NEUROLOGY 2: PAIN, HEADACHE & MIGRAINES. DRUG WITHDRAWAL, CANNABIS Flashcards
describe difference between difference types of headache
- tension type headache ( TTH)
cluster headache
migrane
see pic
headache that is associated with GI symptoms ( nausea) and/or light sensivitiy
migrane
headache that last 4-74 hours
migrane
headache that is not worsen by activity
TTH
when to refer patient with headache
thunderclap onset progressive severity or increased frequency systemic illness/ fever acute glaucoma stiff neck. focal signs, reduced LOC child or elderly temporal arteritis
what is medication over use headache
headache with use of simple analgesics >15 days/ month
or opioids, triptans, analgeic-opioid combo >10 days/ month
drugs associated with intracranial HTN leading to HA
tamoxifen
tetracycline
isotretinoin
first line for TTH
NSAID
( celecoxib - COX2 selective, high risk CV, less GI risk
prophylaxis in TTH
1st: amitriptyline, nortriptyline ( 10-100mg/day)
2nd: mirtazapine ( 30 mg/day)
venlafaxine (150mg /day)
cautions for triptans
caution when used with serotonergic drugs ( due to increased serotonin syndromes)
- drugs inducing or inhibiting enzymes
- do not use in patient with cardiac like symptoms
- do not use triptan within 24 hrs of another triptan
how often can we use triptan
<10 days/ month to avoid medication over use headaches
do not use a triptan within 24 hrs of another triptan
**second dose of triptan unlikely to be effective if 1std dose provided no relief within 2 hrs
CI for triptan
heart disease, uncontrolled HTN, pregnancy, bisilar or hemiplegic migraine
AE of triptans
chest discomfort, fatigue, dizziness, paresthesias, drowsiness, nausea, throat symptoms.
MOA of triptans
All act on serotonin (5-HT) receptors found on blood vessels and neurons to inhibit the release of vasoactive neuropeptides and cause vasoconstriction of the pain-sensitive blood vessels
ERGOT derivatives contraindication
CVD, PVD, sepsis, liver/kidney disease, pregnancy, and patient taking potent inhibitors of CYP3A4
prophylaxis for migraine
beta blocker ( 1st line) propranolol ( best studies), metropolol, nadolol and atenolol ( fewer CNS SE)
TCA: amitriptyline, nortriptyline ( consider if depression, insomnia or TTH)
venlafaxine
candesartan
valproic/ divalproex, topiramate ( if overweight)
lithium
fovastriptan ( menstrually associate migraine)
migriane and pregnancy
non pharm 1st choice
acetaminophen NSAID ( avoid if possible, especially in 3rd trimester)
prophylaxis: propanolol
**no triptan and especially ergot, and topiramate
migraine and breastfeeding
acetaminophen
ibuprofen if NSAID preferred
sumatriptan
prophylaxis: propanolol, magnesium citrate
**avoid ergot, barbiturates and opioids
which triptan is useful for preventing menstrual migraine
Frovatriptan, naratriptan and zolmitriptan
cox 1 and cox 2 inhibition
Cox 1: anti platelets effects
Cox 2: analgesic, anti-inflammatory and antipyretic effects
COX 2: celecoxib, diclofenac *( increased affinity for COX 2 but retain cox-1 acitivity)
which NSAID has highest CV risk among the semi/non-selective agents
diclofenac PO
CI of NSAID
< 18 Y/O with chicken pox, influenza, or flu like symptoms ( risk of reye syndrome)
- hypersensitivity
- 3rd trimester of pregnancy
- active peptic/ulcer, IBD
- severe renal impairment
- severe uncontrolled heart failure
BARS: bleeding, asthma, renal , stomach
- known hyperkalemia
-
which NSAID cannot be used in breast feeding
-celecoxib, diclo, indomethacin,
AE of opioids
- sedation, N/V, constipation
- respiratory and CNS depression
- pruitis if natural opioids ( morphine)
AE of gabapentin, pregabalin
sedation, weight gain, dizziness, peripheral edema
what is bell palsy
unilateral weakness of facial paralysis usually linked to a viral infection
risk factors of bell palsy
diabetes, hypertension, URTI, obesity, pregnant women ( 3rd trimester), pre-eclampsia
treatment for bell palsy
corticosteroid ( pred 60mg x 5 days, then taper over another 5 days for a total of at least 450 mg)
ARV+ corticosteroid in patient with severe paralysis or immunocompromised
ARV alone is not recommend
AE corticosteroids
hyperglycaemia, GI upset, mood swings, hypocalcemia, hypokalemia, sodium and fluid retention
what is guillain barre syndrome ( GBS)
autoimmune
body’s immune system attacks the nervous system often preceded by an infection causing weakness and paralysis of the limbs
bells palsy in children
steroid is not recommend there is no demonstrated benefit from corticosteroid
treatment for GBS
plasma exchange and immunoglobulin
when should we administer immunization after GBS
