Week 1: Alcoholism, Sub Abuse, Epilepsy Flashcards
Alcoholism
A chronic disease that when active results in compulsive, out of control use of alcohol with negative consequences
DSM 5 Criteria for Alcohol Use Disorder
- More than once wanted to cut down or stop drinking, or tried to , but couldn’t
- spent a lot of time drinking? or being sick or getting over other after affects?
- wanted a drink so badly you couldn’t think of anything else?
- found that drinking or being sick from drinking often interfered with taking care of home family, or caused job or school troubles
5.continued to drink even though it was causing troubles with your family and friends
- given up or cut back on activities that were important to you or pleasurable in order to drink
- more than once gotten into situations whole or after drinking that increased your chances of injury
8.continued to drink even though it was making you feel depressed or anxious or adding to another health problem, or having had a memory black out
- had to drink much more than you once did to get the effect you want
10.foun d that when the effects of alcohol were wearing off, you had withdrawal symptoms
DSM5 Alcohol Use Disorder Severity Criteria
a. considered AUD if..
b. Mild:
c: Moderate:
d. Severe
a. the presence of at least 2 of symptom criteria indicated AUD
b. mild: presence of 2-3 symptoms
c. Moderate: the presence of 4-5 symptoms
d. Severe: presence of 6 or more symptoms
Type I Alcoholism
develops gradually over the life span
*equally prevalent in men and women.
*less severe in health consequences
Type II alcoholism
an early on set
more prevalent in men and more severe in its health consequences0
Lab tests that are helpful in Alcoholism dx
MCV (mean corpucle volume) elevation
high levels of liver transaminases (AST, ALT
high levels of uric acid, triglycerides
ethyl glucuronide or ethyl sulfate
effects of etoh @ diff BAC
legal limit: 0.08%
0.13-0.15: gross motor impairment and lack of physical control. blurred vision and major loss of balance. euphoria reduced and dysphoria beginning to appear
0.16-0.20%- dysphoria: NV, sloppy drunk
0.25% needs assistance walk, total mental confusion. dysphoria w. some mental confusion
0.30: loss of conciousness
> /=0.40: onse of coma, possible death
Pharmacodynamics of Alcohol
Alcohol is a cns DEPRESSENT
*Acute: Stimulates GABA(inhibitory neurotransmitter )system
CHRONICALLY: downregulation of inhibitory receptors, so abrupt withdrawal causes less effective inhibitory neaurotransmitters.
*Acute: inhibits NMDA Glutamate (stimulatory) neurotransmitter system
chronically: upregulates stimuatory neurotransmitters so abrupt withdrawal causes more effective stimulation
*activates opioid peptide system: reinforces craving and rewarding effects: contributes to addiction
*also increase dopamine release which is a reqrding system as well
Basic etoh PK
lipid soluble
zero order metabolis(capacity limited)
Absorption:
25% absoprbed in sotmach
75% from small intestine
lipid and protein delay absorption
*can be effected by
Distribution:
Vd=approx total body water
decreasing Vd from men->-women->to obese
Metabolism: Zero order metabolism via alcohol dehydrogenase
ETOH->acetylaldehyde->Acetyl coA–>co2+7ckal/gram+H2O
gender pk differences of ETOH
MEN: MORE WATER, MORE VD
WOMEN: LESS WATER, AND less efficient prehepatic alcohol dehydrogenase
Organ system effected by chronic excessive alcohol use
cns:
*Addiction
*Wernicke-Korsakoff Syndrome
*Cortical atrophy/dementia
hepatic/Pancreatic:
*Steatosis, or fatty liver
alcohol hepatitis
cirrhosis
pancreatitis
wernicke-Korsakoff syndrome
Wernicke encephalopathy
cause:
SS:
action:
SS: confusion
loss of musce coordination ataxia
Leg tremor
vision changes
nystagmus
dyplopia
eyelid drooping
Acute neurologic condition that occurs due to severe actue deficieny of thiamine. due to poor oral intake
action: admin thiamine to anyone suspected of having etoh withdrawal. do not give glucose before thiamine b/c glucose can aexhaust thiamine supply and worsen confusion
REVERSIBLE
wernicke-Korsakoff syndrome
Korsakoff syndrome
cause:
SS:
SS: antregrade amnesia
severe loss of memory
confabulation
hallucinations
results from long standing wernickers
IRREVERSIBLE
Alcohol withdrawal
whendoes-it-occur
howserioous-is-it
how-to-prevent
very serious med complication. lif threatening
can occur in ppl drinking excessively from weeks to months
NEVER TELL PTS with hx alcohol abuse to simply stop
management can be outpt but often require in pt withdrawal management
Patho of Alcohol Withdrawal
Chronic stimulation of GABA inhibitory rceptors downregulate effective gaba receptors, so abrupt withdrawal prevents proper inhibition
chronic INHIBITION OF NMDA stimulatory receptors upregulates stimulatory receptors. causing more effective stimulatory receptors during abrupt etoh withdrawal
alcohol withdrawal presentation
minor withdrawal 5-10 hrs
*autonimic hyperactivity, tremulousness, hyperhydrosis, tachycardia, htn, GI upset, anxiety, insomina, and vivid dreams
Major withdrawal: (12-72 hrs)
*hallucinations (usually sensory, not auditory or visual)
seizures
Delerium tremons (medical emergency)-48-96 hours
*dirordered conciousness (auditory and visual hallucinations)
*Life threatening state
*hallucinations
*disorienatation
*tachycardia
*HTN
