TAHAR ABDULAZIZ SULIMAN MD, PhD

1. TOXICITY OF
PLANT
ALKALOIDS
TAHAR ABDULAZIZ MD, PhD

2. DEFINITION OF PLANT ALKALOID
A basic heterocyclic
nitrogenous compound of
plant origin that are
physiologically active

3. Deviation from Definition
• Basicity: Some alkaloids are not basic
e.g. Colchicine, Piperine,
• Nitrogen: The nitrogen in some
alkaloids is not in a heterocyclic ring
e.g. Ephedrine, Colchicine, Mescaline.
• Plant Origin: Some alkaloids are
derived from Bacteria, Fungi, Insects,
Frogs, Animals.

4. OTHER SOURCES
. castoramine :--- from Canadian beaver

5. Pyocyanine :-- from Pseudomonas
aeruginosa (a bacteria).

6. Muscopyridine :--From Musk of an Deer.

7. General Classification:
1) True (Typical) alkaloids that are derived from
amino acids and have nitrogen in a heterocyclic
ring. e.g Atropine
2) Protoalkaloids that are derived from amino
acids and do not have nitrogen in a heterocyclic
ring. e.g Ephedrine
3) Pseudo alkaloids that are not derived from
amino acids but have nitrogen in a heterocyclic
ring. e.g Caffeine
4) False alkaloids are non alkaloids give false
positive reaction with alkaloidal reagents.

8. • They can be found in one or more parts of
the plant (leaves, fruits, seeds, or whole
plant).
• Generally, non-soluble in water but can be
extracted by organic solvents in alkaline
media.
• The most important alkaloids of
toxicological interest are: opium, atropine,
cocaine, strychnine, nicotine, aconite,
ergot, digitalis, and cannabis.

9. OPIOIDS
A group of narcotic analgesics that
represent one of the most important
groups of CNS depressants.
• Classification:
1- Natural
2- Semi-synthetic
3- Synthetic

10. OPIATES & OPIOIDS
• Opioids exert activity at opioid receptors &
include opioid agonists, antagonists, and
mixed agonist-antagonists.
• Opiates are alkaloid extracts of the opium
poppy.
• Opiates are opioids but the reverse is not
always true.

11. Opioid Receptors
• Majorreceptors
– Mu
– Kappa
– Delta
– nociceptin receptor or NOP also known
as the orphanin FQ receptor or kappa-
type 3 opioid receptor
• Minorreceptors (undetermined role in humans)
– Epsilon
– Zeta

12. MAJOR OPIATE RECEPTORS
Rector Subtypes Location Functions
Delta 1, 2 brain
pontine nuclei
amygdala
olfactory bulbs
deep cortex
peripheral sensory
neurons
•analgesia
•antidepressant effects
•Convulsant effects
•physical dependence
•Perhaps of mu-opioid receptor-
mediated respiratory depression
Kappa 1,2,3 brain
hypothalamus
periaqueductal gray
claustrum
spinal cord
substantia gelatinosa
peripheral sensory
neurons
analgesia
sedation
miosis
inhibition of ADH release
dysphoria

13. Mu 1
,
2
,
3
brain
cortex (laminae III and IV)
thalamus
striosomes
periaqueductal gray
rostral ventromedial medulla
spinal cord
substantia gelatinosa
peripheral sensory neurons
intestinal tract
μ1: analgesia
physical dependence
μ2:
respiratory depression
miosis
euphoria
reduced GI motility
physical dependence
μ3:
possible vasodilation
nociceptin
receptor
(NOP)
(orphanin
FQ receptor)
brain
cortex
amygdala
hippocampus
septal nuclei
habenula
hypothalamus
spinal cord
anxiety
depression
appetite
development of
tolerance to μ
agonists

14. NOP Recptor

15. • About 25 alkaloids are present naturally in
opium.
• Opium is the juice taken from the unripe
capsule of poppy plant fruit (Papever
somniferum).
• Poppy plant is present mainly in Asia and
South America, but can be cultivated
anywhere either in hot or cold countries.
• Fresh opium is plastic, moist, smooth, reddish-
brown, then becomes hard, brittle, and dark-
brown.
• Dry-ripe poppy capsules contain a trace of
opium.

16. PAPEVER
SOMNIFERUM

17. How to obtain Latex from Capsules?

18. Poppy seeds
• Poppy seed or Maw seed is
the dried seed of Papaver
somniferum.
• Poppy seeds contain no
significant quantity of
alkaloids contains 50%
fixed oil.
• Seed used as food and
salad dressing.

