Exam 2 Flashcards
(131 cards)
1
Q
Parkinsonism
A
any disorder presenting with classic signs and symptoms; usually secondary to some other factor; infection, drugs, toxins
2
Q
Parkinson’s disease
A
idiopathic form of parkinsonism
3
Q
pathophysiologic features of parkinson’s
A
- Loss of dopaminergic cells in substantia nigra and basal ganglia
- formation of lewy bodies in remainin SNc neurons and other parts of the brain: medulla, locus coeruleus, raphe nuclei, olfactory bulb
4
Q
UK Parkinson’s disease society brain bank diagnosis criteria
A
Bradykinesia (slowness and difficulty initiating voluntary movement) and at leas 1 of the following:
-limb muscle rigidity (resistance to passive ROM)
-resting tremor
-postural instability
5
Q
clinical presentation of parkinsons
A
primary: bradykinesia, postural instability, resting tremor, rigidity
motor symptoms: decreased dexterity, dysarthria, freezing at initiation of movement, slow turning
autonomic symptoms: bladder & anal sphincter disturbances, constipation, diaphoresis
mental status changes: confusion, dementia, psychosis
6
Q
on vs off
A
on= good movement
off= poor movement
7
Q
approaches to pharm treatment in PD
A
-increase endogenous dopamine
-decrease cholinergic activity
-activity dopamine receptors using synthetic agonists
-block adenosine A2A receptor activity
8
Q
anticholinergics PD
A
Benztropine (Cogentin), Trihexyphenidyl (Artane)
MOA: antimuscarinic
Side effects: possible link to cognitive impairment and decline, anti-SLUDGE
9
Q
drugs that increase endogenous dopamine
A
levodopa, carbidopa, encaptone, tolcapone, opicapone, selegiline, rasagiline, safinamide, amantadine
10
Q
levodopa
A
gold standard
MOA: precursor to dopamine, crosses BBB
CI: breast-feeding, closed angle glaucoma, melanoma
Side effects: dyskinesia, on-off phenomena, decreased effectiveness over time, psychiatric disturbances, vivid dreams, GI effects, orthostatic hypotension, saliva, sweat, or urine discoloration, NMS w abrupt d/c
DDI: dopamine antagonists, non-selective MAOIs, high protein intake, iron salts, pyridoxine
11
Q
carbidopa
A
MOA: noncompetitive dopa decarboxylase inhibitor: inhibits peripheral L-Dopa metabolism, increase both absorption and half life, no over pharmacodynamic actions. never used as monotherapy without levodopa
CI: pregnancy, lactation
Maintain doses at least 70-100 mg/day
12
Q
Sinemet (caridopa/levodopa) CR
A
decrease in total “off” time, decrease dosing frequency, decreased bioavailability compared to IR
*delayed onset of effect (esp. when taken in AM)
13
Q
switching from Sinemet IR to CR
A
start with 50% reduction in frequency
consider giving 25% more CR per day due to decreased bioavailability
14
Q
Duopa
A
Carbidopa/Levodopa intestinal gel
infused through wearable pump in “PEG-J” tube
Most often used in patients with advanced PD (significant off time and/or dyskinesia)
*risk for infection
15
Q
Inbrija
A
Levodopa powder for inhalation
Indication: intermittent treatment of OFF episodes in patients with Parkinson’s disease treated with carbidopa/levodopa (not a replacement for PO)
Side effects: somnoolence, hallucinations dyskinesia, cough, nausea, upper respiratory tract infection, and sputum discolored
CI: MAOI (nonselective) use within 2 weeks
Not recommended in patients with asthma, COPD, or other chronic underlying lung disease
16
Q
COMT inhibitors
A
*Tolcapone, Entacapone, Opicapone
MOA: reversible, selective inhibitor of COMT: prevents breakdown of L-Dopa
NO effect in absence of L-dopa
DDIs: drugs metabolized by COMT, non-selective MAOIs
17
Q
Entacapone (Comtan)
A
shorter half life for COMT inhibitors
Dose: give 200 mg w each dose of levodopa/carbidopa (up to 8 times daily)
Side effects: similar to levodopa, brown/orange urine
Stalevo (carbidopa/levodopa/entacapone)
18
Q
Tolcapone (Tasmar)
A
COMT inhibitor
CI: hepatic disease (tolcapone-induced hepatocellular injury)
Side effects: rarely used today due to risk of hepatocellular injury (increased LFT’s), delayed onset diarrhea
Dose: 100mg TID
