LaGenia Bailey, Pharm.D.
Spring 1998
LaGenia Bailey, Pharm.D.
Spring 1998
Drug Misuse, Abuse, Addiction, Dependence
Drugs of Abuse
I. INTRODUCTION
DEFINITIONS/TERMINOLOGY
1. Abstinence: Non-use of a specific substance. In recovery, non-use of any addictive psychoactive substance. May also denote cessation of addictive behavior, such as gambling, over-eating, etc.
2. Abuse: Harmful use of a specific psychoactive substance. Term also applies to one category of psychoactive substance use disorder. ASAM recommends this term not be used, because of perjorative connotations.
3. Addiction: A disease process characterized by the continued use of a specific psychoactie subsance despite physical, psychological, or social harm.
4. Blackout: Acute antegrade amnesia with no formation of long-term memory, resulting from the ingestion of alcohol or other drugs; i.e. a period of memory loss for which there is no recall of activities.
5. Dependence: (term utilized in three ways)
a. Psychological Dependence-a profound emotional need for the repetitive use of a particular drug or class of drugs.
b. Physical Dependence-a state of altered cellular physiology caused by repetitive use of a drug which may, as a result of acute or gradual withdrawal, precipitate a characteristic abstinence syndrome.
c. one category of psychoactive substance use disorder.
6. Detoxification: a process of withdrawing a person from a specific psychoactive substance in a safe and effective manner.
7. Enabling: Any action by another person or an institution that intentionally or unintentionally has the effect of facilitating the continuation of an individual's addictive process.
8. Impairment: A dysfunctional state resulting from useof psychoactive substances.
9. Intervention: a planned intervention with an individual who may be dependent on one or more psychoactive substances, with the aim of making a full assessment, overcoming denial, interrupting drug-taking behavior, or inducing the individual to initiate treatment. The preferred technique is to present facts regarding psychoactive substance use in a caring, believable and understandable manner.
10. Legalization: Removal of legal restrictions on the cultivation, manufacture, distribution, possession and/or use of a psychoactive substance.
11. Loss of Control: The inability to consistently limit the self-administration of psychoactive substances.
12. Misuse: Any use of a prescription drug that varies from accepted medical practice.
13. Problem Drinking: An informal term describing a pattern of drinking associated with life problems prior to establishing a definitive diagnosis of alcoholism.
14. Recovery: A process of overcoming both physical nd psychological dependence on a psychoactive substance, with a commitment to sobriety.
15. Tolerance: State in which an increased dosage of a psychoactive substance is needed to produce a desired effect.
16. Withdrawal Syndrome: the onset of a predictable constellation of signs and symptoms following the abrupt discontinuation of, or rapid decrease in, dosage of a psychoactive substance.
II. EPIDEMIOLOGY
A. SUBSTANCE ABUSE IN THE GENERAL POPULATION4,5
1990 Household survey of the population aged 12 and older, representative sample of 201 million people
1. Illicit Drugs
37% used in lifetime (74 million people)
13% in past year
6% in the month before the survey
2. Alcohol
83% used in lifetime(167 million)
66% in the past year
51% in the past month
3. Cigarettes
73% used in lifetime(147 million)
32% in past year
27% in past month
4. Most common illicit drugs
Marijuana > Prescription > Cocaine.
33% have used marijuana
12% had ever used psychotherapeutic drugs for non-prescription purposes
11% used cocaine
1% (2 million people) had used either Rx drugs or cocaine in the past month
Less than 8% of the population and fewer than 1% in the last month had used other substances of abuse.
5. Demographics:(illicit drugs)
a. Groups at highest risk for drug use
younger adults (18-25 yrs)
men
african americans
residents of large metropolitan areas
residents of the Western US
b. Breakdown by age: use in the past month
12-17 (1.2 million)
18-25 (4.3 million)
> 25 (7 million)
B. PRESCRIPTION DRUG USAGE
1. National Household Survey of Drug Abuse Population (NHSDA) DATA
215 Million prescriptions per year for psychotherapeutic (stimulants, sedative, tranquilizers, and analgesics)drugs.
Definition of Nonmedical Use: Any use
-on your own without a doctor's prescription
-in greater amounts that prescribed
-more often than prescribed
-or for any reasons outside the indication for the medication
NIDA National Household Survey of Drug Abuse Population Estimates
Trends in Nonmedical Use of Any Psychotheraptic agent (1988-1991)
1988 1990 1991 Number % Number % Number % Lifetime 23,536 11.9 24,025 11.9 25,463 12.6 Past Year 11,399 5.7 8,567 4.3 9,161 4.5 Past Month 3,393 1.7 2,858 1.4 3,062 1.5
2. Drug Abuse Warning Network: Drug related emergency episodes in the Unitied states
1985 1986 1987 1988 1989 Total DAWN Episodes 76,391 87,388 103,500 114,411 109,400 Controlled Prescription Drug Episodes 28,840 27,430 27,219 25,292 23,020 Percent due to RX 37.8 % 31.4 % 26.3 % 22.1 % 21.0 %
Top Twenty Drugs From 1990 DAWN emergency room visits:
# of Mentions # of Suicide Mentions Alcohol in combination 115,162 49,125 Cocaine 80,355 5,203 Lithium Carbonate 44,025 N/A Heroin/Morphine 33,884 1,154 Acetaminophen 25,422 20,938 Aspirin 19,188 15,525 Ibuprofen 16,299 N/A Alprazolam 15,846 10,976 Marijuanan/Hashish 15,706 1,124 Diazepam 14,836 8,604 Amitriptyline 8,642 6,535 Acetaminophen/Codeine 8,222 N/A O.T.C. Sleep Aids 7,984 6,733 Lorazepam 7,625 4,857 D-Propoxyphene 7,417 1,164 Fluoxetine 6,917 6,205 Diphenhydramine 6,483 5,059 Methamphetamine/Speed 5,236 661 Oxycodone 4,526 2,528 PCP/PCP combinations 4,408 244
1990 Illicit Drugs DAWN Emergency Room Visits
# of Mentions # of Suicide Mentions Alcohol in combination 115,162 49,125 Cocaine 80,355 5,203 Heroin/Morphine 33,884 1,154 Marijuana/Hashish 15,706 1,124 Methamphetamine/Speed 5,236 661 PCP/PCP combinations 4,408 244
1990 RX Drugs DAWN Emergency Room Visits
# of Mentions # of Suicide Mentions Lithium Carbonate 44,025 N/A Acetaminophen (Tylenol) 25,422 20,938 Aspirin 19,188 15,525 Ibuprofen 16,299 N/A Alprazolam (Xanax) 15,846 10,976 Diazepam (Valium) 14,836 8,604 Amitriptyline (Elavil) 8,642 6,535 Acetaminophen/Codeine 8,222 N/A O.T.C. Sleep Aids 7,984 6,733 Lorazepam (Ativan) 7,625 4,857 D-Propoxyphene (Darvon) 7,417 1,164 Fluoxetine (Prozac) 6,917 6,205 Diphenhydramine (Benadryl) 6,483 5,059 Oxycodone (Percodan) 4,526 2,528
C. SUBSTANCE USE IN THE MENTALLY ILL POPULATION
Epidemiologic Catchment Area Study (ECA)6,7
Study funded by the National Institute of Mental Health(NIMH) to better characterize mental illness and substance use in the United States.
Includes both community and institutionalized populations.