Low grade fever
agitation
diaphoresis
*elevated cardiac indices
*hyperventilation and respiratory alkalosis
*sensorium clouding
Delerium Tremens
who is mortality risk greater for
eldery
concamitant copd
cor ebody temp>104
co existing liver dx
death usually due to arrhythmia or seocndary complications (pnemonia, heart failure
Management/ Prophylaxis of ETOH withdrawal
thiamine 50-100 mg daily
0.45 NS and D5W (D5W only after thiamine administration)
Multivitamins
standing orders for
*clonidine
benzos
*note some institutions may use CIWA-Ar Scale (Clinical institute withdrawal assessment of alcohol scale
Management of etoh wihdrawal
monitoring
monitor p q4-8hrs by means if ciwa-aR SCAle until score is <8-10 for 24hrs
pts with ciwa-ar <8-10, nonpharmacologic mintoring is cceptable
pts with ciwa-ar 8-15: benefit from medicationthis ruding risk of complications
ciwa-AR ACORE>15: MAJOR RISK OF COMPLICATIONS
System triggered treatment regimen of etoh withdrawal
administer one of the following qh whn ciwa-ar score > 8-10
*diazepam 10-20 mg
*Lorazepam 2-4 mg
not usually used unless closs personal monitoring
fixed schedule regimen for etoh withdrawal
Diazepam 10 mg q6hr for 4 doses, then 5 mg q6hr for 8 doses
Lorazepam 2 mg q6 hr for 4 doses then 1 mg qhr for 8 doses
other benzos may be used at equiv doses.
not short acting benzos because they dont last as long
maintenance of etoh sobriety
group support (AA)
Disulfuram
NAltrexone
Acamprosate
Disulfuram
moA
dosing
AE
moa: inhibits aldehyde dehydrogenous enzyme in alcohol metab pthway. Increases levels of acetaldehyde, which can cause unwanted side effects such as N&V, anxiety, agitation. serves as negative reinforcement
dosing: inital 500 mg once daily for 1-2 weeks
maintenance: 250-500mg once daily. MDD:500 mg.
duratio of therapy is to contirnue until pt is fully recoeverd socially and a basis for permanent self control. maintenance therapy may be needed for months or years
AE: drowsiness, headache, faitgue, psychosis
rash, metallic or garlic-like aftertatse, impotence, hepatitis, hepatic failure, peripheral neuritis and neuropathy, optic enuritis
disulfuram considerations
not selective for etoh. many other substanes have aledyhe dehydrogenase in pathway and can exacerbate the negative symptoms of disulfuram
*ABX->nitromidazoles. e.g metonidazole
*first gen sulfonylureas (tolbutamide)
several cephalosporins (cefoperazone and cefotetan
*antifungals (Griseofulvin)
do not adminster until the pt has been abstinant from etoh for atleast 12 hours
disease concerns: use in caution w. pts with..
diabetes
hepatic impairment
hypothyroidism
nephritis
seizure disorder hx
Naltrexone
moA
dosing
AE–
moA: competative antagonist at opiate receptor sites
dosing: IM 380 mg once every 4 weeks
oral: 50 mg daily
AE
Naltrexone considerationsfor-etoh-maintenance
should pt need opioid analgesics, it will not be effective
choose alternative analgesics.
daily oral and monthly im dosing available
Acamprosate
moa:
dosing:
AR:–
moa: sTRucturally similar to GABA. increases gaba inhibitory and decreases glutamate within system.
dosing: 666 mg 3 x day
Acamprosate considerations
3x a day dosing. 666 mg
dose adjustment for low body weight
treatment should be initiated as soon as possible following the period of alcohol withdraway, when pt has achieved abstinance
renal adjustments:
Crcl 30-50: 333 mg 3xday
<30: contraindicated
addiction:
primary chronic, neurobiological disease, with genetic , psychocial and environmental factors influencing its develoment and manifestation
5C;s:
*chornicity,
*impaired control over drug abuse,
*compulsive use,
*continued use despite harm,
*craving
drug abuse
maladaptive pattern of subatance use chaacterized by repeated adverse consequences related to the repeated use of substance
sensitization
increased response to a drug with repeated use. shifts curve to the left.
takes same or less drug to get effects
tolerance
state of adaption i which exposure to a drug inuces changed that result in diminution of one or more of the drugs over time
2 types:
metabollic: liver enzymes
cellular: receptor downregulation
can be also
acute:
protracted
cross tolerance: tolerance to one drug leads to tolerance in another drug
physical ependence
pt needs the drug to function normally and to avoid withdrawal
physiological depenence
body adapts to presence of drug. needs drug on board to maintain homestasis
specific withdrawal symptoms can be produced by abrupt cessation, rapid dose reductoin, decreasing blood level of a drug and/ or administration
define-withdrawal symptoms
behviors displayed by a user when drug use ends
repeated self adminstration
mesolmbic dopamine system. abused drugs all tend to activate this system
3 stages:
pleasure: huge dopaminergic release
associative learning through classical conditioning: cues or context of abuse substance can induce dopiminergic release
incentive silenced by craving,
evaluating risk factors for substance use disorders
dysfunctional childhood, abuse
ADHD, school problems, conduct disorder
early onset of substance use (esp. before age of 14)
personal history of substance use disorder
genetic predisposition
Toxicology testing for substnces
testingroute
detection-time
pro
con
hair: 7days-3 months
pro: long observation period
cons: few labs, need 150 strands.
