epilepsy, AUD, sub abuse Flashcards
1
Q
what are the four main AED MOAs?
A
1) prolong Na channel INactivation
2) inhibit Ca channels
3) increase GABA Cl efflux
4) glutamate antagonist
2
Q
which AEDs prolong Na channel inactiavtion?
A
- valproate
- carbamazepine
- phenytoin
- lamotrigine
- topiramate
- zonisamide
3
Q
which AEDs inihbit Ca influx?
A
- valproate
- ethosuximide
- trimethadione
4
Q
which AEDs increase GABA Cl efflux?
A
- valproate
- barbituates (phenobarbital)
- benzodiazepines
- gabapentin
- vigabatrin – has GABA in it
- tiagabine – kind of has GABA in it
5
Q
which AEDs are glutamate antagonists?
A
- levetiracetam
6
Q
phenytoin MoA
A
- block Na and Ca influx –> prevent AP –> dec seizure activity
7
Q
phenytoin common uses
A
not common, if used will be in severely diabled pt in an institution
8
Q
phenytoin dose
A
200-400 mg/day
9
Q
phenytoin dose-related AE
A
- GI upset
- sedation
- HA
10
Q
phenytoin non-dose related AE
A
-**hyperplasia of gingival (gum overgrowth)
- hirsutism
- fetal malformations
11
Q
phenytoin metabolism
A
- induces liver enzymes (dec concentration of other drugs)
12
Q
carbamazepine MoA
A
prevent Na influx –> dec AP –> dec seizure activity
13
Q
carbamazepine metabolism
A
-
MOST POTENT INDUCER OF HEPATIC METABOLISM OF ANY DRUG –> dec concentration of other drugs
-auto-induction (induces its own metabolism) –> therefore, will titrate up to a therpeutic concentraton (check concentration, this is the goal now for the pt), then drug concentration will dec, need to increase the dose 2-3 times –> finally reach stable dose
14
Q
carbamazepine dose
A
200-800 mg/day
BID as SR product
15
Q
carbamazepine AE
A
- *hyponatraemia (low Na), water intoxication
- congenital malformations for fetus
- GI
- drowsy
- HA
- rash (hypersensitivity)
16
Q
carbamazepine in pregnancy
A
can cause two different conditions:
1) fetal aplastic anemia (RBC)
2) mild leukopenia (WBC)
therefore…
do baseline CBC –> check CBC in 6 weeks –> will see a dec in WBC which is normal and will rebound, if a dec in other cells types (like RBC) STOP immediately –> aplastic anemia –> check CBC in 1 month –> WBC should be back to normal, if not STOP immediately
17
Q
sodium valproate vs valproic acid
A
valproic acid: poor solubility –> GI problems
18
Q
valproate MoA
A
1) increase GABA (Cl efflux)
2) prevent Na influx
3) prevent Ca influx
19
Q
valproate metabolism
A
inhibitor –> increases concentration of carbamazepine, phenytoin, topiramate, phenobarbital
20
Q
valproate AE
A
- increase appetite
- weight gain
- hepatotoxicity
- **neural tube defects (spina bifida)
21
Q
valproate in pregnancy
A
CONTRAINDICATED
- bc of spina bifida NTD
- need to change med before pregnancy !!!!!
22
Q
first generation AED
A
less tolerable, less effective:
- valproate
- carbamazepine
- phenytoin
23
Q
second generation AED
A
more tolerable, more effective, generally lack DDI, expensive, limited clinical experience:
- lamotrigine
- oxcarbazepine
- topiramate
- zonisamide
- levetiracetam
- vigabatrin
- gabapentin
- tiagabine
24
Q
vigabatrin MoA
A
inhibits GABA metabolism –> inc GABA –> dec AP –> dec seizure activity
25
vigabatrin place in therpay
NOT 1st line bc of side effects
26
vigabatrin AE
- visual field defects
- psychosis, depression --> happens overtime/slow decline
27
vigabatrin CI
any history of phycosis --> hard to Dx what is from drug
28
gabapentin MoA
(structural analog of GABA) --> inc GABA
29
gabapentin CI
predisposition to substance abuse
30
gabapentin metabolism
NOT an inducer/inhibitor
31
gabapentin AE
- somnolence (sleepy)
- dizzy
- fatigue
32
gabapentin place in therapy
ONLY AN ADJUNCT TO THERAPY, not monotherapy!!
