Fibromyalgia

Question 1

Duloxetine [Cymbalta] & Milnacipran [Savella]

Class

Answer 1

Serotonin-Norepinephrine Reuptake Inhibitor class of antidepressants

Question 2

Duloxetine [Cymbalta] & Milnacipran [Savella]

MOA

Answer 2

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

Question 3

Duloxetine [Cymbalta] & Milnacipran [Savella]

Elimination

Answer 3

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

Question 4

Duloxetine [Cymbalta] & Milnacipran [Savella]

Cautions

Answer 4

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!!!!!

Question 5

Pregabalin [Lyrica]

General

Answer 5

related to anti-seizure med gabapentin

Schedule-V drug

Question 6

Pregabalin [Lyrica]

MOA

Answer 6

inhibits presynaptic alpha-2-delta subunits of Ltype calcium channels–> inhibits excitatory transmission by glutamate (neurotransmitter)–> alleviates neuropathic pain, anxiety and pain syndromes

Question 7

Pregabalin [Lyrica]

Elimination

Answer 7

rapid absorption
renal elimination virtually unchanged
(w/ some renal tubular reabsorption)

Reduce dose in renal dysfunction/failure

Question 8

Pregabalin [Lyrica]

Cautions

Answer 8

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

Question 9

Amitriptyline† [Elavil]

Answer 9

off-label for FM

tricyclic antidepressant

helps w/ imbalance b/w ascending and descending spinal pathway transmissions

Question 10

Cyclobenzaprine† [Flexeril]

Answer 10

off-label for FM

{see NCs on muscle relaxers}

Question 11

Fluoxetine† [Prozac]

Answer 11

off-label for FM

selective serotonin reuptake inhibitor (SSRI)

helps w/ imbalance b/w ascending and descending spinal pathway transmissions

Question 12

Carisoprodol [Soma]

General

Answer 12

older drug for musculoskeletal pain

Monitor: serum creatinine/BUN

Question 13

Carisoprodol [Soma]

MOA

Answer 13

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!

Question 14

Carisoprodol [Soma]

Elimination

Answer 14

Extensive hepatic metabolism (CYP2C19) to several less active metabolites–> elimination in urine

Renal/hepatic dysfunction is a problem!

Question 15

Carisoprodol [Soma]

Caution

Answer 15

Drowziness, dizziness, and other CNS effects (i.e. temporary vision loss, orthostatic hypotension, etc.)
CNS effects are additive if combined w/ other sedative agents

Question 16

Cyclobenzaprine [Flexeril]

General

Answer 16

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

Question 17

Cyclobenzaprine [Flexeril]

MOA

Answer 17

Central action (maybe at brain stem?)

Question 18

Cyclobenzaprine [Flexeril]

Elimination

Answer 18

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.

Question 19

Cyclobenzaprine [Flexeril]

Cautions

Answer 19

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

Question 20

Methocarbamol [Marbaxin]

General

Answer 20

Oral, IM or IV administration

For muscle spasms, tetanus

Question 21

Methocarbamol [Marbaxin]

MOA

Answer 21

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.

Question 22

Methocarbamol [Marbaxin]

Elimination

Answer 22

Hepatic dealkylation and hydroxylation with urinary elimination

Significant hepatic and/or renal dysfunction–> problem!!

Question 23

Methocarbamol [Marbaxin]

Cautions

Answer 23

Additive CNS depression with other depressant drugs, and alcohol.

Common side effects include drowsiness, dizziness, lightheadedness, blurred vision,
nausea/vomiting, headache and irritability.

Question 24

Tizanidine [Zanaflex]

General

Answer 24

oral

For multiple sclerosis, spasticity, spinal cord trauma (NOT HTN like clonidine, another a-2 agonist)

Monitor LFTs

Question 25

Tizanidine [Zanaflex] | MOA

Answer 25

pre-synaptic α-2 receptor agonist--> decreased | activation of polysynaptic spinal cord motor neurons --> reduction in muscle tone but NOT muscle strength

Question 26

Tizanidine [Zanaflex] | Elimination

Answer 26

Extensive first-pass metabolism, short half-life with extensive renal excretion of long-lasting metabolites Elderly and renal dysfunction--> problem!!