withheld for one year
difference between CB1 and CB2
CB1 :
abundant in CNS, involved in hemostasis, motor control, cognition, emotional responses, motivation
CB2: immune systems and blood cells, involved in an immune and inflammation response
difference b/w THC and CBD
`THC: psychoactive effects, partial agonist at CB1 and CB2 receptors, releases dopamine in the brain
CBD: no binding to CB1 or CB2
produces physical effects
anti-inflammatory, analgesic, anti-emetic, anti- epileptic properties
evidence on cannabis are on the following medical conditions
pain: refractory neuropathic pain or refractory palliative cancer pain
N/V: refractory CINV
SPASTICITY: refractory spasticity in MS and SCI
what are the cannabis act
possess up to 30g of legal cannabis ( DRIED or equivalent in non-dried form)
share up to 30G with other adults
4 cannabis plant per residence for personal use
cannabis dosing
0.5-1g/ day starting and average dose of 1-3 g/ day
no evidence based dosing recommendations at this tie
2 cannabis product are available in canada
nabilone and tetranabinex/nabidiolex
what is the indication for nabilone
severe N/V from cancer chemotherapy
indication for sativex
adjunctive relief of advanced cancer pain and MS pain
does nabilone contain CBD
yes 1mg= 10 mg THC
cannabis AE
CNS: psychosis, hallucinations
CV: tachycardia, arrhthymias
GI: decreased gastric motility
reproduction: anti-androgenic effects, decreased sperm count and motility
cannabis drug interactions
significant with CNS depressants
metabolized b CYP3A4 and CYP2C9
induces CYP1A2
are stimulants recommend for chronic fatigue syndrome?
no
when should muscle spasticity be treated
should not always be treated as it can worse a patient gait and movement. treat only when it causes pain and interferes with the daily function
treatment for generalized spasticity
baclofen ( first line)
tizanidine ( second line in combo with baclofen)
Gabapentin ( not canada approve indication) but useful if there is neuropathic pain
BZD: helpful for treating nighttime spasms
Cannabinoids: beneficial add on- improves neuropathic pain, sleep disturbance and spasticity
treatment for focal spasticity
phenol injections ( repeated q6months) onabotulinumtoxin A ( botox) - q 3months
clinical presentation of moderate-severe drug withdrawal syndromes
seizures, hallucinations, delirium tremens ( DT)- mortality 5%
supportive care for AWS
IV fluids
replenish electrolytes
nutritional supplementation
why is thiamine and glucose given in AWS supportive care
prevents wernicke’s encephalopathy
first line pharmacotherapy for AWS
BZD- preventing seizures, hallucinations, agitation, tremors, autonomic hyperactivity
**dosing via CIWA-AR score
when is intermediate acting and long acting BZD appropriate?
intermediate: Lorazepam, oxazepam
more suitable for elderly and liver dysfunction
Long acting BZD: less risk of rebound effects or withdrawal seizure, useful in high risk patient with prolong symptoms
chlordiazepoxide, diazepam
score for alcohol withdrawal and opiate withdrawal
CIWA-AR ( alcohol)
COWS ( clinical opiate withdrawal scale)
how long after opiate cessation will you start to feel symptoms of withdrawal
short acting ( heroine)- 8-24 hours of last dose long acting opioids ( methadone) 12-48 hours after last dose
first line therapy for opiate withdrawal
Buprenorphine/naloxone ( Suboxone)- for detoxication and maintenance
safer than methadone ( lower risk of respiratory depression) but can precipitate opioid withdrawal symptoms
2nd line for OW
methadone- long acting 24-36 hrs
agent used to decreased sympathetic activity of withdrawal
clonidine ( blunts autonomic withdrawal symptoms ( sweating, abdominal craps, chills, anxiety, insomnia and tremor)
AE of clonidine
sedation, dry mouth, orthostatic hypotension**
how long after BZD cessation will you start to feel symptoms of withdrawal
short acting: after 12-24 hrs of last dose
long acting: 5 days ( peak 1-9 days of the last dose
score to assess withdrawal severity for BZD
CIWA-BENZO
therapeutic approach in BZD withdrawal
titrate to effect with long acting BZD, then taper over a few months
therapeutic approach to stimulant withdrawal
no approved medication
? potential methylphenidate may be used as maintenance therapy
what is MS and explain the pathophysiology
chronic neurologic disease in which the body’s immune system damages its own nerve cells (myelin destruction) and connections b/w the brain and spinal cord
clinical presentation of MS
numbness, weakness, fatigue, cognitive difficulties, ataxia, optic neuritis, bowel/bladder abnormalities and neuropathic pain.