N=20,291
1. Overall findings
a. Lifetime Population Prevalence rates:
Non-substance abuse psychiatric disorder: 22.5% Alcohol Dependence: 13.5% Other Drug dependence/Abuse: 6.1%
b. Dual diagnosis:(those patients with a psychiatric disorder)
Odds ratio: 2.7 X greater Lifetime prevalence: (22% alcohol and 15% drug) 29% (combination)
c. Alcohol Dependence:
Co-morbid psychiatric disorder: 37%
d. Drug dependence:(other than alcohol)
Co-morbid psychiatric disorder: 53%
Odds ratio: 4.5
2. Specific Populations, lifetime abuse:
a. Psychiatric Hospitals:
Substance abuse: 39.6% Alcohol Disorders: 34.1% Drug Abuse: 16.1% Approximately one third of patients in general psychiatric settings.1,8
b. Prisoners:
Substance abuse: 72% Alcohol: 56.2% Drug: 53.7%
c. Nursing Homes:
Substance abuse: 14.3%
d. Emergency Rooms:
Greater than one half of patients in psychiatric emergency rooms or inpatients psychiatric programs have problems substantially affected by substance use or dependence.1,8
3. Specific Diagnosis
a. Schizophrenia or Schizophreniform Disorder
1.5% of the US population
Inpatient histories may be higher percentages than outpatient treatment due to higher admission rate for substance abusing patients.
Substance abuse: 47% Odds ratio: 4.6 Alcohol disorder: 33.7% Odds ratio: 3.3 Other drug diagnosis: 27.5% Odds ratio: 6.2 Hypothesis for use:
Cocaine:
socialization
self-medication (apathy, withdrawal, unresponsiveness, extrapyramidal side effects)
increase sexual dysfunction
Opioids:
decrease psychotic symptoms
b. Affective Disorders
i. Depression
Substance abuse: 27.2% Odds ratio: 1.9 Alcohol disorder: 16.5% Odds ratio: 1.3 other drug diagnosis: 18.0% Odds ratio: 3.8 Symptom Resolution:
Much of the depression identified during alcohol withdrawal subsides after 2-4 weeks of abstinence from alcohol.
In 90% of heavy drinkers who display depressive symptoms, the diagnosis is alcoholism and not primary affective illness.
ii. Bipolar
Substance abuse: 56.1% Odds ratio: 6.6 Alcohol disorder: 43.6% Odds ratio: 5.1 other drug diagnosis: 33.6% Odds ratio: 8.3 " Self-treatment"
c. Anxiety Disorders
Substance abuse: 23.7% Odds ratio: 1.7 Alcohol disorder: 17.9% Odds ratio: 1.5 other drug diagnosis: 11.9% Odds ratio: 2.5
i. Panic Disorder:
Substance abuse: 35.8% Odds ratio: 2.9 Alcohol disorder: 28.7% Odds ratio: 2.6 other drug diagnosis: 16.7% Odds ratio: 4.4
ii. Phobia :
Substance abuse: 22.9% Odds ratio: 1.6 Alcohol disorder: 17.3% Odds ratio: 1.4 other drug diagnosis: 11.2% Odds ratio: 2.2
iii. Obsessive-Compulsive Disorder
Substance abuse: 32.8% Odds ratio: 2.5 Alcohol disorder: 24.0% Odds ratio: 2.1 other drug diagnosis: 18.4% Odds ratio: 3.7
d. Eating Disorders9-11
Alcohol and/or drug use to decrease discomfort, ease guilt, hide feelings.
86% used diet pills, laxatives and/or diuretics to control eating disorder.
OTC/Rx Drug Usage:
i. Laxatives: (60%)(20% daily use)
Most common; Ex-Lax or Correctol. Documentation of initial use of 15 to 20 laxatives each day working up to 100 ingestion's per day. As many as 300 to 600 laxatives per day have been reported.
ii. Diet Pills: (50%)
iii. Diuretics: (30%) Up to 2 gms/d of furosemide.
iv. Syrup of ipecac:.(17%)
C. Health Professionals
1. Pharmacists:
Tried Drugs: 42% pharmacists, 62% pharmacy students
Users: 19% pharmacists, 41% pharmacy students
2. Physicians:
Tried Drugs: 59% M.D.'s, 77% medical students
Users: 33 % M.D.'s, 44% medical students
III. RISK FACTORS FOR DRUG ABUSE
A. DRUG USAGE RISK IN THE GENERAL POPULATION: 12
Negative Affective States
Impaired Cognition
Misinterpretation of internal cues
Poor self-esteem
Lack of a sense of self-control and self-efficacy
Poor role performance
Impaired social skills
Restricted coping capacities
Disturbances of vegetative functions
Lack of social supports
B. PSYCHIATRIC RISK FACTORS:1,2
Access increased due to deinstitutionalization
Downward shift into poor urban living situations
Alleviate, self-medicate the signs and symptoms of mental illness or side effects of psychiatric medication
Develop an identity more acceptable than a mental patient
Facilitate social interactions
Younger Age
Male sex
IV. IMPACT ADDICTION 2,13
A. Societal Impact
Alcohol:
40% ofall reported assaults, 1/3 of all rape/molestation cases
50% of inmates reported being under the influence during crimes
50% of all U. S. traffic fatalities, 80 % between the hours of 8pm-4am
B. Dual Diagnosis Patients2,13
Increase in hospitalization rates
Increase in utilization of acute care services
Increased housing instability and homelessness
Increased violent and criminal behavior
Increased suicidal behavior
Poor medication compliance
Poor response to traditional substance abuse treatment programs
Difficulties with social skills, maintaining regular meals, financial management, participation in activities
V. DIAGNOSTIC CRITERIA ( DSM-IV)
A. SUBSTANCE DEPENDENCE
Patient must meet three (3 or more) of the following characteristics in a 12 month period.
1. Tolerance:
Need more of drug/alcohol to get high/effect
Less effectwith use of the same amount of substance
2. Withdrawal:
Drug/alcohol withdrawal occurs if you stop taking drug/alcohol
Drug/alcohol is taken to relieve signs of withdrawal5. Often takes the substance to relieve or avoid withdrawal syndrome
3. Taking more of drug/alcohol in larger amounts or over a longer period than intended
4. Persistent desire or unsuccessful efforts to cut down or control use
5. A great deal of time in activities to obtain substance(driving long distances, visiting doctors) or recovering from use of the substance
6. Has given up or reduced important social, occupational, or recreational activity to seek or take substance
7. Continues to use substance despite a knowledge of having a persistant or recurrent physical or psychological problem that is likely to have been caused or worsened by the substance. i.e. depression, ulcers
B. SUBSTANCE ABUSE
Pattern of substance use leading to impairment of distress and shown by one or more of the following occuring in a 12 month period
1. Recurrent substance use resulting in failure to fulfill major role obligations at work, school, or home. (neglect of kids, family, expulsion, absences from work, poor work performance)
2. Recurrent use in situations in which it is physically hazardous(driving, operating machinery)
3. Recurrent substance-related legal problems(DWI's or disorderly conduct)
4. Continued substance use despite having persistent or reurrent social or interpersonal problesm caused or exacerbated by the effects of the substances(arguments about consequences of intoxications, fights)
C. Rating Scales: CAGE/MAST/SMAST
DRUGS OF ABUSE
I. ALCOHOL
A. NEUROCHEMICAL EFFECTS
1. Intoxication
Alcohol causes increased uptake of norepinephrine into phenylethanolamine-N-methyltransferase (PMNT) containing cells. Norepinephrine is metabolized by PMNT to epinephrine extraneuronally. Extraneuronal epinephrine then causes sedative and intoxicating effects by blocking the further outflow of norepinephrine. This effect occurs through the negative feedback of the alpha-2 receptor. Increased PMNT activity is correlated with downregulation of the the alpha-2 receptor, further adding influence to the effect of epinephrine on the receptor.