Question 27

Tizanidine [Zanaflex] | Cautions

Answer 27

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

Question 28

Baclofen | General

Answer 28

multiple sclerosis muscle spasm spasticity spinal cord trauma.

Question 29

Baclofen | MOA

Answer 29

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

Question 30

Baclofen | Elimination

Answer 30

An orally active drug that undergoes extensive renal elimination Renal dysfunction--> problems!!! (i.e. encephalopathy, abdominal pain, seizures, respiratory depression)

Question 31

Baclofen | Cautions

Answer 31

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

Question 32

DANTROLENE [Dantrium] | General

Answer 32

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

Question 33

DANTROLENE [Dantrium] | MOA

Answer 33

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.

Question 34

DANTROLENE [Dantrium] | Elimination

Answer 34

Hepatic metabolism with inactive metabolites renally eliminated. Dantrolene crosses the placenta producing the aptly named “floppy child syndrome” if used during Caesarean section.

Question 35

DANTROLENE [Dantrium] | Cautions

Answer 35

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.

Question 36

Botulinum toxin

Answer 36

used for spasticity

Question 37

Indicated for FM

Answer 37

``` Duloxetine [Cymbalta] Amitriptyline† [Elavil] Milnacipran [Savella] Cyclobenzaprine† [Flexeril] Pregabalin [Lyrica] Fluoxetine† [Prozac] ```

Question 38

Indicated for Skeletal muscle relaxation

Answer 38

Carisoprodol [Soma] Methocarbamol [Relaxin] Cyclobenzaprine [Flexeril] Tizanidine [Zanaflex]

Question 39

Indicated for musculoskeletal pain

Answer 39

Carisoprodol

Question 40

Indicated for Muscle spasm

Answer 40

Cyclobenzaprine [Flexeril] Methocarbamol [Marbaxin] BACLOFEN [Lioresal]

Question 41

Indicated for Tetanus

Answer 41

Methocarbamol [Marbaxin]

Question 42

Indicated for Spasticity

Answer 42

Baclofen [Lioresal] Dantrolene [Dantrium] Botulinum toxin Tizanidine [Zanaflex]

Question 43

Indicated for Multiple Sclerosis

Answer 43

Tizanidine [Zanaflex] BACLOFEN [Lioresal] DANTROLENE [Dantrium]

Question 44

Indicated for Spinal cord trauma

Answer 44

Tizanidine [Zanaflex] | BACLOFEN [Lioresal]

Question 45

Indicated for malignant hyperthermia and neuroleptic malignant syndrome

Answer 45

DANTROLENE [Dantrium]

Question 46

Indicated for musculoskeletal pain

Answer 46

Carisoprodol

Question 47

Indicated for Muscle spasm

Answer 47

Cyclobenzaprine [Flexeril] Methocarbamol [Marbaxin] BACLOFEN [Lioresal]

Question 48

Indicated for Tetanus

Answer 48

Methocarbamol [Marbaxin]

Question 49

Indicated for Spasticity

Answer 49

Baclofen [Lioresal] Dantrolene [Dantrium] Botulinum toxin Tizanidine [Zanaflex]

Question 50

Indicated for Multiple Sclerosis

Answer 50

Tizanidine [Zanaflex] BACLOFEN [Lioresal] DANTROLENE [Dantrium]

Question 51

Indicated for Spinal cord trauma

Answer 51

Tizanidine [Zanaflex] | BACLOFEN [Lioresal]

Question 52

Indicated for malignant hyperthermia and neuroleptic malignant syndrome

Answer 52

DANTROLENE [Dantrium]