Abuse intoxication and withdrawal symptoms Flashcards
- Substance dependence
- Physiologic dependence
- Tolerance
- Withdrawal
- Sensitization
A. Substance Dependence (the disorder)- A maladaptive pattern of substance
use leading to significant impairment or distress. A chronic, progressive, relapsing disorder (disease?) of continued substance use despite negative consequences.
B. Physiologic Dependence- The state of the body as a result of the ongoing
exposure to a substance. An adaptation of the cells to the presence of a drug. Present if the person displays tolerance or withdrawal.
C. Tolerance- A diminished biological or behavioral response to repeated
administration of the same amount of a substance or, the need for increasing amounts of a substance to achieve the same effect.
D. Withdrawal- The physical and/or psychological disturbances that occur after
the cessation of use of a substance to which the body has developed tolerance.
E. Sensitization- (“Reverse Tolerance”) An increased biological or behavioral response
to repeated administration of the same amount of a substance.
Basic concepts
A. Intoxication & withdrawal syndromes are fairly specific to each class of substance
B. Time frame varies with route of administration and pharmacology of specific drug
C. Because many patients often use more than one substance at a time, the
syndromes are often not seen in their “pure” forms
D. Synergistic effects are seen when certain types of substances are combined – Such as sedatives or alcohol with opioids
E. Often, illicit drugs are “cut” with other substances. This can confuse the picture.
Intoxication you can die from
Cocaine Opioids Amphetamines Phencyclidine Benzodiazepines Steroids Alcohol Inhalants Barbiturates Designer Drugs
Withdrawal you can die from
Alcohol
Barbiturates
Benzos
Opioids –> neonates and severely ill
Cocaine intoxication
- May result in cardiac arrhythmia, MI, stroke, rhabdomyolysis and death
- Typically seen within 7 seconds to 30 minutes of use
a. onset depends on route of administration (smoked«<)
coma auditory hallucinations
headache anorexia
insomnia
hyper sexuality
nausea/vomiting
muscle aches
bruxism
Cocaine intoxication - treatment
a. largely supportive
i. medications generally needed only for agitation
ii. provide a quiet, stimulus-free environment
b. seizures
i. diazepam, phenytoin or phenobarbital
ii. intravenous or via nasogastric tube
c. psychosis
i. high potency neuroleptic
ii. only if psychosis is prolonged
iii. may worsen sympathomimetic, cardiovascular, and seizure effects
d. agitation
i. benzodiazepine
ii. rarely, causes further disinhibition
e. chest pain
i. benzodiazepine
ii. nitroglycerin, if severe, with EKG changes
Cocaine withdrawal
- Typically seen within a few hours to several days after last use
- May last for several days
- Severity depends on amount, chronicity, and route of administration
Signs & Symptoms fatigue dysphoric mood hypersomnia suicidal ideation increased appetite vivid, unpleasant dreams psychomotor retardation irritability lethargy cocaine craving
Treatment
a. supportive only
b. avoid temptation to start an antidepressant immediately as this does not
reverse the depression
Amphetamines intoxication
- Basically the same as for cocaine
- Effects may last up to 24 hours, depending on drug and route of administration
- Psychotic symptoms more common than with cocaine
- Treatment
a. basically the same as for cocaine
b. largely supportive
Amphetamines withdrawal
Same as cocaine, symptoms may last longer
Caffeine intoxication
- Typically seen with >250-500mg of caffeine (>3-5 cups brewed coffee)
- Can be lethal at doses of 5-10 grams
Signs & Symptoms
tachycardia restlessness
palpitations nervousness/excitement
frequent urination insomnia
diarrhea rambling/rapid speech
muscle twitching inexhaustibility
flushed face psychomotor agitation
Treatment
a. Primarily supportive
Caffeine withdrawal
- Not listed in DSM-IV but definitely seen clinically
- Generally mild
- Unclear relationship to dose or duration of use
a. Some reports of withdrawal after less than one week of use - Typically begins 12-24 hours after last dose of caffeine
- May last from 2-7 days
Signs & Symptoms headache difficulty concentrating nausea fatigue vomiting drowsiness muscle aches depressed mood hot & cold spells irritability anxiety
Treatment
a. tapered doses of caffeine
b. symptomatic treatments for headache, etc.
