Professional Documents
Culture Documents
(Season 1)
Sukamto S M
Neurotoxicity
2
Neurotoxicity
The ability of certain substances to damage either structure or function of
nervous system
Types of neurotoxicity
Normal
Neuronopathy Vulnerability
• There is no ability to
Myelinopathy regenerate (irreversible).
• The surface area of nervous
Axonopathy system is large.
Transmission
toxicity
3
Neurotoxicity
Neuronopathy
• Loss is permanent (irreversible)
• Doxorubicin
• Anticancer which is associated
with PNS injuries (dorsal root
ganglia and autonomic ganglia)
• Methyl mercury
• Antifungal agent & fat soluble
• Injures neurons of the cerebral
cortex and cerebellar cortex
• Organotin
• Plasticizers and antifungal agent
• Injures limbic-cerebral neurons
4
Neurotoxicity
Axonopathy
8
Environmental and occupational exposure to toxic Ocular Toxicity
chemicals, gases, and vapors, as well as the side
effects of therapeutic drugs, frequently results in
The retina and the central visual system are
structural and functional alterations in the eye and
especially vulnerable to toxic insult.
the central visual system.
Cornea
13
Cardiotoxicity – Vascular Toxicity
14
Cardiotoxicant &
Vasculotoxicant
Actions
• Interference of ion
homeostasis.
Na+ K+ ATPase
Na+ Channel blockade
K+ Channel blockade
Ca2+ Channel blockade
• Altered coronary blood flow.
o Coronary vasoconstriction
o Chronotropic agents
• Oxidative stress
• Organellar dysfunction
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Cardiac Glycoside Plants
• Cardiac glycosides are organic compounds containing a glycoside acting
on cardiac muscle.
• The glycosides (digitalis, digitoxin, digoxin and ouabain) are found as
secondary metabolites in several plants.
18
Hypothalamus –
Pituitary – Organs
• Hypothalamus produces releasing-
or inhibiting- hormones.
• Those hormones stimulate or inhibit
release of other hormones produced
by pituitary gland
• Finally, hormones produced by
pituitary play roles in related
organs.
• Toxicants can affect 1)
hypothalamus 2) pituitary 3)
endocrine glands in organs
• The effects can be at synthesis,
storage or release stages of the
hormones.
Adrenal Gland
• Reasons of adrenal gland vulnerability:
1. It contains large store of lipids used to steroid synthesis.
Many xenobiotics are lipophilic.
2. It has many enzymes capable of metabolizing
xenobiotics.
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Spironolactone
Thyroid Gland
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thyroid-goiter-hypothyroidism.jpg
Reproductive Toxicity
24
Reproductive toxicity
• Reproductive toxicity refers to any adverse effect
on any aspect of male or female sexual structure,
function, and lactation including effects on the
reproductive potential and viability of the
offspring.
• Behavioral teratogenicity.
• Developmental toxicity. 25
Physiology of Reproductive System
CNS
(–) (–)
Hypothalamus
Releasing
hormone (GnRH)
Tropic hormones
Anterior pituitary
(FSH, LH) (–)
Target organ hormones
(testosterone, estrogen)
(+)
Target organs
26
Mechanisms and Targets of Male & Female
Reproductive Toxicants
C
Use with caution if benefits outweigh risks.
(fluoroquinolones, aspirin)
D
Use in LIFE-THREATENING emergencies when no safer
drug available. (tetracyclines, ACE inhibitors)
X
Do not use in pregnancy.
(thalidomide, oral contraceptives, statins)
28
Dermatotoxicity
Assignment!!!
29
TOXINS FROM PLANTS
& ANIMALS
SUKAMTO S M
Toxins from Animals
Toxin vs Toxicant
• TOXICANT A manufactured chemical (drugs, pesticides,
industrial chemicals, by-products
• TOXIN Produced by an organism (algae, fungi, invertebrates,
vertebrates)
Toxicant Any chemical, either natural or synthetic, producing bad effects to the living
organisms.