19. • Opium is used for sedative, antitussive, and
constipating effects.
• Opium alkaloids are combined with
meconic acid, and divided into 2 groups:
–Hypnotic (depressant) alkaloids:
morphine (10%); codeine (0.5%); narceine
(0.2%).
–Convulsant (stimulant) alkaloids:
papaverine (1%); narcotine (6%);
thebaine (0.3%).

20. MORPHINE

21. chemically and pharmacologically related to opium:
• Heroin: diacetylmorphine (addictive drug).
• Dionin: ethylmorphine hydrochloride (for corneal
ulcer).
• Apomorphine: central emetic agent.
• Dilaudid: dihydroxymorphine (potent analgesic
with short duration).
• Metopan: methyldilaudid (potent analgesic with
short duration).

23. A group of chemically synthesized drugs, which
are remote in chemical structure from that of
opium but have similar pharmacologic effect.
Examples:
• Pethidine (Meperidine): potent analgesic
usually used as postoperative analgesic and for
labor pain.
• Methadone: potent analgesic usually used to
antagonize withdrawal manifestations during
treatment of heroin and morphine
dependence.

24. Pharmacokinetics of opiates:
Well absorbed from GIT, nasal mucosa, pulmonary mucosa, subcutaneous and
intramuscular routes.
Metabolism mainly in liver by conjugation with glucuronic acid, hydrolysis &
oxidation.
Widely distributed into liver, kidneys, lungs, spleen, brain, placenta, intestinal
mucosa, and skeletal muscles.
Excretion mainly by kidneys, where more than 50% are excreted within 8 hours,
about 40% up to 24 hours, and traces are still detectable in urine after 48 hours
by classic methods of detection and for longer periods by sophisticated
techniques.
Small percentage is excreted in bile, saliva, sweat, & milk.

25. Stimulate
• Pupillo-constrictor
center (pin-point
pupil)
• Vagal center (slow
full pulse &
hypotension)
• Medullary CTZ
(vomiting).
Inhibit
• Sensory cortex
(analgesia)
• Medullary
respiratory center
(respiratory
depression)
• Cough center
(suppression of
cough).

26. Most opiates are agonists for mu and kappa
receptors.
• Opiate agonist – antagonist:
– Synthetic drugs have both agonist and antagonist effects i.e.
they oppose the effect of opiates when they are given simultaneously,
but produce similar effects when given alone.
– These drugs are used widely as potent analgesics.
Examples: Pentazocine (Sosegone). Buprenorphine (Norphine).
Nalbuphine (Nubain).
• Pure opiate antagonist:
– They block all opiate receptors.
– They have reversal effect
– They are used in the treatment of opiate toxicity
Examples: Naloxone (Narcan); Naltroxone.

27. • Mainly accidental overdose
among addicts or may be
iatrogenic.
• May be suicidal.
• Rarely homicidal.
• Hot-shoot phenomenon.

28. Clinical Manifestations
• TRIAD (TOXIDROMES):
1- pin-point pupil
2- respiratory depression: slowing or
irregularity of respiratory rate (not on the depth) due to
direct effect on respiratory center.
3- coma.

29. Clinical Features (cont.)
• Subnormal temperature or even hypothermia.
• Decreased all body secretions except sweating
leading to moist cold skin (cold sweat).
• Cyanosis.
• Rhabdomyolysis: elevated CPK.
• Cardiac conduction defects including LBBB
• Wide QRS (more with propoxyphene).
• Noncardiogenic pulmonary edema, particularly with
heroin, codeine, and methadone overdoses.

30. • Antidote: Naloxone IV in doses 0.2-4 mg, then
observe for positive response (changes in
respiratory rate & level of consciousness, and size
of pupils). If the response is delayed give more
Naloxone (up to 10 mg) until positive response
occurs.
• Naloxone plasma half-life (t½) is 30 – 80 minutes
but its effect after IV bolus may last for 10 minutes
only and relapse occurs, so, give repeated doses at
frequent intervals as required.
• Some cases may need IV infusion & NaHCO3
similar to effects in Tricyclic.

31. HEROIN (Diacetyl Morphine)
• It was synthesized from morphine in 1874, but
become popular after the discovery of Mexican
heroin (black tea) in 1970, which is much more
potent and cheaper than the first one. Heroin can
be taken well absorbed by any route; this is
because of its high lipid solubility.
• Heroin distributes to all tissues and converted to
morphine by hepatic enzymes and it is eliminated
by kidneys as morphine in free and conjugated
forms.

