Cholinergic

100% NT
Q&A: Pharmacology Drugs acting on parasympathetic nervous system
ANS pharmacology
S d ti hypnotics
Sedative h ti 1. Cholinergic drugs, muscarinic agonists
Opioids 2. Anticholinesterase agents, cholinesterase inhibitors
Antiepileptics 3. Anticholinergic drugs, antimuscarinic drugs,
Drug abuse muscarinic antagonists
Toxicology
gy ((heavyy metal, occupational
p toxicology)
gy)
.


somsmorn.c@psu.ac.th 1 2

ANS Cholinergic
NLE1 Q&A p.170

Influx ion neurotransmitter

a. Na+ b. K+ Acetylcholine
C 2+
c. Ca d M
d. Mg2+ synthesis

3 4
 ANS
NLE1 Q&A p.185 ANS

somatic nervous system

a. GABA b SSerotonin
b. t i
c. Dopamine d. ACh
e. NE

Cholinergic fiber
Adrenergic fiber
Dopaminergic fiber
5 6

NLE1 Q&A p.82 AntiChE

Organophosphate
g p p
Cholinergic
a. ACh
b
b. ACh
c. ACh esterase
d. reuptake ACh
e. sensitivity ACh receptor

MG anticholinesterase
side effect
A.

B.
C.
7 8
 NLE1 Q&A p.76, p.205 AntiChE
NLE1 Q&A p.80 AntiChE
(Irreversible antiChE)

organophosphate
h h t
muscle
l fasciculation
f i l ti
PR 60 /min, BP 120/80 atropine Organophosphate muscle fasciculation
a
a. b
b.

c. d. PR 60 /min a. Bind to nicotinic receptor
e Muscle fasciculation
e. b Bind to muscarinic receptor
b.
(reversible antiChE)
27 carbamate , muscle fasciculation, , , PR c. Excess ACh bind to nicotinic receptor
60 beat/min atropine d. Excess ACh bind to muscarinic receptor
a. b. Muscle fasciculation
c. d.
e. PR 60 beat/min

Atropine is given as a treatment for SLUDGE syndrome (salivation, lacrimation,

urination,
i ti di diaphoresis,
h i gastrointestinal
t i t ti l motility,
tilit emesis)
i ) symptoms
t causedd bby
organophosphate poisoning. 9 10

NLE1 Q&A p.166 AntiChE NLE1 Q&A p.85 AntiChE

(organophosphate)

a. Norepinephrine b. Adenergic agonist
a.
beta receptor
c. Anticholinesterase inhibitor
b. nicotinic receptor
NLE1 Q&A p.83 c. muscarinic receptor
organophosphate
d ACh
d. nicotinic receptor
acetylcholinesterase e. ACh muscarinic receptor
a.
b
b.
c. d.
11 12
 NLE1 Q&A p.80 AntiChE NLE1 Q&A p.77 AntiChE

25 .




organophosphate


a. Adrenergic agonist
a. Neostigmine b. Atropine
b Adrenergic blockage
b.
c. Epinephrine d. Activated charcoal
c. Cholinergic antagonist
e. NN-acetylcysteine
acetylcysteine
d. Acetylcholinesterase inhibitor
e Dopaminergic antagonist
e.

13 14

AntiChE NLE1 Q&A p.78 Anticholinergic

United Nation (UN) reported that sarin (nerve gas; chemical weapons) was
used in a rocket attack in the Syrian capital. Survivors quickly experienced Atropine
acetylcholine
a range of symptoms, including shortness of breath, disorientation, eye (receptor)

irritation, lacrimation, nausea, vomiting and general weakness. a. Nicotinic receptor
What is the mechanism of action of sarin?
b. Serotonin receptor
A Stimulated muscarinic receptor
A.
c. Adrenergic receptor
B. inhibited cholinesterase enzyme
C. Released acetylcholine d Muscarinic receptor
d.
D. Blocked neurotransmitter reuptake e. Acetylcholine receptor
E. Blocked nicotinic receptor

15 16
 Muscarinic receptors ANS NLE1 Q&A p.82 Anticholinergic
70
atropine

Receptor Functions

M1 EPSP ini autonomic
t i ganglia,
li secretion
ti from
f salivary
li glands
l d andd
a. b. Anuria
stomach, in CNS (memory?)
y
c. Polyuria d. Urine retention
M2 slow heart rate, reduce contractile forces of atrium, reduce
conduction velocity of AV node, in CNS, homotropic inhibition e. Urine incontinence
M3 smooth muscle contraction, bronchoconstriction, increase
Atropine overdose may cause which one of the following
intracellular calcium in vascular endothelium, increased endocrine
A Gastrointestinal smooth muscle cramping
A.
and exocrine gland secretions, in CNS, eye accommodation,
B. Increased cardiac rate
vasodilation, induce emesis
C Pupillary constriction
C.
M4 Activation of M4 causes decreased locomotion, in CNS D. Increased gastric secretion
M5 Activation of M4 causes decreased locomotion,
locomotion in CNS E Urinary frequency
E.
17 18

Anticholinergic NLE1 Q&A p.85 p.86 AntiChE+anticholinergic

muscarinic agonists
organophosphate
A. ( muscarinic) atropine
B
B. atropine
antidote


C. a. Chemical antagonist
D. ciliary muscle b. Physiologic antagonist
E
E.
circular muscle
c Pharmacologic antagonist
c.
aqueous humor canal of Schlemm d. Noncompetitive antagonist

e. Nonpharmacologic antagonist

19 20
 AntiChE AntiChE+toxico
NLE1 Q&A p.81

BP 180/60
4 6 20 mmHg,g, RR 24/min,, PR 100/min,, ppupil
p 2 mm,, hyperactive
yp bowel
sound, hypersecretion,



A. 2-PAM B. Paraquat

C. HCl acid D. Organophosphate
a. Glutamate b. Serotonin
E Permethrin
E. P th i
c. Dopamine d. Acetylcholine
e. Adrenaline

21 22

Toxicology ANS
2 PAM (pralidoxime)
2-PAM
specific antidote for acute organophosphate poisoning
Pralidoxime has an important role in reversing paralysis of the
respiratory muscles but due to its poor bloodbrain barrier
penetration, it has little effect on centrally-mediated respiratory
depression.
This is why atropine
atropine, which has excellent bloodbrain barrier
penetration, is concomitantly administered with pralidoxime
d i the
during h treatment off organophosphate
h h poisoning.
i i Acetylcholinesterase
Acetylcholine Choline + Acetic acid
23 24
http://www.atsdr.cdc.gov/csem/csem.asp?csem=11&po=23
 AntiChE AntiChE

Irreversible
anticholinesterase

Reversible anticholinesterase 25 26

AntiChE AntiChE

Aged enzyme

2 PAM mechanism
2-PAM h i
27 28
 Toxicology Toxicology
Paraquat (herbicide) HCl
Paraquat
q is often used in science to catalyze y the formation of reactive oxygen
yg Acute Effects: Hydrochloric acid is corrosive to the eyes, skin, and
species (ROS), more specifically, the superoxide free radical mucous membranes. Acute inhalation exposure may cause coughing,
may cause severe corrosive injury when ingested, injected, or applied to the hoarseness, inflammation and ulceration of the respiratory tract, chest
skin, eyes, or mucous membranes. pain, and pulmonary edema in humans.
leading to acute respiratory distress syndrome (ARDS). Although there are no Acute oral exposure may cause corrosion of the mucous membranes,
specific antidotes,
antidotes fuller's
fuller s earth or activated charcoal is an effective treatment if
taken in time. esophagus, and stomach, with nausea, vomiting, and diarrhea
Paraquat may also damage the kidneys, liver, and esophagus reported in humans. Dermal contact may produce severe burns,
Avoid excessive oxygen administration, as oxygen is the substrate from which ulceration, and scarring.
create harmful free radical species. Treat significant hypoxemia with Pulmonary irritation, lesions of the upper respiratory tract, and
supplemental oxygen, but use only the lowest amount needed to achieve a laryngeal and pulmonary edema have been reported in rodents
PO2 of about 60 mmHg.
Treat pain due to corrosive injury with adequate doses of opioids.
opioids acutely exposed by inhalation.
29 30