Hallucinagen intoxication
Rarely life-threatening except as related to delusions or perceptual distortion
- Typically seen within several minutes to a few hours of use
a. depends on specific drug, route of administration and setting - Effects typically last for several hours
a. exception with DMT which is very short-acting - Reality testing is usually intact
Signs & Symptoms tachycardia intensified perceptions diaphoresis depersonalization pupillary dilation derealization blurred vision illusions palpitations synesthesia tremulousness visual hallucinations incoordination auditory hallucinations nausea/vomitting tactile hallucinations restlessness delusions disorientation mood lability hyperthermia impaired judgment
Hallucinagen intoxication treatment
a. largely supportive
i. medications generally not necessary
b. agitation
i. benzodiazepine if moderate
ii. may add an antipsychotic if severe
a) . high potency safer
c. psychosis
i. a few studies have shown that antipsychotic shorten the episode
Hallucinagen withdrawal
Hallucinogen persisting perception disorder (“flashback”)
No real withdrawal syndrome
- Occurs after the cessation of use of hallucinogens
- May continue for several months to many years after last use
- Often triggered by stress, fatigue, anxiety, dark environment, other drug use
- Reality testing remains intact
Symptoms geometric hallucinations flashes of color trailing images intensified colors positive afterimages halos around objects macropsia/micropsia peripheral-field images
Opioid intoxication
- Can be fatal due to central respiratory depression
- Typically seen within seconds to minutes of use
a. onset depends on route of administration (smoked«<oral) - Effects typically last for several hours
a. largely dependent on half-life of the particular substance
Signs & Symptoms
pupillary constriction(except anoxia) euphoria (initially)
drowsiness
apathy
slurred speech impaired judgment
respiratory depression impaired attention
coma inattention to environment
seizures (extremely rare) psychomotor retardation
constipation psychomotor agitation(rare)
pruritis
Opioid intoxication treatment
a. first response is to establish adequate airway
b. Naloxone (Narcan)
i. a virtually pure mu antagonist
ii. short acting
iii. give IV (can be given IM if no IV access)
iv. 0.3-0.5mg is often enough to reverse respiratory depression
v. use cautious increments to avoid precipitating acute withdrawal
vi. response is typically seen in 1-2 minutes, generally, if no response to 5-10mg of naloxone, another etiology is likely to be responsible
vii. may need to repeat dose if overdose is with an opiate with a long t1/2
Opioid withdrawal
- Typically seen within 6-24 hours of last use (for shorter-acting drugs)
a. may be several days for longer-acting drugs (methadone and Oxycontin) - Acute symptoms last for one to seven days (peak within one to three days}
a. may last for weeks with longer-acting drugs - Sub-acute symptoms can last for weeks to months
- Not life-threatening except in neonates and severely debilitated
Signs & Symptoms pupillary dilation dysphoria piloerection anxiety diaphoresis irritability lacrimation restlessness rhinorrhea achy feeling (especially back and legs) nausea/vomiting abdominal cramping diarrhea craving fever insomnia tachycardia hyperalgesia hypertension yawning involuntary muscle movements seizures (in dependent neonates)
Opioid withdrawal treatment
a. usually treat pharmacologically even though not life threatening
b. Clonidine
i. alpha 2-adrenergic agonist
ii. appears to work by suppressing autonomic activity in locus ceruleus
iii. reduces some physiological signs/symptoms of withdrawal
iv. does not really reduce psychological symptoms (ie. craving, lethargy)
v. can be used alone or in combination with other treatments
vi. no time limitation as it is not a scheduled substance
vii. decreased blood pressure is most significant problem
viii. can also cause sedation
a) .caution patient about driving and operating equipment
ix. need to be cautious tapering too quickly (rebound hypertension)
x. use cautiously if patient on TCA or beta-blocker
xi. do not use if patient is pregnant
c. Lofexidine
i. similar to clonidine
ii. much less effect on blood pressure
iii. currently not used in U.S.