33
lamotrigine MoA
prolong Na channel inactivation (prevent Na influx) --> dec AP --> dec seizure activity
34
lamotrigine AE
-**SJS RASH
- dizzy/vertigo
- somnolence (sleepy) --> can reduce with slow titration
- influenza-like
35
lamotrigine metabolism
NOT an inducer/inhibitor
36
lamotrigine SJS
usually develops short term after treatment
- always ask pt if they have a rash
37
lamotrigine initiation
NEED to titrate long and slow or will not be tolerated!!!
38
lamotrigine CI
too high risk seizure where a long slow titration cannot occur
39
topiramate MoA
prevent Na influx --> dec AP --> dec seizure activity
also inc GABA
40
other use of topiramate
migraine prophylaxis
41
topiramate initiation
slowly titrated over 3 weeks (not as slow as lamotrigine) --> if dose too high, will cause intoxication
42
topiramate AE
- **tip of the tongue syndrome: hard to find words --> DO NOT INCREASE DOSE anymore once this occurs
- **BILATERAL parasthesia (tingling/pricking in extremities) --> stroke would be unilateral
- **dehydration --> retinal issue in ONE EYE (inc pressure, one eyed glaucoma), AND, kidney stones --> are preventable
- psychological or cognitive dysfunction
- weight loss
- urolithiasis (kidney stones in urinary system)
- teratogenicity (in animals not humans)
43
oxcarbazepine MoA
prevent Na influx --> dec AP --> dec seizure activity
44
oxcarbazepine AE
similar to carbazepine
- less likely to cause rash
if change carb to oxcar, pt will probably react the same to it
45
what is Keppra?
levetiracetam
46
levetiracetam MoA
antagonist at the AMPA glutamate receptor --> prevent ENT --> dec AP --> dec seizure activity
47
levetiracetam benefits
very effective, very well tolerated, very common
48
levetiracetam metabolism
renally cleared!! --> the only AED that is --> therefore need renal dosing!
49
levetiracetam dose
IR: 500mg BID --> inc to max dose of 1.5g BID (makes sense that IR is BID)
ER: 1g qd --> inc to max 3 g qd
**renal dosing!! --> dec max IR to 750mg or 500mg
50
levetiracetam AE
- enhance CNS depressants
- weight gain
51
tiagabine MoA
inhibit GABA uptake --> inc GABA --> inc inhibition --> dec AP --> dec seizure activity
52
tiagabine AE
- sedation
- mild memory impairment
- abdominal pain
- abnormal physical weakness/lack of energy (asthenia)
53
zonisamide MoA
prevent Na influx --> dec AP --> dec seizure activity
54
zonisamide AE
- drowsy
- HA
- N/V
- loss of appetite
55
when to change AEDs in patient seeking pregnancy
6-12 months before pregnant --> most common time to have seizures is when changing drugs
56
AEDs CI in pregnancy
- phenytoin
- valproate
57
AEDs recommended in pregnancy
- phenobarbital
- lamotrigine
- oxcarbazapine
- ethosuximide
- (topiramate)
oxcarb better than carb!!
58
which AEDs cause contraceptive failure
- phenytoin
- **carbamazepine
- oxcarbazepine
59
2 big concerns about sharing needles
1) abcesses: skin popping
2) xylazine: **severe necrotic skin ulcerations --> not always at injection site
60
classes of substance abuse drugs
1) alcohol
2) tobacco
3) stimulants
4) depressants
5) hallucinogens
6) marijuana
7) inhalants
8) misc
61
types of depressants
1) sedative-hypnotics
2) GHB
3) opiates
4) DXM
62
types of sedative-hypnotics
1) benzos
2) barbiturates
63
benzodiazepine MoA
increase GABA inhibition --> therefore inc inhibition --> therefore depressant
64
benzo metabolism
by liver --> inactive and active metabolites
***active metabolites INCREASE effect --> caution elderly
65
benzo half life
long half life, accumulation of drug
66
benzo tolerance
rapid tolerance with chronic dosing
67
benzo AEs
- dec BP
- drowsy
- GI upset
- urinary retention
- anterograde amnesia (don't remember drug administration)
- respiratory and CNS depression
68
benzo withdrawl
- **anxiety
- **insomnia
- muscle tension
- irritable
- depression
- paranoia
69
benzo OD treatment
1) supportive
2) flumazenil
70
flumazenil MoA
competitive inhibition of benxo receptor on GABA --> inhibits the inhibition of GABA --> increases stimulation to prevent the over-depressant effect
71
flumazenil dose
0.2 mg/min --> 3 mg max
72
flumazenil CI
- TCA use (-triplylines)
- benzo dependent
**withdrawal seizures
73
in general, OD treatments will cause what side effects?
