DSA: muscle relaxants and MS drugs (Waller) - SRS Flashcards
(50 cards)
1
Q
What are the centrally acting spasmolytics?
A
- Baclofen
- Tizanidine (Zanaflex)
- Diazepam (Valium)
- Gabapentin & pregabalin
- Drugs Used for Local Muscle Spasm
2
Q
What are the drugs used for local muscle spasm?
2 red, 6 total
A
- Carisoprodol (Soma)
- Chlorzoxazone
- Cyclobenzaprine (Flexeril)
- Metaxalone (Skelaxin)
- Methocarbamol (Robaxin)
- Orphenadrine
3
Q
What are the non-centrally acting spasmolytics?
A
- Dantrolene
- Botulinum toxin
4
Q
What are the injectible (IM and Sub-q) immunological drugs for MS?
A
-
Interferons
- Interferon-beta-1a (Avonex, Rebif)
- Interferon-beta-1b (Betaseron)
- Glatiramer acetate (Copaxone)
5
Q
What are the infusion drugs used to treat MS?
A
- Mitoxantrone
- Natalizumab (Tysabri)
6
Q
What are the oral drugs used to treat MS?
A
- Dimethyl fumarate (Tecfidera)
- Fingolimod (Gilenya)
- Teriflunomide (Aubagio)
7
Q
What are some of the “other” treatments for MS?
A
- Azathioprine
- Cyclophosphamide
- Dalfampridine
- Glucocorticoids
8
Q
Drugs which affect skeletal muscle function can be subdivided into two, distinct therapeutic groups, which are?
A
- Those that produce muscle paralysis (neuromuscular blockers)
- those that reduce spasticity (spasmolytics)
9
Q
Spasticity results d/t upper or lower motor neuron damage?
A
Upper
10
Q
Drugs modifying the stretch reflex arc in spasticity modulate excitatory or inhibitory synapses by what two mechanisms?
A
- Reduce the activity of Ia fibers which excite the primary motor neuron;
- Enhance activity of inhibitory interneurons.
11
Q
MOA for baclofen?
A
MOA: agonist at GABAB receptors.
- Results in hyperpolarization due to: closure of presynaptic calcium channels, increased postsynaptic K+ conductance, and inhibition of dendritic calcium influx channels.
- Through reduced release of excitatory neurotransmitters in the brain and spinal cord, suppresses activity of Ia sensory afferents, spinal interneurons, and motor neurons.
- May reduce pain via inhibition of substance P (neurokinin-1) in the spinal cord
12
Q
How does Baclofen compare to dantrolen and diazepam?
A
Vs diazepam: equally effective and less drowsiness
Vs. dantrolene: does not reduce overall muscle strength as much as dantrolene
13
Q
What are the therapeutic indications for baclofen?
A
reversible spasticity associated with multiple sclerosis or spinal cord lesions
14
Q
Riddle me some ADRs for baclofen.
A
- Drowsiness
- increased seizure activity in epileptic patients
- confusion
- dizziness
- hypotonia
- psychiatric disturbances
- insomnia
- slurred speech
- ataxia
- muscle weakness
15
Q
What is the MOA of tizanidine?
A
-
MOA: alpha2-adrenergic agonist (chemically similar to clonidine) that reinforces presynaptic and postsynaptic inhibition in the cord. Also inhibits nociceptive transmission in the spinal dorsal horn.
- Thought to be mediated through restoration of inhibitory suppression of interneurons without inducing changes in intrinsic muscle properties.
16
Q
How does tizanidine compare as far as efficacy in release of muscle spasm to:
- Dantrolene
- Baclofen
- Diazepam
?
A
Comparable to all three
17
Q
What are two therapeutic uses for tizandine?
A
- Muscle spasticity
- chronic migraine
18
Q
What are the ADRs associated with Tizandine?
7
A
- Drowsiness (take at night)
- hypotension
- dizziness
- dry mouth
- asthenia
- hepatotoxicity
- weakness (although less than other spasmolytics)
19
Q
What is the MOA of Diazepam?
A
- MOA: benzodiazepine; promotes binding of g-aminobutyric acid (GABA) to the GABAA receptor, enhances GABA-induced ion currents; leads to increased inhibitory transmission and a reduction in spasticity.
20
Q
What are some therapeutic uses for diazepam? 5
A
- sedation
- hypnotic effects
- muscle relaxation
- anxiolytic
- anticonvulsant
21
Q
What are some ADRs of diazepam? 4
A
- Generalized CNS depression
- sedation at doses needed to reduce muscle tone
- risk of dependence
- amnesia
22
Q
Can Gabapentin and Pregabalin be used for muscle spasm?
A
Sure can
23
Q
Where do the drugs used to treat local muscle spasm typically work?
A
Level of the brainstem
24
Q
What is the MOA of carisoprodol?
A
Good question, it is unclear. All we know is it acts as a CNS depressant.
25
What is the therapeutic use of **carisoprodol?**
1. short-term treatment (2-3 weeks, lack of evidence of effectiveness with prolonged use) of musculoskeletal pain.
26
What are the ADRs associated with **carisoprodol?**
1. drowsiness
2. dizziness
3. addictive propensity
27
What is the MOA of **cyclobenzaprine**?
