Substance Related disorder
Written by
Noor Kadhim Mohammed
Zainab Eassa Jassim
Zainab Attaa
Clinical Pharmacy Department
College of Pharmacy
University of Baghdad
PhD candidates
Substance Related disorder
Which is also called as Substance use disorder (SUD) is a chronic
disease with progressive deterioration of psychological and
physiologic activity secondary to the habitual use of substance that
may cause euphoria.
This complex disease disrupts many if not all aspects of an
individual’s life; therefore, multimodal treatment is necessary.
Pharmacotherapy has a role in treatment of some SUD,
including intoxication, withdrawal, and/or long-term
relapse prevention.
These substances include
1- CNS depressants (Alcohol & benzodiazepines)
2-CNS Stimulants (Nicotine, Cocaine, amphetamines)
3-Opioids (Morphine, Codeine, ect.)
4- Other (Cannabinoids)
Physical signs of SUD
*Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
substance use leading to clinically significant impairment or distress;
manifested by ≥ 2 of the following, occurring within a 12-month
period
GENERAL APPROACH TO THE TREATMENT OF SUD
1-Goals of Treatment: cessation of use of the substance,
termination of substanceseeking behaviors, and return to
normal functioning.
2-Assess comorbid psychiatric conditions such as anxiety,
depression, insomnia, and pain because they increase risk of
relapse to substance use.
3- Complete abstinence may be desirable, harm reduction
may be sufficient in certain cases.
Harm reduction strategies that seek to reduce negative
consequences associated with substance use.
Nonpharmacologic Therapy
Psychotherapy is the core therapeutic intervention.
(Behavioral and life long process)
1-Motivation enhancement to stop or reduce substance
use
2-Coping skills education
3-Providing alternative reinforcement
4-Managing painful affect (e.g, dysphoria)
5- Enhancing social support and interpersonal
functioning
TREATMENT OF SUBSTANCE USE DISORDER
Patients with SUDs require more than pharmacotherapy
to achieve sustained remission.
Medications alleviate the effects of intoxication
Attenuate withdrawal symptoms (Detoxification)
Decrease craving and likelihood of relapse
1-Central Nervous System Depressants
Alcohol
Specific Effects of Alcohol Related to Blood Alcohol Concentration (BAC)
1-Alcohol Intoxication
In treating acute intoxications of CNS depressants
1-Support of vital functions (respiratory & cardiac)
2-Screens are desired, blood (BAC) or urine test.
Mild-Moderate Reassurance and safe place
Severe (impaired consciousness) Thiamine 100mg iv
or im for 3 days
Aggressive or agitated Haloperidol (antipsychotic)
Note : 1-sedation with BDZ in alcoholist increase respiratory
depression
2-Antipyschotic lower seizure threshold and best avoided.
2-Alcohol Withdrawal
Occur on cessation or reduction of alcohol consumption in
heavy drinker with physical dependence.
* Uncomplicated: nausea, vomiting, tremor, tachycardia, HT,
insomnia.
*Complicated: seizures, delirium, hallucinosis, and potentially death.
Symptoms assessed by validated scale, such as the Clinical Institute
Withdrawal Assessment–Alcohol, Revised (CIWA-Ar).
(< 10: mild withdrawal, 10–18: moderate withdrawal, > 18: severe
withdrawal).
Treatment of Alcohol Withdrawal
1-Benzodiazepines (BDZ) considered the drugs of choice for
alcohol withdrawal
• modulate anxiolysis by stimulating GABAA receptors and, in
doing so, substitute pharmacologically for alcohol, also
effective in preventing seizures.
• Longer-acting BDZ(chlordiazepoxide and diazepam) effective
for acute alcohol withdrawal and causes fewer rebound effects
and withdrawal seizures on discontinuation.
• Shorter-acting agents (lorazepam or oxazepam) require more
frequent dosing but may be more appropriate for alcoholics
with liver disease and the elderly.
Adjunctive therapeutic
1-IV fluids & electrolytes (K and Mg).
2-Thiamine and multivitamins as well as folate 1mg
(deficient of thiamine and have a higher risk for developing Wernicke
encephalopathy).
3-Clonidine (α2-adrenergic agonist) may given to decrease
autonomic tone rebound and hyperactivity, hypertensive urgency.
4-Antipsychotics (e.g., haloperidol, quetiapine)
can be used for managing hallucinations and severe agitation
3-Alcohol Use Disorder
*Long-term maintenance for alcohol dependence focus on relapse
prevention by psychosocial treatment with adjuvant pharmacotherapy.
1-Disulfiram: produces an aversive reaction if the patient drinks.
It inhibits aldehyde dehydrogenase accumulation acetaldehyde
flushing, vomiting, headache, palpitations, tachycardia, fever, and
hypotension.
Inhibition of the enzyme continues for as long as 2weeks after
stopping disulfiram.
Disadvantage:
1-Severe reactions include respiratory depression, arrhythmias, MI,
seizures, and death.
2-Hepatotoxic monitor liver function.