ENDPOINT: DECREASED OUTFLOW OF NOREPINEPHRINE
A. DISEASE STATE VS PSYCHOLOGIC DEPENDENCE
1. Animal Studies
Tetrahydroisoquinoline compounds (THIQ)
Tetrahydropapaveroline (THP)
Precursor of morphine found in the opium poppy and in mammalian tissues after exposure to ethanol.
Development may be dependent on aldehyde concentrations
Enzymes controlling the production of this substance may be genetically determined
Current area of research for addictive potential of alcohol is some individuals
Salsolinol: Product of Dopamine and Acetaldehyde, mu receptor activity
2. Genetic Evidence
Ethnic groups with increased risk:
Irish Catholic
American Indians
Scandinavians
Concordance rates:
Children, siblings, parents-25%
Fraternal Twins-31%
Identical Twins-54%
Adoptees whose biologic parents were alcoholic-2 to 3 times more likely than those whose biologic parents were not alcoholic
B. PHARMACODYNAMIC CONSIDERATIONS
1. Absorbtion
Rapidly absorbed, influenced by food(1 to 2 hours but up to 6 hours with food), volume of liquid ingested, concentration of alcohol, and rate of administration.
Beer is more slowly absorbed than wine and wine is more slowly absorbed than distilled spirits
Reflex pylorospasm may limit absorption and alcohol may be passed into the intestine-fluctuations in intoxication may occur
2. Distribution:
Uniformly distributed, Vd 0.58-0.70 L/Kg
3. Metabolism:
Michaelis-Menton kinetics
90-98% metabolized
Ethanol is converted to acetaldehyde through the action of alcohol dehydrogenase.
Acetaldehyde is then converted to acetic acid then to acetyl coenzyme A (CoA) which is then oxidized via the kreb's cycle to CO2 and water.
Oxidation rate:
Men: 15 mg/dL/hour
Women: 18mg/dL/hour/hr
Chronic/Heavy Drinkers: oxiidize ethanol at twice the rate of normals with a gradual return to baseline with sobriety
4. Elimination:
Small unoxidized portion(2-10%) of ingested alcohol is excreted through the kidneys and lungs
Km = 9.7 % mg%; range(8-14 mg%)
Vmax = 23.3 mg% (22-24 mg%)
Ethanol concentration less than Km then rate of elimination is first order. If it is greater than Km the rate of elimination is zero order and is contant at 100 mg/kg/hr or 15 mg%/hr(0.015%/hr) in terms of BAC elimination rate. This translates to an estimate for a 150 lb. male to be able to metabolize approximately 10 ml/hr of absolute ethanol (one shot of liquor).
C. INTOXICATION
1. Blood concentrations
50-100 mg/dl (0.05-0.10%) mild intoxication
100 mg/dl (0.1%) or > impairment of motor coordination
legal limit for intoxication
2. Acute intoxication
Inhibition of integrating and inhibitory control of the cortex by lower brain centers.
CLINICAL SYMPTOMS/DESCRIPTION BLOOD ALCOHOL CONCENTRATION BRAIN AREA MILD 0.05-0.10 % FRONTAL LOBE Decreased inhibitions Slight Visua impairment
Slowing of reaction time
Increased confidence
MODERATE 0.15-0.30% Ataxia Slurred speech
Decreased motor skills
Decreased attention
Diplopia
Altered perception
Altered equilibrium
PARIETAL LOBE OCCIPITAL LOBE
CEREBELLUM
SEVERE 0.3-0.5% Vision impairment OCCIPITAL LOBE Equilibrium CEREBELLUM Stupor DIENCEPHALON COMA 0.5 % Respiratory failure MEDULLA
ACUTE INTOXICATION-OTHER SYMPTOMS
Outgoing, Loquacious, Emotionally labile, Sedation, Slurred speech, Flushed face, Irritability, Euphoria, Impaired attention and concentration, Perceived verbal and manual performance, Recent memory impairment, Diminished insight
3. Pathological Intoxication
Transitory but profound state of intoxication!!
Confusion, disorientation, delusions, impaired consciousness ("BLACKOUTS"), increased activity, impulsivity, aggressiveness with accompanying rage reactions and violence. If preexisting depression exists-suicide attempts may occur. Most episodes last 2-3 hours followed by a deep sleep. On awakening, there is usually amnesia for the events.
D. MEDICAL COMPLICATIONS
1. Polyneuropathy
absent ankle jerks main sign
burning feet
pain paresthesias
distal muscle weakness
damage may be permanent
2. Wernicke's Disease
Thiamine (Vitamin B1) deficiency
Nystagmus, bilateral sixth cranial nerve palsies, paralysis of conjugate gaze, ataxia, and delirium characterized by apathy, lassitude, disorientation, and drowsiness.
3. Korsakoff's psychosis (alcohol amnestic disorder)
Profound anterograde and retrograde amnesia in an alert individual.
Treatment exists of administration of Thiamine 50 mg IV and 50 mg IM followed by 50 mg IM or PO q day until symptoms improve. Symptoms of Wernicke's may improve however Korsakoff's syndrome may continue with residual symptoms.
4. Cerebellar degeneration
Difficulty with stance and gait
5. Vitamin deficiency amblyopia
Blurred vision, central scotomata and if untreated, optic nerve atrophy
6. Other system effects:
Liver:
Alcoholic Fatty Liver
Alcoholic Hepatitis
Cirrhosis
Gastrointestinal:
Gastritis
Pancreatitis
Gastric and Duodenal Ulcers
Malabsorption Syndrome
Esophageal Varicies
Hematologic:
Macrocytic anemia (Folate defiency)
Cardiovascular:
Cardiomyopathy
Teratogenicity:
Fetal Alcohol Syndrome-low birth weight, microcephaly, mental retardation, short palpebral fissure, epicanthic folds, maxillary hypoplasia, abnormal palmar creases, cardiac anomalies, capillary hemangiomas, slowed postnatal growth rate. Infants sleep and feed poorly, are irritable, tremulous, and hyperactive. Mortality rate 17%, 44% of surviving children are mentally handicapped.
GU: Testicular atrophy and decreased testosterone production
E. WITHDRAWAL: Excessive sympathetic drive!
1. Neurochemical effects
a. Norepinephrine
Excessive release of norepinephrine in brain and perifery
Increase in norepinephrine correlates with severity of symptoms of withdrawal
Alpha-2 receptor subsensitive during withdrawal thus does not modulate outflow of norepinephrine
"Kindling": phenomena of increased severity of ethanol withdrawal with shorter drinking episodes upon repeated abuse of alcohol
b. Gamma-amino butyric acid (GABA)
Decrease may lead to CNS excitation and seizures
c. Dopamine
Excess may result in psychosis
2. Phases of withdrawal:
Usually begins within 24-72 hours and may last for 3 to 5 days.
