamines.
GI problems are the MOST significant, e.g.
paralytic ileus.
TCAs have been reported to increase QT interval, use with caution in presence of antiarrhythmics and other drugs prolonging QT
Methocarbamol [Marbaxin]
General
Oral, IM or IV administration
For muscle spasms, tetanus
Methocarbamol [Marbaxin]
MOA
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.
Methocarbamol [Marbaxin]
Elimination
Hepatic dealkylation and hydroxylation with urinary elimination
Significant hepatic and/or renal dysfunction–> problem!!
Methocarbamol [Marbaxin]
Cautions
Additive CNS depression with other depressant drugs, and alcohol.
Common side effects include drowsiness, dizziness, lightheadedness, blurred vision,
nausea/vomiting, headache and irritability.
Tizanidine [Zanaflex]
General
oral
For multiple sclerosis, spasticity, spinal cord trauma (NOT HTN like clonidine, another a-2 agonist)
Monitor LFTs
Tizanidine [Zanaflex]
MOA
pre-synaptic α-2 receptor agonist–> decreased
activation of polysynaptic spinal cord motor neurons –> reduction in muscle tone but NOT muscle strength
Tizanidine [Zanaflex]
Elimination
Extensive first-pass metabolism, short half-life with extensive renal excretion of long-lasting
metabolites
Elderly and renal dysfunction–> problem!!
Tizanidine [Zanaflex]
Cautions
Hepatocellular toxicity has been reported; liver tests are required.
Recommendation is for tapered cessation of Tx to avoid rebound hypertonicity, tachycardia and
hypertension, especially after high drug doses.
Additive CNS depression with CNS depressants.
Additive hypotension with clonidine, methyldopa, guanfacine or guanabenz.
Common side effects generally correlate with the actions of a central α-2 agonist;asthenia,
xerostomia, dizziness, sedation, hypotension
Baclofen
General
multiple sclerosis
muscle spasm
spasticity
spinal cord trauma.
Baclofen
MOA
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. —-Pain relief in spinal cord comes from inhibition of substance P action.
- -In high doses, baclofen–> sedation, although not as effectively as diazepam [Valium], therefore some drug activity is doubtless derived from supraspinal actions
Baclofen
Elimination
An orally active drug that undergoes extensive renal elimination
Renal dysfunction–> problems!!! (i.e. encephalopathy, abdominal pain, seizures, respiratory depression)
Baclofen
Cautions
BBW: Rebound neural activity–> seizures, confusion, hallucinations, psychiatric disturbances, increased spasticity (even–> rhabdomyolysis, MOF, death)…SO TAPER DOSE DOWN over two or more wks!!!
Additive CNS depression occurs with other depressants.
Additive hypotension with antihypertensive agents and MAOIs.
Dose adjustment of antidiabetic agents may be necessary; baclofen increases blood glucose.
Common side effects include drowsiness (63%) asthenia, confusion, dizziness, fatigue and
headache; other CNS toxicities rarely observed, except with renal failure or abrupt withdrawal
DANTROLENE [Dantrium]
General
Used for malignant hyperthermia, multiple sclerosis, neuroleptic malignant syndrome,
spasticity
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!
Monitor LFTs
DANTROLENE [Dantrium]
MOA
dantrolene decreases muscle contraction by directly interfering (RyRs) with calcium ion release from the SR w/in skeletal muscle cells.
–it “uncouples” the excitation-contraction process; (makes dantrolene useful in treating malignant hyperthermia)
Dantrolene does not work like a calcium channel blocker, e.g., verapamil, nor does it block Ach release from the endplate
Dantrolene has little or no effect on
cardiac or smooth muscle at doses used for skeletal muscle relaxation. The extent of its CNS
effect is not known.
DANTROLENE [Dantrium]
Elimination
Hepatic metabolism with inactive metabolites renally eliminated.
Dantrolene crosses the placenta producing the aptly named “floppy child syndrome” if used
during Caesarean section.
DANTROLENE [Dantrium]
Cautions
Additive CNS depression with other CNS depressants!
IV dantrolene combined with calcium channel blockers (in the Tx of malignant hyperthermia)
may produce Vfib and CV collapse
Common side effects include muscle weakness leading to drooling, dysarthria, enuresis,
myalgias and backache.
Botulinum toxin
used for spasticity
Indicated for FM
Duloxetine [Cymbalta] Amitriptyline† [Elavil] Milnacipran [Savella] Cyclobenzaprine† [Flexeril] Pregabalin [Lyrica] Fluoxetine† [Prozac]
Indicated for Skeletal muscle relaxation
Carisoprodol [Soma]
Methocarbamol [Relaxin]
Cyclobenzaprine [Flexeril]
Tizanidine [Zanaflex]
Indicated for musculoskeletal pain
Carisoprodol
Indicated for Muscle spasm
Cyclobenzaprine [Flexeril]
Methocarbamol [Marbaxin]
BACLOFEN [Lioresal]
Indicated for Tetanus
Methocarbamol [Marbaxin]
Indicated for Spasticity
Baclofen [Lioresal]
Dantrolene [Dantrium]
Botulinum toxin
Tizanidine [Zanaflex]
Indicated for Multiple Sclerosis
Tizanidine [Zanaflex]
BACLOFEN [Lioresal]
DANTROLENE [Dantrium]
Indicated for Spinal cord trauma
Tizanidine [Zanaflex]
BACLOFEN [Lioresal]
Indicated for malignant hyperthermia and neuroleptic malignant syndrome
DANTROLENE [Dantrium]
Indicated for musculoskeletal pain
Carisoprodol
Indicated for Muscle spasm
Cyclobenzaprine [Flexeril]
Methocarbamol [Marbaxin]
BACLOFEN [Lioresal]
Indicated for Tetanus
Methocarbamol [Marbaxin]
Indicated for Spasticity
Baclofen [Lioresal]
Dantrolene [Dantrium]
Botulinum toxin
Tizanidine [Zanaflex]
Indicated for Multiple Sclerosis
Tizanidine [Zanaflex]
BACLOFEN [Lioresal]
DANTROLENE [Dantrium]
Indicated for Spinal cord trauma
Tizanidine [Zanaflex]
BACLOFEN [Lioresal]
Indicated for malignant hyperthermia and neuroleptic malignant syndrome
DANTROLENE [Dantrium]