urine: gold standars
pro: reasonable detection limits
can or need to normalize creatinine
cons: pts. can falsify. need teo be temp stabilied
blood:
con: short tection time
somewhat inasive
pro: can use if cant get urine or solive. can observe
Interpreting qualitative Immunoassays for substance detection
- synthetic opioids(methadone, fentanyl) do not produce a positive test for opiates
2.some opiates (oxycodone, buprenorphine) typically do not produce a positive test for opiates
3.some benzos (clonazepam) may not produce a positive test for benzos
4.some otc meds (pseudoephedrine) may notproduce a positive test for amphetamines
5.environmental exposure to marijuana will not produce a positive test
interprating urine toxicology results
drugs w. short half lives (methamphetamine, lorazepam, cocaine, heroin) will cause the urine toxicology test to be positive for only a few days fter last use
drugs w. long halflives (e.g buprenorphine, cannabinoids, diazepam, methadone) may cause the urine test to be positive for several days-weeks after last use
how to normalize creatinine
Creatinine-normalized drug level
= [urine drug level]/[urine Cr] x100
General substance abuse treatment consideratoins
pharmacotherapy
Outpt vs inpt addiction treatment
counseling
groups: Narcotics anonym./Alcoholic Anon.
Identifying comorbid conditions
Lab: nutritional exams, LFT,thyroid, CBC, metabolic panel, HIV, Hep C
psychiatric dx: other substances, ptsd, SUBSTANCE ABUSE PSYCHIATRIC DISORDERS, ANTISOCIAL AND BORderline personality disorder,, bipolar, SzPh, depression, anxiety
Depressants
class:Benzos
examples:
moa:
SS effects:
SS withdrawal
class: Benxodiazepam: sedative hypnotics
usually end in -PAM (lorezepam)
moa: potentiate GABA inhibitory receptos within cns
SS effects:
*decrease bp
*MEMORY IMPAIRMENT
*confusion
*anterograde amnesia
*gi effects
*urinary retention
slurred speach
poor coordinationrespirstory depression
SS withdrawal
*anxiety
*insomnia
*muscle tention
*irritability
*SEIZURES
*hallucinations
*nightmares
*LIFE THREATENING
Benzo Overdose General Treatment
*mainly supportive
*rarely use FLumazenil
moa: competitive antagonist of GABA benzo receptor
dose: 0.2mg/min up to 3mg max
Flumazenil Treatment considerations
effects occur in 1-3 min
CI in bezo dependant pts. or pts. w. hx of seizures
AE: SS of withdrawal +N&V
Benzo withdrawal treatment (for pt who needs to get off)
Taper benzo depending on dose and duration
Depressants
class: BArbiturates
examples:
moa:
SS effects:
SS withdrawal
ex: end in -barbital
moa: potentiate GABA inhibitory receptos within cns (same as ETOH and benzos
SS effects:
*decrease bp
*MEMORY IMPAIRMENT
*confusion
*anterograde amnesia
*gi effects
*urinary retention
slurred speach
poor coordinationrespirstory depression
SS withdrawal
*anxiety
*insomnia
*muscle tention
*irritability
*SEIZURES
*hallucinations
*nightmares
*LIFE THREATENING
Barbiturate general overdose treatment
supportive
Barbiturate withdrawal tratment (for pt that needs to get off)
taper
change to longer acting barb (phenobarb)
if using barb for anticonvulsive therapy, substitute anticonvulsant
Depressants
class: Gamma-hydroxybutyrate (GHB)
examples:
moa:
SS effects:
SS withdrawal:
SS toxicity
Depressants
class: GHB
examples:
moa: derived from GABA. has inhibitory effects in cns. . short half life
SS effects:
*amnesia
*hypotonia
*often use as date rape drug
SS withdrawal:
*agitation
*mental status changes
*elevated bp. hr
*tachycardia
SS toxicity:
*coma
*seizures
*respiratory depression
*vomiting
GHB general overdose treatment
supportive
vent
O2
fluids
thiamine
Depressants
class: opiatesDepressants
moa:
SS effects:
SS withdrawal:
Depressants
class: opiates
examples: fentanyl, hydrocodone, codeine, ec.
moa: bing to opiate receptors in cns, causing inhibition of ascending pain pathways, altering response to pain produces generalized cns depression.