Phase I (onset 6-8 hours after BAL fall)
Tremor, autonomic hyperactivity, nausea, tachycardia, diaphoresis, labile blood pressure, anxiety, vomiting
Phase II (onset 24 hours, lasts 3-5 days)
Perceptual disturbances, auditory, visual, or tactile hallucinations
Phase III (7- 48 hours)(4% of patients)
Generalized seizures (30 seconds-4 minutes)
Status epilepticus in 3% of patients
"rum fits"
Phase IV (3-5 days after onset of w/d symptoms)(5% of patients)
Delirium Tremens: acute autonomic hyperactivity and delirium with severe hyperthermia
Fever and untreated seizures are prognostic
Confusion, hallucinations, illusions, agitation, tachycardia, diaphoresis, mydriasis and fever
Mortality rate-20%
Deaths related to cardiovascular collapse, shock, cardiac arrhythmias, aspiration, hyperthermia, infection, trauma or stroke
3. Treatment: Alcohol Withdrawal
a. Detoxification
Benzodiazepines are the treatment of choice!!
Treatment must begin in progression to the DT's. Use objective signs phase one of withdrawal to prevent and symptoms as a guideline for initiation of treatment: flushing, increase in temperature, tremor, BP lability, increase in heart rate.
i.e. HR > 100
Temp > 100 F
BP diastolic >90 mmHg
Starting dosages:
Chlordiazepoxide (Librium) 50 mg TID or QID
Oxazepam(Serax) 30mg TID-QID
Lorazepam(Ativan) 2mg TID-QID
Guidelines:
Be specific about benzodiazepine use in a patient with an abuse history. Limited use for withdrawal only.
Taper all benzodiazepines from the date of initiation over 5 to 7 days when utilized for alcohol withdrawal.
If withdrawal symptoms resurface, increase to last dose where symptoms were stable and institute a slower taper.
Examples of tapering schedules:
i.e.
Oxazepam
30 mg TID x 2 days
30 mg BID x 2 days
30 mg q hs x 1 day then discontinue
Lorazepam
2 mg QID x 1 day
2 mg TID x 1 day
1 mg TID x 1 day
1 mg BID x 1 day
0.5 mg BID x 1 day
0.5 mg qhs x 1 day then discontinue
b. Hallucinations:
Haldol 2-5 mg daily x 2-3 days if hallucinations or psychosis persist. This may decrease seizure threshold and worsen hypertheramia. It is rarely necessary if benzodiazepines are used correctly.
c. Seizures:
Lorazepam 2 mg IM after seizure ends; increase the dosage of benzodiazepine detoxification schedule and consider a slower taper. Phenytoin is utilized only if patient progresses to status. Long term maintenance is not necessary unless a seizure focus can be identified.
d. Other:
Thiamine 100 mg IM then 100 mg po daily x 2 weeks
Folate 1 mg po daily x 2 weeks
Magnesium sulfate 1 gm IM x 1-3 days
4. Maintenance
a. Self-help Groups-Alcoholics Anonymous (AA)
Most effective, group environment, free of charge. Patients generally go to 2 to 5 meetings per week.
b. Naltrexone(ReVia, Dupont)
Pure Opioid Antagonist : Utilized in combination with a treatment program in order to achieve the best results.
Absorption: 96% from GI Tract
Distribution: 1350 Liters
21% Protein Bound
Metabolism: 6 B-Naltrexol (major metabolite)
Elimination: By glomerular filtration, no adequate studies in renal impairment.
Contraindications:
Pts. receiving opioid analgestics
Pts. currently dependent op opioids
Pts. in acute opioid withdrawal
Any individual who has failed the NARCAN CHALLENGE
test or who has a positive urine screen for opioids.
Any individual with a history of sensitivity to naltrexones or naloxone
Any individual with acute hepatitis or liver failure.
Warnings:
Hepatotoxicity
Unintended precipitation of Abstinence
Drug Interactions:
Antipsychotics: four cases of increased lethargy and sleepiness
Insulin: one case of increased insulin requirements
Adverse Reactions:
Alcoholics: Nausea(10%), Headache(7%), Depression(7%), Dizziness, nervousness, Fatigue(4%), Insomnia, vomiting(3%)
Narcotic addiction:(all >10%) Difficulty sleeping, Anxiety, nervousness, abdominal pain/cramps, Nausea, vomiting, low energy, joint and muscle pain, headache
Abuse Potential: 4 case reports, increased euphoria/alertness, 2 + benzo's
Dosage: 25 mg the first day then 50 mg per day
Alternative Dosing Schedules:
Once a day
50 mg on weekdays with 100 mg on Saturday
100 mg every other day
150mg every third day
50 mg monday through Thursday and 150 mg on Friday
Naloxone(Narcan) Challenge:
Some clinicians recommend the administration of a Naloxone Challenge prior to administering ReVia.
IV: 0.2 mg, observe 30 seconds, then administer 0.6 mg
SQ: 0.8 mg, observe for 20 minutes
Pregnancy Category C:
Patient information: Be sure to utilize patient ID cards in the patients wallet in case of emergency, accident, etc.
This is not adversive therapy but rather therapy to help decrease craving for alcohol in patients in whom craving is a major cause of relapse to drinking. ReVia should be
c. Disulfiram (Antibuse, Ayerst)
Inhibits enzyme aldehyde dehydrogenase
Reaction with alcohol: Flushing, nausea, vomiting, headache, palpitations, sweating, fever, hypotension
Inhibition of enzyme is still apparent 2 weeks after discontinuation
Patient Education is crucial including cautions concerning drinking, after shave lotion, perfumes, cough and cold preps, mouthwashes. Patient must also be informed not to drink for 2 weeks after stopping the medication.
Dosage: 250-500 mg q day
Side effects: rash, headache, lethargy, metallic taste, impotency
II. COCAINE
Snow, flake, blow, lady, Happy Trails,Nose Candy, Toot,Crack, Readyrock, Teeth, Gold Dust, Rock, and eight ball.
A. MOA/RECEPTOR EFFECTS
1. Dopaminergic system
Blocks reuptake of dopamine and facilitates release
Acute increase in synaptic dopamine level and transmission to limbic areas are responsible for euphoria
Dopamine supersensitivity with increased receptor binding may occur
Chronic use may result in a decrease in available dopamine. Cocaine craving may result from this dopaminergic depletion
Thioridazine has been shown to increase cocaine craving
Bromocriptine has been shown to diminish cocaine craving
2. Norepinephrine
Blocks reuptake of norepinephrine, and facilitates norepinephrine release both centrally and peripherally
Acutely dramatic increase in CNS concentrations followed by a decrease below baseline
Increases in postsynaptic receptor concentrations have been seen 12 hours after administration, chronic administration results in marked increases in receptor density and population
Ultimate effect, reduced turnover or NE and inhibition of NE neurons
3. Serotonin
Involved in production of a generalized sense of well-being, arousal, mood, and aggression
Release and reuptake postulated to be blocked by cocaine
Cocaine blocks activity of tryptophan hydroxylase
Decrease in serotonin metabolites after cocaine
Chronic administration: depletion of tryptophan and serotonin stores and an inhibition of tryptophan hydroxylase activity
B. FORMS USED IN THE ADMINISTRATION OF COCAINE
Route Onset of Euphoria(seconds) Duration of Euphoria(minutes) Oral 600-800 45-90 Intranasal 120-180 30-45 Intravenous 30-45 10-20 Inhalation 8-10 5-10
1. Hydrochloride salt
Intranasally, injectable
Plasma peak 60-120 minutes
Water soluble
Melting Point: 195 C
2. Base
Melted and inhaled or ground, mixed with tobacco or marijuana and smoked
Called crack due to sound when heating
Higher percentage of people become addicted
Intense high, speed of onset is comparable to IV administration, but does not last as long.