19
Q
Opicapone (Ongentys)
A
decreased absorption with moderate-fat/calorie meal
Once-daily dosing: 50 mg QHS; do not eat for 1 hour before and at least 1 hour after dose
CI: use if nonselective MAOIs; phenochromocytoma, paraganglioma, or other catecholamine secreting neoplasm
Use in caution in patients with mild to moderate hepatic impairment; avoid use in severe impairment
20
Q
MAOIs (selegiline, rasagiline, safinamide)
A
MOA: noncompetitive, selective antagonists of monoamine oxidase type B (MAO-B). This decreases breakdown of dopamine. Decrease free radical production (disease-modifying)
Mono or adjunctive therapy
21
Q
Selegiline [Eldepryl, Zelapar (transbuccal)]
A
Labeled indication: adjunctive therapy only (can also be used mono in early PD)
Eldepryl (PO tab): 5 mg qd-bid
Zelapar (dissolving tablet): 1.25 mg QD- 2.5 mg QD after 6 weeks. No food or drink 5 mins before/after
CI: no absolute! dementia, severe psychosis, concomitant use of meperidine, tramadol, methadone, propoxyphene
Side effects: CNS, GI, hypertensive crisis, serotonin syndrome, insomnia, jitteriness, headache, irritation of buccal mucosa (zelapar)
22
Q
Amantadine (Symmetrel, Gocovri, Osmolex ER)
A
MOA: somewhat poorly understood. decrease rigidity, tremor, bradykinesia, L-dopa induced dyskinesia
Precautions: Pts with CHF, orthostatic hypotension, or peripheral edema
AEs: orthostatic hypotension, falls, hallucinations, sedation (or insomnia), anticholinergic AEs, livedo reticularis (mottling of skin with LE edema), NMS with abrupt discontinuation
DIs: flumist (LAIV), Quinine/quinidine, HCTZ and triamterene
22
Q
Rasagiline (Azilect)
A
Potentially disease modifying
Dose: 0.5 mg QD w levodopa, 1 mg as monotherapy
Side effects: monotherapy (headache, arthralgia, GI upset, falls) with levodopa (dyskinesia, GI upset, headaches, weight loss, arthralgia, and orthostasis) orthostasis is most common during the first two months of treatment
CI: meperidine, tramadol, methadone, propoxyphene, dextromethorphan, St. johns wort, mirtazapine, cyclobenzaprine, vasoconstrictors
22
Q
Safinamide (Xadago)
A
MOA: selective MAOB-I. Na and K channel blocker, decrease glutamate release
Indication: adjunctive to L-Dopa for wearing off
Dose: Start with 50 mg PO QD; after 2 weeks, inc to 100 mg QD if needed
CI: Child-Pugh Class C
Side effecs: dopaminergic, daytime somnolence, withdrawal-emergent NMS-like syndrome, retinal pathology
22
Pramipexole (Mirapex)
MOA: D2 and D3 dopamine agonist
DIs: inhibitor of renal tubular secretion (cimetidine)
Dose: IR 0.125 mg TID; titrate to MDD of 1.5 mg TID
ER: 0.375 mg QD; titrate to MDD of 4.5 mg QD
22
Dopamine agonists
May be used as monotherapy
-reduced risk of developing motor complications when used as monotherapy compared to L-Dopa
Used as adjunctive agents in case of deterioration in response to L-Dopa
-fluctuations in L-Dopa response
-unable to tolerate increased doses of L-dopa
Non-motor side effects are more frequent compared to levodopa, especially in older or more frail patients
-impulsive behaviors, psychosis, n/v, vivid dreams, daytime sedation, orthostatic hypotension
23
Ropinirole (Requip)
MOA: D2 and D3 dopamine agonist
IR: 0.25 mg TID; titrate to MDD of 24 mg
XL: 2 mg QD; titrate to MDD of 24 mg
CI: abrupt discontinuation, hepatic disease
DIS: inhibitors of Cyp 1A2 (cimetidine, siprofloxacin, clarithromycin, diltiazem, enoxacin, erythromycin, fluvoxamine, mexiletine, norfloxacin, omeprazole, ritonavir and troleandomycin). Inducers (carbamazepine, phenobarbital, phenytoin, and rifampin, cigarette smoking)
24
Rotigotine (Neupro) Transdermal Patch
MOA: D1 and D2 and D3 agonist (primarily D2)
Precautions: heath, MRI, allergic-type reactions
Side effects: CNS, GI peripheral edema, application site reaction
DI: dopamine antagonists, such as antipsychotics or metoclopramide
Dosage: start at 2 mg/24hr, increase weekly by 2 mg/24hr up to 6 mg. 4 mg = minimum effective dose
25
Apomorphine (Apokyn)
Used in advanced PD for off episodes
MOA: stimulates postsynaptic D2 type receptors