d. Methadone
i. long acting mu opioid agonist
ii. can be used legally for opioid withdrawal for 72 hours on out-patient basis
a) . needs to be administered by the physician
iii. can be used for as long as needed in general hospital
a) . provided patient admitted for reason other than addiction
iv. generally recommended to start with 20mg/day orally if moderate use is suspected and 30 mg/day orally if heavy use is suspected
v. should suppress withdrawal symptoms within 60 mins
a) . if not, an additional 5-10mg can be given
vi. taper by 5-10mg/day
e. Buprenorphine
i. a partial mu opioid agonist
ii. rapid onset
iii. dissociates slowly from opiate receptors
iv. ceiling effect on all mu opioid mediated effects
a) . minimal respiratory depression
b) . produces lower level withdrawal signs/symptoms
c) . analgesic effects good for mild to moderate pain
v. DEA schedule III
vi. sublingual form which combines buprenorphine with naloxone (Suboxone)
a) . theoretically reduces the potential for abuse
vii. DEA waiver required to use on out-patient basis
viii. can be used for as long as needed in general hospital without DEA waiver
a) . provided patient admitted for reason other than addiction
ix. generally recommended to start with 4-8mg/day sublingually
f. Other mixed agonist/antagonists or partial agonists
i. butorphanol, dezocine, nalbuphine, pentazocine
g. Other mu opioid agonists
i. not well studied
h. ”Rapid Detox”
i. uses clonidine, benzodiazepine and naltrexone
ii. naltrexone precipitates withdrawal to “speed up the process”
i. ”Ultra Rapid Detox”
i. uses clonidine, naltrexone and general anesthesia
ii. performed in “specialized” centers by anesthesiologists
iii. claim to achieve full detoxification in 24 hours
iv. no good studies demonstrating efficacy or benefits over other methods
v. added risk of general anesthesia
vi. expensive
Symptomatic adjuncts for opioid withdrawal
i. used along with any of above detoxification methods
ii. muscle aches
a) . ibuprofen, acetaminophen, tramadol (less recommended)
iii. muscle spasms
a) . methocarbamol, cyclobenzaprine
iv. anxiety/irritability
a) . benzodiazepine, diphenhydramine
v. insomnia
a) . trazadone, doxepin, amitriptyline, zolpidem, benzodiazepine
vi. nausea
a) . phenergan, metoclopramide
vii. diarrhea
a) . Pepto-Bismol, imodium
Marijuana intoxication
- Not life-threatening
- Typically seen within several minutes to several hours of use
a. onset depends on route of administration (smoked«<oral)
b. setting and expectations very important - Effects typically last three to four hours
a. may be longer if ingested orally
Signs & Symptoms
conjunctival injection
euphoria
increased appetite inappropriate laughter
dry mouth impaired concentration
tachycardia impaired judgment
sedation distorted sensory perception
lethargy sensation of time passing slowly
impaired motor performance impaired short-term memory
anxiety (rare)
social withdrawal
Marijuana intoxication treatment
a. largely supportive
i. medications generally not necessary
b. anxiety/panic
i. benzodiazepine
a) . only if anxiety is severe
Marijuana withdrawal
- Generally occurs late, is very non-specific and is very prolonged
Signs & Symptoms tremulousness irritability diaphoresis anxiety nausea sleep disturbance
Treatment
a. no medication needed
Alcohol intoxication
- Typically seen within 5-30 minutes of use (in non-tolerant individual)
a. onset and duration largely dependent on tolerance
b. correlates with blood alcohol level (in non-tolerant individual)
c. gender and race very important in metabolism - May be life-threatening due to respiratory depression
Signs & Symptoms slurred speech diplopia incoordination decreased visual acuity unsteady gait mood lability nystagmus decreased inhibitions flushing impaired judgment feeling of warmth impaired motor performance hypothermia confusion diuresis disorientation hypotonia impaired attention nausea/vomiting stupor/coma
Alcohol intoxication treatment
a. largely supportive
b. coma
i. airway support
ii. 50% dextrose
iii. evaluate for evidence of trauma
c. irritability/violence
i. use largely behavioral methods to de-escalate
ii. can use low dose benzodiazepine
Alcohol withdrawal
- 95% of cases are self-limited and uncomplicated
