The document discusses several newer narcotics including their origin, pharmacological properties, medical uses, and risks of abuse. Opium is obtained from the opium poppy and contains morphine along with other alkaloids. Morphine can be processed chemically to produce semi-synthetic opioids like levorphanol, an potent analgesic also used to reduce anaesthetic doses. Meperidine is a synthetic opioid analgesic with a toxic metabolite that can accumulate and cause seizures. Fentanyl is a very potent synthetic opioid related to phenylpiperidines. Sufentanil and remifentanil are even more potent synthetic opioids used in anesthesia. Methadone is an orally active opioid used to treat opioid

1. NEWER NARCOTICS
S. Parasuraman M.Pharm., Ph.D.,
Senior Lecturer, Faculty of Pharmacy,
AIMST University,
Bedong 08100, Malaysia.

2. Newer Narcotics
• Opium: It is a dried latex obtained from the opium
poppy (Papaver somniferum). Latex of opium
contains approx. 12% of the analgesic alkaloid
MOEPHINE. Latex also contains codeine, thebaine
and other non-analgesic alkaloids such as papaverine
and noscapine.
• Morphine processed chemically to produce semi-
synthetic and synthetic opioids for illicit and licit use.

3. Apothecary vessel for
storage of opium as a
pharmaceutical, Germany,
18th or 19th century
Poppy crop from the
Malwa in India
Opium users in Java during the
Dutch colonial period, circa
1870
An artist's view of an
Ottoman opium seller
An opium den in 18th-
century China through the
eyes of a Western artist

4. A Chinese opium house,
photograph 1902
British opium ships
International drug routes

5. LEVORPHANOL (levo- Dromoran)
• Levorphanol [(−)-3-hydroxy-N-methyl-morphinan] is
an potent synthetic opioid agonist used to treat
moderate to severe pain.
• It is orally active morphine-like analgesic agent used
as NMDA antagonist an monoamine reuptake
inhibitor.
• Levorphanol combination with thiopental to reduce
the latter drug’s anaesthetic dose and to decrease
postoperative recovery time.
• The D-isomer of levorphanol does not possess
opioid analgesic activity but is a useful antitussive.

6. LEVORPHANOL (levo- Dromoran)
• Repeated administration of levorphanol produce
dependence and tolerance. Discontinuation of
chronic use results withdrawal syndromes.
• Over dose may produce signs of respiratory
depression, cardiovascular failure, central nervous
system depression, extreme somnolence
progressing to stupor or coma, skeletal muscle
flaccidity, cold and clammy skin, constricted pupils,
and sometimes bradycardia and hypotension.
• Levorphanol over dose may treated with i.v. injection
of naloxone.

7. Meperidine (pethidine) and Congeners
(demerol)
• Petnidine (t1/2 = 3-5 hours) is a synthetic opioid
analgesic of the phenylpiperidine class, used for the
treatment of moderate to severe pain.
• Toxic metabolite of pethidine i.e., nor-pethidine (t1/2
= 15-20 hours) was more toxic than other opioids (in
chronic use). Nor-pethidine have serotonergic effect
and cause serotonin syndrome.
• Large doses on short intervals may produce an
excitatory syndrome due to the accumulation of nor-
pethidine. It is characterized by hallucinations,
tremors, muscle twitches, dilated pupils, hyperactive
reflexes, and convulsions.

8. Meperidine (pethidine)
• 75-100 mg pethidine is approximately equivalent to 10
mg morphine. The analgesic effects starts 15 minutes
after oral administration and peak action in about 1 to 2
hours, and subside gradually.
• Pethidine produces sedation, respiratory depression and
euphoria like morphine.
• Pethidine crosses the placental barrier and produce
delayed respiration, decreased respiratory minute
volume, or decreased oxygen saturation in delivered
babies.
• Untoward effects are similar to those of morphine, but
constipation and urinary retention may be less common.

9. Meperidine (pethidine)
• Street Names: demmies, pethidine
• Abuse:
– Pethidine can be abused and is subject to criminal
diversion.
– Short-term use may precipitate the seizures.
– Early abuse may produce euphoric ‘rush’ and increase
serious risks.
– Meperidine contraindicated with alcohol and other
opioids (fentanyl, hydromorphone, morphine, and
oxycodone). It will increase the risk of CNS depression,
and respiratory failure.

10. Meperidine (pethidine)
• Symptoms of over dose:
– Respiratory depression
– Extreme somnolence progressing to stupor or coma
– Skeletal muscle flaccidity (lack of tone)
– Cold and clammy skin
– Bradycardia and hypotension.
• Intravinous over dose of meperidine causes apnea, circulatory collapse,
cardiac arrest and death.
APNEA CIRCULATORY COLLAPSE

11. Meperidine (pethidine)
• Management of meperidine poisoning:
– Reestablishment of adequate respiration (clearance of
airway; assisted or controlled ventilation)
– Intravenous naloxone (antagonist should not be
administered in the absence of clinically significant
respiratory or cardiovascular depression).
– Stomach should be evacuated by emesis or gastric
lavage.

12. Fentanyl
• Fentanyl is a synthetic opioid related to the
phenylpiperidines
• Its congeners are sufentanil, remifentanil, and
alfentanil.
• Fentanyl is approximately 80 to 100 times more potent
than morphine and roughly 15 to 20 times more potent
than heroin.
• fentanyl is known as Actiq, Duragesic, and Sublimaze.
• Street names: Apache, China girl, China white, dance
fever, friend, goodfella, jackpot, murder 8, TNT, as well
as Tango and Cash.