32. Heroin Body Packers Syndrome
• Body Packers (mules)
– Intentional swallowing or
storing the packets in
orifices to smuggle and
avoid authorities.
– Packets are well prepared
– More quantity
• Body Stuffers
– Hastily conceal illicit
packets in orifices
just prior detection
– Pakets are not well
prepared
– Less quantity

34. COCAINE
• Cocaine is present in the leaves of Erythroxylon coca, which
grows in South America.
• Cocaine is a powerful CNS stimulant and sympathomimetic
agent with local anesthetic effect but chemically related to
atropine.
• It inhibits reuptake of epinephrine & NE in peripheral ganglia &
increase their secretion centrally
• Its medical use is local anesthetic (paralysis of nerve endings by
blocking fast Na channels)
• Local vasoconstriction (N.B. xylocaine vasodilatation).

35. Erythroxylon coca

36. Autonomic Effects: tachycardia, hypertension, hyperthermia, tachypnea, mydriasis.
CNS Effects: behavioral and psychiatric disorders such as irritability, hyperactivity,
insomnia, agitation, psychosis (often paranoid), delirium, stupor, seizures, coma.
Heart: sympathetic stimulation of the heart may lead to tachyarrhythmias, myocardial
ischemia, myocarditis, impaired cardiac conduction (local anesthetic effect).
Organ Ischemia: myocardial, renal, and/or intestinal infarction, and limb ischemia.
Shock: hypotension and shock
Pulmonary Effects: pulmonary edema (cardiogenic & noncardiogenic) , adult respiratory
distress syndrome
Other Effects: rhabdomyolysis, coagulopathy.

37. • No specific finding in autopsy, except for nasal
septal perforation

38. CANNABIS
• From the group of hallucinogens
• Psychological & Neurological: affects behavior,
cognition, perception, and performance.
• These effects are dose-dependent.
• Disorientation in time and place.
• Euphoric, talkative, joking and pleased with
himself, may have fear of death and dysphoria.
• Hallucinations , illusions, delusions
• Accentuation of auditory perception.
• Hyperphagia, especially to sweets.

39. • Marijuana consists of the leaves and
flowering parts of the plant Cannabis sativa
and is usually smoked in cigarettes (“joints”).
• Resin from the plant may be dried and
compressed into blocks called hashish.
• Marijuana contains a number of
cannabinoids; the primary psychoactive one is
delta-9-tetrahydrocannabinol (THC).

42. HASHISH

43. THC binds to anandamide receptors
in the brain, may have
effectsdepending on the dose and
time after consumption.
• stimulant,
• sedative, or
• hallucinogenic

44.  Nervous disorders such as:
 Dilated reactive pupils (with conjunctival
injection).
 Ataxia.
 Tinnitus.
 Hyperreflexia.
 Hypothermia.
 With large doses, the effect varies from mild anxiety to
paranoid behavior to acute psychosis with impaired
complex motor functions.
 Cardiovascular: tachycardia with blood pressure changes
and increase in myocardial O2 demand (may be due to
autonomic NS stimulation).
 Respiratory: chronic bronchitis, rhinitis, pharyngitis,
horsiness of voice (due to smoking).

45. Chronic users
• 6 fold increase in schizophrenia
• Mouth, jaw, lung cancers
• Nonlymphoblastic leukemia in
children from mother smokers
• Decreased sperm activity and
change in morphology

46. Urine Test• THC can be detected 3 – 8 weeks in
chronic users & 3 days in sporadic
users.
• Passive inhalation ± give false-
positive test
• False positive: rarely brufen,
naproxen.
• False negative: diuretic use, vinegar

47. • Anticholinergics are antagonists for the
neurotransmitter acetylcholine.
• Acetylcholine receptors are the muscarinic &
nicotininc receptors in the periphery and
cholinergic receptors centrally.
• Anticholinergics can be natural or synthetic
compounds.

48. 1- Natural Alkaloids (Tropane Group):
A) Atropa belladonna; atropine
B) Hyoscyamus; hyoscine, hyoscyamine
C) Datura, hyoscine, hyoscyamine,
atropine
2- Parmacological Preparations :
a) Tricyclic antidepressants (imipramine).
b) Antipsychotics (phenothiazines, haloperidol)
c) Antihistaminics (chlorephenhydramine).
d) Antiparkinsonism (benzotropine).
e) Antispasmodics (propantheline).
f) Ophthalmic solutions (cyclopentolate).