- Always try to get a history of previous DTs or seizures
- Absolute blood alcohol level less important than tolerance
a. it is the decrease in blood alcohol level that seems to be important
b. more concerning if patient has very high level but doesn’t seem intoxicated - Can be fatal due to delirium tremens or seizures
- Most cases progress in a fairly predictable fashion and time-course
- This may be greatly delayed and prolonged if patient also dependent on other CNS depressant (eg. benzodiazepine)
Stages of alcohol withdrawal
Stage I i. typically seen within 24 hours of last use ii. in mild cases, symptoms generally abate in 24-48 hours iii. Signs & Symptoms tremulousness anxiety hypertension agitation tachycardia derealization (mild) diaphoresis slowed thinking nausea clouded sensorium (mild) hyperactive reflexes insomnia fever headache
Stage II
i. typically seen within 48 hours of last use
ii. signs and symptoms as in Stage I but more severe
iii. in addition, see hallucinations
a) . generally auditory but may be visual
b) . generally non-threatening
c) . often called “hallucinosis”
iv. patient usually with intact reality testing
Stage III (“Delirium Tremens”)
i. < 1% of alcohol withdrawal cases
ii. typically seen about 72 hours after last use
iii. may last three to seven days (if patient doesn’t die first)
iv. rarely, can see this without passing through Stage II
v. usually seen in patients with another, complicating medical condition
vi. signs and symptoms as in Stages I and II but even more severe
vii. hallucinations may be visual, olfactory, auditory, or tactile
a) . small animals or people-“classic”
b) . often threatening
viii. patient typically very anxious and fearful with severe affective lability
ix. patient is markedly disoriented; generally worse at night
Alcohol withdrawal seizures
a. independent of delirium tremens
b. generalized tonic-clonic
c. typically seen 12- 48 hours after last use
i. may occur as much as a week later
d. <5% of withdrawal
e. most are self-limited
f. always evaluate for other causes of seizure
i. head trauma, intracranial bleed, metabolic
Alcohol withdrawal treatment
a. suggested criteria for in-patient detoxification
hepatic decompensation
history of DTs or withdrawal seizures
significant dehydration extreme agitation
malnutrition tachycardia >100/minute
infection
severe tremor
cardiovascular collapse
fever > 38.5 C
cardiac arrhythmias Wernicke’s encephalopathy
confusion or delirium
hallucinations
recent head injury with loss of consciousness
Alcohol withdrawal treatment - benzos
i. most commonly used treatment
ii. have anticonvulsant effects
iii. low toxicity
a).less respiratory depression (compared to other CNS depressants)
iv. attenuate autonomic signs and symptoms of withdrawal
v. can be given parenterally (IV/IM) if patient is uncooperative
vi. evidence that they are best used if titrated according to severity
vii. practically, due to staffing, etc. it is often better to place the patient
on a standing dose with a fixed taper
viii. no clear evidence that one benzodiazepine is better than another
a). lorazepam & oxazepam preferable if patient is in liver failure
b). longer acting(chlordiazepoxide; diazepam) provide smoother withdrawal
ix. often need much higher doses once DTs have begun
x. lower doses are needed if patient is in liver failure
xi. generally start with a dose and taper by 20-25%/day
a). chlordiazepoxide 25-50 mg p.o. q 6 hours
b). diazepam 10-20 mg p.o. or i.v. q 4-6 hours
xiii. depending on patient’s tolerance, may need much higher doses
Alcohol withdrawal treatment
- beta blockers
- carbamazepine
valproic acid
ß adrenergic blockers
i. few well-controlled data ii. may be helpful in mild-moderate withdrawal in addition to benzodiazepine iii. need to be cautious not to “mask” signs of impending DTs iv. no anti-seizure activity v. use in combination with a benzodiazepine, if used at all
Carbamazepine
i. used extensively in Europe for alcohol withdrawal
ii. some studies show it to be equally effective to benzodiazepines
iii. may suppress kindling effect (increased severity of withdrawal with
repeated episodes)
Valproic Acid