13. Fentanyl
• Mixing fentanyl with street-sold heroin or cocaine
markedly amplifies their potency and potential dangers.
• Effects include: euphoria, drowsiness/respiratory
depression and arrest, nausea, confusion, constipation,
sedation, unconsciousness, coma, tolerance, and
addiction.
• Fentanyl is used as adjuvant anaesthetic agent.
Buprenorphine antagonizes the respiratory depression produced by
anesthetic doses of fentanyl

14. Fentanyl
• signs of an allergic reaction to fentanyl:
– weak or shallow breathing
– fast or slow heart rate
– stiff muscles
– severe weakness, feeling light-headed or fainting.
• Common side effects :
– slowed breathing
– slow heart rate
– muscle stiffness
– dizziness, vision problem;
– nausea, vomiting
– itching, sweating
– high blood pressure (confusion, anxiety, pounding in your neck or
ears).

15. Sufentanil
• Sufentanil is a synthetic opioid analgesic drug
approximately 5 to 10 times more potent than its parent
drug, fentanyl, and 500 times as potent as morphine.
• Sufentanil is an analgesic component of general
anesthesia; at intravenous doses ≥8 µg/kg, Sufentanil
produces a deep level of anaesthesia. Sufentanil
produces a dose related attenuation of catecholamine
release, particularly norepinephrine.

16. Sufentanil
• Over dose management:
– Sufentanil is very potent, patient exhibit symptoms of overdose
such as respiratory depression or respiratory arrest. Naloxone is
used to overcome the sufentanil overdose.

17. Sufentanil
• Adverse effect:
– Cardiovascular: Bradycardia, hypertension, hypotension.
– Musculoskeletal: Chest wall rigidity.
– Central Nervous System: Somnolence.
– Dermatological: Pruritus.
– Gastrointestinal: Nausea, vomiting.
– Body as a whole: anaphylaxis.
– Musculoskeletal: Skeletal muscle rigidity of neck and
extremities.
– Respiratory: Apnea, bronchospasm, postoperative respiratory
depression.
– Miscellaneous: Intraoperative muscle movement.

18. Remifentanil
• Remifentanil is a potent ultra short-acting synthetic
opioid analgesic drug.
• Remifentanil is used for sedation as well as combined
with other medications for use in general anaesthesia.
• The pharmacological properties are similar to those of
fentanyl and sufentanil.
• Adverse effect: Reduce sympathetic nervous system
tone, respiratory depression, dose-dependent decrease
in heart rate, arterial pressure, respiratory rate, tidal
volume. Muscle rigidity is rarely occur.

19. Methadone and congeners

20. Methadone and congeners
• Methadone is a orally, long-acting µ-receptor agonist
and its pharmacological properties qualitatively
similar to morphine.
• L isomer of methadone is 8 to 50 times more potent
than the D isomer. D-methadone lacks significant
respiratory depressant action and addiction liability.
• Street names: Amidone, Chocolate chip cookies
(methadone or heroin with MDMA), Fizzies, Street
methadone Wafer.

21. Methadone
• Methadone is commonly used to treat addiction to
opioids (such as heroin).
• Methadone reduces the cravings and withdrawal
symptoms caused by opioids use by blocking the
"high" and preventing the intense euphoric rush of
these drugs.
• Miotic and respiratory-depressant effects can be detected
by 24 hours after a single dose.

22. Methadone
• Reinforcing effects of methadone are limited, as the drug is
designed to block the pleasurable effects of opiates. Some of
the physical and side effects of methadone are:
• Short-term: Restlessness
– Vomiting
– Nausea
– Slowed breathing
– Itchy skin
– Pupil contraction
– Severe sweating
– Constipation
– Sexual Dysfunction
– Death
• Long-term: Lung and respiration problems
• Effects on women:
– Menstrual cycle changes or lapse in cycles
– Pregnancy complications if users reduce dosage levels during pregnancy

23. Methadone
• Addiction, Tolerance, Withdrawal, and Dependence
– Tolerance to methadone can occur with frequent
administration.
– Withdrawal symptoms occurring from the use of methadone
are not as common.
– Psychological and physical dependence can develop with the
use of methadone.
• Alternatives to Methadone
– Bupernorphine.
– L-alpha-acetyl-methadol (LAAM)

24. Methadone
• Pharmacokinetics:
– Orally active, well absorbed in buccal mucosa and GIT,
detected in plasma within 30 min of oral ingestion and
reaches peck concentrations at about 4 hours.
– It metabolized in liver by N-demethylation and cyclization
reactions.
– Metabolites are excreted in urine and bile, acidification of
urine promotes urinary excretion.
– Tolerance to the constipating effect of methadone does not
develop as fully as it does to other effects.
– Physical dependence is developed during the long-term
administration of methadone.

25. Methadone
• Risks:
– Withdrawal symptoms: Muscle tremors, nausea, diarrhea,
vomiting, and abdominal cramps.
– Overdosing on methadone poses an additional risk.
– Individuals who abuse other narcotics (such as heroin) turn
to methadone because of its increasing availability.
– Methadone does not produce the euphoric rush associated
with those other drugs.
– Methadone overdoses are associated with severe respiratory
depression, decreases in heart rate and blood pressure,
coma and death.

26. Methadone
• Management of methadone poisoning:
• Do not allow to slip into unconsciousness.
• Snoring or gurgling sounds.
• Do not let their head fall forward or back (due to restricts
oxygen flow to the lungs)
– Management:
• If the person is unconscious, turn them on their side to reduce
the risk of them vomiting and choking.
• Make sure their airways are clear
• Do not leave them alone.
• If breathing has stopped, give mouth-to-mouth resuscitation.
• If there is no pulse, commence CPR (Cardiopulmonary
resuscitation) if you are trained.
• Overdose is treated with naloxone.