1. **MOA:** unclear; reduces tonic somatic motor activity by influencing both alpha and gamma motor neurons.
28
What is the MOA for chlorzoxazone? (not in red, but why not)
1. **MOA:** acts on the spinal cord and subcortical levels by depressing polysynaptic reflex arcs.
29
What metabolizes cyclobenzaprine?
CYP450s
30
What are the therapeutic uses for cyclobenzaprine?
What is it ineffective in treating?
1. treatment of muscle spasm associated with acute, painful musculoskeletal conditions (do not use longer than 2-3 weeks);
2. ineffective in treating muscle spasm due to cerebral palsy or spinal cord injury.
31
What are some ADRs of cyclobenzaprine?
1. antimuscarinic effects (structurally related to tricyclic antidepressants)
2. dizziness
3. xerostomia
32
What is the MOA of **dantrolene**?
1. **MOA**: causes inhibition of the ryanodine receptor (RyR) calcium channel; blocks the release of calcium through the sarcoplasmic reticulum and muscle contraction is impaired.
33
What impact does dantrolene have on cardiac and smooth muscle?
None, they have a different RyR channel subtype. Thankfully
34
What are the therapeutic uses for dantrolene?
1. Treatment of spasticity associated with upper motor neuron disorders
* spinal cord injury
* stroke
* cerebral palsy
* MS
2. Management of malignant hyperthermia
35
What is the MOA of Botulinum Toxin?
1. **MOA**: zinc endopeptidase cleaves specific proteins involved in vesicle fusion. Disruption of fusion proteins prevents the release of acetylcholine.
36
What are therapeutic uses for botox? 7
1. cervical dystonia
2. blepharospasm
3. line/wrinkles of the face
4. severe primary axillary hyperhydrosis
5. generalized spasticity
6. prophylaxis of migraine headache
7. treatment of overactive bladder
37
What is the ADR of botox?
focal muscle weakness in the area of injection which may last up to several months
38
1. The typical patient with multiple sclerosis presents as a young adult with ≥ two clinically distinct episodes of central nervous system dysfunction with at least partial resolution.
1. Common signs/symptoms: sensory symptoms (limbs or face), unilateral visual loss, motor weakness, diplopia, gait disturbance and balance problems, Lhermitte sign, vertigo, bladder problems, limb ataxia, acute transverse myelitis, and pain.
So, what the hell is Lhermitte sign?
electric shock-like sensations that run down the back and/or limbs upon flexion of the neck
39
Disease modifying therapy agents are typically continued indefinitely in stable patients unless side effects are intolerable.
What are is an exception to this, and why?
**_natalizumab:_**
1. progressive multifocal leukoencephalopathy
2. pregnancy: potential teratogenicity
40
What is the MOA of interferon-beta-1a?
1. **MOA**: enhances suppressor T cell activity, reduces proinflammatory cytokines, down-regulates antigen presentation, reduces trafficking of lymphocytes into the CNS.
41
What is the MOA of interferon-beta-1b?
1. **MOA**: enhances suppressor T cell activity, reduces proinflammatory cytokines, down-regulates antigen presentation, reduces trafficking of lymphocytes into the CNS.
Same as 1a
42
What are the goals that interferons help acheive?
1. Improces lesions seen on MRI
2. Decrease relapse rate
3. decrease severity in patients with secondary progressive MS
43
What are the ADRs associated with Interferon?
1. Injection site reactions
2. flu-like symptoms
3. high prevalence of asymptomatic liver dysfunction
4. leukopenia
5. anemia
6. suicide
44
Glatiramer acetate is a biological agent used for management of what type of MS?
Relapsing-remitting MS
45
What is the MOA of glatiramer acetate?
1. **MOA:** mixture of random polymers of four amino acids (L-alanine, L-glutamic acid, L-lysine, and L-tyrosine) that is antigenically similar to myelin basic protein, which is an important component of the myelin sheath of nerves.
1. Thought to induce and activate T-lymphocyte suppressor cells specific for a myelin antigen; also proposed to interfere with the antigen-presenting function of certain immune cells opposing pathogenic T-cell function.
46
What are the ADRs of glatiramer acetate?
1. Local injection site reactions
2. transient systemic post injection reactions
* Chest pain
* flushing
* dyspnea
* palpitations
* anxiety
47
What is the MOA of natalizumab?
1. **MOA:** monoclonal antibody against the alpha-4 subunit of integrin molecules (play a role in adhesion and migration of cells from the vasculature into inflamed tissue).
1. Blocks integrin association with vascular receptors, limiting adhesion and transmigration of leukocytes; efficacy in multiple sclerosis may be related to blockade of T-lymphocyte migration into the central nervous system and results in a decreased frequency of relapse.
48
What are the ADRs of natalizumab?
1. Infusion related
1. headache
2. flushing
3. erythema
4. nausea
5. dizziness
2. Fatigue
3. anxiety
4. infections
5. peripheral edema
6. PML
49
Glucocorticoids are used to treat acute MS relapses and improves short term outcomes. What is the dosing strategy for these meds?
1. Monthly bolus IV glucocorticoids (typically 1000 mg of methylprednisolone) are used for treatment of primary or secondary progressive MS alone or in combination with other immunomodulatory or immunosuppressive medications.
50