Toxicology Toxicology
NLE1 Q&A p.84
Permethrin (pyrethroid)
The toxic effects of pyrethroids are mediate through

25



preventing the closure of the voltage-gated sodium
channels
h l iin th the axonall membranes.
b When
Wh th the ttoxin
i

keeps the channels in their open state, the nerves a. Paraquat b. Arsenic compound
cannot repolarize, leaving the axonal membrane c. CCl4 d. Organophosphate
permamentally depolarized, thereby paralyzing the
organism
Excessive
E cessi e exposure
e pos re to permethrin can cause
ca se
nausea, headache, muscle weakness, excessive
salivation, shortness of breath, and seizures.
31 32
 Toxicology Toxicology
NLE1 Q&A p.3

cell injury
paraquat superoxide
A. B1 ((Thiamine)
a e) B. B66
C. A (Retinoic acid) D. C (Ascorbic acid)
E. B5 Pantothenic acid

33 34

Cholinergic+Toxicology Toxicology
Zinc phosphide (rodenticide, fumigant) to generate the toxic
4-5 20 . phosphine gas.
. Other pesticides similar to zinc phosphide are aluminium phosphide and
calcium phosphide.

A. Zinc phosphide
B. Chlorinated hydrocarbon
y
C. Organophosphate
D Paraquat
D.
E. Botulinum toxin
Chlorinated hydrocarbons (Organochlorine insecticides): Na+
cchannel
a e ,, G
GABA receptor
ecep o
35 36
 NLE1 Q&A p.70 Cholinergic Adrenergic

A 45 year-old man presents with episodes of headache, palpitation and

20 sweating. On examination he is found to hypertensive. Adrenal





tumor is suspected.
Which of the following urine examination used for differential diagnosis?
a. Atropine A. Cortisol
b Adrenaline
b. B. Dopamine
p
c. Neostigmine C. Aldosterone
D 17-ketosteroid
D. 17 k t t id
d. Organophosphate
E. Vanillylmandelic acid
e. Activated
A ti t d charcoal
h l

37 38

Adrenergic Adrenergic
Adrenal tumor
Tumors of the Adrenal Cortex
Adrenocortical adenoma produce glucocorticoids, mineralcorticoids, and/or sex
steroids, resulting in endocrine disorders such as Cushing's syndrome, Conn's
syndrome (hyperaldosteronism), virilization of females, or feminization of males.
Adrenocortical carcinoma produce steroid hormones and consequent endocrine
dysfunction.
Tumors of the Adrenal Medulla
Neuroblastomaproduce elevated levels of catecholamine hormone precursors, such
as vanillylmandelic acid (VMA) and homovanillic acid, and may produce severe
watery diarrhea through production of vasoactive intestinal peptide.
PheochromocytomaThis may lead to potentially life-threatening high blood pressure,
or cardiac arrythmias,
arrythmias and numerous symptoms such as headache,
headache palpitations,
palpitations
anxiety attacks, sweating, weight loss, and tremor. Diagnosis is most easily confirmed
through urinary measurement of catecholamine metabolites such as VMA and
metanephrines.
39
Catecholamine metabolism 40
 Adrenergic Adrenergic
NLE1 Q&A p.248 NLE1 Q&A p.364

beta1-adrenergic receptor epinephrine

a. Pupil constriction
a
a. b Bronchoconstriction
b. B h t i ti
b. contractility c. gastrointestinal motility
c. cytosolic Ca2+ systole d. Vasoconstriction
d cc-AMP
d. AMP
e. glycogenolysis
e. contraction period
Stimulate beta1 receptor-
Gs renders
d adenylate
d l t cyclase l activated,
ti t d resulting
lti iin iincrease off cAMP.
AMP
41 42

Adrenergic Adrenergic
Adrenergic receptors
BP 100/70 mmHg Alpha receptors
HR 90 beat/min
130/100 mmHg HR 100 beat/min 1:

receptor 2: presynaptic membrane adrenergic
A. Alpha1, beta2 Beta receptors
B Alpha1,
B. Alpha1 beta1 1:

C. Alpha2, beta2 2:
D. Alpha2, beta2 3:
E Beta1,
E. Beta1 beta1

43 44
 Adrenergic NLE1 Q&A p.73 Adrenergic
9

BP 60/40 mmHg,
mmHg HR 120,
120 wheezing,
wheezing
bronchospasm 6 BP 60/40 PR 50 bpm RR
A. Adrenaline 18/min PE: swelling fg lip and face epinephrine IM 2
B. Dexamethasone
C. Dopamine a. Hydrocortisone IV
NLE1 Q&A p.228
b Diphenhydramine
b. Di h h d i IV
5 c. Aminophyline IV
wheeze
h 2


a. Loratadine b. Sulbutamol d. Epinephrine 1:10000 IV
c. Hydroxyxine d. Chlorpheniramine e. Nebulized Beta2 agonist IV
e Adrenaline
e.
45 46

Adrenergic
Medications for Anaphylaxis Treatment NLE1 Q&A p.220
An adrenaline infusion (0.05 - 1mcg/kg/min) should be considered if repeated doses of IM 60
adrenaline are required. terbutaline
Corticosteroids, antihistamines and antileukotrienes has no proven benefit on the
immediate and life threatening anaphylaxis.
metabolic effect
Nebulised salbutamol is recommended if the patient has respiratory distress with wheezing a
a.

or consider other antiasthma medications. b.
Fi liline ((priority
First i i medication)
di i )
c. Lactic acid
Epinephrine (adrenaline) 1:1,000 (1 mg/mL) for intramuscular injection 0.01 mg/kg, to a
maximum of 0.5 0 5 mg d.

Second line medications e.
H1-antihistamine
H1 tihi t i ffor intravenous
it iinfusion
f i eg. Chlorpheniramine
Chl h i i or diphenhydramine
di h h d i
Alpha2 receptor inhibit insulin release in the pancreas and induce glucagon release
2-adrenergic agonist, eg. salbutamol (albuterol) solution given by nebulizer and face from the pancreas.
mask Beta2 receptor stimulates insulin secretion.
glucocorticoid for intravenous infusion, eg. hydrocortisone or methylprednisolone 47 48
 Adrenergic NLE1 Q&A p.178 Adrenergic
45 asthma . open
p angleg glaucoma

beta-blocker
beta blocker
glaucoma timolol eye drop

timolol eye drop


a. aqueous humor
A. Nasal mucosa
b. trabecular membrane
B. Conjunctiva c. Iris dilator muscle
C. Trabecular meshwork d Papillary muscle
d.
D. Choroid
glaucoma

E. Iris
A. Timolol
AAqueous humor
h trabecular
t b l meshworkh k
canall off Schlemm
S hl
B. Pilocarpine
aqueous vein C. Phenylephrine
episcleral
i l l vein i ((anterior
t i ciliary
ili veins)
i )
D. Latanoprost
49 50

Adrenergic+cholinergic Adrenergic
Timolol is a non-selective
non selective beta-adrenergic
beta adrenergic receptor antagonist.
antagonist It is Phenylephrine is a selective 1-adrenergic receptor agonist used
used to treat open-angle and occasionally secondary glaucoma by primarily as a decongestant, as an agent to dilate the pupil, and to
reducing aqueous humour production through blockage of the beta
receptors on the ciliary epithelium. increase blood pressure. Narrow-angle glaucoma is a
Pilocarpine
p is a a non-selective muscarinic receptor p agonist
g in the contraindication to phenylephrine use.
parasympathetic nervous system. It acts at the muscarinic acetylcholine Latanoprost is a topical medication used for controlling the
receptor M3 due to its topical application, e.g., in glaucoma and progression of glaucoma or ocular hypertension by reducing
xerostomia. Muscarinic receptor (M3) found on the iris sphincter muscle, intraocular pressure. It is a prostaglandin F2 analogue that works
causing the muscle to contract and engage in miosis. Pilocarpine also
acts on the ciliary muscle and causes it to contract.
contract When the ciliary by increasing the outflow of aqueous fluid from the eyes (through
muscle contracts, it opens the trabecular meshwork through increased the uvealsclearal tract). When latanoprost and timolol are used in
tension on the scleral spur.
p This action facilitates the rate that aqueous
q combination, there is a greater reduction in pressure than when
humor leaves the eye to decrease intraocular pressure. either drug is used alone. Its side effects included blurred vision.

