Opioid dependence

Dr Ayedh Alkhadem

Classification
Naturally occurring opioids: Called opiates opium and morphine extracted from the plant Papaver somniferum (the opium poppy) • Endogenous neural polypeptides(endorphin,enkephalin s,dynorphin) • • • •

• Semi-synthetic opioids: • a type of chemical synthesis that uses compounds isolated from natural sources (eg, plants) as starting materials • heroin, oxycodone, oxymorphone, and hydrocodone

• Synthetic opioids: • total synthesis in which large molecules are synthesized from a stepwise combination of small building blocks • buprenorphine, methadone, fentanyl, alfentanil, levorphanol, pethidine, codeine, and propoxyphene.

Abuse
1.failure to fulfill major role obligations at work, school, or home 2.use in situations in which it is physically hazardous 3.recurrent substance-related legal problems 4.continued use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance 5.The sx have never met the criteria for substance dependence for this class

dependence syndrome
• Priority of drug seeking • loss of control • neuroadaptation • •

• Toelarance • Withdrawl • the subs. is taken in larger amounts or over a longer period • a persistent desire or unsuccessful efforts to cut down or control subs. use • alot of time is spent in activities necessary to obtain the , use , or recover from subs. effects • important social, occupational, or recreational activities are given up or reduced b/c of sub. use • the subs. use is continued despite knowledge of having a physical or psychological problem that is likely to have been caused or exacerbated by the substance

Receptors
• (mu • Supraspinal and spinal analgesia; sedation; inhibition of • respiration; slowed GI transit; modulation of hormone and • neurotransmitter release

• (delta) • Supraspinal and spinal analgesia; modulation of hormone • and neurotransmitter release • (kappa) • Supraspinal and spinal analgesia; psychotomimetic effects; • slowed GI transit • dysphoria

• Degrees of Tolerance • High Moderate Minimal Analgesia Bradycardia Miosis • Euphoria, dysphoria Constipation • Mental clouding Convulsions • Sedation • Respiratory depression • Antidiuresis • Nausea and vomiting

Mechanism of dependence
• Reward circuit: • The mesolimbic DA pathway is the final common pathway of reward • Natural Highs: • Endorphins(brain’s morphine) • Anandamide(brain’s marijuana) • Acetylcholine(brain’s nicotine) • DA(brain’s cocaine &amphetamine) • Accomplishments and achievements • Eating ,sex

Reactive reward circuit
• From bottom up • Responsible 4 the impulsive automatic obligatory drug seeking Invoves VTA,Amygdala,Nucleus accumbens Learns to trigger drug seeking behavior Brings back memories ,expectations,and prospects of drug

Reflective reward system
Top down Prefrontal cortex: Orbitofrontal:regulates impulsivity DLpfc: analysing and taking the decision • VMPFC:integrate impusiveness with analysis and cognitive flexibility 2 come up e a final decision • Insula,sensory areas: past experiences • • • •

Biological factors
• susceptibility to acute psychopharmacologic effects of a given drug • metabolism of the drug • cellular adaptation within the CNS • predisposing personality characteristics • susceptibility to medical and neuropsychiatric complications

Genetic
• Genetic epidemiologic studies suggest a high degree of heritable vulnerability for opioid dependence • Gene polymorphisms for dopamine receptors/transporters • opioid receptors, serotonin receptors/transporters, proenkephalin, and catechol-Omethyltransferase (COMT)

Psychological factors
• presence of co-occurring psychopathology • medical illnesses • past or present severe stress • The possibility exists that susceptibility to psychological stressors and substance-use disorders may have similar etiologies

• Ego defects : • Opioids are theorized to help the ego in managing painful effects such as anxiety, guilt, and anger

social factors
• peer group • the availability of drugs Social attitude towards a substance poor parental functioning higher crime and unemployment rates

Behavioral Mechanisms
• positive reinforcing influence • Euphoria • alleviation of negative affective states (e.g., anxiety, depression), • functional enhancement • alleviation of withdrawal

Intoxication
• feelings of euphoria • alterations in consciousness/sedation • decreased or absent respirations • pinpoint pupils • central nervous system depression/unconsciousness • cardiopulmonary arrest

Withdrawal
• Physical dependence is expected after 2-10 days of continuous use • Pethidine withdrawal symptoms peak in 8-12 hours and last for 4-5 days • Heroin withdrawal symptoms usually peak within 36-72 hours and may last for 7-14 days

• Autonomic symptoms - Diarrhea, rhinorrhea, diaphoresis, lacrimation, shivering, nausea, emesis, piloerection • Central nervous system arousal Sleeplessness, restlessness, tremors • Pain - Abdominal cramping, bone pains, and diffuse muscle aching • Craving - For the medication

Physical signs
• Dependence: • Small-sized pupils • Inflamed nasal mucosa • Venous marks • Withdrawal: • Tachycardia, high blood pressure, fever, piloerection • mydriasis, lacrimation, Irritability, Yawning

• In intoxication: • Respiratory depression (may occur while the patient maintains consciousness) • Alterations in temperature regulations • Hypovolemia (true as well as relative), leading to hypotension • Miosis • Needle marks or soft tissue infection • Increase sphincter tone (can lead to urinary retention)

Medical complications
• HIV, hepatitis B, and hepatitis C • Abscesses and other bacterial infections • Endocarditis • Emboli • Arthritis and other rheumatologic problems

Differential Diagnosis
• Gastroenteritis, Influenza Pancreatitis, Acute Toxicity, Barbiturate Toxicity, Benzodiazepine Antisocial personality Panic attack Pontine infarct or hemorrhage Depressed mood

Treatment
• severe opioid intoxication : • basic principles of basic life support and advanced cardiac life support • Naloxone 0.4 to 0.8mg iv, im, or s.c repeated at approximately 2-min intervals Pts on longer acting opioids, such as SR oxycodone, may need to be placed on a naloxone drip

• Acute withdrawal is typically treated symptomatically • Trazodone 50mg for insomnia Loperamide for abdominal cramping and diarrhea hydroxyzine 25mg po 6hrly 4 anxiety and restlessness Clonidine 0.1mg po every 4 to 6 hours.

Maintenance treatment
• • • • Methadone a long acting opioid agonist half-life approx. 24 hours high-dose methadone maintenance therapy (60-109 mg/d) was more effective than low-dose MMT (either 40-59 mg/d or 1-39 mg/d)

Buprenorphine mu-opioid partial agonist "ceiling effect Buprenorphine has been combined with naloxone7 in a 4:1 ratio (Suboxone) 12-16 mg/d SL as single dose during induction (supervised) phase, then begin buprenorphine and naloxone SL (Suboxone) during maintenance (unsupervised) phase

Tramadol
• is a central-acting analgesic\ • enhances serotonergic neurotransmission. • As such, its analgesic effectiveness can be blocked by the serotonin (5-HT3) receptor antagonist ondansetron. • Inhibits norepinephrine transporter function • a weak u receptor agonist, since it is only partially antagonized by naloxone. • The recommended dosage is 50–100 mg orally four times daily. • Toxicity includes association with seizures; nausea and dizziness, • Surprisingly, no clinically relevant effects on respiration or the cardiovascular system have thus far • been reported. • may be useful in atypical pain such as chronic

References
• Oxford handbook of psychiatry,1st american editon 2008 • Current D&T Psychiatry,2nd edition • Katzung Pharmacology,9th edition • Stahl’s essential psychophamacology,3rd edition • Neurobiology of mental illness 2nd edition,oup • The Maudsley Prescribing Guidelines 10th ed.

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