SS effects:
euphoria
dysphoria
apathy
motor retardation
sedation
slurred speech
attention impairment
miosis
constipation
SS withdrawal:
not fatal(but delerious)
lacrimation
rhinnorhea
mydriasis
piloerection
diaphoresis
diarrhea
yawning
fever
insomnia
muscle ache
General Opioid overdose treatment
Supportive
Naloxone
moa: pure opioid antagonist, competes and displaces narcotics@opioid receptor sites
dose: naloxone 0.4-2 mg iv/im/sq Q2-3 MIN
SPRAY: 2 or 4 mg (contents of 1 nasal spray)as a single dose in one nostril. may repeat q 2-3 min until help arrives
naloxone consideration
used for opioid overdose
rapid onset
nasal spray availble
use if unconcious or respirtory depressed
multiple-uses-may-be-needed-every-two-to-three-min
genral list of opiod withdraal therapies
methadone
LAAM
Buprenorphine
clonidine
Lofexidine (lucemyra)
Methadone
moa:
indications (as far as substance abuse)
PK:
metabolism
dosing:
moa: opiate that binds to opiate receptors, causing inhibition pain pathways , altering perception of resoonse to pain, generalized cns depression
indications (as far as substance abuse):
opioid use disorder withdrawal opioid use disorder maintenance
PK: long t 1/2
metaboism: major cyp3A4
major AE: qt prolongation
dosing: differ for withdrawal and detox
Methadone considerations for use in opioid withdrawal
dosing: 20-80 mg, taper 5-10 mg daily.
decreases tolerance , so pt has risk of overdose if pt relapses due to using pretolerance amount
goals of methadone maintenance therapy for opioid use disorder
goals:
1) supress symptoms of withdrawal
2)extinguish opiate craving
3) block the reinforcing effects of illicit opiates
Methadone considerations for use in opioid use disroder maintenance
START LOW AND GO SLOW
(induction. half of each days dose remains in body and is added to next days dose so levels increase w.o dose increase
initial dose no greater than 30-40mg in day 1
peak levels should be no more than twice the trough
SS can be effective indicators of stages:
relef withdrawal
reach tolerace
establish adequate maintenance dose
standard-of-care-for-maintenance-trtmt-in-pregnant-women
Methadone maintenance program
pt must report qday and take dose in witnessed manner
must complete physical exam and labs within 14 dys of initiating methadone maintenance program
can evntually qualify to take their methadone home only after demonstrating…
capable of andling and taking unsupervised
abstinence from unauthorized substances
regular atendance
stable homeand social environments
methadone can be safely stored
Buprenorphine
moa:
indications (as far as substance abuse)
PK:–
metabolism
dosing:
moa: exerts its analgesic effects via high affinity binding to mu opiate recptor. partial opiate agonists
indications (as far as substance abuse)
PK:–
metabolism; cyp3a4
dosing: general: 4mg-32mg/day
many different formulations
Buprenorphine considerations for use in opioid use disorder withdrawal
MUST BE IN OPIATE WITHDRAWAL ALREADY BEFORE USE
(due to strong opiate reeptor affintiy. will bump off opiates from receptor and precipitate withdrawal)
limited opiod effects due to partial agonism, but also continues to block other opioids from attatching to receptor
Buprenorphine considerations for use in opioid maintenance
induction phase: find minimum dose pt d/c or drastically reduced opioid use
stabilization: marked by pt experiencing no withdrawl effects
maintenance: may be indefinite, psychosocial services
unlikely candidates for buprenorphine maintenance therapy
overall, is the pt willing and able to safely possess a controlled substace and use it properly.
comorbid depenence on other cns depressants should NOT neesarily proclude someone from buprenorphine maintenance therapy
Buprenorphine formulations
formulation:
dosage form:
drugs included in formulations
1)Subutex
ONLY buprenorphine
SL tablet
dose:2 or 8 mg
2)suboxone= buprenorphine/naloxone at higher doses b/c lower bioavailability
SL tablets or film
3)Zubsolv= buprenorphine/naloxone at lower doses(higher bioavailability) (lower dose reduces abuse potential if misused )
SL tablets
4)Bunavail
buprenorphine/ naloxone (at even lower doses)
buccal films
5)sublocade
bupenorphine ONLY
SQ injection
dose conversions from suboxone to Zubsolv
suboxone Zusolv
8mg/2mg 5.7/1.4 mg
2mg/0.5 mg 1.4 mg/0.36 mg
overall: 8 mg suboxone=5.7 mg Zubsolv
dose conversion of subaxone to buvanail
approximately 2:1
suboxone Buvanail
4mg/1mg 2.1mg/0.3mg
8mg/
12mg/
Sublocade treatment considerations
Long acting buprenorphine formulation for patients on 8mg or more of buprenorphine
LAI (SQ)
benefits:reduce diversion and abuse.
good option for noncompliant pts-do not need to take a sl tab or film q day
once a month injection
BBW: if adminstered IV, will form solid mass. also do not admin IM.
Sublocade treatment considerations
Long acting buprenorphine formulation for patients on 8mg or more of buprenorphine containing product for atleast 7 days
LAI (SQ)-rotate injection. will form small lump that will last 7 days. dont rub
benefits:reduce diversion and abuse.
good option for noncompliant pts-do not need to take a sl tab or film q day
once a month injection
BBW: if adminstered IV, will form solid mass. also do not admin IM.