51 52
 ANS
Accommodation ANS

The circular ciliary muscle fibers affect zonular fibers in the eye (fibers that suspend
the lens in position during accommodation). When the ciliary muscle contracts, the
zonular fibers caused the release tension on the lens. This release of tension of the
zonular fibers causes the lens to become more spherical, adapting to short range
f
focus. Th
The relaxation
l ti off th the ciliary
ili musclel causes ththe zonular
l fibers
fib to t bbecome ttaut,t
flattening the lens, increasing the focal distance.
Sympathetic activation of the beta-2 receptors result in relaxation and increase in
ciliary body size. This tautens the zonule fibers and the lens is stretched flat,
th b ddecreasing
thereby i itits refractive
f ti power appropriately
i t l ffor far
f didistance
t vision.
ii a. Normal: b. Accommodation:
Parasympathetic activation of the M3 muscarinic receptors causes ciliary muscle Ciliary Muscle Relaxed Ciliary Muscle Contracts
Suspensory Ligaments Under Tension Reduced Tension on Suspensory Ligaments
contraction, the effect of contraction is to decrease the diameter of the ring of ciliary Lens is Flattened Lens becomes Round
muscle. The zonule fibers relax and the lens becomes more spherical, increasing its Focus on Distant Objects Focus on Near Objects
power to refract light for near vision.
The parasympathetic tone is dominant over the adrenergic tone. 53
http://www.vision-and-eye-health.com/eye-exercises.html
54

ANS ANS
NLE1 Q&A p.75
a
a. Atropine - muscarinic antagonist
mydriasis cycloplegia Circular muscle of iris relax mydriasis
Ciliary muscle of lens relax cycloplegia
a. Atropine b. Pilocarpine b. Pilocarpine - muscarinic agonist
Circular muscle of iris contraction meiosis
c. Neostigmine
g d. Pheniramine m scle of lens contraction accommodation
Ciliar muscle
Ciliary
e. Phenylephrine c. Neostigmine Cholinesterase inhibitor ACh accumulation
d. Pheniramine - antihistamine with anticholinergic properties used to treat allergic
conditions such as hay fever or urticaria.
e. Phenylephrine Alpha1 agonist decongestant, mydriatic agent
The radial muscles of the iris are innervated by neurons with alpha one receptors
thus it causes dilation when stimulated. However the ciliary body of the eye
(which controls accommodation) is controlled by M3 cholinergic receptors.
receptors That
pathway for accommodation remains unaffected while the iris is dilated.

55 56
 Adrenergic Adrenergic
NLE1 Q&A p.229, p.71 NLE1 Q&A p.230

25 pseudoephedrine
Terbutaline sulfate


a. 1antagonist b. 2agonist a. Inhibit histamine synthesis
c 1agonist
c. 1 agonist d 2agonist
d. 2 agonist b IInhibit
b. hibit bradykinin
b d ki i synthesis
th i
e. Antimuscarinic c. Muscarinic receptor antagonist
d. Adenosine receptor agonist
asthma
p g receptor
e. Alpha-adrenergic p agonist
g


a. adenergic
g receptor
p PPseudoephedrine
d h d i isi a mixed i d acting
ti sympathomimetic
th i ti drug
d off the
th amphetamine
ht i
chemical classes. It may be used as a nasal/sinus decongestant, as a stimulant, or as
a wakefulness-promoting
p g agent.
g
57 58

NLE1 Q&A p.71 Adrenergic Adrenergic

NLE1 Q&A p.78

25 asthma
corticosteroid 2-3 35
PR 135/min, BP 160/95
salbutamol, chlorpheniramine, bronhexine,
mmHg, bilateral dilated pupils
dextromethorphan




side effect a. Adrenergic agonist
b Cholinergic agonist
b.
a. Salbutamol b. Bromhexine
c. Dopamine agonist
c. Corticosteroid d. Chlorpheniramine
d. Serotonin antagonist
e. Dextromethorphan
e. Histamine antagonist
Salbutamol: The most common side effects are fine tremor, anxiety,
h d h muscle
headache, l cramps, ddry mouth,
th andd palpitation.
l it ti
59 60
 Adrenergic
Orlistat

20
Orlistat is a potent natural inhibitor of pancreatic lipases that
hydrolyzes dietary fat molecules in the human digestive system,
converting triglyceride substrates found in ingested oils to
A. Orlistat B. Sibutramine monoglycerides and free fatty acids.
C. Phentermine D. Fenfluramine The effectiveness of orlistat in promoting weight loss is definite.
E. Phenylpropanolamine Its
It gastrointestinal
t i t ti l side
id effects
ff t can iinclude
l d steatorrhea
t t h (oily,( il
loose stools).

61 62

Adrenergic NMJ
Sibutramine is a neurotransmitter reuptake inhibitor that reduces
the reuptake of serotonin (by 53%), norepinephrine (by 54%), and 30 2 2
dopamine (by 16%).
16%)

Phentermine works on the hypothalamus portion of the brain to A. Peripheral nerve
stimulate
ti l t th
the adrenal
d l glands
l d tto release
l norepinephrine.
i hi B. Anterior horn cell
Myasthenia gravis (MG)
( G) is an autoimmune
neuromuscular disease leading to fluctuating
Fenfluramine causes the release of serotonin by disrupting
vesicular storage of the neurotransmitter, and reversing serotonin C Neuromuscular junction muscle weakness and fatigue.
C. fatigue Muscle
weakness is caused by circulating antibodies
transporter function. The result is a feeling of fullness and loss of D. Sympathetic chain that block acetylcholine receptors at the
appetite. E. Muscle? postsynaptic neuromuscular junction,
inhibiting the excitatory effects of the
Phenylpropanolamine
yp p is a ppsychoactive
y drugg used as a stimulant,, neurotransmitter
t itt acetylcholine
t l h li on nicotinic
i ti i
decongestant, and anorectic agent. receptors at neuromuscular junctions.