the withdrawal side effects of the drug of abuse
74
benzo withdrawl treatment
1) taper down
**convert to 1 long-acting benzo --> taper down from there
75
what are roofies
flunitrazepam --> benzo
76
barbiturate MoA
depressant --> inc GABA inhibition
77
barbiturate effects/AEs
intoxication similar to alcohol, similar benzo effects too
- disinhition
- mood
- unsteady gait
- slur speech
- poor judgement
- amnesia
78
barbiturate OD treatment
suportive
79
barbiturate withdrawal treatment
taper barb down --> change to one long acting barb
**add an anticonvulsant if at high risk of withdrawal seizures
80
barbiturate withdrawal s/s
- anxiety
- postural hypotension
- **seizures
- insomia
81
long acting benzo
diazepam
82
long acting barb
phenobarbital
83
gamma-hydroxybutyrate (GHB) (Xyrem) MoA
derived from GABA --> inc GABA and GHB receptor inhibition --> depressant
- CIII Xyrem used for narcolepsy
84
GHB PK
- fast half life, fast time to peak, no active metabolites --> therefore quick and hard to catch on toxicology --> hence date rape drug
85
GHB effects
- **amnesia
- hypotonia (weak muscle tone)
86
GHB toxic effects
- coma
- seizure
- repiratory depression
87
GHB withdrawal effects
- agitations
- mental status change
- inc BP
- inc HR
88
GHB OD therapy
supportive --> fluids, vent, O2
maybe thiamine
89
common opioid lacing concerns
1) cocaine is laced with fentanyl
2) heroin is laced with xylazine
90
xylazine MoA
central alpha 2 -adrenergic agonist --> dec NE and DA release --> depressant
allows for longer highs from other drugs
91
xylazine withdrawal effects
- agitation
- severe enxiety
92
xylazine OD effects
- coma
- cardiac failure
- respiratory depression/arrest
- disfiguring skin ulcers
- infections --> gangrene --> limb amputation
*ulcers can develop away from injection site
93
what is not effective for xylazine OD?
- Narcan or naloxone --> bc not an opioid
- animal reversal OD agents --> not sure if safe/effective in humans
94
xylazine elimination
rapid!!! (short half life)
- not show up on tox reports anyways -- need special detection
95
xylazine OD treatment
supportive
**consider that this may be present if pt is not responding to Narcan
96
xylazine withdrawl treatment
clonidine -->acts the same as xylazine, will dec the inc in NE from withdrawl of drug that is causing agitation
97
opioid MoA
bind opioid receptors in CNS --> inhibit ascending pain pathways --> general CNS depressant
98
opiate drugs
- heroin
- morphine
- codeine
- hydrocodone
- hydromorhphone
- fentanyl
- oxycodone
- tramadol
- tapentadol
- meperidine
99
opioid effects
- euphoria
- sedation
- *constipation
- slur speech
- miosis (pinpoint pupils)
100
opioid withdrawal s/s
- lacrimation (tears)
- mydriasis (large pupils)
- insomnia
- **restless leg syndrome
- physical pain
- insomnia
101
opioid overdose treatment
1) naloxone (Narcan)
2) supportive
102
naloxone MoA
pure opioid antagonist --> displaces narcotic at receptor
103
naloxone dose
0.4-2 mg IV/IM/SQ q2-3min
OR
2mg or 4 mg IN as a single dose in one nostril, alternate nostrils q2-3 min until assistance comes
*administer if unconcscious and respiratory depression
104
opioid withdrawal treatment categories
1) withdrawal/detox
2) maintenance
3) abstinence
105
opioid withdrawal options
- methadone
- LAAM
- buprenorphine
- clonidine
- lofexidine
106
opioid withdrawal maintenance options
- methadone
- LAAM
- buprenorphine
107
opioid withdrawal abstinence options
- naltrexone
108
methadone MoA
full opioid agonist
** want to gradually titrate up and therefore stop use of street drugs --> converting patient fully to this
109
methadone metabolism
substrate and inihibitor of P450!!! --> many DDIs!!!!