i. limited, but growing, research ii. theoretically, effective because of action on GABA receptors iii. well tolerated
Alcohol withdrawal treatment
- gabapentin
- antipsychotics
- ethanol
- propofol
- other experimental agents
Gabapentin
i. currently under investigation ii. likely to be effective because of action on GABA receptors
Antipsychotics
i. generally not used because of effect of lowering seizure threshold ii. only used in severe cases of DTs iii. if used, use high potency
Ethanol
i. used PO or IV ii. more popular on surgical/trauma services iii. no controlled studies showing superiority over benzodiazepines iv. no established dosing guidelines
Propofol
i. sedative anesthetic
ii. several reports of efficacy in severe withdrawal
iii. see significant respiratory depression
a) . needs to be used in ICU setting
other experimental agents
i. GHB, chlormethiazole, magnesium, topiramate, dexmedetomidine
Benzo intoxication
- Basically as for alcohol
- Onset and duration of symptoms largely dependent on various properties
of the specific drug (half-life, absorption, active metabolites, lipid solubility) - Minimal direct respiratory effects when used alone
a. rarely fatal - Potential for mortality much higher when combined with alcohol or barbiturate
Treatment
a. coma
i. Flumazenil
a) . specific benzodiazepine antagonist
b) . use very cautiously!!!
- –>. may precipitate withdrawal (DTs/seizures) if patient dependent
ii. if serum levels very high, consider dialysis/charcoal resin hemoperfusion
iii. alkalinization of urine not generally recommended any more
Benzos withdrawal
- Can be fatal
- Basically as for alcohol
a. onset typically later
i. depends on half-life of particular drug
ii. may be one to two weeks after last use
b. course typically longer
i. symptoms may last for several weeks - Incidence of seizures may be higher than with alcohol withdrawal
Benzos withdrawal treatment
a. detoxification often needs to be much more gradual than for alcohol
b. several ways of performing detoxification:
i. tapering the benzodiazepine that the patient is already taking
a). can use if patient is being prescribed the medication and you are
fairly confident of the amount being used
b). taper may need to be slowed toward the end of the protocol
ii. converting to a long-acting benzodiazepine and tapering it
a). often used if patient is using a short-acting drug
iii. converting to phenobarbital
a). longer acting with more stable blood levels
b). some clinicians feel it is psychologically easier for the
patient to detox using a medication that they are not dependent on
c. Tolerance testing
i. used when it is not certain how much the patient is using
a). Pentobarbital challenge
b). Diazepam challenge
d. Anticonvulsants
i. Valproic acid & carbamazepine may be effective in treating withdrawal
Barbiturates - intoxication and withdrawal
Intoxication - same as alcohol
Withdrawal - same as benzos
Phencyclidine intoxication
- Typically seen within 10 seconds to 30 minutes of use
a. onset depends on route of administration (smoked<po) - Effects typically last for several hours to several days
a. often see a waxing and waning clinical presentation - Effects largely dose-dependent symptoms directly correlate with blood levels
- Often commit dangerous acts without knowing it because of analgesic effects
Signs & Symptoms nystagmus (vertical or horizontal) euphoria hypertension mood lability tachycardia disorganized thinking decreased responsiveness to pain slowed reaction time ataxia distorted body image dysarthria/slurred speech depersonalization muscle rigidity derealization seizures combativeness/belligerence coma irritability respiratory depression amnesia hyperacusis impaired judgment hyperthermia disorientation
Phencyclidine intoxication treatment
a. largely supportive
i. medications generally not necessary
b. agitation
i. may use a benzodiazepine if severe
a) .need to be cautious in case other CNS depressants were also used
c. psychosis
i. high potency neuroleptic
ii. only if psychosis is prolonged
d. acidification of the urine is not generally recommended any more
Phencyclidine withdrawal
Supportive only
Inhalants classification
Volatile Organic Compounds(toluene, acetone,butane, xylene, gasoline, etc.)