63 64
 NMJ NLE1 Q&A p.128 NMJ
30


thymus
a. Immediate hypersensitivity
b. Delay type hypersensitivity
c. Immune complex hypersensitivity
d Ab-cytotoxic
d. Ab cytotoxic hypersensitivity
e. Complement activation

MG: In type II hypersensitivity (or cytotoxic hypersensitivity) the

(A) A 61-year-old woman with marked generalized myasthenia gravis, 2 days after plasma
exchange treatment, with only minimal spontaneous ptosis at baseline. (B) After 10 seconds antibodies produced by the immune response bind to antigens on the
of upward gaze. (C) After 30 seconds of upward gaze. (D) Maximal voluntary lid closure for patient's own cell surfaces.
10 seconds.
seconds (E) Almost complete recovery upon lid opening.
opening (F) Reoccurrence of ptosis
after another 10 seconds of upward gaze. 65 66

NMJ NLE1 Q&A p.167, p.209 NMJ

NLE1 Q&A p.171







50 (myasthenia gravis)
neostigmine
a
a. acetylcholine
b. acetylcholine receptor
a. antimuscarinic c acetylcholine
c. synaptic cleft
b. Oculomotor d. acetylcholine presynaptics
c. Spinal cord C1 e.
turnover
t ACh receptort

g terminal
d. Adrenergic 45
autoantibody
e. Ab nicotinic receptor antigen
a. Acetylcholine receptor b. Double-stranded DNA
c. Histone d. IgG
e. Ribonucleoprotein
67 68
 NLE1 Q&A p.173 NMJ NLE1 Q&A p.82 NMJ

25

receptor



myasthenia gravis antibody muscarinic
nicotinic

a. Acetylcholine esterase
a Duration action potential
a.
b. Muscarinic receptor agonist
b. Amplitude action potential
c. Muscarinic
M i i receptor
t antagonist
t it
c. Amplitude end plate potential
d. Acetylcholinesterase inhibitor
d RRefractory
d. f t period i d action
ti potential
t ti l
e. excitatory post-synaptic potential
For patients with MG, repetitive nerve stimulation will cause a depletion of
quanta and reduce the amplitude of the EPP.
69 70

NMJ NMJ
NLE1 Q&A p.41 NLE1 Q&A p.76, p.196

18 50 neuromuscular blocker
fasciculation
(pathophysiology) a. Dantrolene
a. Block excitation-contraction coupling
a Thymectomy
a. b. Atracurium b Competitive NM blocking drug
b.
c. Rocuronium c. Competitive NM blocking drug
b. Pyridostigmine d. Muscarinic agonist
Plasmapheresis plasma exchange d Methacholine
d. M th h li e. Depolarized NM blocking drug
c. Prednisolone e. Succinylcholine
d Plasmaphresis
d. fresh frozen plasma albumin

e. Immunosuppressive agent muscle fasciculation

a. Atracurium b. Pancuronium
Myasthenia is treated medically with acetylcholinesterase inhibitors or
c. Tubocurarine d. Succinylcholine
immunosuppressants and,
immunosuppressants, and in selected cases
cases, thymectomy.
thymectomy
71 72
 NMJ NMJ
Male ppatient had the homozygous
yg for atypical
yp pplasma cholinesterase ggene.
What is the neuromuscular blocking agent contraindicated in this patient? succinylcholine
A. Pancuronium
(malignant hyperthermia) acidosis
masseter

B. Curare

C Vecuronium
C. A Diazepam
A.
D. Atracurium
B. Paracetamol
E Succinylcholine
E.
C. Pancuronium
NLE1 Q&A p.212
D. Dantrolene
neuromuscular blocker
side effect
E. Phenyltoin
a. Vecuronium b. Succinylcholine
c. d-tubocurarine d. Pancuronium

73 74

NLE1 Q&A p.80, p.169

NMJ NMJ
NLE1 Q&A p.202

pancuronium a. Amygdalin
yg b. Tetrodotoxin
10 / c. Botulinum toxin d. Fish liver toxin
a Atropine
a. b Dopamine
b. e. Bromic
B i acid id
c. Epinephrine d. Neostigmine ion channel
e. Succinylcholine a. Cl- b. K+
N+
c. Na d CCa2+
d.
Pancuronium- competitive NM blocking drug e. Mg2+
Neostigmine- cholinesterase inhibitor Tetrodotoxin blocks action potentials in nerves by binding to the voltage-gated, fast
sodium channels in nerve cell membranes, essentially preventing any affected nerve
cells from firing by blocking the channels used in the process. The binding site of this
75 toxin is located at the pore opening of the voltage-gated Na+ channel. 76
 NLE1 Q&A p.14, p.166 NMJ NMJ
Botulinum toxin A ((Botox)) action receptor
p NLE1 Q&A p.41

A. Catalytic receptor
54 Botox
B Intra-cellular
B. I t ll l receptor t
C. G-protein coupled receptor
a
a. choline
D. tyrosine kinase
E. Ligand gated ion channel
b. synaptic vesicle exocytosis
c. endocytosis presynaptic membrane
botulinum toxin
d
d. SNARE complex presynaptic membrane


e. acetylecholine nicotinic cholinergic receptor motor
a Acetylcholine
a. b GABA
b.
end plate
c. Glycine d. Norepinephrine
e. Dopamine
77 78

NMJ NMJ
()


A. Curare B. Tetrodotoxin
C Muscarine
C. D Cyanotoxin
D.
E. Botulinum toxin

A. Curare ( )
C. Muscarine Amanita muscaria
D. Cyanotoxins are toxins produced by bacteria called cyanobacteria (blue-
green algae). Cyanotoxins are some of the most powerful natural poisons
known, can cause rapid death by respiratory failure. The toxins include
potent neurotoxins, hepatotoxins, cytotoxins, and endotoxins.
80
http://www.epharmapedia.com/news/details/11/220?lang=en
 NLE1 Q&A p.165 NMJ

alpha-Bungarotoxin
alpha Bungarotoxin

a. Decrease nicotinic
b. Decrease Na+ channel muscle cell
c. Increase ACh vestibular mobilization
d. Decrease muscarinic B t i (BTX)
Bungarotoxin
( BTX) isi one off theth bungarotoxins,
b t i components t off ththe
venom of the elapid snake ( ). It is a type of
e. Decrease acetylcholine
neurotoxin,
t i a neurotoxic
t i protein
t i that
th t isi kknown tto bind
bi d irreversibly
i ibl andd
competitively to the nicotinic acetylcholine receptor found at the
neuromuscular
l jjunction,
ti causing i paralysis,
l i respiratory
i t ffailure
il andd ddeathth iin th
the
81 victim. 82

CNS: Opioid NLE1 Q&A p.61

CNS: Opioid

morphine antipsychotic
a)) nerve conduction
d ti tranquilizer

b) pain reaction a. diarrhea
c) pain receptor b. bradycardia
d) phospholipase c sedation effect
c.
e) dull pain sharp pain d. sedation
e.

83 84
 NLE1 Q&A p.73 CNS: Opioid NLE1 Q&A p.80 CNS: Opioid

60


50 RR 7/min, muscle twitch, pin-point-pupil
abdominal ultrasonography gall bladder
contraindication
a Morphine
a. b Tramadol
b.
a. Morphine b. Hyoscine
c. Diazepam d. Diclofinac
c. Diclofenac
Di l f d Meperidine
d. M idi
e. Acetaminophen
e. Paracetamol

Tramadol acts as a opioid receptor agonist, serotonin releasing agent, norepinephrine

reuptake inhibitor, NMDA receptor antagonist, 5-HT2C receptor antagonist, (7)5 nicotinic
acetylcholine receptor antagonist, TRPV1 receptor agonist, and M1 and M3 muscarinic
acetylcholine
t l h li receptort antagonist.
t it
85 86

CNS: Opioid Heroin overdose symptoms CNS: Opioid

Symptoms
15 pupil constrict, pulse 65 Airways and lungs
No breathing
A. Atropine Shallow breathing
B. Naloxone Slow and difficult breathing
C Adrenaline
C. Eyes, ears, nose, and throat
Dry mouth
D. Methadone
Extremelyy small ppupils,
p , sometimes as small as the head of a ppin (("pinpoint
p p
pupils")
Tongue
o gue ddiscoloration
sco o a o
Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol
dependence and opioid dependence. Heart and blood
Low blood pressure
87 Weak pulse 88
 NLE1 Q&A p.171
CNS: Opioid CNS: Opioid
NLE1 Q&A p.285

methadone 42 20 1


a. withdrawal symptom

b. addiction
a. Hemorrhoid b. Angiodysplasia
c
c. constipation
c. Megacolon d. Perirectal fistula
d. half life
e Adenocarcinoma
e.