REMS treatment
Conversion from buprenorpine to Sublocade
8 mg buprenorphine=300 mg SQ q month for 2 months, then 100 mg q mo therafter
Clonidine
moa:
indication:
AE:
metabolism
dosing:
moa: stimaulates alpha-2 receptors, acitvating inhibitory neorins, reducing sympathetic outflow from the cns (which negated withdrawal’s sympathetic stimulation )
INDICATION:opioid withdrawal
AE: orthostatic hypotension, bradycardia, hypotension, insonia, dizziness, drowsiness, (basically parasympathetic activation)
metabolism
dosing:
Lucimera
moa:
indication:
AE:
SAME AS CLONIDINE,
moa: stimaulates alpha-2 receptors, acitvating inhibitory neorins, reducing sympathetic outflow from the cns (which negated withdrawal’s sympathetic stimulation )
indication: single indication for opioid withdrawal
AE: orthostatic hypotension, bradycardia, hypotension, insonia, dizziness, drowsiness, (basically parasympathetic activation)
Other symptom anagement for opioid withdrawal
pain management
*NSAIDS, APA, muscle relants, neuropathic agents
N$V management: with *N:metoclopramide, ondansetron
*diarrhea: antidiarrheals
anxiety: insomnia medications, muscle relaxants, hydroxyzine
Naltrexone for opioid maintenance
moa:
indication:
AE:
moa: attenuates or blocks reversible subjective affects of iv administered opioids by binding to opioid receptor
indication: maintenance
AE: GI upset for oral, injectio site reaction for IM
naltrexone for opioid use disorder maintenance considerations
must be opiate free for atleast 7-10 days. if given when not opiate free, may induce withdrawal symptoms
BBW: acute hepatits,
IM naltrexone preffered in opioid maintenance over oral naltrexone
(dose 380 mg IM q 4 weeks
Vivitrol (Naltrexone XR)
IM
why is repeated doses of naloxone (narcan) sometimes needed, especially if pt is overdosed on opioids such as fentanyl, or carfentanyl.
fentanyl has higher binding affintiy and longer half life than naloxone, so once nalaxone dissipates, fentanyl will rebind to opioid receptors.
readministration is needed until help arrives and pt can be transferred to a hospital
Non opiate pain management
APAP
Nsaids- ibuprofen or keterolac
neuropathic pain: TCA, gabapentin/pregablin
Depressants
class: Dextromethrophan (DXM)
examples:
moa:
SS effects:
SS withdrawal
moa: inhibits NMDA(stimulatory) receptors
SS effects:
heightened sense of perceptual awareness
altered time perception
visual hallucinations
lethargy
ataxia
slurred speech
sweating
hypertension
abuse can cause death, brain damage, seizure, loss of conciousness, and irregular heartbeat
Stimulants
class: Cocaine
examples:
moa:
SS effects:
SS withdrawal
class:
examples:
moa: NE and DE reuptake inhibitor
metabolites: ecgonine methyl ester
benzoylecgonine
cocaethyline only in presense of alcohol
SS effects:
euphoria
loquacity
mydriasis
change in bp, tachycardia
sweat chills
n&V
decreased fatigue
paranoia
aggression
motor agitation
Toxicity: cardiacarrest
nasal septum ulceration
SS withdrawal
depression
fatigue
nightmares
sleep disturbance
increased appetite
bradyarrthmyias
tremor
geenral cocaine overdose treatment
supportive
if needed..
lorazepam (benzos)
haldol
antiarrythmiac agents prn cardiac complications
Stimulants
class: Amphetamine
examples:
moa:
SS effects:
SS withdrawal
Stimulants
class:
examples:
moa: block reuptake of DA and NE, increase release of DA and NE, MAOi
SS effects:
decreased fatigue
alert awake
increased activity
hyperthermia
irritability
meth mouth
tremor
confusion
convulsions
SS withdrawal
fatigue
depression
cognitive impairment
LABS: fires, explosions
amphetime over dose treatment
suppportive
haldol
lorazepam
Stimulants
class: Ecstasy MDMA
examples:
moa:
SS effects:
SS withdrawal
Stimulants
class:
examples:
moa: unknown
SS effects:
EMPATHY
RELAXATION
rave
euphoria
anxiety
decreased inhibition
paranoia
touch
hyperthermia
increase HR and BP
SS withdrawal
Stimulants
class: PCP aka angel dusty
examples:
moa:
SS effects:
SS withdrawal
Stimulants
class: Cocaine
examples:
moa: DA, 5HT, NE reuptake inhibitor
SS effects:
euphoria, dellusion
hostility
hallucinatoins
emotion lability
SS withdrawal
Stimulants
class: Ketamine
examples:
moa:
SS effects:
SS withdrawal
Stimulants
class: Ketamine
examples:
moa: PRODUCES CATALEPTIC STATE IN WIHCH PT IS DISSOCIATED FROM SURROUNDING ENVIRONMENT BY DIRECT ACTION OF THE LIMBIC SYSTEM
SS effects:
increased bp, hr
hallucinations
vivid dreams
delerium
resp. depression
SS withdrawal
Hallucinogenics
class: LSD
examples:
moa:
SS effects:
SS withdrawal
class:
examples:
moa: stimulate presynaptic 5HT1a and 1b and post synaptic 5HT2
SS effects:
mydriasis
increased temp bp hr
sweating
losso f apetite
dry mouth
tremor
hallucinations
sensory crossover (smell colors)
SS withdrawal
LSD overdose treatment
supportive
lorazepam (for ttrmt of psychosis)
haldol (agitation)
Marijuana
examples:
moa:
SS effects:
SS withdrawal