Cost is decreasing:
$5 for a small rock
$10 of rock will give two good highs
Melting Point: 98 C
3. Body Packers
Method of smuggling cocaine by placing cocaine in a condom, tying them off and then swallowing them . Retrived by use of a cathartic laxative. Severe cocaine toxicity if the condom ruptures. Each packet may carry up to 7gms of cocaine.
C. INTOXICATION
1. Stimulation
Motor agitation, elation/euphoria, grandiosity, loquacity, hypervigilance, tachycardia, mydriasis, elevated blood pressure, sweating or chills, nausea and vomiting, seizures
2. Cocaine Psychosis
Paranoia, delusions of persecution, parasitosis, unprovoked violence, auditory, visual, or tactile hallucinations
3. Decreased hunger and sleep
4. Respiratory Drive
Rapid and shallow respiration, stimulation of respiration may be followed by depression, irregular, Cheyne-Stokes respiration may appear
5. Motor
Hyperreflexia, stereotyped movements may occur
6. Cardiac Events
Ventricular ectopy may progress to ventricular fibrillation with increasing hypoxia. Sudden death probably due to ventricular fibrillation although cardiac standstill may occur due to direct cardiotoxicity. May be attributable to cocethylene.
7. Temperature disregulation
Hyperthermia may occur due to increased muscle activity, vasoconstriction, and direct effect on the hypothalamus
D. PATTERN OF COCAINE USE
Gawin F. Psychosomatics 1986;27(11S):24-29.
Highest Risk of relapse occurs during Phase 2 .
E. TREATMENT
1. Acutely
Supportive therapy for any adverse sequelae as described above.
Seizures: Diazepam-often resistant to phenytoin and phenobarbital
Hypertension: short-lived and often followed by hypotension, paradoxical reaction has been seen with use of propranolol
Hypotension: Trendelenburg position, IV fluids, pressor agents
Arrhythmias: As per hospital protocol
Hyperthermia: cooling blanket, tepid water
Psychosis/Anxiety: benzodiazepines, antipsychotics
2. Longitudinal
Relapse prevention
Attendance at CA, NA
Treatment: Outpatient and inpatient
Reversal of the neurochemical changes induced by chronic cocaine abuse
Serotonergic system:
Provide precursors to a depleted serotonergic system
Dopamine:
Precursors for a depleted dopaminergic system
Subsensitize presynaptic autoreceptors and postsynaptic dopamine receptor populations by providing more dopamine or dopamine agonist
Noradrenergic system:
Provide precursors to a depleted noradrenergic system
Blockade of cocaine binding at reuptake site with desipramine to decrease craving
Provide antidepressants to subsensitize beta-receptors
3. Pharmacologic Treatments
MEDICATION DOSAGE COMMENT (length of txt) Tyrosine 400-800 mg t.i.d. Give between meals on an empty stomach. l-Tryptophan 1000-1500 mg q hs Give with a high 2 weeks carbohydrate snack. Amantadine 100 mg b.i.d. - q.i.d. Caution regarding 2 weeks seisure and pychosis. Precursor loading with tyrosine is recommended. Bromocriptine 0.625-2.5 mg t.i.d. Start with lower 10 days dose. Desipramine 150-300 mg h.s. Start at 25-50 mg h.s. 8 weeks and increase by same increment q 2-3 days to target dose.
OTHERS:
SINEMET
TEGRETOL
PROZAC
Unfortunately, recent studies have shown desipramine and prozac not to be effective in the treatment of cocaine dependency with desipramine actually lengthening hospital days due to side effects. The information concerning the efficacy of the other modalities is limited to small trials and case reports. Adjuctive medications are sometimes utilized in treatment resistent patients but should not be considered standard therapies.
III. HALLUCINOGENS
Drugs capable of inducing hallucinations, delusions, paranoia, and alterations in mood or thinking.
Terms: psychodelic, psychotomimetic, psychotogens, mysticomimetic, pseudohallucinations, phantastica, psychotaraxic, psycholeptic, psychomystic, entactogen(description of MBDB, MDMA).
Use dates back centuries in some cultures for religious and ceremonial rites; to enhance creativity, at one time as an adjunct in psychotherapy.
General MOA: Strong correlation between hallucinogenic potency and 5HT2 receptor affinity.
Five Main Catagories(varies depending on the reference you read)
1. LSD like
LSD, Mescaline, Psilocybin, Psilocin
2. Probably LSD-like
DMA, DOM, DMT
3. LSD-like with other properties
MDA, MMDA
4. Probably not LSD-like
BOL, 5-hydroytryptophan
5. Not LSD-like
Amphetamine, Æ-9 THC, DOET, bufotenine, scopalamine
A. PHENCYCLIDINE
PCP, Angle dust, angel mist, angel hair, animal tranquilizer, busy bee, cadilliac, CJ, crystal cyclones, DOA, dust elephant tranquilizer, embalming fluid, goon, gorilla biscuits, hog, horse tranquilizer, jetfuel, KJ, Kay Jay, killer weed, kristal joint, magic mist, mint dew, mint weed, monkey, peace, pits, rocket fuel, scuffle, Selma, sheets, sherm, sherman, snorts, soma stardust, supergrass, super kools, surfer, T, Tac, Tic, tranks, whack, woobble weed, zombie dust
1958: Parke Davis-withdrawn in 1965 secondary to dysphoria, delerium and psychotic reactions
1967: Approved for veterinary use
1979: All legal mfg.. stopped
1. EFFECTS
In General:
Stimulant, depressant, hallucinogenic, analgesic depending on the dose and route of administration.
A common adulterant to marijuana.
Half-life: Serum: 45 min. to 89 hours ave: 12 hours
May see fluctuations in mental status and intoxication due to reabsorption in the alkaline ph of the small intestine.
Urine screens: positive up to one week
a. Acute Intoxication
5 mg or less: depressant effect on the CNS, blank stare, muscular incoordination, numbness of the extremities, mild ptosis of the eyelids, vertical or horizontal nystagmus, miotic or normal-sized pupils, and absent corneal reflexes. Impaired perception, mild analgesia and other motor disturbances.
5-10mg: nystagmus, slurred speech, ataxia, hyperreflexia, and increased muscle tone.
> 20 mg: hypertensive crisis, muscular rigidity, seizures, respiratory depression, coma, and death.
b. Subjective effects:
Changes in body image, feelings of dissociation, perceptual distortions, auditory and visual hallucinations, "nothingness" amnesia for the period of intoxication, mood elevation, anxiety, restlessness, disorientation, and increased sensitivity to external stimuli.
c. PCP psychosis (3 phases, 5 days each phase):
Phase I: paranoid delusions, hyperactivity, anorexia, insomnia, agitation, unpredictable assaultiveness
Phase II: paranoia and restlessness remain but patient is usually calmer and intermittently in control of his/her behavior
Phase III: depression with gradual resolution of symptoms
d. Characteristic ER presentation:
"bizarre behavior with nystagmus, hypertension, and drooling".
2. TREATMENT(PCP)
a. Intoxication
Decrease external stimulation-quiet room, do not try to talk these patients down. Stimilation may worsen agitation due to the hallucinogenic properties of this drug.