i. primarily CNS depressants (act first on cortex and then on brainstem)
ii. decrease the partial pressure of inhaled oxygen causing hypoxia
Nitrites (amyl nitrite, butyl nitrite, isobutyl nitrite)
i. exact mechanism of euphoria is not fully understood
a) . likely due to generalized CNS hypoxia
ii. smooth muscle relaxation from dephosphorylation of myosin light chains
a) . significant vasodilation, GI sphincter relaxation, decreased rectal tone, increased penile blood flow
Nitrous Oxide
i. CNS depressant
ii. probably acts by altering neuronal membranes
iii. may have effects on dopamine and opiate systems
iv. blunts respiratory drive
a) . displaces oxygen leading to decreased oxygen tension
Inhalants intoxication
- Typically seen within several seconds to several minutes of use
- Effects typically last for 30 seconds to one hour
Signs & Symptoms nystagmus dizziness/light-headedness unsteady gait psychomotor retardation slurred speech incoordination depressed reflexes euphoria tremulousness blurred vision/diplopia muscle weakness giddiness nausea/vomiting lethargy stupor headache coma
Treatment
a. supportive measures generally sufficient
b. may require supplemental oxygen
Inhalants withdrawal
- Not well defined
- Typically seen within one to two days of last use
- May last for two to five days
Signs & Symptoms
tremulousness irritability
diaphoresis illusions (fleeting)
nausea insomnia
Treatment
a. supportive measures generally sufficient
Anabolic steroid intoxication
headaches anxiety diaphoresis emotional instability increased blood pressure irritability tachycardia aggressiveness (“roid rage”) abdominal pain increased self-confidence increased appetite combativeness impotence paranoid behavior insomnia depression
Anabolic steroid intoxication treatment
a. largely supportive
i. medications generally needed only for agitation
ii. provide a quiet, stimulus-free environment
b. psychosis
i. high potency neuroleptic
ii. only if psychosis is prolonged
iii. may worsen sympathomimetic, cardiovascular, and seizure effects
c. agitation
i. benzodiazepine
ii. rarely, causes further disinhibition
Anabolic steroid withdrawal
- Often very non-specific
- May begin within one day of last use
insomnia depression
irritability paranoia
decreased energy decreased motivation
decreased appetite
Treatment
a. Detoxification from high doses of prescribed anabolic steroids is
generally accomplished by a slow taper of the steroid being used.
b.Theoretically, it would be possible to detoxify a person who is
abusing illicitly obtained steroids using a slow taper of another steroid.
Designer drugs
- intoxication
- withdrawal
B. Intoxication
- Similar to that of other substances in the related drug class
- Time frames vary with specific drug
- Treatment
a. very little specific data
b. treat as you would other substances in the related class
C. Withdrawal
- Similar to that of other substances in the related drug class
- Time frames vary with specific drug
- Treatment
a. very little specific data
b. treat as you would other substances in the related class
OTC meds/herbal drugs
- Many substances not benign
- Very few data on abuse this but is felt to be common
- Some evidence that it is more common in women & elderly
- Can cause significant intoxication and withdrawal depending on the drug
a. especially those with anticholinergic effects