moa: cannabinoid receptors, release dopamine. primary psycoactive molecule is delta 9-THC
SS effects:
euphoria
disinhibition
blood shot eyes
euphoria
hunger
thirst
dry mouth
tachycardia
fear, distrust, panis
decreased coordination
amennorhea
SS withdrawal
inhalants
moa:
SS effects:
SS withdrawal
“huffing” glues, butane, gasolane, aerosols
moa: rapidlt absorbed via cappilaries in the lungs. penetrate BB
effects:
nausea
headache
deprived o2 in brain
arrythmias
suffocation
brain damage
decreased bp
lossof coordination
combo drugs of abuse
cocaine+etoh>cocathylene
Q-ball=quetiapne+cocaine
Speedball= heroine+cocaine
stimulant +depressent are very dangerous
Krokodil
derived fromcodeine
contains solvents like gasoline and lighter fluid
can cause ulcers skin necrosis and infection
overdose: slow shallow breathing (its an opiate)
small pupils
slurred speech
bath salts
synthetic stimulants
belong to phenyethylamine
amphetamine like stimulatory effects: euphoria, energy, alert
intoxication: cambativenedd, hallucinations, agitation, paranoia, confusion , hallucinatoins
overdose: tachycardia, htn, agitated delerium, diaphoresis, mydriasis, hyperthermia
most common cause of death: arrhythmias, hyperthermia, intracerbral hemmorhae
treatment: iv benzos, fluid resuscitation
synthetic cannabinoids
much mor epotent than THC from natully occuring marjuana
Kratom
ree native to africa and asia
13x more potent than morphine
stimilants at low doses
opiate effects at higher doses
can results in addiction and dependence.
can experience withdrawal
can result in psychosis and death
SEizures
uncontrolled electrical activity in the brain, which may produce a physical convulsion, minor physical signs, thought disturbances, or a combo of these symptos
epilepsy
condition characterized by a relatively long term distubance of brain sturctures and / or function hat produces an increased suceptibility to seizures
atleast 2 seizures unattriuted to some other disease processes
new onset seizures in ages >50 are atributed to
tumor
bleed
infection
fibrosis secondary to a stroke 6-12 mo. earlier
generally dont hve good prognosis
Nonepileptic seizer-causes
usualyl causd by ..
extreme metabolic disruption,local effects of brian tumor
infection
withdraal form sedarive/hypnotic drugs including ETOH
RENAL FAILURE
HYPOXIC ENCEPHALOpathy(near drowning if they survive)
febrile convulsions
epileptic seiazures
disorder of brain where there are a cluster of cells (eleptogenic foci) that begin to fire at an abnormal rate
typically epileptics reccurent seizures have relatively predictable pattern
seizure classification
single seizure (non EPILEPTIC)
A. determine if cause is due to
metabolic
toxic
hemodynamic
psychogenic
if another one occurs and non attributed to other causes, pt is considered an
EPILEPTIC
seizures further classified to
A) generalized seizures
b)partial seizures
partial sezires
begin at discrete and relatively limited focus
pattern depends on function of area stimulated
smple partial seizure: uncomplicated, affects only limited aspects of neural function
motor or sensory symptoms (ex pt smells an awful smell )
conciousness and memory undisturbed
complex partial seizures:
alteration of conciousness follows initial siple seizure. may be aware and alert. may exhiit automatisms, purposeless and automatic behaviors(lip smacking, suching, fumbling with clothing, etc.
geenralized seizures
involves entire cerebellum
- absence seizures (petit mal)
minor impairment of short duration
A. blank stare or other facial expression
B. after 2-10 seconds resumes pre-seizure activity
C. disruption in intentional behavior
may include lip smacking, puting, eyeblinking
can occur 100s of times/day
a. tonic clonic sezire (grand mal)
maximal seizure response of brain in which brain systems can be recruited
some ppl have prodrome -depression, irribitality, apathy or malaise, or euphoria
1-2 myoclonic jerks
3 phases:
a: tonic (10-20 seconds)
brief muscle flexing, pronounced extension, bladder empty,breathing stops.
b.clonic: 1/2-2min
muscle relaxation
violent spasms of contraction and relaxation(strongets muscles dominate)
resperiations resume but innefective
terminal phase:
limp and quiet with normal breathing
may be follwed by several hours of deep sleep
or may become conciousness with no recollection of seizure
geenralized seizures
involves entire cerebellum
absene seizures (petit mal)
minor impairment of short duration
blank stare or other facial expression
after 2-10 seconds resumes pre-seizure activity
disruption in intentional behavior
may include lip smacking, puting, eyeblinking
can occur 100s of times/day
a. tonic clonic sezire (grand mal)
maximal seizure response of brain in which brain systems can be recruited
some ppl have prodrome -depression, irribitality, apathy or malaise, or euphoria
1-2 myoclonic jerks
3 phases:
a: tonic (10-20 seconds)
brief muscle flexing, pronounced extension, bladder empty,breathing stops.