Methadone is a mu-opioid agonist.

Dependence
p and tolerance were less than heroin.
89 90

CNS: Opioid NLE1 Q&A p.77 CNS: Opioids

NLE1 Q&A p.84
50

25
2


pentazocine

a. Nicotine withdrawal b. Morphine withdrawal
a. b.
c. Inhalant intoxication d. Cannabis intoxication
c.
d.
e. Amphetamine intoxication
e.

Morphine withdrawal: Abdominal (stomach) cramps, Insomnia, Nausea, Loss of
appetite, Vomiting, Diarrhea, a rapid heart rate. Pentazocine is a partial agonist at mu receptor and agonist at kappa
receptor (opioid analgesic) used to treat moderate to moderately severe
pain.
91 92
 CNS: Opioid CNS: Opioid
NLE1 Q&A p.79

codeine Cyp2D6 morphine

A Acetylcysteine
A.

B. Dextromethophan ultra rapid metabolizer codeine
C Pseudoephridine
C. P d h idi
D. CPM (chlorpheniramine) a.
b. clearance
c
c.
d. GI
e. albumin

93 94

CNS: Opioid CNS: Opioid

Metabolismpathway 95 96
 CNS: Sedative CNS: Sedative
NLE1 Q&A p.218

anxiety diazepam 1 25 unconciousness

3-4
3 4

hypoxia
A. Irritability a. Shunt
B. Cataplexy b. Hypoventilation
Benzodiazepine p withdrawal syndrome
y severe
C Constipation
C. C ti ti c. Diffusion impaired
sleep disturbance, irritability, increased tension
D. Bradycardia and anxiety,y, ppanic attacks,, hand tremor,, sweating,
g, d V/Q mismatching
d.
E. Sleep apnea difficulty with concentration, confusion and
cognitive
g difficulty,
y, memoryy pproblems,, dryy retchingg
and nausea, weight loss, palpitations, headache,
muscular ppain and stiffness,,
97 98

NLE1 Q&A p.168 CNS: Sedative

barbiturate 35 year old female patient will get the breast tumor surgery.

Which of the following hypnotic drugs is used intravenously as
induction anesthesia?
a. b.
c.

d.


A. Thiopental
e.
B Phenobarbital
B. Ph b bit l
Symptoms of barbiturate overdose typically include sluggishness, incoordination, difficulty C. Flurazepam
in thinking, slowness of speech, faulty judgment, drowsiness, shallow breathing, and D. Zolpidem
staggering. In severe cases, coma and death can result. E. Diazepam
Barbiturate overdose with other CNS depressants, such as alcohol, opiates or
benzodiazepines, is even more dangerous due to additive CNS and respiratory depressant
effects.
ff t
NaHCO3 to alkalize the urine to increase rate of excretion. 99 100
 CNS: Antiepileptics NLE1 Q&A p.75 CNS: Antiepileptics
NLE1 Q&A p.72

6 Phenytoin phase I phase II

phase II



a. Phenytoin
a.
b.

b Phenobarbital
b.
c. d.
c. Carbamazepine
e
e.

101 102

CNS: Antiepileptics CNS: Antiepileptics

NLE1 Q&A p.81



phenytoin
h t i


a. binding protein
b GFR
b. Phenytoin
y metabolism
c. intravascular volume
d. GI motility
e
e. metabolism

FDA lists phenytoin in Pregnancy Category D. Phenytoin is an inducer of the CYP3A4 and
CYP2C19.
Warfarin (Coumadin) and trimethoprim increase serum phenytoin levels and prolong the
serum half-life of phenytoin by inhibiting its metabolism.
103 104
 CNS: Antiepileptics
NLE1 Q&A p.170

carbamazepine
a. Na+ Blocker
b Gl
b. Glutamate
t t antagonist
t it
c. Inhibit GABA transaminase
d. T- calcium channel
e. GABA on Cl- channel

Putative mechanisms of action of AEDs at an excitatory synapse in CNS.

105
McElroy, S.L.; Keck, P.E.; Post, R.M. 2008. Antiepileptic drugs to treat psychiatric disorders
106

CNS: Antiepileptics CNS: Antiepileptics

20 ER Patient suffered from trigeminal neuralgia. He had the

10 characterized by episodes of intense facial pain that last from a
few seconds to several minutes or hours.
A Phenytoin
A. Which of the followingg antiseizure drugs
g is also effective in this
treatment?
B. Diazepam
A Primidone
A.
C. Valpoic acid B. Topiramat
D Phenobarbital
D. Ph b bit l C. Carbamazepine
E. Carbamazepine D. Lamotrigine
E. Phenyltoin
intravenous benzodiazepines (diazepam IV, lorazepam IV)
107 108
 NLE1 Q&A p.180 CNS: LA CNS: LA
NLE1 Q&A p.248
30 lidocaine
lidocaine
A. membrane refractory period (antiarrhythmic drug)
B
B. voltage
voltage-dependent
dependent sodium channel a. K+ channel
h l bl blocker
k
C. nerve fiber
b. Na+ channel blocker
D. resting membrane potential
c. Ca2+ channel blocker
E. resting membrane potential
d. Beta-Adrenoceptor blocker
e. Adenosine receptor blocker

109 110

CNS: LA
Relative size and susceptibility of Different Types of Nerve Fibers
30

t LLocall AAnesthetics
to th ti CNS LA
CNS:

nerve fiber ? Fiber type Function Diameter (m) Sensitivity to block

A. A B. A Type A
C A
C. A D B
D. alpha Proprioception, motor
Proprioception 12-20
12 20 +
E. C beta Touch, pressure 5-12 ++
gamma Muscle spindles 3-6 ++
delta Pain, temperature 2-5 +++
Type B Preganglionic <3 ++++
Type C
Dorsal root Pain 0.4-1.2 ++++
Sympathetic Postganglionic 0.3-1.3 ++++
111 112
 NLE1 Q&A p.164 CNS: LA CNS: LA
NLE1 Q&A p.164
epidural anesthesia


sacral canal
a. Ligamentum flavum b. Subcutaneous fat block nerve
c. Posterior sacral ligament a. Ulnar nerve b. Musculocutaneous nerve
d. Interspinous ligament c. Median nerve d. Radial nerve
e. Axillary nerve

113 114

CNS: LA CNS: Stimulants

20 methamphetamine


A. Syrup of ipecac
Amphetamine is a weak base.
B. Atropine Pharmacokinetics: Weak bases will be excreted faster in acidic
C Naloxone
C. Nl urine.
Major drug interactions:
D. NH4Cl Drugs that alkalinize the urine (carbonic
(carbonic-anhydrase
anhydrase
E. NaHCO3 inhibitors, sodium bicarbonate, thiazide diuretics) reduce
renal elimination of amphetamine & other weak bases.
Drugs that acidify the urine (ascorbic acid, aluminum
chloride, ammonium chloride) can increase the renal
elimination of weak bases by keeping them in their charged
115 form. 116
 CNS: Stimulants CNS: Stimulants
NLE1 Q&A p.179

38 amphetamine
BP 170/110 mmHg

amphetamine

BP
a. potent 1adrenergic agonist
b potent 2adrenergic
b. 2 adrenergic agonist
c. inhibition of catecholamine metabolism
d. release of internal catecholamine
e metabolism to false neurochemical transmitter
e.