2mg SC test dose under medical supervision
Pre-treat with antiemetic (3 days before, continue for 2 months and reassess) - not 5HT3 antagonists or antidopaminergic
AEs: N/V, dizziness, somnolence, chest pain/pressure, dyskinesia, falls, yawning, rhinorrhea
CI: 5HT3 antagonists (increase hypotensive effects)
DDI: QT prolonging drugs may have additive effects, dopamine antagonists may decrease effectiveness
26
Istradefylline (Nourianz)
Used for treatment of PD in combination with levodopa/carbidopa, in adult patients experiencing "off"
MOA: adenosine A2A receptor antagonist
Dose: 20 mg PO QAM; may further increase dose based on response and tolerability to a maximum dose of 40 mg once daily (adjust dose for smoking)
AEs: dyskinesia, insomnia, hallucinations, dizziness
DDIs: avoid use with strong CYP3A4 inducers
27
Non-pharmacologic PD treatments
Surgery
Physical therapy and exercise
Nutrition
Occupational therapy and fall precautions
28
Approach to psychosis in PD
1. Evaluate hypoxemia, infection, electrolyte disturbance
2. Simplify regimen - D/C meds with highest risk:benefit
*anticholinergics
*taper and D/C amantadine (abrupt withdrawal ca cause delirium)
*Selegiline
*Taper and D?C DA agonists
*Consider dec L-Dopa (end of day) and D/C COMT
3. Consider atypical antipsychotic drugs
*quetipine, clozapine, pimavanserin tartrate
29
what is MS
a chronic autoimmune disease that impairs the nerves ability to send electrical impulses. Inflammation and immune activity include T and B lymphocytes, macrophages, destructive cytokines, antibodies and complement, results in demyelination and damage to axons
30
MS symptoms
muscle weakness
blurry + double vision
unsteady gait/ balance issues
pain/ paresthesias
emotional/ cognitive disturbances
fatigue
sexual dysfunction
speech
swallowing
abnormal sensations
sensitivity to heat
bladder and bowel problems
31
MS diagnosis
At least 2 documented clinical exacerbations separated by time and space as well as 2 distinct MRI lesions separated by time and space.
32
Dissemination in time
simultaneous presence of gadolinium enhancing lesions and non-enhancing lesions or a new lesion on a follow-up MRI when compared to a previous MRI
33
Dissemination in space
distinctly different anatomical lesions on imaging occurring in areas known to be affected by MS
34
PPMS diagnosis
after one year of disease progression and if the patient meets 2 of the following criteria: DIS in the brain, DIS within the spinal cord and/or positive CSF
35
CIS diagnosis
after 1 exacerbation and 1 lesion while the clinician awaits a second exacerbation and lesion to be able to make the diagnosis of MS
36
Relapsing-remitting MS (RRMS)
most common form of MS
patients experience worsening of pre-existing symptoms or onset of new symptoms for periods of greater than 48 hours without concomitant fever, known as relapse, flare-ups, or exacerbations of MS
Contrasted by symptom free periods known as remissions
37
Secondary Progressive MS (SPMS)
A progression of RRMS
Disease course in steadily progressing
Can present with or without clear cut relapses
38
Primary Progressive MS (PPMS)
Disease course is characterized by a steady decline, without clear cut relapses
39
Progressive relapsing MS (PRMS)
Steady disease progression in addition to clear cut periods of exacerbations of MS
40
treating an acute severe MS attack
corticosteriods
methylprednisone (Solumedrol) 1g IV for 3-5 days followed by prednisone
H2 blocker/PPI for ulcer prophylaxis
Monitor blood glucose and watch for infection
Corticotropin
Acthar gel
41
Interferon beta
MOA= specific interferon-induced proteins and mechanisms by which interferon beta exerts its effects in MS have not been fully defined
Indication: relapsing forms including clinically isolated syndrome, RRMS and active SPMS
42
Avonex (interferon beta-1a)
IM injection given once weekly
Dose: 30 mcg
To decrease flu-like symptoms, may initiate once weekly dosing with 7.5 mcg IM (week 1) then increase dose in increments of 7.5 mcg IM once weekly (weeks 2-4) up to recommended dose