b.clonic: 1/2-2min
muscle relaxation
violent spasms of contraction and relaxation(strongets muscles dominate)
resperiations resume but innefective
terminal phase:
limp and quiet with normal breathing
may be follwed by several hours of deep sleep
or may become conciousness with no recollection of seizure
status epilepticus (medical emergency
management of epilepsy
- accurate dx for proper mangement
notes: choice of therapy does not depent on seizure type
goal therapy is to reduce the number of seizures to lowest frequency possible with manageble side effcts.. not to completely stop seizures
first aide for seizures
A. generalized tonic-clonic seizures
- record time of seizure onset
stay with pt until seizure ends
have someone call 911
prevent person from hurting him or her self. place something under the head, loosen ight clothing, and clear area of sharp or hard objects
do not force any objects into pts. mouth
so not restrain pt
turn parient on side to allow saliva to drain from mouth
stay w.patient until seizure ends naturally
do not pour liquids into pts mouth or offer any food, drink or medicatoin until fully awake
give artifical respiration if pt does not resume breathing after seizure
provide area for pt to rest until fully awakened, accompanied by responsile adult
be reassuring and supportiv when conciousness returns
medical emergency for seizures
greater than 10min
difficulty in rousing at 20 min intervals
complaints of difficulty with vision
vomiting
persistent headache after rest period
uncociousness with failure to respond
unequal size pupils or excessively dilated
polytherapy considerations for epilepsy
for refractory pts.
risk factors: inadequate response o 1st AED prescribed
pharmacist pt in a seizure hx
when was your first seizure
how often do you have seizures
when was your most recent seizures
what did u do, eat, or take the day of your most recent seizure
what anticonvulsant medications have u used in the past
what medications are u currently taking
medication specific questions regarding toxicity
determine relevant counseling oints for this pt and thir specific meications
be sure pt understands the goal of therapy
gengo rule of life#14, your pt, your decision, your responsibility
AED and oral contraceptives
many Anti epileptic Drugs are enzyme inducing
phenobarbital, phenytoin, primidone, and carbamezapine increase clearance of estrogen, reducing OC effectiveness
management:
counsel pt on use of additional forms of contraceptive
might want to discuss w. neurologst to switch to non enzyme inducing AED if possible
do not recommend increasing estrogen dose. increases risk of stroke
Pregnancy and epilepsy
STRESS that..
*seizures are deletarious to fetus/mother
*care should be provided by an experienced clinican
*clinican should be establish prior to conception
diet should ocntain folate, aong w. folate supplementation
discuss withdrawal of aed WITH obgyn/ neurologist
use AED if necessary at the lowest dose
avoid valproic acid and carbamezapine . if not avoidabl use lower dvided doses
avoid lamatrogene
avoid vpa+cbz+pb polytherapy
if phenobarbital is used be alert for neonatal withdrawal
AED and breast feeding
no reason not to have woman breast feeding (baby has already been exposed to this drug in mom at possible higher concentrations)
which AED cause neural tube dfects
carbamezapine
valproic acid
Levetracetam (Keppra)
moa:
AE
Dose:
advantages–
disadvantages–
moa: non competitive antagonist at AMPA glutamate receptor
AE: generally well tolerated, weight gain. enhances cns depressants
Dose: immediate release: initial 500 mg twice daily
Leveteracetam considerations
renal adjustments
Crcl-thirty-tofifty-:twofifty-sevenfifty-BID
Crcl
Oxcarbamazepine
moa:
PK:
AE
Dose:
advantages
disadvantages–
monitoring
moa:
PK:
AE: most commin in children (somnelance and headaches. N&V)
rash
27% cross reactivity with tegretol
Dose:five-mg/kg/day,w-weekly-increments-of-same
target-thirty-fifty-mg/kg/day
BID
advantages: lower potential for drug interactions
disadvantages
lab monitoring:
sodium
hepatic
doesnt need routine hematologic
Lamotrigine
moa:
PK:
AE
Dose:
advantages
disadvantages
moa:
PK:
AE
Dose:Start 0.5 mg/kg/day (divided bid) x 2weeks, then then 1 mg/kg/day x 2 weeks, then increase in 1 mg/kg/ day q 2 weeks until respond
MAXFOURHUNDRED
advantages: broad spectrum of activity
low teratogenic potential
non sedative
disadvantages
rash: STEVEN-JOHNSON esp w. rapid titrtion or coadmin with vpa
TITRATE SLOW
Gabapentin
moa:
PK:
AE
Dose:
advantages
disadvantages
moa:
PK: higher the dose, the lower the precentage absorbed
AE: occasional somnelance, dizziness, ataxia, weight gain at high doses
may have potential for abuse
Dose:
advantages: low incidence of neurotoxic side effects
useful for comorbid neuropathis pain and or mood stabilization
disadvantages:
TID dosing
not considered very potent
complex absorption, leads for need of rapid dose increase
phenytoin
moa:
PK:
AE
Dose:
advantages
disadvantages
moa:
PK: terrible aquoes absorption.