Toxin Toxicant produced by living organisms
All toxins are toxicants; Not all toxicants are toxins
Toxins from Animals
• Produced by the animals as either
protective or attacking mechanisms.
Toxin forms
• There are two types of animals
producing toxins. • Enzymes
• Passive toxin – producing animals • Peptide/protein possessing
(poisonous/hewan beracun) neurotoxic or cardiotoxic
Pufferfish properties
• Active toxin – producing animals • Small molecules such as
(venomous/hewan berbisa) Snake biogenic amines
Bee venom
Biogenic amines Histamines
Enzymes Phospholipase A2
Peptides Mast cell degranulators
Venomous/Poisonous Mammals
• Thermoreception
• Increase cGMP
• Bees
• Spiders
• Centipedes
• Scorpions
• Urticating caterpillars
Funnel web spider Centipede
• Produces delta-hexatoxins. • The venom contains:
• Repetitive firing and prolongation of • Histamine
action potential • 5-HT
• Excessive release of neurotransmitters • Phospholipase A
• Epinephrine • Cardiotoxic protein
• Acetylcholine
• Medications
• Medications
• Analgesic
• Antivenom (IgG from rabbit serum)
• Local anesthetic
• Anticholinergic agents (atropine)
• Antihistamine
Venomous/Poisonous Marine Animals
Pufferfish Sea Snake
• Produces tetrodotoxin • Produces neurotoxins & myotoxins.
concentrated in the liver, gonad • Peripheral paralysis
& skin. • Muscle necrosis
• Blocks diffusion of sodium • Hyperkalemia
through sodium channel. • Does not affect blood caogulation
• Depresses respiratory &
vasomotor centers in the brain. • Medications
• Antivenom
• Medications • Dialysis
• Activated charcoal (1-2 hours • Antihistamines
after ingestion)
• Steroid
• Cholinergic agents (Neostigmine)
Spines Prickles
Aflatoxin Thorns
Amatoxin
Phase II
• Temporary symptom resolution.
• Worsening hepatorenal function.
Phase III
• 3-5 days after ingestion, renal and hepatic failure.
• Multi organs failure, shock and death.
Treatments of GIT decontamination
Amatoxin activated charcoal in early
stage of ingestion.
Intoxication
Sylimarin It can competitively
antagonize toxin binding to liver cell
membrane receptors. It also acts as
hepatoprotective, antioxidant &
antiinflammatory.
• Synthesized from
Erythroxylon coca
Terima Kasih
CLINICAL TOXICOLOGY
SUKAMTO S M
SALICYLATES
COOH COONa
• Mechanism of toxicity OH OH
• Respiratory alkalosis
• Metabolic acidosis
• Hypoglycemia
COOCH3 COOH
• Dehydration
OH OCCH3H
• Treatment? O
CYANIDE
• Mechanism of toxicity
• N-Acetyl-p-Quinone-Imine
(NAPQI)
• Combination with alcohol will
increase acetaminophen –
induced hepatotoxicity
• Antidote?
BENZODIAZEPINES
• Depressant
• Mechanism of toxicity
• Combination with other
depressants?
• Effects induced by depressants
overdose?
• Antidote?
CARISOPRODOL
• Mechanism of action?
• Mechanism of toxicity?
• Treatment?
IBUPROFEN
• Toxicity mechanism
• Prostaglandin
• Treatments?
TUGAS
• SETIAP ORANG menuliskan RESUME dari ke-6 topik toksikan yang
memuat:
• Mekanisme toksisitas
• Penanganan dan antidot yang dapat diberikan
• RESUME diketik komputer dengan aturan
• Maksimal 3 halaman kertas A4 (di luar lembar sampul)
• Spasi 1.5
• Margin 4,4,3,3
• Times New Roman
• Dikumpul hardcopy paling lambat 19 Oktober 2017
• KERJA SENDIRI…!!!
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