Pregnancy category C
43
Rebif (interferon beta-1a)
SQ injection gives 3x a week
Dose: 22 or 44 mcg (gradually titrate)
Pregnancy category C
44
Plegridy (interferon beta-1a)
SQ injection given every 14 day
Pregnancy category C
Pegylated interferon
45
Betaseron, Extavia (interferon beta-1b)
subcutaneous injection given every other day
titrate over 6 weeks
pregnancy category C
46
Interferon beta side effects
FLU LIKE SYMPTOMS
-pre-medicate before injection and following day with ibuprofen or acetaminophen
injection site rxn
depression
myalgia
arthralgia
asthenia
malaise
diaphoresis
myasthenia
abdominal pain
47
Glatiramer acetate (Copazone, Glatopa)
MOA= not fully known
SQ injection given QD
Pregnancy category B
Indication: relapsing forms including CIS, RRMS, and active SPMS
48
Glatiramer acetate side effects
INJECTION SITE RXN
transient flushing
vasodilation
chest tightness/pain
asthenia
N/V
pain
arthralgia
anxiety
palpitations
dyspnea
constriction of the throat
49
natalizumab (Tysabri)
MOA: antagonizes a4-integrin of the adhesion molecule very late activating antigen (VLA)-4 on leukocytes. inhibits a4-mediated adhesion of leukocytes to their counter-receptors. prevents the transmigration of leukocytes across the endothelium into inflamed parenchymal tissue
Humanized monoclonal antibody
IV infusion given once every 4 weeks (300mg)
Pregnancy category C
Indication: relapsing forms including CIS, RRMS and active SPMS
50
natalizumab and PML
-progressive multifocal leukoencephalopathy is sometimes a fatal viral opportunistic infection that has been observed in patients receiving natalizumab.
-activation from latent John Cunningham polyomavirus in immunocompromised patients
-TOUCH prescribing program
51
natalizumab side effects
infusion rxn
respiratory tract infection
urinary tract infection
depression
headache
fatigue
diarrhea
cholelithiasis
arthralgia
PML
52
Alemtuzumab (Lemtrada)
MOA= humanized monoclonal antibody. Targets CD52 on T and B lymphocytes, natural killer cells, macrophages and monocytes, causing long term reduction of circulating T cells
IV infusion for RRMS and SPMS, reserved for inadequate response to 2 or more medications
Premedicate with corticosteroids for the 1st 3 days of each course. Antihistamines +/ or antipyretics. administer antiviral prophylaxis beginning on the 1st day of treatment and continue for 2 months after completing alemtuzumab and CD4 count is >200mm3
53
alemtuzumab side effects
DEVELOPMENT OF AUTOIMMUNE THYROID DISORDERS
rash in 90% of pts
headache
pyrexia
fatigue
pruritis, urticaria
N/V/D
neurologic problems, paresthesia, dizziness
chills
insomnia
chest discomfort
dyspnea, nasopharyngitis
musculoskeltal pain/discomfort
dyspepsia
flushing
UTI sinusitis, URI, fungal infections
54
alemtuzumab BBW
-immune thrombocytopenia and anti-glomerular basement membrane disease
-infusion reactions. infusion under personnel and monitor for 2 hours after infusion
-malignancy- thyroid cancer, melanoma, lymphoproliferative disorders
55
alemtuzumab monitoring
CBC w diff & SCr prior then monthly until 48 months after last infusion
Urinalysis w urine cell count prior then monthly
TSH at baseline and every 3 months till 48m
ECG prior to each treatment course
No live vaccines, wait 6 weeks after VzV
Annual HPV screening
PML
skin exams
56
Ocrelizumab (Ocrevus)
Humanized monoclonal antibody
MOA: binds to CD20 on surface B cells--> depletes them from circulation. B cells make antibodies
IV infusion
Indication: PPMS*** and relapsing forms of MS, including CIS, RRMS and active SPMS
57
Ocrelizumab side effects
Infusion reaction
-more common during 1st infusion and at higher dose
urinary tract infection
upper respiratory infection
headache
nausea
58
ocrelizumab CI and precautions
CI: history of life threatening infusion reaction to ocrelizumab or formulation, active HBV infection
Warnings: hepatitis B reactivation, herpes infections
59
Ofatunumab (kesimpta)