which environmental factor are associated with increased risk of MS
deficiency of Vitamin d ( especially in pregnancy or in neonates)
initial presentation of MS
80% of patient present with clinically isolated syndrome
ypically presents as unilateral optic neuritis, partial myelopathy or focal syndromes
list 4 subtypes of MS
clinically isolated syndrome ( CIS) relapsing- remitting MS ( RRMS) secondary progressive MS (SPMS) primary progressive MS ( PPMS) Progressive relapsing (PRMS)
what is PPMS (primary progressive MS), how it is different from secondary progressive MS
primary: 10-15% onset, neurologic disability that steadily worsens from disease onset , no distinct period of remission or relapse
SPMS- progressive that follows after RRMS
symptoms slowly worsen with viable remission and relapses
is there a cure for MS, what is the role of DMT ( disease- modifying therapies)
no
reduce relapse rate in RRMS ( relapsing- remitting)
no role/ no impact on PPMS or SPMS unless patient have a progressive disease with frequent relapses
first line DMTs for MS
interferon beta: standard first line, reduces relapses rate and # of size of MRI detectable lesions , reduce conversion
glatiramer actate: reduces relapse rates ( does NOT prevent disease progression) and reduces MRI detectable lesion
Dimethyl fumurate: activates nuclear factor like 2 pathway, reduces the # and rate of relapses
teriflunomide: reduces B and T cells; reduces relapses rate and disease progression teratogenenity
2nd line DMT for MS
High efficacy therapy: more efficacious than first line but increase toxicity: “early intensive therapy “
ocrelizumab: approved for PPMS and arms
alemtuzumab life-threatening and fatal cases of autoimmune hepatitis, hemophagocytic lymphohistiocytosis and cardiovascular reaction
cladribine- higher grade lymphopenia, which is linked to herpes zoster infection.
fingolimod - skin cancer, variella zoster infection, macular weeks
Siponimod: active SPMS only
natalizumab- case of PML
which drug can be used to reduce length and severity of acute relapses in MS
high dose methylprednisolone 1G IV daily for 3-5 days (short term) followed by oral prednisone for a few days
** this regimen does not have an effect on the disease course**
what is the time to effect for interferon beta?
3 months
drug use increases what in the brain
dopamine- responsible for feelings of pleasure or euphoric effects
- reinforces our behaviour to report pleasurable activities
list drugs that are consider stimulants
cocaine, amphetamine, methamphetamine, methylphenidate, nicotine, caffeine
1st and 2nd line treatment of OUD?
1: suboxone
2: methadone
normal dose of suboxone
2-24 mg/ day once daily or alternate day dosing
AE of suboxone
headache, decreased libido, constipation, sweating
what is the role of naloxone in combo with buprenorphine?
to deter crushing and injecting subxone
what is sublocade and when can it be administered?
sublocade is buprenorphine extended release SC injection ( once-monthly)
patient must be stabilized on subocone for at least 7 days and must be between 8-24 mg
** starting dose is 300mg monthly x 2 months then MD 100mg x monthly
when is buprenorphine subdermal implant indicated?
delivers buprenorphine continuously for 6 months
indicated for patient clinically stabilized on 8mg or less of trans mucosal buprenorphine per day
And stabilized on SL for 3 months prior to starting
MOA of suboxone and methadone
buprenorphine: partial mu opioid agonist and weak kappa antagonist, naloxone is opioid antagonist
methadone: full opioid agonist
AE of methadone
QT prolongation, sedation, sexual dysfunction, constipation
advantages and disadvantages of suboxone and methadone
suboxone: less risk of overdose ( ceiling effect), shorter time to achieve therapeutic dose, fewer drug interactions
Dis: suboptimal for individuals with high opioid tolerant
methadone: better treatment retention, no max dose ( high opioid tolerance patient), easier to initiate treatment
Dis: many drug interactions, higher risk of QT prolongation, higher risk of overdose
how handle missed methadone dose:
missed 1-2 days, 3 days, 4 or more
**how to deal with emesis
1-2: give as usual
3 days, need to be assessed by MD, do not provide dose until seen by MD
4 or more: major loss of tolerance, see MD and may restart on low initial doses
emesis: not replace unless observed by pharmacy staff
<15 mins: replaced
>15 mins: not replaced
what is used for opioid overdose
naloxone ( duh!)
when can u repeat naloxone dose?