49. D. Stramonium Plant

50. D. Stramonium flower

51. D. Stramonium unripe seeds

52.  Hyoscine (scopolamine) differs from
atropine and hyoscyamine in that it has:
 Depressant effect from the start.
 Milder peripheral action
Toxidrome: Coma + Dry Skin + Hyperthermia +
Cycloplegia + Absence Of Odor

53. CLINICAL PICTURE
PERIPHERAL EFFECTS:
• Diminish of body secretion lead to
• Dry mouth and throat cause hoarseness of voice, thirst and
dysphagia.
• Dry skin lead to fever.
• Flushing of skin.
• Dilated fixed pupil leading to blurring of vision, diplopia and
photophobia.
• Rapid pluse due to vagal block. Sinus tachycardia is the most
sensitive sign of toxicity
• Urinary retention and decrease intestinal motility.

54. CENTRAL EFFECTS
Stage of stimulation
• Occupational purposeless movement as (rolling
cigarette, threading needles and catching flies).
• Restlessness, anxiety, talkativeness and free laughing.
• Convulsion
Stage of depression
• Patient is drowsy, stupor and gradually become
comatosed.
Coma characterized by :
• Rise in temperature.
• Dry flushed skin.
• Dilated fixed pupil.
• When depression in medulla occur pulse and
respiration become slow weak and irregular.
• Respiratory failure (Central asphyxia).

55. Postmortem Appearance
• No specific findings

56. STRYCHNINE
• It is the main alkaloid
found in the seeds of
Strychnos Nux vomica.
The seeds are hard, flat
biconcave discoid in
shape, 1-2 cm in
diameter, brownish-gray
and covered with hair
(velvet appearance).
• Mainly accidental
toxicity.
• Fatal dose about 30 mg.
• Fatal period: 2h.

57. • Absorption through GIT & nasal mucosa.
• After absorption, about half of the dose is
distributed in all tissues in about 5 min.
• Metabolized in the liver.
• 5-20% of dose excreted unchanged in urine
within 24 hrs.
• Action: causes stimulation of the spinal cord,
brainstem, & thalamus by competitive
inhibition of postsynaptic glycine receptors,
which is an inhibitory neurotransmitter in the
spinal cord.

58. Clinical Manifestations
 TOXIDROME: Symmetrical
generalized fits + Opisthotonus +
Risus sardonicus + Full
consciousness
 Onset of symptoms after 15-30 minutes.
 Starting as restlessness, increased visual &
auditory acuity, nausea, vomiting, and
muscle twitching, then sudden onset of
generalized, extremely painful tonic fits
while patient is fully conscious.

59. Opisthotonus

60. Risus sardonicus

61.  Strychnine fits are characterized by:
Sudden onset.
Generalized tonic convulsions.
Last 0.5-2 min with 10-15 min intervals of complete
relaxation between fits.
Retraction of the jaw gives peculiar complexion
called risus sardonicus (devil's laugh).
Body takes extensor position called opisthotonus.
 During fits there may be apnea, bulging of
eyeballs, cyanosis, bloody froth, dilated pupils,
bradycardia, hypertension, hyperthermia, lactic
acidosis, and rhabdomyolysis.
 Patient cannot tolerate frequent fits; they die
from exhaustion or asphyxia.

62. Differential Diagnoses
1-Tetanus. 2- Head injury. 3- Meningitis. 4- Epilepsy. 5- Hysteria.
STRYCHNINE TETANUS
HISTORY Taking food with bitter taste Wound
ONSET Sudden Gradual
CLINICAL
FEATURES
Generalized fits with relaxation
in between
Tonic contractions start at
lower jaw
DEATH Rapid (2hrs) Delayed (24 hrs)
DIAGNOSIS Chemical detection Bacterial isolation

63. Antidote:
• Mephenisine (20-30 mg IV)
• Suxamethonium 0.06-0.1
mg/kg IV.

64. Postmortem Appearance
• No specific signs have been
described
• Early rigor mortis
• Postmortem cooling

65. TOXICITY OF CARDIAC GLYCOSIDE
PLANTS

66. Digitalis lanata

67. Digitalis purpurea

68. Nerium Oleander

69. Nerium oleander

70. Sea onion

71. Strophanthus gratus