Diazepam (10-20 mg po, 2.5 mg IV) or
Lorazepam (1mg IM or po) q 4-6 hours for agitation or muscle hypertonicity
Urine acidification: (controversial)
Cranberry juice ad libitum
Ascorbic acid or ammonium chloride 2-3 gms q 6 hr po and then furosemide 20-40 mg po when urine ph is below 5.0 (if renal function is not compromised) until 2-3 urine drug screens are negative (3 days)
Nasogastric lavage and ipecac should not be used due to PCP's predisposing the patient to laryngospasm and the possibility of status
Seizures/status: per hospital/ER protocol
Rhabdomyalysis: important to monitor renal function including daily assessments of the following tests: SMA-6, UA, CPK, liver function tests
b. PCP Overdose
Maintain airway
Lavage if ingestion is less than four hours
Hypertensive crisis-per hospital protocol
Status-per hospital protocol
Acidification of Urine: (if renal function is stable)
Ammonium chloride via N/G tube, 2.75 mEq/Kg in 60 cc Saline
Ascorbic Acid 2mg/500cc IV solution q 6 hours until urine ph drops below 5.0.
Continue ion trapping treatment until toxicology screen is negative for PCP for at least 3 days.
B. Other Hallucinogens
1. LSD
Found naturally in morning-glory seeds or prepared synthetically
Synthesized by Hoffman in 1943
Experimentation in 50's and 60's
1970's put in schedule I
t1/2 = 2.5 hours
0.001% croses the BBB
MOA:
Actions at multiple sites in the CNS
Agonist actions at 5HT receptors in midbrain
Effects at alpha receptors
Blocked by 5HT antagonists (ritanserin, cyproheptadine, chlorproamazine, haloperidol)
Effects of LSD:
dizziness, weakness, drowsiness, parasthesias, euphoric effects predominate
Feelings of inner tension relieved by laughing, crying
2-3 hours:
visual illusions affective symptoms, wave-like perceptual changes
synesthesias
slowed movement of time, loss of boundaries
thoughts and feelings unxpectedly emerge
lability of mood
tension/anxiety may reach panic proportions
4-5 hours
sense of detachment
feeling of being magically in control
Physical Effects
increased BP, HR, tremor, nausea, pupillary dilation, muscular weakness, hyperreflexia
Trip lasts about 12 hours
Some evidence of long-term changes in personality and beliefs
100 times more potent that psilocin
4000 time more potent that mescaline
Tolerance
High degree after 3-4 days of daily use
Cross-tolerance with mescaline and psilocin
No evidence of withdrawal
Adverse Effects
Panic attacks most common: treat with reassurance and antianxiety agents
Flashbacks
Serious depression, paranoid behavior
Prolonged psychotic episodes/carbamazepine
2. MDMA
MDA-3,4-methylenedioxyamphetamine
MDMA-Adam, ecstasy, XTC, "RAVE Parties"
N-methyl analog of MDA related both to mescaline and amphetamines
$50-120/gram which yields 5-15 doses taken orally
"yuppie psychedelic"
More amphetamine-like effects
Made illegal 1985
Effects:
Enhances emotions, empathy, decreased anxiety without hallucinations, changes in perceptions without distortions, increased self-esteem, mood
CNS: insightfulnes, inner-contentment, euphoria, panic , paranoia, increased sexual responsiveness,
Physical: motor restlessness, treors, ataxia, nystagmus, blurred vision, increased HR.
Trip lasts: 1-12 hours, residual effects for 32 hours, with a hangover effect.
Tolerance on repeated doses, increased SE, decreased pleasurable effects.
Neuronal effects: Single dose decreases serotonin in monkey for 2 weeks, and for 12 months in the rat. Selective destruction of nerve terminals in hypothalamus and cerebral cortex, some recovery after several months but recovery may be incomplete.
3. Amphetamine-like stimulants
a. Neurochemical effects: Similar to cocaine
Prevent catecholamine, dopaminergic reuptake
Facilitate catacholamine release from the presynaptic neuron
b. Effects:
Euphoria, anxiety, increased energy and concentation, decreased hunger and fatigue, restlessness, extreme hyperactivity, irritability, insomnia, headache, seizures, hyperpyrexia, hyperreflexia, coma, stroke, cerebral ischemia, hypertension, tachycardia, arrhythimias, infarction, cardiac collapse, urinary retention, onstipation, dry mouth, increased deep tendon reflexes, fine tremor in hands, slurred, rapid, incoherent speech; fidgety, jerky, random movements, delusion, paranoia.
Withdrawal: depression, decreased thinking, deliberate, methodical movements, fatigue, increased appetite, memory loss, confusion paranoia.
c. Newer Agents
i. Methamphetamine: N-methyl homologue of amphetamine
Speed, crystal, meth: d-, l-, d/l-
Crank, ice: d-isomer; Volatile-can be smoked
Epidemiology
Rapidly increasing drug of choice in pacific coast states
San Diego County 1987
Role in 40% in all drug related homocides
52% increase in meth drug related crimes over the previous year
1989-prefered by 80% of adolescent admissions to drug unit
Intoxication:
"ICEMAN"
Agitation, paranoid delusions, aggressiveness, widely dilated pupils, hyperthermia, hypertensive, tachycardic, diarrhea, vomiting, and abdominal cramps, seizures, diaphoresis, muscle fasiculations and/or ridgidity
Death-as little as 1.5 mg/kg
Secondary to acute cardiac failure, hyperpyrexia or cerebrovascular hemorrhage.
Tolerance occurs with long time abusers reportedly using as much as 5,000 to 15,000 mg/day
Differential DX
Anticholinergic overdose, another sympathomeimetic
Treatment
Oral Ingestion:
Do not use ipecac-increased risk for seizure, hypertensive hemorrhage, or cardiac complications
Careful gastric lavage/activated charcoal
Hypertension
> 110 mmHg-Nitroprusside
Agitation:
Decrease stimuli
Benzodiazepine (Lorazepam 1-2 mg IM repeat q 4-6 hour)
or Antipsychotic (Haloperidol 5 mg IM repeat q 4-6 hours or q 1/2 hour till clinical response, max 40 mg/day)(caution: worsening of hyperthermia)
Seizures:
Diazepam 2 mg slow IVP
Hyperthermia:
Cool compresses, sponging, cooling blankets
Severe-ice bath
High temperature is a poor prognostic sign
d. Plants with Hallucinogenic Properties
i. Jimson Weed
CNS Effects:
dizziness, giddiness, anxiety, excitement, euphoria, visual halucinations, reality detachment, fear of death.