117 118

CNS: Abuse CNS: Abuse

NLE1 Q&A p.73

Female patient get some substance abuse for a long time. She had tooth
caries and skin abscess from delusional parasitosis.
parasitosis
35


Which one is this substance abuse?

A. Heroin

B. ICE (pure methamphetamine)
a Amphetamine
a. b Marijuana
b.
C. Cocaine
D. Alprazolam (Love pill)
c. Gasoline d. Alcohol
E. Pseudoephedrine

119 120
 CNS: Abuse CNS: Abuse
Amphetamine Marijuana and hashish
Symptoms of Amphetamine Addiction
Tetrahydrocannabinol (THC) found in marijuana and hashish.
Signs of use and dependence can include:
Paranoia -Depression
A heightened sense of visual, auditory and taste perception
Suicidal thoughts -Weight loss Poor memory
Poor judgment -Irritability Increased blood pressure and heart rate
Sleep disorders -Malnutrition
Malnutrition Red
R d eyes
Hyperactivity -Nervous reactions Decreased coordination
Rapid heart beat -Increased blood pressure Difficulty concentrating
Tremors Increased appetite
Slowed reaction time
Paranoid thinking
121 122

CNS: Abuse CNS: Abuse

Inhalants Alcohol
Inhalants produce an effect that may be similar Long-term alcohol abuse can cause a number of physical symptoms,
to alcohol intoxication.
intoxication Symptoms were include including cirrhosis of the liver
liver, pancreatitis
pancreatitis, epilepsy
epilepsy, polyneuropathy,
polyneuropathy
Drowsiness -lightheadedness alcoholic dementia, heart disease, nutritional deficiencies, peptic ulcers and
sexual dysfunction,
dysfunction and can eventually be fatal
fatal.
loss of inhibition -Dizziness
withdrawal symptoms
Hallucinations or delusions -Belligerence
g
Anxiety or jumpiness -Shakiness or trembling
Apathy -Impaired judgment
Sweating -Nausea and vomiting
depression
d i andd moodd changes
h -weight
i ht loss
l Insomnia -Depression
Inattentiveness -lack of coordination Irritability -Fatigue
Fatigue
Irritability -weakness Loss of appetite -Headache

123 124
 NLE1 Q&A p.84 p.176 CNS: Stimulants CNS: Stimulants
20

cocaine



a
a. plasma esterase activity
b. monoamine oxidase (MAO) activity
c. noradrenaline reuptake
d. Block alpha adrenergic receptor
e. Block beta adrenergic receptor
26 intracerebral hemorrhage

a. Dopaminergic effect b. Renin hypersecretion
c. Excess catecholamine d. Sodium retention
125 126

NLE1 Q&A p.70, p.3 CNS: Abuse CNS: Abuse

35 methanol
ethanol
Ethanol methanol
a Production inhibition
a.
b. Irreversible inhibition
c. Competitive
p inhibition
d. Non-specific inhibition
e. Non-competitive inhibition

ethanol
ethanol

A. Product inhibitor B. Allosteric inhibitor
C Irreversible inhibitor
C. D Competitive inhibitor
D.
E. Feedback inhibitor

127 128
 NLE1 Q&A p.8 CNS: Abuse NLE1 Q&A p.59, p.85 CNS: Abuse

alcohol disulfiram alcohol drug interaction

a. Pharmakokinetic interaction
A. Alcohol dehydrogenase b. Pharmacodynamic interaction
c. Phycologic interaction
B. Acetaldehyde dehydrogenase
d. Physiologic interaction

disulfiram
Acetaldehyde is more toxic than alcohol and is responsible for many hangover disulfiram

symptoms. Typical symptoms of a hangover may include headache, nausea,
a. CYP 450
increased cardiac output, vasodilation, sleep deprivation, drowsiness,
concentration problems, dry mouth, dizziness, fatigue, gastrointestinal b Amine oxidase
b.
complaints, sweating, hyper-excitability and anxiety. c. Alcohol dehydrogenase
d. Aldehyde dehyodrogenase
129 130

CNS: Abuse CNS: Abuse

NLE1 Q&A p.46 NLE1 Q&A p.301

alcohol
40

a. Dysplasia b. Disruption
a
a. b
b. c Teratogen
c. d Deformation
d.
c. d. e. Malformation

Gastritis is an inflammation of the lining of the stomach, and has many possible
causes The main acute causes are excessive alcohol consumption or prolonged use
causes. Chronic maternal alcohol abuse during pregnancy is associated with teratogenic effects,
effects and
of NSAIDs. alcohol is a leading cause of mental retardation and congenital malformation. The
abnormalities that have been characterized as fetal alcohol syndrome include (1) intrauterine
growth retardation, (2) microcephaly, (3) poor coordination, (4) underdevelopment of
131
midfacial region (appearing as a flattened face), and (5) minor joint anomalies. 132
 Toxicology Toxicology
NLE1 Q&A p.4, p.145
Sulfhemoglobin: A sulfur atom is incorporated into the hemoglobin
molecule. When hydrogen sulfide (H2S) (or sulfide ions) and ferric ions
combine in the blood, the blood is incapable of carrying oxygen.
Deoxyhemoglobin: Hemoglobin forms an unstable, reversible bond with
A. Sulfhemoglobin oxygen. In its oxygen-loaded form it is oxyhemoglobin and is bright red.
B. Deoxyhemoglobin In the oxygen-unloaded
oxygen unloaded form it is called deoxyhemoglobin and is purple-
purple
blue.
y g
C. Carboxyhemoglobin Methemoglobin is a form of the oxygen-carrying
oxygen carrying metalloprotein
D. Methemoglobin hemoglobin, in which the iron in the heme group is in the Fe3+ (ferric)
state, not the Fe2+ ((ferrous)) of normal hemoglobin.
g Methemoglobin
g cannot
E. Carbaminohemoglobin bind oxygen, unlike oxyhemoglobin. It is bluish chocolate-brown in color.
Carbon monoxide mainly causes adverse effects in humans by combining with hemoglobin Carbaminohemoglobin is a compound of haemoglobin and carbon
to form carboxyhemoglobin (HbCO) in the blood. This prevents hemoglobin from releasing dioxide, and is one of the forms in which carbon dioxide exists in the
oxygen in tissues, effectively reducing the oxygen-carrying capacity of the blood, leading to blood.
hypoxia. Treatment of poisoning largely consists of administering 100% oxygen or providing
hyperbaric oxygen therapy 133 134

NLE1 Q&A p.170 Toxicology Toxicology

NLE1 Q&A p.35

carbon monoxide
a.



b.
a.
c
c.


b.
d.
c. Plt ??
e. Oxygen-carrying capacity

CO
pathognomonic signs
hypoxia Lead does not appear to be directly genotoxic in vivo or in vitro, and lead may
((91%),) ((77%),) ((47%)) , , flu-like
i t t with
interact ith other
th ttoxicants
i t tto ffacilitate
ilit t chemical
h i l carcinogenesis.
i i
illness, angina
cherry red skin, lips 2-3% Lead is a nephrocarcinogen in adult rodents.
CO lactic acidosis, myocardial ischemia, rhabdomyolysis (Ramathibodi Poison
Center) 135 136
 NLE1 Q&A p.148 Toxicology NLE1 Q&A p.159 Toxicology
10