110
methadone and pregnancy
***induce hepatic enzymes during pregnancy to dec half life --> may need to inc dose***
111
methadone AE
QT prolongation
112
methdone dosing
withdrawal/detox:
20-80mg, taper down by 5-10mg/day
*huge risk if taper off --> dec tolerance --> if go back on street heroin at same dose as before --> life threatening!!
113
three goals of methadone maintenance
1) suppress s/s of opioid withdrawal
2) extinguish opioid craving
3) stop reinforcing effective of illicit opioids by increasing opioid tolerance --> street drugs have less of an effect now
114
methadone maintenance dosing
initial: 30-40mg day 1 --> induction phase will keep half the dose until the next day, therefore concentration will inc without dose increasing --> MDD about 100mg/day
115
how to titrate methadone maintenance dose
use s/s withdrawal
- relieve withdrawal
- reach tolerance
- stop craving
- get to adequate dose
- perserve thee effects!
116
what needs to be done within 14 days of starting methadone maintenance therapy?
labs and physical exam!!
117
how do methadone maintenance pts get dose?
everyday supervised dose administration
start going everyday --> after 90 days can go twice a week --> after 2 years can go once a month
need to prove compliance, safe storage, etc...
118
buprenorphine MoA
partial opioid agonist
good bc --> has a higher affinity than most full agonists so it kicks them off --> also has weak opioid activity to prevent/relieve withdrawal symptoms --- ohhhhhhhh
counsel to take when feel withdrawal, not when take other opioid
119
buprenorphine in preg
induces metabolism --> dec concentration
120
buprenorphine metabolites
active with longer half life --> norbuprenorphine
121
buprenorphine detox
induction, dose reduction
*transition opioid until go opioid free
122
buprenorphine maintenance steps
1: induction -- find minimum dose where no craving, no opioid use, no AEs, no withdrawal
2: stabilization at that dose
3: maintenance of that dose indefinitiely
123
good candidiates for buprenorphine
- addicted not just dependent
- no CIs
- interested
- expect compliance
- willing to follow safety protocol
124
bad candidiates for buprenorphine
- dependence on other CNS depressant as well
- untreated psych
- multiple relapses
- poor response
- complec medical
125
major diffence between methadone and buprenorphine
methadone: more follow up
buprenorphine: more accessible
126
buprenorphine dosing
SAME for detox and maintenance
general:
buprenorphine 4mg-32mg/day
can do qd or bid (?)
127
buprenorphine options
Subutex
Probuphine
Sublocade
128
buprenorphine/naloxone options
Suboxone
Zubsolv
Bunavail
129
which bup products are tablets?
Subutex
Suboxone -- SL tab or film
Zubsolv
130
which bup products are films
Suboxone -- SL film
Bunavail --> buccal film
131
which bup products is an implant
Probuphine
132
which bup product is SQ
Sublocade
133
why is there naloxone in bup?
prevent abuse -- people injecting the bup into their veins
oral bup: poor bioavaliabillity
parental bup: high bioavliability
134
how do the bioavaliability of the bup/nalox products compare?
Zubsolv and Bunavail have higher F than Suboxone --> therefore less Bup is needed for some concentration --> less abuse potential
135
what is a low creatinine indicative of?
very dilute urine (drank water)
136
what is a low drug level indicative of
missed dose --> may have diverted it!
137
what bup products are first line
bup/nalox
138
sublocade benefits
- injectable --> reduce diversion, increase compliance
139
sublocade dose
300mg SQ qmonth x2 months --> 100mg SQ qmonth ---> if withdrawal, inc to 300mg SQ qmonth
140
what is special about sublocade?
1) BBW: harm/death if IV -- forms clump
2) REMS required
141
sublocade indication
maintenance treatment of opioid dependence
AFTER
adjusted to 8-24mg of transmucosal bup product x7 days
142
sublocade counseling
do not rub injection site
143
clonidine MoA
stimulate alpha 2 adrenergic receptors --> dec sympathetic --> dec NE --> prevent fight/fight withdrawal
**works against xylazine bc have same MoA
144
clonidine AEs
- drowsy
- dizzy
- dry mouth
- HA
- abdominal pain
145
lofexdine MoA
stimlate alpha 2 adrenergic receptors --> same as clonidine
146
lofexidine AEs
- orthostatic hypotension
- insomnia
- dizzy
- dry mouth
- drowsy
147
naltrexone MoA
competitive complete opioid antagonist
148
naltrexone dose
25mg po qd x1week, then 50 mg qd
OR
380mg IM qmonth
149
naltrexone requirement
MUST BE OPIOID FREE 7-10 DAYS
- if not, will cause withdrawal
- IM needs tox negative
150
naltrexone BBW
acute hepatitis
hepatocellular injury
151
which drugs do you need to be opioid free for 7-10 days for?