Physical:
flushing, urinary retention, constipation, increased heart rate, palpitations, nausea, vomiting, abdominal pain, labile BP, resembles anticholinergic poisoning
Treatment:
supportive, keep patient calm, lavage
ii. Morning Glory: similar in structure to LSD
CNS Effects:
perceptual distortions, mood changes, hallucinations, increased awareness of color, depersonalization
Physical:
N/V/D, drowsiness, muscular tightness, complicated by fungicide sprayed on seeds
Treatment: supportive
iii. Peyote (mescaline)
Eaten as buttons on top of the cactus, or synthetic, often mixed with PCP or LSD
CNS Effects:
Hallucinations, psychotic behavior, unusual perception of space and time, paranoia, fear
Physical Effects:
labile BP , HR, decreased respirations, diziness, ataxia, weakness, drowsiness
1-2 hr: NVD (subsides in about 2 hours)
2 hr: physical effects peak
4-6 hr: Hallucinogenic effects peak
Trip lasts 6-12 hours
Treatment: Calm environment, supportive, diazepam, haloperidol
iv. Mushrooms
Amantia Muscaria
CNS Effects: drowsiness, confusion, innebriation-like symptoms, mania euphoria, delerium, visions
Physical Effects: facial flushing, increased HR/BP, mydriasis, dizziness, parasthesias, ataxia, N/V, seizures
Psilocybe: psilocin, psilocybin
CNS Effects: color abnormalities, innapropriate laughter, distortion of time and space, impaired judgment, hallucinations
Physical Effects: facial flushing, increased HR/BP, mydriasis, dizziness, parasthesias, N/V, ataxia, seizures
Onset: 5-30 minutes
Duration: 4-8 hours
Panaeolus: Much like psilocibe, Contains large amounts of serotonin
v. Other
Toad Licking: Bufo Toads
Glandular secretions from the back of the bufo toads containing dopamine, norepinephrine, serotonin, bufotenine
Licking or milking live bufo toads
Sensationalizd by the press in the mid-80's
Reports of use go as far back as roman times
IV. OPIATES
A. TYPES
Natural: opium, morphine, codeine
Semisynthetic: diacetylmorphine(heroin), hydromorphone(dilaudid), oxycodone(Percodan)
Synthetic: meperidine(Demerol), methadone(dolophine), propoxyphene(Darvon)
Opiate(trade name) duration(hrs,IM,SQ) t 1/2(hrs) Morphine 4-5 2 Heroin 4-5 0.5 Hydromorphone(dilaudid) 4-5 2-3 Oxymorphone(numorphan) 4-6 2-3 Levorphanol(levo-dromoran) 4-5 12-16 Methadone(dolophine) 4-5 15-40 Meperidine(demerol) 3-5 3-4 Fentanyl(sublimaze) 1-2 3-4 Codeine 4-6 2-4 Hydrocodone(hycodan) 4-5(po) 4 Drocode(synalgos-dc) 4-5(po) 4 Oxycodone(roxicodone) 4-5(po) _ Propoxyphene(darvon) 4-6(po) 6-12 Buprenorphine(buprenex) 4-5 5 Pentazocine(talwin) 4-6 4-5 Nalbuphine(nubain) 4-6 2-3 Butorphanol(Stadol) 4-6 2.5-3.5
B. Heroin: General Information
Street Names: China White(generally fentanyl), persian brown, mexican tar
Route: IV injection, Snorted, smoked(less common)
Sold: Balloons containing 250-400mg of powder (quarter-$25 bag, or dime-$10 bag).
More recently: "Cribbies, Bindles" (china white/persian brown(92% heroin) which are 25 mg packaged in wax paper or aluminum foil envelopes.
"Mexican brown" Tarry, sticky ball which contains 40-80% pure heroin. Recently a lactose cooked look alike product which is 3-4% heroin has been introduced, thus responsible for many overdose deaths due to confusion between the purer form and the look-alike.
C. EFFECTS: Heroin Intoxication
1. Acute:
Heroin: rush, euphoria, tranquility
Drowsiness, lability of mood, mental clouding, apathy, motor retardation, respiratory depression, nausea and vomiting, orthostatic hypotension, decreased secretion of stomach, biliary tract, and pancreas, constipation, urinary hesitancy, and pinpoint pupils.
2. Tolerance: 2, 3 days to one week
3. Overdose:
Stupor, coma, constricted pupils, decreased pulse and respiration. Hypothermia and pulmonary edema are usually present
a. Supportive measures
b. Naloxone 0.4 mg IV q 5 minutes
4. Withdrawal:
Usually not life threatening, but very uncomfortable. If other symptoms are seen that are not consistent with this presentation mixed substance abuse should be suspected and treated accordingly.
(Heroin withdrawal)
6-12 hours: yawning, sweats, running of nose and eyes, anxiety, craving for opiates and drug-seeking behavior. Progressively: dilated pupils, gooseflesh, fever and chills, loss of appetite, muscle cramps, tremor, insomnia or restless sleep.
18-24 hours: nausea, vomiting, elevations in blood pressure, pulse, respiratory rate, and temperature occur.
24-36 hours: leukocytosis, ketosis, electrolyte imbalance
Resolution usually occurs in 7-10 days
Methadone withdrawal is characterized by a slower onset (24-72 hours) and a gradual resolutions of symptoms (3-7 weeks).
5. Detoxification:
Methadone:
10-40 mg/d dosages of methadone will prevent withdrawal(Dosages of 50 mg or more have been associated with euphoria)
Duration of action: 24 hours
T1/2=17-40 hours; ave=25 hours
TXT: Start patient on 20mg/d po of methadone for detoxificationUsual taper consists of 20% per day (5-10 mg)
Short term(during withdrawal phase only) symptomatic treatment:
Benzodiazepines=for anxiety/may be utilzed for sleep as well
Antidiarrheals=for diarrhea
Hypnotics=for sleep
Antihistarmines=for rhinorrhea, etc.
Clonidine: Opiate withdrawal may actually be a function of noradrenergic sensitivity. Chronic opioid use inhibits norepinephrine (NE) system activity. Due to this inhibition of norepinephrine, receptors may become subsensitized. Clonidine decreases NE neuronal activity in the locus coeruleus by acting as an alpha-2 receptor agonist. Clonidine would be expected to ameliorate withdrawal symptoms and normalize receptor sensitivity. Generally start at 0.1 mg bid and titrate to vitals, S/S of withdrawal. Dosages as high as 1.2 mg/d have been utilized.
6. Maintenance
a. Methadone: Daily clinic visits with patients taking 30-100 mg/d of methadone.
Some reports of methadone at higher dosages (70-100 mg/d) may provide better treatment outcome than low dose maintenance(20-50 mg/d). Many treatment facilities are heading toward abstinence as a goal rather than continued drug support.
If a patient is taking four cribbies(packets) of heroin/day(120mg/heroin) this would be equivilant to 60 mg/d of methadone(2:1 ratio heroin/methadone)
Note: Cribbies generally have approximately 30mg/heroin per packet. It is very difficult to evaluate due to street adulteration. Generally patients are started on a 20-30 mg dosage of methadone to safe-guard against respiratory depression. The patient is then titrated upward to their maintenance dose of methadone depending on prevention of withdrawal and decrease of reports of craving.
b. LAAM: Levomethadyl Acetate
A Prodrug with long onset and duration of action(72 hours)
Dosing complex due to long half-life.
Patients only need to come in for dosing 3 times per week thus LAAM is good to use to avoid daily visits to the clinic. Important if pt. is stable and actively employed.
Dosing of LAAM: If on methadone: Dose of methadone X 1.2 = LAAM dose not to exceed 120mg/d. If not on methadone: starting dose of 30 mg/d with increase of 5-10mg every 2nd to 3rd dose (i.e every 2-3 days; very important!!!). Too rapid titration may result in oversedation and accumulation.
C. Fentanyl
1. Characteristics
Originally for surgical use
2. Fentanyl Derivatives:
3-METHYLFENTANYL (TMF):
1000 X the potency of morphine
Usual effective dose: 0.01-0.05 mg
Peak effectiveness: 4 minutes
Urine detection: 4-72 hours after use
TMF appeared in california under the name of "China White"
Other Names: "PERSIAN WHITE, CHINA WHITE, SYNTHETIC HEROIN, FENTANYL, MEXICAN BROWN", TANGO AND CASH
Effects resemble heroin after cutting
3. Toxicity
PROBLEMS BREATHING
DECREASED HEART RATE
DROP IN BLOOD PRESSURE
"WOODEN CHEST" (paralysis of respiration)
4. Mortality
1986-104 deaths in california reported however rate has delcined over the last 5 years
1988: 16 deaths in Pennsylvania (99 other demographically similar deaths from 1986-1988)
1991-12 deaths reported in New York, suspected cases in Chicago
Usually used as a SPEED BALL (cocaine and heroin mixed), thus only cocaine is detected and death attributed cocaine. Incidence is probably underreported. Some UDS positive for opiates as well.