MOA: monoclonal antibody binds to CD20 molecule resulting in potent complement dependent cell lysis and antibody dependent cell mediated toxicity in cells that overexpress CD20
*administer all live or live-attenuated vaccines at least 4 weeks prior and non-live vaccines at least 2 weeks prior to initiation of therapy
SQ injection once weekly for 3 doses, then once monthly
60
Mitoxantrone (novantrone)
MOA: intercalates with DNA strands causing breaks, and inhibits DNA repair through topoisomerase II
IV infusion given once Q3 monts
dose 12mg/m2- lifetime dose = 100 mg/m2
Pregnancy category D
Indication: SPMS, PRMS, or worsening or RRMS to reduce neurologic disability and/or frequency of relapse
*Limitation: not indicated for treatment of PPMS
61
Mitoxantrone side effects
cardiotoxicity
bone marrow suppresion
stomatitis, esophagitis, oral ulceration
N/V
alopecia
headache
fatigue
hepatic dysfunction
62
Mavenclad (cladribine, 2-chlorodeoxyadenosine)
Indication: treatment of relapsing forms of multiple sclerosis (RRMS) and active SPMS in adults who have inadequate response or are intolerant to other therapies for MS
*not recommended for patients with CIS
MOA: purine nucleoside analogue.--> depletion of lymphocytes
63
mavenclad (cladribine, 2-chlorodeoxyadenosine) boxed warning
malignancies
teratogenicity
64
mavenclad (cladribine, 2-chlorodeoxyadenosine) side effects
headache
nausea
lymphocytopenia
bone marrow depression
decreased Hg
thrombocytopenia
hypersensitivity reaction
infection
URI
fever
65
mavenclad monitoring
1. CBC including lymphocyte count (before each treatment course, 2 + 6 months after the start of each yearly course) and periodically after treatment
2. evaluate HIV, tuberculosis, hepatitis B, hepatitis C status (prior)
3. VZV antibody status (prior)
4.pregnancy test
5. liver function tests
6. MRI at baseline, PML- obtain brain MRI scan
7. standard cancer screening
8. signs or symptoms of acute infection
66
Fingolimod (gilenya)
MOA= acts on S1P receptors S1P1 and S1P3-5 on the surface of lymphocytes
-depletes CD4 CD8 and T lymphocytes in blood stream
-inhibits lymphocyte release from lymphatic organs decreasing overall numbers in circulation
indication: relapsing forms of multiple sclerosis, including CIS, RRMS, and active SPMS, in patients >10yo
67
fingolimod first dose monitoring
ECG needed prior
Monitor for 6 hrs post 1st dose for bradycardia
-continue if bpm <45 post 6 hr
repeat monitoring if patient misses 1 dose in 2 weeks, 7 days in 3rd/4th weeks, or 14 days after a month
higher risk: proonged QTc, drugs w torsades
CI*: recent MI, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, Class III or Class IV heart failure, history of mobitz type II secod or third degree AV block or sick sinus syndrome, baseline QTc > 500msec, concurrent Class Ia or Class II anti-arryhtmic drugs
68
fingolimod side effects
headache
lymphopenia, leukopenia
upper respiratory tract infection, cough sinusitis, nasopharyngitis
macular edema
increase in BP, hypertension
elevation in LFTs
abdominal pain, back pain, pain in extremities
diarrhea
69
mayzent/ siponimod
treatment of relapsing forms including CIS, RRMS, and active SPMS
MOA; S1p receptor modulator --> decrease in lymphocytes available to the CNS --> reduce central inflammation
70
mayzent/ siponimod genotypes
CYP1C9
*1/*1, *1/*2,*2/*2- typical dosing
*1/*3 or *2/*3- reduced dosing
*3/*3- CI
71
REM sleep
rapid eye movement
-paradoxical sleep
-brain active, muscles paralyzed
-controlled by cholinergic cells in the mesencephalic, medullary and pontine gigantocellular areas
72
NREM sleep
non-rapid eye movement
3 stages
dreaming is rare
muscles are not paralyzed
controlled by the basal forebrain, lower brain stem to the thalamus and hypothalamus
73
signs and symptoms of sleep disorders
EDS (excessive daytime sleepiness)
impaired daytime functioning
irregular breathing
increased movement during sleep
irregular sleep and wake cycle
difficulty falling asleep
74
common types of sleep disorders
insomnia
sleep apnea
narcolepsy