3 mins if first dose does not work
OUD in pregnancy and breastfeeding, what can be used?
preg: ??methadone ( risk/benefit must be evaluated), buprenorphine ( safe)
beastfeeding: methadones and buprenorphine safe
does naloxone reverse overdose cause by BZD, stimulants and alcohol?
NO, opioids only
1st line treatment for alcohol use disorder?
acamprosate: glutamate antagonist- indicated in patient with hepatic insufficiency, cannot used in severe renal impairment, reduce dose between 30-50 ml/min
naltrexone: opioid antagonist - decreased euphoria and cravings related to drinking alcohol. cautions in patient with hepatic dysfunction
when can you start acamprosate and naltrexone
acamprostate: >/ 4 days of alcohol abstinence
naltrexone: opioid free for >/ 7 days prior to initiation
2nd line for AUD?
disulfiram: causes a disulfiram reaction within 12-24 hours of drinking - aversive therapy
topiramate, gabapentin
which MS drug cannot be used in pregnancy
teriflunomide
which MS drug have interaction with warfarin
Teriflunomide ( decreases INR)
which MS medication can cause blue-green discolouration of the urine
mitoxantrone
important counselling points for dimethyl fumarate
avoid live vaccines such as measles, mumps and varicella
what is consider chronic pain
pain lasting >3-6 months
nociceptive pain is separated into what
somatic pain ( skin, bone, joint, muscle or connective tissue), visceral pain ( in the internal organs)
place in therapy for duloxetine in pain
1st line peripheral diabetic neuropathy and fibromyalgia
place in therapy for opioids
3rd line for severe nociceptive pain or Neuropathatic ( adjunctive)
if GI risk is the primary concern, use what NSAID
if CV risk is the primary concern?
GI risk: celecoxib+ PPI
CV risk: naproxen +PPI
which opioid is effective for neuropathic pain
tramadol
what is the opioid dose for breakthrough pain
about 10% of total daly dose and order q1h prn
opioid drug interactions
Serotonin drugs, respiratory depressant ( BZD, alcohol) CNS depressant
know morphine equivalence conversion
see pic
what is the difference between adaptive vs maladaptive pain?
nociceptive and inflammatory pain is adaptive. Maladaptive becomes disengaged from noxious stimuli or healing and is chronic. EX: IBS, fibromyalgia
what is an adequate trial of gabapentin
2 months
which TCA have the most potent anticholinergic effectst
amitriptyline, desipramine has the least
which opioids should be avoided in chronic kidney disease
morphine, codeine and meperidine
HM, fentanyl, methadone and buprenorphine can be used
max dose of MEQ daily
90 mg
which opioids reduce seizure threshold
tramadol
methadone should not be titrated more than?
5-7 dyas
which agent have a canada approved indication for chronic migraine?
Botulinum toxic
what is the official indication for propranolol in migraine
episodic migraine prophylaxis
what is the official indication for propranolol in migraine
episodic migraine prophylaxis
is codeine recommended for patient <12 years old?
NO
clinical pearls for tramadol
1) related to morphine and codeine
2) has less abuse potential than opioids
3) 2 postulated MOA
Tramadol’s metabolism is variable and unpredictable.
Toxic effects include seizures and serotonin syndrome.
what is the recommended dose of naloxone iV
0.4 to 2 mg IV every 2-3 mins.
what opioid has significant life threatening interaction with MAOI
meperidine
what is the dose recommendation for morphine in a child?
0.01 to 0.05mg/kg/hour
how often can topical diclofenac be applied
QID for effectiveness
what is the approach with chronic non cancer pain with active substance use disorder?
Opiates is not recommend. sing acetaminophen and an NSAID is a start, however this patient needs to be reassessed since it may not be enough for pai
what is the recommended tapering regimen for opioids
the rate of taper can vary from 10% of the total daily dose every day, to 10% of the total daily dose every 1-2 weeks. Slower tapers are recommended for patients who are anxious about tapering, may be psychologically dependent on opioids, have co-morbid cardio-respiratory conditions, or express a preference for a slow taper. Once one-third of the original dose is reached, slow the taper to one-half or less of the previous rate
if one opioids such as morphine did not relieve back, would switching to another opioid such as HM help?
there is no evidence for switching to opioid will relieve pain
why is naloxone not given orally for overdose?
Although absorbed readily from the GI tract, naloxone is almost completely metabolized by the liver before reaching the systemic circulation and thus must be administered parenterally.
Which MS drug with highest PML
Natalizumab