D. MEPERIDINE LIKE DRUGS
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridoine)
Contaminant from production of MPPP (1-methyl-4-phenyl-4-propionxypiperidine)
1. Effects
Toxic to neurons in the substantia nigra, therefore permanent indiopath parkinsons's disease may result.
Immediate:
BURNING ON INJECTION
DISORIENTED HIGH
BLURRED VISION
METALLIC OR MEDICINAL TASTE
Later:
NUMBNESS OF EXTREMITIES
STIFFNESS OF MUSCLES
SLOW MOVEMENT
JERKING OF LIMBS
2. Treatment
None, parkinson's treatment modalities
Patients who are asypmtomatic now may develop parkinson's disease as they age.
V. PHARMACOTHERAPEUTIC ISSUES
A. HISTORICAL
Drug abuse: Psychiatry felt that drug use was secondary to underlying pathology and conflicts. Upon stopping drug/alcohol use-Psychopathology may be rapidly modified or eliminated. Psychotherapy and psychotropic drug therapy was often not addressed until abstinence was assured for at least one year. In patient's with co-existing psychopathology at times were not able to maintain abstinence due to the severity of symptoms.
B. CONSIDERATIONS IN PHARMACOLOGIC TREATMENT
1. Characteristic Intoxication
Urine toxicology screen
Signs and Symptoms
Half-life of the substance:
2. Characteristic Withdrawal Phenomena
Typical time course for withdrawal: i.e. psychosis from schizohrenia does not dissapate in 3 days
Length of Abuse
Organic Diagnosis (symptoms as a result from the drug abuse)
3. Patient History
Role of drug of abuse (what difficulties, symptoms arose from the abuse)
"Which Came First the Chicken or the Egg?"
4. Medical Evaluation29
Physical Exam
Vital signs
Serum electrolytes
Glucose
CBC with differential
If at Risk: HIV test
5. Severity of Symptomatology
Danger to self or others (patient may need inpatient hospitalization)
6. Potential for abuse of prescription drugs which may lead to relapse to primary drug of abuse.
Anticholinergic agents
Benzodiazepines
7. Patients have complex feelings and attitudes about their medication.
"Addiction to their medication"
Conflicting viewpoints of some support systems
Feeling of failure due to not being able to go drug free
These issues must be addresssed in a supportive, understanding environment. (support, understanding, does not necessarily mean that the treatment team necessarily agrees with the patient)
8. Compliance(provide education to decrease the"Myths" regarding medication)
a. Escalation of dose:
American Ideal: "one is good, three is better"
Tolerance
b. Medication Cure
Medication will cure illness
Illness is just due to drug of abuse
c. All or nothing effect:
Rejects any "foreign substance" in the body
D. Specific Psychopathology
1. Anxiety Disorders:
a. Abstinence Phobias30:
Many patients have a difficult time just being with out the drug. They have lived with the drug for so long, they do not know how to live with out it.
b. Drug Therapy
Antidepressants
Non-benzodiazepine anti-anxiety agents
Avoid use of benzodiazapines
If necessary:
Limited time
Specific objectives
2. Affective Disorders
a. Contribution of drugs/alcohol
Disinhibiting and depressant effects of alcohol and drugs may significantly contribute to changes in mood.
b. Time-course for resolution of symptoms
Most substance induced mood disorders (SIMD) clear within 3 to 4 weeks of continued abstinence .
c. Relapse
Patients who relapse have more depressive symptoms thus identification primary depressive disorders is important in relapse prevention.
d. Indicators of primary affective disorder:
Symptoms prior to drinking or after 2-3 months of abstinence
Hypomanic reaction to antidepressants
History of affective illness in two primary blood relatives or two generations
An early childhood history of separation anxiety, phobic behavior or panic disorder
A positive dexamethasone suppression test after 4 weeks of abstinence
e. Prognostic factors for suicide in alcoholics:
History of peptic ulcer
Lability of affect with explosiveness
Depression, irritability, and insomnia
Hypersensitivity to interpersonal rejections
f. Drug therapy
If indicated, insure a therapeutic trial
Monoamine oxidase inhibitors may not be the best choice due to impulse control difficulties and interactions with alcohol..
Blood monitoring for antimanic agents for compliance and effectiveness due to high risk for drug/alcohol use in bipolar patients. The concept of "self-treatment".
Potentiation of symptoms, side effects
Suicidal Ideation:
ONLY ONE WEEK'S WORTH OF MEDICATION MAY BE DISPENSED!!!
Food or drug interactions
Disulfiram (Antabuse): contraindicated for both schizophrenic and depressed individuals due to reports of psychotic reactions
3. Psychosis
a. Utilization of Antipsychotics During Intoxication
Avoid antipsychotic usage unless psychotic symptoms are disturbing to the patient or if the patient is violently acting out.
Stimulant Intoxication: antipsychotic agents may worsen hyperthermia, decrease seizure threshold, and increase cocaine craving
b. Potentiation of Side Effects: non-intoxicated state32
Increased severity of side effects in patients with a history of substance use. (i.e. Tardive Dyskinesia).
c. Education Requirements
Thought process disturbances may be accompanied by concreteness of thought(lack of ability to interpret implied meanings or statements).
Education may need to be repeated and explained thoroughly with patients repeating information conveyed in their own words to insure understanding.
VI. PHARMACIST ROLES IN THE MANAGEMENT OF THE DUAL DIAGNOSIS PATIENT
A. ASSESSMENT
1. Medication and Substance Use History
a. Current Status of intoxication
Physical assessment for signs and symptoms of intoxication
Interpretation of toxicology Results
t 1/2 of agent
length of time for excretion into urine
b. History
Identification of severity, and sequelae of drug use. Gather data which may be useful in providing education and support for the patient.
Ask specific questions!!!!
i. Drug/alcohol use:
by name
by street name
amount
frequency of use
particular circumstances of use
cost
amt. spent per use
# of highs for amt. spent/per use
# of hours spent using drug
ii. Reason for use:
Effects of use: both benefits and negative effects
Know the effects of the particular drug and ask about those effects if information is not volunteered
Homicidal or Suicidal ideation while intoxicated
iii. Abstinence:
Treatment Programs
Support Services Utilized
Length of abstinence
Stressors/circumstances leading back to use
iv. Withdrawal reactions:
Symptoms
Severity
Past treatments
v. Problems Incurred Secondary to Drug Use:
Has the patient ever been told they are addicted to any substance or that they should stop using a particular substance?
Family, Financial, Job related, Legal, Medical i.e. blackouts, fights, falls, head injury, organ damage, admissions (psychiatric or medical)
B. COUNSELING OF PATIENT
1. Drug/Alcohol
Signs and symptoms of intoxication
Neurochemical basis for effects
Effects on the Central Nervous system: short term or chronic use
Effects on the body functions
Interactions with disease
Interactions with medication
Support Services
2. Prescription Medications
Fears about addiction to medication/compliance
Symptoms of disease state
Symptoms medications are meant to treat
Biologic Basis of disease state
Mechanism of action of medication
Neurochemical exacerbations caused by drugs/alcohol
Side effects and coping mechanisms for side effects
Compliance
Needed dosage
Working with health care provider
Storage
Refill information
Missed dosage information
Encouragement to ask questions and take an active role in his/her own health care
C. REFERRAL RESOURCE
Community Education Provider
Volunteer
Information booklets
Treatment centers
12 step program numbers
National Alliance for the Mentally Ill (NAMI)
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