circadian rhythm disorders
parasomnia
restless leg syndrome
75
Insomnia
most common
difficulty falling, maintaining or nonrestorative sleep
transient= several days
short term= less than 3 months
chronic = at least 3 nights per week for 3 months
76
Risk factors for chronic insomnia
psychiatric conditions- depression, anxiety, substance use disorders, PTSD
medical conditions- COPD, asthma, rheumatologic, cardiovascular, hyperthyroidism, nocturia, GERD, diabetes, cancer, pregnancy, menopause
neurological conditions- neurodegenerative diseases, neuromuscular disorders, brain tumors, headache syndromes,
77
Drugs that can worsen insomnia ***
alcohol, caffeine, nicotine
anticholinergics
SSRIs/SNRIs
alpha blockers
beta blockers
ACEi and ARBs
cholinesterase inhibitors
bronchodilators
CNS stimulants
corticosteroids
decongestants
diuretics
H2RAs
statins
opioids
78
treatment of transient and short term insomnia
Goal: correct underlying sleep complaint, avoid adverse effects of medications
identify stressors and start good sleep hygiene
short term use of medication (patient dependent)
79
sleep hygiene
regular sleep schedule
avoid napping
establish calm bedroom
dont spend awake time in bed
limit intake of nicotine, caffeine and alcohol
exercise regularly, not close to bedtime
avoid large meal close to bedtime
avoid watching the clock
80
treatment of long-term insomnia
cognitive behavior therapy +/- medications
-better than medications alone
81
Benzodiazepine Receptor agonists (BZDRAs)
agonist effects on GABA receptors
caution for complex sleep behaviors
always take before bedtime
caution in elderly
drowsiness, dizziness, confusion, risk of falls
avoid use with alcohol, opioids
withdrawal symptoms upon abrupt discontinuations- tremors, muscle cramps, seizures
82
Benzodiazepines (BZDs)
reduce sleep latency
increase stage 2 sleep and decrease delta sleep
anxiolytic effect
caution in patients with sleep apnea or substance abuse
avoid alcohol and CNS depressant
side effects are dose dependent
83
Nonbenzodiazepine GABAa agonists
"z" drugs
more selective
increase total sleep time
less disruptive of sleep stages
generally have less withdrawal, tolerance, and rebound insomnia
associated with parasomnic episodes with amnesia
84
benzodiazepines boxed warnings
1. Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death
2. Use of benzodiazepines exposes user to risks of abuse
3. Continued use may lead to clinically significant physical dependence
85
Z drugs boxed warning
complex sleep behaviors (sleep walking, driving, other activities)
*****discontinue IMMEDIATELY
86
BZD beers list
avoid in elderly
87
Z drugs beers lists
avoid in elderly
88
eszopiclone (lunesta)
CIV
Z drug
rapid absorption- delayed onset if taken w food
approved for sleep onset or sleep maintenance insomnia
DOA: 6-9hr
can use up to 6 months
Major CYP3A4 substrate
-monitor w inhibitors
89
zaleplon (sonata)
CIV
z drug
ultra short acting, rapid onset
- avoid taking w high fat meal
short term treatment of insomnia (up to 30 days)
-good for sleep onset not maintenance
duration 3-4hr
Major CYP3A4 substrat
-interaction w induces -cimetidine, rifampin
90
zolpidem
CIV
Z drug
rapid onset, short half life
avoid in severe hepatic impairment
different formulations dosing and indications
91
Intermezzo (SL zolpidem tab)
for middle of the night awakening; take if more than 4 hours remain before waking
1.7mg females, 3.5 males
92
Edular (SL zolpidem tab)
sleep onset, maintenance off label
take immediately before bed w 7-8 hours of planned sleep
93
ambien CR (ER zolpidem tab)
sleep onset or maintenance
take immediately before bedtime w 7-8 hrs before waking
94
ambien (IR zolpidem tab)
sleep onset, off label maintenance
take before bed w 7-8 hrs before waking
95
generic zolpidem capsule
sleep onset, off label for maintenance
if 5 mg of another zolpidem IR product is not effective, may increase dose to 7.5 mg
96
DORAs
CIV
turns off wake signaling, assists in getting to sleep and maintaining sleep
approved for sleep onset or sleep maintenance insomnia