Lead poisoning


BP drop 5


a. Acute leukemia b.
a. N acetylcysteine b. Deferoxamine
c. d.
p
c. D-penicillamine Copper d. Resmocepil?
p
e. Edetate calcium disodium Lead
Lead poisoning symptoms: 1.Headaches, irritability, fatigue, difficulty sleeping, difficulty The first indication of iron poisoning by ingestion is a pain in the stomach, as the stomach
learning or concentrating, aggressive behaviour 2. Stomach pain, constipation, lining becomes ulcerated. This is accompanied by nausea and vomiting. The pain then
vomiting,
iti nausea, weight
i ht lloss 3.
3 Hearing
H i lloss 4.
4 Anemia,
A i unusuall paleness, l slowed
l d abates for 24 hours as the iron passes deeper into the body resulting in metabolic acidosis
acidosis,
growth, seizures, coma, staggering walk 5. Kidney damage, loss of appetite 6. which in turn damages internal organs, particularly the brain and the liver. The body goes
Reduced sensations 7. Muscle weakness into shock and death from liver failure. Later stage treatment consists of cleaning the iron
from the blood, using a chelating agent such as deferoxamine. If this fails then dialysis is
137 the next step. 138

Toxicology Toxicology
NLE1 Q&A p.39
20 E 20
2 . .
48 . A. N-acetylcysteine

B. Deferoxamine
A. Botox B. Cyanide
C. Adrenaline
C. Snake venom D. Radiation
D. Fumazenil
E. Resin
E. Syrup of ipecae
Radiation toxicity: The gastrointestinal system and bone marrow are highly
sensitive to radiation. Symptoms: nausea, vomiting, diarrhea, headache,
fever
139 140
 Toxicology Toxicology
NLE1 Q&A p.3, p.71 NLE1 Q&A p.76, p.82

paracetamol 10 . Paracetamol overdose

N-acetylcsyteine
N-acetylcsyteine toxic
paracetamol a. Glutathione conjugation b. Glucoronide conjugation
A. Ascorbic Acid B. Glutathione c. N-acetylation d. Sulfate conjugation
C. Retinoid D. Tocopherol e. N-hydroxylation
E Cholecalciferol
E.
N-acetylcysteine paracetalmol toxicity

liver
acetaminophen

cell injury a. N-acetylation b. N-hydroxylation
a. Ascorbic b. vitamin E c. sulfer conjugate d. glutathione conjugate
c. glutathione d. folic acid e. glucorunide conjugate

141 142

Toxicology Toxicology

143 144
 Paracetamol toxicity Toxicology Toxicology
FFollowing
ll i a therapeutic
th ti ddose, it iis mostly
tl converted
t d tto nontoxic
t i metabolites
t b lit via
i Ph
Phase II
metabolism by conjugation with sulfate and glucuronide, with a small portion being 50 20 (500
oxidized via the cytochrome P450 enzyme system. Cytochromes P450 2E1 and 3A4 mg) 10
4 .


convert approximately 5% of paracetamol to a highly-reactive intermediary metabolite, N-
acetyl-p-benzoquinoneimine (NAPQI). Under normal conditions, NAPQI is detoxified by paracetamol toxicity
conjugation with glutathione to form cysteine and mercapturic acid conjugates. A. Hepatic CYP450 induction
In cases of paracetamol overdose, the sulfate and glucuronide pathways become
saturated, and more paracetamol is shunted to the cytochrome P450 system to produce B Decrease renal clearance
B.
NAPQI. As a result, hepatocellular supplies of glutathione become depleted, as the C. Decrease hepatic glucoronidation
demand for glutathione is higher than its regeneration.
regeneration NAPQI therefore remains in its toxic
form in the liver and reacts with cellular membrane molecules, resulting in widespread D. Increase paracetamol absorption
hepatocyte damage and death, leading to acute hepatic necrosis. In animal studies,
hepatic glutathione must be depleted to less than 70% of normal levels before
E Increase hepatocyte glutathione
E.
hepatotoxicity occurs.
Acetylcysteine, also called N-acetylcysteine or NAC, works to reduce paracetamol toxicity
by replenishing body stores of the antioxidant glutathione. 145 146

Toxicology Toxicology
Arsenic (As, )

Arsenic is a toxic and carcinogenic metalloid. Occupational
A. Arsenic B. Mercury exposure to arsenic occurs in the manufacture of pesticides,
pesticides
C. Cadmium D. Lead herbicides, and other agricultural products. Environmental
arsenic exposure mainly occurs from arsenic-contaminated
arsenic contaminated
drinking water.
(itai itai), - Acute exposure to a single high dose can produce
encephalopathy, with signs and symptoms of headache,
The lethargy, mental confusion, hallucination, seizures, and even
bones become soft (osteomalacia), lose bone mineral density coma.
(osteoporosis) and become weaker. Chronic Toxicity Skin cancer is common with protracted high-
p
level arsenical exposure.
147 148
 Toxicology
Mercury (Hg, ) Toxicology
The natural biomethylation
y reaction pproduces methylmercury
y y ((MeHg).
g)
Methylmercury enters the aquatic food chain starting with plankton, then herbivorous fish, and
finally ascending to carnivorous fish and sea mammals.
Occupational exposure may also occur during manufacture of a variety of scientific
instruments and electrical control devices, and in dentistry where mercury amalgams are
used in tooth restoration.
Inhalation of high concentration mercury may produce an acute, corrosive bronchitis and
interstitial pneumonitis.
In humans, the early glomerular nephritis may progress to interstitial immune-complex
nephritis. Methylmercury is neurotoxicity. Clinical manifestations of neurotoxicity include
paresthesia (a numbness and tingling sensation around the mouth, lips) and ataxia,
manifested as a clumsy, stumbling gait, and difficulty in swallowing and articulating words.
Other signs include neurasthenia (a generalized sensation of weakness), vision and hearing
loss, and spasticity and tremor. 149

Administration of chelating agents for mercury, such as cysteine, EDTA, dimercaprol (BAL),
or penicillamine. The Movement of Mercury in the Environment. 150

Cadmium (Cd, ) Toxicology Toxicology

About 75% of cadmium produced is used in batteries, especially nickel nickelcadmium
cadmium
batteries, electroplating or galvanizing alloys for corrosion resistance, color pigment
for paints and plastics, in solders, as a barrier to control nuclear fission, as a plastic
stabilizer and in some special application alloys.
The majorj long-term
g toxic effects are renal injury,
j y obstructive ppulmonaryy disease,
osteoporosis, and cardiovascular disease. Cancer is primarily a concern in
occupationally exposed groups.
Cadmium-induced renal toxicity is reflected by proteinuria as a result of renal tubular
dysfunction.
Occupational cadmium exposure is a well recognized cause for renal tubular
dysfunction associated with hypercalciuria, renal stone formation, osteomalacia, and
osteoporosis. The long-term consumption of cadmium contaminated rice caused Itai-
Itai disease, which occurred mostly in multiparous elderly women and was Cadmium Transport, Protein-Binding, and Toxicity.
characterized by severe osteomalacia and osteoporosis, resulting in bone GSH, glutathione; MT, metallothionein; aa, amino acids; Cd-Alb, Cd-albumin; Cd-
deformities. 151 LMWPr, Cd associated with low molecular weight proteins. 152
 Toxicology Toxicology
Lead (Pb, )
LLeadd in
i blood
bl d isi primarily
i il (99%) ini erytrocytes
t t bound b d tto hhemoglobin.
l bi
Symptoms of lead encephalopathy begin with lethargy, vomiting, irritability, loss of appetite,
and dizziness,
dizziness progressing to obvious ataxia
ataxia, and a reduced level of consciousness,
consciousness which
may progress to coma and death.
Peripheral neuropathy is characterized by segmental demyelination and possibly axonal
degeneration. Motor nerve dysfunction,
Hematologicg Effects Lead has multiplep hematologic g effects,, ranging
g g from increased urinaryy
porphyrins, coproporphyrins, -aminolevulinic acid (ALA), and zinc-protoporphyrin to
anemia. The most sensitive effects of lead are the inhibition of aminolevulinic acid
dehydratase (ALAD) and ferrochelatase. Anemia only occurs in very marked cases of lead
toxicity, and is microcytic and hypochromic, as in iron deficiency.
Chronic lead nephrotoxicity consists of interstitial fibrosis and progressive nephron loss,
azotaemia and renal failure Lead Interruption of Heme Biosynthesis.
The
Th orall chelating
h l ti agentt dimercaptosuccinic
di t i i acidid (DMSA
(DMSA, alsol called
ll d Succimer)
S i ) has h ALA, -aminolevulinate;
ALA i l li t Pb, Pb sites
it for
f lead
l d effects.
ff t ThThe major
j lleadd iinhibition
hibiti sites
it
advantages over EDTA. 153 are ALA dehydrogenase and ferrochelatase. 154