naltrexone po
naltrexone IM
Vivitrol (naltrexone XR) (po or IM)
152
naltrexone AE
GI upset
153
dextromethorphan MoA
inhibit NMDA receptor --> dec stimulation --> depressant
154
DXM effects
-hallucinations
- slur speech
- HTN
- lethargy
- altered time perception
155
stimulants
- cocaine
- amphetamine
- methamphetamine
- PCP
- ketamine
156
cocaine MoA
inhibit NE and DA reuptake --> inc NE and DA --> hence stimulant
snort, inject, smoke, gum
HCl vs crack form
157
cocaine effects
- *nasal septum ulceration
- *kindling -- hallucinations, psychosis --> the more you use, the more potential for these
- mydriasis
- aggression
- sweats
- N/V
158
cocaine withdrawal
- depression
- fatigue
- nightmares
- sleep disturbance
- tremor
159
cocaine metabolites
inactive
160
bromocriptine MoA
dopamine agonist
hence why maybe cocaine withdrawal bc same MoA as cocaine
161
amphetamine MoA
block DA and NE reuptake + inc DA and NE release + inhibit monoamine oxidase --> stimulant
162
amphetamine effects
- *meth mouth --> DONT GET IF RX AMOUNTS ahhhhh
- alert
- dec fatigure
- irritable
- insomnia
- confused
- anxiety
163
amphetamine withdrawal
- fatigue
- depression
- cog impairment
if cooking at home --> fires, explosions
164
what is ecstatsy MDMA
derivative of amphetamine, destroys serotonin producing neurons
165
ecstasy MDMA
- empathy
- suppress need to eat, drink, sleep
- amphetamine ones
166
PCP MoA
DA, 5HT, NE reuptake inhibitor --> stimulant
167
PCP effects
euphoria, delusion, hallucination
low doses: sedation, slur speech, paresthesia
high doses: inc HR, inc BP, muscle rigidity, coma, seizure
168
ketamine MoA
anesthetic, cataleptic (muscle rigidity), release catecolamines (E, NE) to maintain BP and HR --> stimulant
169
ketamine effects
- inc BP
- inc HR
- hallucinate
- delirium
- vivid dreams
- seizures
- cardiac arrest
170
hallucinogens
-LSD
-psilocybin
-mescaline
171
LSD MoA
stimulate pre and post synaptic serptonin --> inc serotonin --> hallucinate
172
LSD effects
- mydriasis
- inc temp, bp, hr
- dry mouth
- dizzy
- flashbacks
173
marijiana MoA
cannabinoid receptors, release dopamine
174
marijiana effects
- euphoria
- disinhibition
- impaired cognition --> short term, memory, skills
- bronchioles relax and enlarge
- hunger
- thrist
175
marijuana metabolites
lots of metabolites
176
inhalants MoA
huff glues, solvents, gas, etc... --> rapidly absorbed by lungs --> penetrate BBB
177
inhalant effects
- Nausea
- HA
- brain low O2
- brain damage
- suffocation
- impaired pulmonary function
178
combo drugs
more prone to OD because don't appreciate the toxicitity of each individually
179
misc drugs
- krokodil
- bath salts
- synthetic marijuana
- kratom
180
krokodil MoA
from codeine, potent short acting opioid --> therefore depressant
**impure and contaminated
181
krokodil effects
SQ --> local tissue damage, ulcers, skin necorisis, infection
182
krokodil OD effects
- slow shallow breathing
- small pupils
- slur speech
183
bath salts MoA
synthetic stimulants
184
bath salt effects
amphetamine like stimulatory effects
185
bath salts OD effects
- tachycardia
- HTN
- hyperthermia --> most common cause of death
186
bath salts OD treatment
- IV benzos
- fluids
-sedation
187
synthetic cannabinoids MoA
much more potent receptor agonists that marijuana
188
synthetic cannabinoid effects
more pronounced effect than marijuana bc synthetic
189
kratom MoA
stimulate aplha 2 adrenergic, block serotonin, opioid
190
kratom effects
stimulant at low doses
depressant at high doses
191
pregnancy risks for patients
- test infant hair
- HIV risk
192
pregnancy opioid use disorder recommendations
1st: methadone
2nd: Subutex > Suboxone
193