no dorse proportionality
easy to reach toxicity (concentration dependent and independent)
AE:
concentration dependent: nystagmust, double invision, blurred vision, incoordination, drowsiness, dizziness (look like ETOH intoxication)
idio sycratic : aplastic anemia, granlucytopenia, hepatotoxicty, rash, steven johnson
chronic: hum hypertrophy, acne hirsutism, peripheral neuopathy, chrnic cerebellum damage, osteoporosis, fetl vitamin k depletion
Dose:
advantages
disadvantages
Fosphenytoin
moa:
PK:
AE
Dose:
advantages
disadvantages
moa:
PK:
AE
Dose:
advantages:PHOSPHORYLATED-FENYTOIN-FOR-IV-ADMIN
disadvantages
Valproic Acid
moa:
PK:
AE
Dose:
advantages
disadvantages
moa:
PK:first order pk
AE: GI, elevated LFT, neural tube defect in children when used in pregnancy
CI in hepativ dysfunction and heavy drinkers or hepatic cirrhosis
Dose:
advantages
disadvantages:NEURAL-TUBE-DEFECTS
valproic acid-CONSIDERATIONS
cleaning agent for floor .
GI
drug interactions
gi dosing decrease
pt instuctions
dont break chew tablet or capsule
carbamezapine moa:
PK:
AE
Dose:
advantages
disadvantages
moa:
PK:
AE: dizziness, drowsiness, hyponatremia, water intoxication
Dose:
advantages
disadvantages
carbamezapine considerations
autoinduction: usually fo r2 cycles
hyponatremia
can cause aplastic anemia(fatal) and transient leukopenia.d/c only if ANC goes below <1500 and decrease platlet count and red bloodcell count
monitor:baseline cbc and platelet
monitor serum levels due to autoinduction
Patho of seizures
Shift in balance between inhibitory neurotransmitter (GABA) and excitatory neurotransmitter (Glutamate) transmission,
Increase glutamate activity-> causes increase in action potentials from irritable focus area
*cause by increased depolarization due to influx of positive ions such as Na+ and Ca+.
decrease in GABA-> causes inhibition of hyper polarization that is supposed to decrease action potential-> thus potentiating an action potential to occur n
Also there can be an increase in GABA reuptake
Can also be an increase in GABA breakdown
Mechanisms of Inhibiting Glutamate activity
(And drug examples to inhibit them)
A. MOA: inhibit sodium channels. Prevents depolarization of neuron, and prevents the release of glutamate ( an excitatory amino acid)
Carbamazepine
Oxcarbezapine
Phenytoin
Fosphenytoin
Lamotrigine
Topiramate
Valproate
Lacosamide
B. MOA: calcium channel blockade
MOA: block calcium channels in neuron. Prevents fusion of vesicle to neuron cell membrane, that releases the excitatory NT glutamate
Ex: Ethosuximide
C. MOA: prevent Vesicle fusion to cell membrane to prevent glutamate release
Ex: Levetiracetam (keppra)
D. MOA: prevent glutamate from binding to neuron via NMDA RECEPTOR to create an action potential
Ex: Ketamine
Mechanisms of increasing GABA activity
Mechanisms of increasing GABA activity for seizures
- Stimulate GABA A receptors to increase frequency of cl channel opening, in order for cl to flow in and hyperpolarize the cell, causing a decrease in action potentials
Ex: benzodiazepines
- Bind to GABA A RECEPTORS, increases duration of colorize channel openings
Ex: phenobarbital,
Propofol
Topirmate ( has glutamate inhibition activity AND increasing gaba activity )
BEN LIKES IT MORE FREQUENT, BARB LIKES IT LONGER
- Inhibits GABA REUPTAKE BY INHIBITING reuptake receptor.
Ex: TIAGABINE( not generally used. Used when inadequate response to first line therapy) - Prevent breakdown of GABA by inhibiting enzyme that breaKS DOWN GABA once taken back up
Ex: VIGABETRON
Valproate (decreases glutamate activity AND increases GABA activity )
First line Specific agents for types of seizures
NOTE: this is what I learned from YouTube. Not class
Focal : carbamezapjme
Oxcarbezapine
Generalized (absence): ethosuxemide
Generalized( myoclonic): valproate, levetiracetam
Generalized (tonic clinic): valproate, levetiracetam, phenobarbital
Status Epilepticus:
1st step. Benzodiazepines
2nd step. Ppx. Prevents further seizures
A. Fosphenytoim
B. Valproate
C. Levetiracetam
D.lacosamide
Step 3: if pt is still having seizures, propofol, ketamine
Last line if pt still has seizures: phenobarbital
AED AE
Cardiac/resp. Depression
1. Benzos
2. Barbiturates
3. Propofol
Steven Johnson syndrome
1. Lacosamide
2. Carbamezapine
3. Ethosuximide
Hepatotoxicity
1. Valproate
2. Carbamezapine
CYP450 interactions
CYP INDUCERS:
1. Barbiturates
2. Phenytoin
3. Carbamezapine
NOTE: CAN DECREASE EFFICACY IF ESTROGEN. COUNSEL PTS ON COC TO USE BACKUP CONTRACEPTION
CYP450 INHIBITORS: Valproate
Teratogenic
1. Valproate: neural tube defects
2. Phenytoin, fosphenytoin-fetal hydrantoin
3. Carbamezapine: cleft palate
Specific ADR FOR AED
Valproate: pancreatitis
Carbamezapine: SIADH
PHENYTOIN/phosphenytoin: gingival hyperplasia
Topiramate: metabolic acidosis. Kidney stones