10
Toxicology Specific treatment Toxicology




1. Decontamination: cyanide

A. EDTA (activated charcoal) cyanide
B. Deferoxamine
C. N-Acetyl cysteine a.
cytochrome oxidase linamarin
D. Atropine and 2-PAM cyanide
E. Sodium nitrite and Sodium thiosulfate 2. Antidote: sodium nitrite sodium thiosulfate antidote 2
stable half-life sodium nitrite IV
Cassava (() 5 monitor BP vasodilate
hydrocyanic acid 30
The cyanide
y ion halts cellular respiration
p byy inhibitingg an enzyme
y in the hydroxocobalamin
y ((vitamin B
mitochondria called cytochrome c oxidase. A cherry red skin color may be 12a) hydroxy group cyanide
ppresent as the result of increased venous hemoglobing oxygen
yg saturation. cyanocobalamin
y
155 156
 Toxicology Toxicology
NLE1 Q&A p.214 NLE1 Q&A p.223, p.236

35
Small nodule at both lungs, bronchi
10
a. Byssinosis
B i i a. Obstructive defect
b. Siderosis Siderosis is the deposition of iron in tissue. b. Restrictive defect
c. Asbestosis c. Reversible obstructive airway
d. Silicosis d Irreversible obstructive airway
d.
e. Bagassosis e. Obstructive and restrictive

Pulmonary function testing may reveal airflow limitation, restrictive defects,

reduced diffusion capacity, mixed defects, or may be normal (especially
157 without complicated disease). 158

Toxicology Toxicology
NLE1 Q&A p.230 NLE1 Q&A p.237

40 2 (asbestos)
4

a Nose
a. b Nasopharynx
b. a. Osteosarcoma
c. Trachea d. Bronchus b. Renal cell carcainoma
e. Alveoli c. Malignant mesothelioma
d Hepatocellular carcinoma
d.

(CaCO3)When small silica dust particles are inhaled, they can embed Asbestos cancer is called mesothelioma (lung cancer).
themselves deeply
p y into the tinyy alveolar sacs and ducts
159 160
 NLE1 Q&A p.241
Toxicology Occupational lung disease Toxicology

Pneumoconiosis
Silicosis
a. silicosis b. asbestosis Asbestosis
c sarcosis
c. d bagasstosis
d. Allergic response
e. Farmers lung disease (spore of Thermophilic actinomycetes)
Organic fiber disease
Bagassosis
B i : dried
d i d sugar cane
Byssinosis :

161 162

Toxicology Toxicology
Patients with advanced silicosis
often have greater susceptibility to
respiratory infections such as
tuberculosis.
Silicosis Asbestosis

163 164
 NLE1 Q&A p.304 Doping drugs Doping drugs
The World Anti-Doping Code

25

400 m

THE 2014 PROHIBITED LIST INTERNATIONAL STANDARD
S1. ANABOLIC AGENTS



S2. PEPTIDE HORMONES, GROWTH FACTORS AND RELATED SUBSTANCES-
a. Caffeine b. Erythropoietin erythropoietin, Chorionic Gonadotrophin (CG) and Luteinizing Hormone Growth
c. Propanolol d. Hydrochlorothiazide Hormone
e. Nandrolone anabolic steroid S3. BETA-2 AGONISTS
S4. HORMONE AND METABOLIC MODULATORS
S5. DIURETICS AND OTHER MASKING AGENTS
In-Competition only: Bupropion, caffeine, nicotine, phenylephrine, phenylpropanolamine, S6. STIMULANTS
pipradrol, pseudoephedrine (< 150 micrograms per milliliter) S7. NARCOTICS
S8. CANNABINOIDS
Nandrolone (19-nortestosterone) is an anabolic steroid. The positive effects of the drug
include muscle ggrowth,, appetite
pp stimulation and increased red blood cell pproduction and S9. GLUCOCORTICOSTEROIDS
bone density.
165 166

PROHIBITED METHODS Doping drugs

NLE1 Q&A p.64
M1 MANIPULATION OF BLOOD AND BLOOD COMPONENTS
M1.
M2. CHEMICAL AND PHYSICAL MANIPULATION
1 4 50 kg 30 kg 6
M3 GENE DOPING
M3.
SUBSTANCES PROHIBITED IN PARTICULAR SPORTS 1 hr
P1 ALCOHOL Th
P1. The ddoping
i violation
i l ti th
threshold
h ld iis equivalent
i l t tto a bl
bloodd alcohol
l hl


concentration of 0.10 g/L. a. Bulimia b. Schizophenia
Air Sports - Archery
Automobile - Karate
c. Anorexia nervosa d. Hyperthyroidism
Motorcycling - Powerboating e Hypothalamo..?
e. Hypothalamo ?
P2. BETA-BLOCKERS
Archery - Automobile
Billiards - Darts
Golf
G lf - Shooting
Sh ti
Skiing/Snowboarding 167 168
 NLE1 Q&A p.73
DI
Eating disorder 70 2
Anorexia nervosa is characterized by immoderate food restriction and irrational cerebro-vascular thrombosis 1
fear of ggainingg weight,
g , as well as a distorted bodyy self-perception
p p . warfarin

Bulimia nervosa is characterized by binge eating and purging, or consuming a
5
g amount of food in a short amount of time followed byy an attempt
large p to rid
oneself of the food consumed (purging), typically by vomiting, taking a laxative,
Lab prolonged PTT
diuretic,, or stimulant,, and/or excessive exercise,, because of an extensive a. Ranitidine b. Cimetidine
concern for body weight. c. Famotidine d. Misoprostal
Binge
g eatingg disorder ((BED)) is characterized byy binge g eatingg without
subsequent purging episodes. e. Omeprazole
Pica is characterized byy an appetite
pp for substances largelyg y non-nutritive, such Tagamet (cimetidine) reduced the hepatic metabolism of warfarin therefore,
therefore
as clay, chalk, dirt, or sand. close monitoring of prothrombin time is recommended, and adjustment of the
anticoagulant dose.
dose
169 170

NLE1 Q&A p.77

FDA Pregnancy Categories
Category A: Adequate and well-controlled studies have failed to demonstrate a risk to the
35 36 weeks category D (fatal) fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
Category B : Animal reproduction studies have failed to demonstrate a risk to the fetus and
a. there are no adequate and well-controlled studies in pregnant women.
b
b. Category
Ct CC: Animal
A i l reproduction
d ti studies
t di hhave shown
h an adverse
d effect
ff t on ththe ffetus
t andd
there are no adequate and well-controlled studies in humans, but potential benefits may
c. warrant use of the drugg in ppregnant
g women despite
p ppotential risks.
d. Category D: There is positive evidence of human fetal risk based on adverse reaction data
from investigational or marketing experience or studies in humans, but potential benefits
e.
may warrant use of the drug in pregnant women despite potential risks.
Category X: Studies in animals or humans have demonstrated fetal abnormalities and/or
there is positive evidence of human fetal risk based on adverse reaction data from
investigational or marketing experience, and the risks involved in use of the drug in
pregnantt women clearly
l l outweigh
t i h potential
t ti l benefits.
b fit
171 172