THE NARCOTIC ANALGESICS

1
THE NARCOTIC ANALGESICS Narcotics block the
transmission of the nerve signal across nerve
gaps, the minor analgesics blocked prostaglandin
synthesis
The more important ones Morphine, codeine,
oxycodone (PERCODAN), hydromorphone (DILAUDID),
methadone, heroin not legal meperidine
(DEMEROL), pentazocine (TALWIN), fentanyl
(SUBLIMAZE), buprenorphine (BUPRENEX),
2
Morphine Opium est. 10,000 tons extracted
from the poppy Papaver somniferum, Afghanistan
estimated 92 of supply.
Currently a glut, Afghan farm price 150/kg!!!,
2/mg here
3
contains about 10 morphine, can be
recrystallized as white morphine sulfate (first
pure form in about 1803) Used orally (LAUDANUM)
before 1856 when syringe was invented
4

• Normal dose to kill pain 5-10mg injected
• analgesic - kills pain
• constipator - anti-dysentery side effect
• narcotic - induces drowsiness, lethargy
• DEPRESSES RESPIRATORY SYSTEM
• usual overdose effect
• some euphoria
• - addictive

5
Morphine binds to opiate receptors that control
passage of Ca2 and K through channels which
in turn control acetylcholine (nerve transmitter)
flow across synapses
6
Codeine (½ of opium), made synthetically
(60,000 kg/y USA) only about 10 of pain relief
of morphine, though better cough
suppressant Legal OTC if lt 2.2 mg/mL or in
combination with aspirin or Tylenol, Egs. 222,
292 Tylenol 1 (8mg) Tylenol 2 (16mg), Tylenol 3
(30 mg)
7
HEROIN Bayer labs (1874) sold soluble HCl salt
as 'cough syrup'
H itself has mp 173oC, white, bitter taste H.HCl
salt has mp 243-244oC H passes the blood-brain
barrier faster (bigger rush) than morphine (more
fat like) BUT IS BROKEN DOWN TO MORPHINE in brain
for use Street H typically used to be 1-13 pure,
now some batches much more pure
8
OPIATES narcotics - induce drowsiness
insomnia, irritability constrict pupil of eye
(pin-point pupils) depress respiration (overdose
danger) reduce bowel activity -
constipation diarrhea reduce all secretions
(gastric, bile) chills, cramps,nausea
Timing of effects 8-12h runny nose, eyes,
sweating 12-16h insomnia 16-48h loss of
appetite, nausea, vomiting, diarrhea,
irritability 48-72h tremors, sneezing, chills,
flushes, ejaculation/orgasm, abnormal white cell
counts
9
Opiates CROSS TOLERATE, so need larger doses
(increased enzyme production) injection at any
point suppresses symptoms HENCE ADDICTION at
2/mg most addicts need gt2 fixes (10-20mg x
2)per day, expensive Even in hospitals, patients
on longer term morphine build up a
tolerance Recent Queens U study suggests small
injection of the antagonist naloxone returns
sensitivity to the drug
10
NATURAL PAIN KILLERS in body are pentapeptides
(small proteins, 5 amino acids long) called
ENKEPALINS Methionine enkepalin
Tyr-Gly-Gly-Phe-Met Leucine enkepalin
Tyr-Gly-Gly-Phe-Leu these are often part of
larger proteins, eg. b-endorphin contains 31
amino acids, first 5 of which are shown above
(Met) NEUREX Corp. has developed SNX-111, a
26-peptide which is injected spinally to block Ca
channels in spinal cord, available now as
ZICONOTIDE (US).
11
SYNTHETIC OPIATES
Vicodin
HYDROMORPHINONE (hydromorphone, DILAUDID) 5-7x
more potent than morphine so 1.5 - 2
mg equivalent to 10 mg morphine, but lasts a
little less, only 2-4 h used in Victoria for
cancer patients pills can be ground and
injected for high (50/street).
12
Hydrocodone Vicodin Hycodan in Canada as an
antitussive (cough) 5mg
13
OXYMORPHONE (NUMORPHAN) 1.5 mg equivalent to 10
mg morphine, lasts 3-6 h 2003 - extended release
version did not work well, caused many
addictions, lawsuits in US
14
Pethidine
DEMEROL (1930's) 15 of morphine's effectiveness
dose 50-150mg/4h (up to 75mg if by i.v.) NO
nausea, no affect on pupils CAUSES sedation,
