You are on page 1of 39

Opioid dependence

Dr Ayedh Alkhadem
• Naturally occurring opioids:
• Called opiates
• opium and morphine
• extracted from the plant Papaver
somniferum (the opium poppy)
• Endogenous neural
• 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.
1.failure to fulfill major role obligations at
work, school, or home
2.use in situations in which it is physically
3.recurrent substance-related legal
4.continued use despite having
persistent or recurrent social or
interpersonal problems caused or
exacerbated by the effects of the
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.
• 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
• (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
• Mental clouding
• 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
obligatory drug seeking

Invoves VTA,Amygdala,Nucleus

Learns to trigger drug seeking

Brings back memories

,expectations,and prospects of drug

Reflective reward system
• Top down
• Prefrontal cortex:
• Orbitofrontal:regulates impulsivity
• DLpfc: analysing and taking the
• VMPFC:integrate impusiveness with
analysis and cognitive flexibility 2
come up e a final decision
• Insula,sensory areas: past
Biological factors
• susceptibility to acute
psychopharmacologic effects of a
given drug
• metabolism of the drug
• cellular adaptation within the CNS
• predisposing personality
• susceptibility to medical and
neuropsychiatric complications
• Genetic epidemiologic studies
suggest a high degree of heritable
vulnerability for opioid dependence
• Gene polymorphisms for dopamine
• opioid receptors, serotonin
proenkephalin, and catechol-O-
methyltransferase (COMT)
Psychological factors
• presence of co-occurring
• medical illnesses
• past or present severe stress
• The possibility exists that
susceptibility to psychological
stressors and substance-use
disorders may have similar
• 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
• feelings of euphoria
• alterations in consciousness/sedation
• decreased or absent respirations
• pinpoint pupils
• central nervous system
• cardiopulmonary arrest
• 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,
• 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,
• In intoxication:
• Respiratory depression (may occur
while the patient maintains
• 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
• Endocarditis
• Emboli
• Arthritis and other rheumatologic
Differential Diagnosis
• Gastroenteritis,
Pancreatitis, Acute
Toxicity, Barbiturate
Toxicity, Benzodiazepine
Antisocial personality
Panic attack
Pontine infarct or hemorrhage
Depressed mood
• 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
at approximately 2-min intervals

Pts on longer acting opioids, such as S-

R oxycodone, may need to be placed on

a naloxone drip
• Acute withdrawal is typically treated
• Trazodone 50mg for insomnia
Loperamide for abdominal cramping and

hydroxyzine 25mg po 6hrly 4 anxiety and

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)
mu-opioid partial agonist

"ceiling effect

Buprenorphine has been combined

with naloxone7 in a 4:1 ratio

12-16 mg/d SL as single dose during

induction (supervised) phase,

then begin buprenorphine and

naloxone SL (Suboxone) during

maintenance (unsupervised) phase
• is a central-acting analgesic\
• enhances serotonergic neurotransmission.
• As such, its analgesic effectiveness can be blocked by
the serotonin (5-HT3) receptor antagonist
• 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
• Surprisingly, no clinically relevant effects on
respiration or the cardiovascular system have thus
• been reported.
• may be useful in atypical pain such as chronic
• 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
• The Maudsley Prescribing Guidelines
10th ed.