interactions with CYP3A4 inhibitors/induces
take at bed time w at least 7 hr before waking
CI in narcolepsy
97
suvorexant (belsomra)
DORA
onset <30minns
T1/2=12 hrs
interactions w CYP3A4 inh/ind
-decrease dose w moderate inh, not recommended w strong inh
side effects: sleep paralysis, abnormal dreams
98
lemborexant (dayvigo)
DORA
onset <30m
t1/2=17-19h
interactons w CYP3A4 inh/ind
*next day drowsiness and increased risk of falling
side effects: complex sleep behaviors, abnormal dreams
99
daridorexant (quviviq)
DORA
onset <30 m
T1/2= 8 hr
CYP3A4 interactions
onset may be delayed if taken w food
side effects: complex sleep behaviors, hallucinations, sleep paralysis
100
Ramelteon (rozerem)
melatonin receptor agonist, selective for MT1 and MT2 (MT1>)
MT1= induces sleepiness
MT2= regulates circadian rhythm
take at bedtime to induce sleep
onset 30 mins
t1/2=1-2.6 hr
approved for treatment of sleep onset insomnia and for long term use
not as effective in patients who have already been treated w a BZDRA
CI w fluvoxamine (CYP1A2 inhibitor)
101
doxepin
TCA
3-6mg/day for insomnia (lower than depression)
indicated for sleep maintenance
do not take within 3 hours of a meal
102
melatonin
not approved by FDA
beneficial effects on sleep-onset latency, shift workers, and jet lag
should be avoided in patients with autoimmune conditions
not recommended for use in pts w alzheimers
103
first generation antihistamines
avoid in older adults
tolerance to sedative effects develops quickly
anticholinergic side effects
104
trazodone
may improve sleep continuity; off label use
boxed warning: suicidal thoughts and behaviors
may be useful in patients with a history of substance abuse and/or depression
side effects: carryover sedation and alpha adrenergic blockade - orthostasis can result be careful in elderly
when discontinuing, gradually taper dose over 2-4 wks
105
elderly insomnia options
*Ramelteon
*low dose doxepin
eszopiclone
zolpidem
106
pregnancy insomnia options
non pharm -1st line
diphenhydramine
low-dose doxepin
107
sleep apnea
repeated episodes of cessation of breathing during sleep, followed by blood oxygen desaturation and arousal from sleep to restart breathing
108
types of sleep apnea
diagnosed using polysomnography
central- impairment of respiratory drive
obstructive- upper airway collapse and obstruction
mixed- both
109
obstructive sleep apnea treatment
behavior modification (weight loss, altered sleep position, avoidance of alcohol and sedatives)
standard is positive airway pressure during sleep
avoid CNS depressants and drugs that cause weight gain
medication for excessive daytime sleepiness
-modafinil, armodafinil, solriamfetol, pitolisant
110
alcohol and CNS depressants in OSA
alcohol
-avoid or reduce alcohol within 2-4hr prior to sleep
-can exacerbate OSA, worsening sleepiness, promote weight gain
other CNS depressants
-may exacerbate OSA and worsen daytime sleepiness
-use extreme caution with opioid medications
111
Modafinil and armodafinil
for excessive daytime sleepiness in OSA
CIV
administer in the morning
avoid use in pregnancy
may decrease effectiveness of contraceptives (CYP3A4 inducers)
use with caution in patients w cardiovascular disease
-use is not recommended in patients with a history of left ventricular hypertrophy
AEs: headache
SJS, TEN, DRESS have been reported
Warnigs: mania + exacerbation of psychotic or manic symptoms, CV events, chest pain, HTN, palpitations, tachycardia
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Solriamfetol (sunosi)
for excessive daytime sleepiness in OSA
CIV
MOA: dopamine and norepinephrine reuptake inhibitor
administer once daily upon awakening
-avoid administration within 9 hours of planned bedtime
CI w MAOI ( do not use within 14 days)
Avoid use in patients with unstable CV disease, arrhythmias
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Pitolisant (wakix)
off label for excessive day time sleepiness in OSA
*not a controlled substance
MOA: antagonist/ inverse agonist at histamine-3 receptors