*A similar reaction may occur if patient take ??
2-Naltrixone
Reduce craving by blocks the action of endorphins when alcohol
is consumed.
A depot formulation allows monthly administration
✔ Side Effects: nausea, headache, dizziness, nervousness,
insomnia, and somnolence.
✔ Contraindication: in patients currently taking opioids, and
hepatitis, liver failure (hepatotoxic).
3-camprosate
is a glutamate modulator that reduces alcohol craving.
✔ The most common acamprosate adverse effect is diarrhea.
✔ Undergoes renal elimination
Opioid Intoxication
• The word opioid refers to medications and substances that
exert their action through the opioid system. Opioids
encompass a wide range of substances, including naturally
occurring (eg, morphine) and synthetic (eg, oxycodone).
Signs and Symptoms of Opioid
Intoxication
Drug Behavioral Effects Physiologic Effects
Opioids Drowsiness, sedation, slurred Nausea, vomiting, respiratory
speech, impaired memory and depression (dose-related), stupor,
attention, psychomotor coma, itching,
retardation miosis, hypothermia, bradycardia
• One strategy is to reverse intoxication using naloxone 0.4 to 2 mg IV
every 2 to 3 minutes up to 10 mg;
• IM, subcutaneous, or intranasal (IN) route may be used
• if IV access is unavailable. Naloxone is shorter-acting than many
• opioids and may require re-administration at periodic intervals;
• Secure the airway and ensure breathing in cases of opioid
over dose. In some cases, intubation and manual or
mechanical ventilation may be required to avoid oxygen
desaturation leading to brain hypoxia or anoxia and brain
damage or death.
• New opportunities for “take-home” naloxone have emerged in an
effort to prevent overdose deaths.
• FDA has approved a naloxone autoinjector and IN naloxone for this
purpose.
• IN naloxone is commonly used in nonmedical settings due to ease of
use. Educate patients and caregivers on naloxone, including when to
use, how to assemble, proper administration, and notifying emergency
services.
Opioid Withdrawal
• Signs and Symptoms of Drug Withdrawal
Drug Symptoms
Opioids EENT: lacrimation, mydriasis, rhinorrhea
GI: nausea, vomiting, diarrhea
Cardiovascular: increased heart rate and blood pressure
CNS: irritability, restlessness, yawning
Musculoskeletal: increased body temperature, piloerection
Medically Supervised Withdrawal
• Buprenorphine is a partial μ-opioid receptor agonist and is available in
multiple formulations with varying pharmacokinetic profiles. For
example, buprenorphine in combination with naloxone is available as
• sublingual tablet,
• sublingual film,
• and buccal film.
Certain formulations (eg, sublingual film) may have greater
buprenorphine bioavailability, and hence lower dosage requirements
than other formulations (eg, sublingual tablets).
Risk of developing physiologic tolerance to buprenorphine is high
if used for prolonged periods. In this case, buprenorphine requires
a slow taper to discontinuation. Withdrawal from buprenorphine is
generally easier and less severe than withdrawal from a full agonist,
such as methadone.
symptom-specific medications
Opioid Use Disorder
• After conclusion of withdrawal, patients may not feel their usual
selves for some time and could relapse to using opioids, just to “feel
normal.”
• Long-term use of opioids results in neuroadaptations, and the brain
might not readily return to its prior homeostasis.
• The goal of treatment is to encourage stability, both in the body and in
the patient’s life. If an individual is not successful in quitting opioids
(eg, because of withdrawal symptoms or postacute craving), then
maintenance treatment should be considered.
• Methadone, buprenorphine, and long-acting naltrexone are used for
maintenance treatment, also called medication assisted treatment, of
opioid use disorder.
• typically in oral formulations also containing naloxone.
Two long-acting buprenorphine formulations are also available:
• subcutaneous injection
• subdermal implants.
Cannabinoid Intoxication
Synthetic cannabinoids are more likely than cannabis to produce serious
psychiatric disturbances that result from potent full-agonist activity and
the lack of cannabidiol in synthetic products.
Cannabidiol has been associated with diminishing anxious and
psychotic symptoms and behaviors
Cannabinoid Withdrawal Symptoms
• Cannabinoid Withdrawal Symptoms of cannabinoid withdrawal are
primarily behavioral. For example, significant anxiety may accompany
cannabinoid withdrawal, which can lead many individuals to resume
substance use.
• Pharmacotherapy aimed at improving anxiety or sleep difficulties (eg,
buspirone, gabapentin) shows promise for the management of
cannabinoid withdrawal.
• Currently, no medications are FDA approved to specifically target
cannabinoid withdrawal.
Cannabinoid Use Disorder
• There are no proven pharmacotherapies for treatment of cannabinoid
use disorder. As previously described for cannabinoid withdrawal,
promising medication management approaches for cannabinoid use
disorders target symptoms of anxiety or sleep difficulties that
complicate cessation of cannabinoid use.
• Pharmacotherapy trials have emerged in the literature, but universally
accepted medication treatment strategies have yet to emerge.