euphoria and is addictive MORPHINE AGONIST, goes
to same receptor sites
15
Newer synthetic opioids
Butorphanol Nalbuphine
Stadol, Torbutrol long used by vets
Nubain Oct 2006 Canada (Sandoz)
2 mg injected 10 mg injected both are mixed
agonist/antagonist (against different receptors)
16
08 gt250,000 users of methadone
METHADONE equally potent to morphine or
heroin highly addictive orally NO sedation or
sleepiness (addict can hold a job), STOPS
Withdrawal symptoms, blocks action of heroin only
need one dose per day if oral (30-120 mg)(slower
acting), cheap 10 cents per dose Best supplied
in orange juice, since if injected can get rush
(1/mg on street for powder) Addicts claim harder
to get off methadone than heroin
17
Propoxyphene
DARVON 50mg is equiv to 10 mg morphine, sold in
100mg oral capsules, somewhat addictive overdoses
kill 1000-2000 per year in USA by respiratory
depression PHYSICIAN WARNING do not prescribe to
suicidal patients, MAX 600mg/day 800-1200mg dose
causes convulsions.
18
THE FENTANYLS - DESIGNER DRUGS
R1 R2 R3 Name H H H fentanyl Me H H 3-Me-fentanyl
H H F p-F-fentanyl H Me H a-Me-fentanyl
Fentanyl (SUBLIMAZE) 150 x morphine, used in
major surgery 2-3mg/kg, DOSE 0.1-0.2 mg
injected very short acting, very
addictive illegal ones 10 x more active
19
Newer, legal ones
Sufentanil Alfentanil Sufenta Alfenta
Dose 0.01-0.04 mg 0.4-0.8 mg injected
20
RUSSIA - OCT 23 2002 - Chechen terrorists took
800 people hostage in a Moscow theater Russia
pumped fentanyl gas thru ventilation system on
day 3, but refused to identify gas to local
medics 130 people died, Russian military lost no
one. Antidote Naloxone!!
3-Me-fentanyl 3000 x morphine - overdoses easy,
death
21
A DRUG GONE WRONG
In 1980's, MPPP was a popular, easy to
make-at-home drug Ca. 25x stronger than Demerol
(CO2Et compd) Poor batch control led to ester
elimination to give MPTP (1-methyl-4-phenyl-1,2,3,
6-tetrahydropyridine) Several hospitals reported
patients suffering from rigidity and
Parkinsons-like symptoms All had taken street
heroin that was in fact MPTP
22
Crosses into brain, kills dopamine producing
cells, induces tremors, rigidity, loss of muscle
control, i.e. PARKINSON's symptoms
Nov. 2005 Can. Chem. News Barry Kidston, U.
Maryland grad student First synthesized MPPP and
injected himself after several months, he brewed
a bad batch, and was hospitalized, eventually the
doctors tried L-DOPA which improved his fate
for 2 yrs, until he died of an overdose of
cocaine!
23
ANTAGONISTS FOR HEROIN
Inject Oral
oxymorphone with new R groups
NARCAN Naloxone.HCl 0.4 - 2 mg injected,
repeat in 3 min if nec. is best antidote for
heroin overdose no overdoses of naloxone
recorded
24
BLOCKS action of heroin, no narcotic activity,
no respiratory depression prevents addicts
getting high (pregnant mothers....) Methenex
methadone naloxone no rush
ReVia Naltrexone.HCl ORAL, 50mg/day for 3
days, or one 150 mg dose
25
THE AZOCINES - mixed agonist-antagonists
Pentazocine TALWIN 60mg injected dose or
180mg oral dose is equiv to 10mg injected
morphine blocks euphoric effect of morphine, but
less respiratory depression
26
EQUIVALENT DOSES to 10 mg morphine injected
injected oral Sufentanil 0.01-0.04 - Fenta
nyl 0.1-0.2 - Alfentanil 0.4-0.8 - Oxymorpho
ne 1.5 - Hydromorphone 2 4-6 Butorphanol 2
- Morphine 10 20-30 Nalbuphine 10 - Oxy
codone - 30 Propoxyphene 50 100 Pentazocine
60 180 Meperidine 75 300 Codeine 120
200
27
VIGABATRIN V SABRIL (Aventis) an
anti-epilepsy drug in Canada reduces the effect
of heroin, methamphetamine, alcohol V is an
inhibitor of GABA transaminase, the enzyme which
breaks GABA down If GABA is high, less dopamine
(the brain exciting amine) is produced
GABA Vigabatrin g-aminobutyric
acid