CI in severe hepatic impairment
may prolong QT (avoid use in patients with known arrhythmias)
AE; headache
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Narcolepsy
impairment of both onset and offset of REM and NREM
patho: loss of normal function of hypocretin-orexin neurotransmitter system
2 types:
1= narcolepsy with cataplexy (muscle weakness)
2=narcolepsy without cataplexy
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narcolepsy treatment
non pharm: good sleep hygiene and scheduled daytime naps
avoid drugs that can worsen daytime sleepiness
Pharm:
Goal= achieve normal alertness during conventional waking hours or to maximize alertness at important times of the day
-no disease modifying therapies available to date
-treat symptoms: EDS, cataplexy and REM sleep abnormalities
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Sodium oxybate (xyrem)
CIII
approved for treatment of cataplexy or excessive daytime sleepiness in adults with narcolepsy
BBW:
1. CNS depression
2. abuse/misuse
3. restricted access (REMS)
admin on empty stomach (>2hr after eating)
admin while pt is in bed, pt should lie down immediately after and remain in bed- 2nd dose 2.5-4 hrs later
MOA: CNS depressant
no hazardous activities requiring mental alertness or motor coordination for at least 6 hrs
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sodium oxybate ER suspension (lumryz)
admin on empty stomach, in bed, remain in bed
suspend dose in 1/3 cup of water - admin within 30 mins of mixing
taken as single dose at bedtime
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oxybate salts (xywav)
not just sodium- contains calcium, magnesium, potassium, and sodium
otherwise similar to xyrem form of sodium oxybate
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medications for cateplexy in narcolepsy
REM-suppressing drugs
-venlafaxine, fluoxetine, duloxetine, clomipramine
--abrupt withdrawal from these antidepressants can trigger status cataplecticus (severe nearly continuous rebound cataplexy that can last several hours.
*Pitolisant
*sodium oxybate
*treat both EDS and cataplexy
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circadian rhythm disorders
abnormalities in sleep wake pattern
may present as insomnia and/or EDS
Different types
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Jet lag disorder
non pharm approaches:
-napping
-timed light exposure
pharmacologic options
-melatonin
-ramelteoon
-z drugs, benzos (risk for next day drowsiness)
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shift work disorder
difficulty with sleep or wakefulness at times that are imposed by shifts running counter to the light-dark cycle
NON-pharm:
sleep hygiene, napping, sleep schedule, exposure to bright lights at night and darkness during the day, CBT-I
PHARM:
melatonin
ramelteon
suvorexant
Z-drugs benzos
modafinil and armodafinil
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restless leg syndrome
paresthesias felt deep in the calf muscles, thighs, and arms with an urge to keep limbs in motion; often bilateral - temporarily relieved by movement
associated with CKD, iron deficiency, vitamin B or folate deficiency, pregnancy, peripheral neuropathies
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rule out/ treat possible causes of RLS
nutrition: iron deficiency, vitamin B or folate deficiency, reduce caffeine and alcohol use, weight loss
smoking cessation
regular moderate exercise
sleep
withdrawal of centrally acting antihistamines, antidepressants (not buproprion), antipsychotics, anti nausea that blocks dopamine
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intermittent RLS symptoms
carbidopa-levodopa
BZDRA- clonazepam (caution carryover sedation)
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chronic and persistent RLS symptoms
Alpha 2 delta calcium channel ligands: pregabalin, gabapentin
Dopamine agonists: immediate release pramipexole, ropinirole, rotigotine
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