Antidotes

Bromocriptine
Cyproheptadine
Dantrolene
Naloxone
Sodium nitroprusside


ISBN
1

978-616-406-085-2
2558
2,000

270 6 10400
0 2201 1084 0 2201 1085 1

766/36-39 .107
10120
. 0-229-0279-81, 0-2688-4840-41
Fax. 0-2688-4842
Email : scanart03@yahoo.com

257 . 1 . .
. 10270
. 0-2387-1452-4
Fax. 0-2387-1455
Email : scanandprint2010@yahoo.com

II

5


1-4

( )

III

2554
web based application stock
GIS real-time 2559
16


Diphtheria antitoxin Botulinum antitoxin

( )

(Bromocriptine)

(Cyproheptadine)
(Dantrolene)
(Naloxone)

(Sodium nitroprusside)

11
16
19
22
26

(Common toxidromes)

(Case study: Rodenticide poisoning)

(Case study: Ergotism)

(Case study: Opioid poisoning)

1
(Case study 1: Snake bites)
2
(Case study 2: Snake bites)

31
37
41
44
48
51

1. 3 57
2. Antidotes ()
Botulinum antitoxin inj. Diphtheria antitoxin inj.
61
3.
66

VI

1.

2553

(.)

Vendor Managed Inventory (VMI)

2.

2559 16

1
Dimercaprol inj.


2
Sodium nitrite inj.

3
Sodium thiosulfate inj.

4
Methylene blue inj.


5
Botulinum antitoxin inj.

6 Diphtheria antitoxin inj.

7
Succimer cap.

8
Calcium disodium edetate inj.

9
Diphenhydramine inj

10

11

arsenic, gold, mercury, lead,

copper

12

13

14

15

16

Cyanide poisoning, Hydrogen sulfide

Cyanide poisoning
Methemoglobinaemia, Toxic encephalopathy
ifosfamide
Botulinum toxin
Diphtheria toxin

dystonia

1.

2.

(Polyvalent antivenom for neurotoxin)

3. Digoxin specific antibody fragment

inj. Esmolol inj.

2558

3.

3.1


3.2


.
( )
4.

4.1 .
/

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/ Geographic Information System (GIS)
http://drug.nhso.go.th/Antidotes/

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5.

5.1
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5.2
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5.3
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l 1367

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5.5

.

. 5.1

5.6

.

PO PO

5.7

5.8 Diphtheria antitoxin inj Botulinum antitoxin inj

Diphtheria antitoxin Botulinum antitoxin 2

5.9

.
4

Initial stock
6.

2

6.1 .

(1) Dimercaprol inj

(2) Sodium nitrite inj.

(3) Sodium thiosulfate inj.

(4) Methylene blue inj.

(5) Diptheria antitoxin inj.

(6) Calcium disodium edentate inj.

6.1.1 Initial
.

1 .

6.1.2
.

6.1.3
initial .

6.1.4 .


6.1.5 .
.


6.2

(1)

(2)

(3)

(4)

(5)

(6)
(Polyvalent antivenom for hematotoxin)

(7)
(Polyvalent antivenom for neurotoxin)

(8)
Esmolol inj.

(9)
Diphenhydramine inj.

6.2.1 Initial
.

1 7
.

6.2.2 .

6.2.3 . stock
.

6.2.4
.

6.2.5
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6.2.6 .


6.2.7 .
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6.1 ( 24 )

1)

2) Internet

3)
4)

5)

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l : 02-2011084-5 1

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l Website: www.ra.mahidol.ac.th/poisoncenter/ : PoisonCenter.mahidol.ac.th

l Line ID: poisrequest

l ........

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6.2 ( 24 )
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02-4197317-8
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6.3
8.30 16.30 .

1. 02-2520161-4 125
2. 02-2540212
3. Email: queensaovabha@hotmail.com
4. Website URL: www.saovabha.com
5.

1871 4 10330

7.

1.
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4 : 084-3878045
4 Email address : wannapa.k@nhso.go.th
4 Email address : tanl_rx@yahoo.com
2.
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4 : 0-2201-1084-5
4 : 1367
4 Email address: charuwan.sri@mahidol.ac.th
3.
l
4 : 02-5903196-9, 081-6478831
4 Fax 02-9659152

10


(Bromocriptine)

(Bromocriptine) (Bromocriptine mesylate)

(dopamine receptor agonist) (serotonin agonist)

(Prolactin)
(acromegaly),
(prolacinoma), (female infertility
of pituitary hypothalamic origin prolactinemia, hyperprolactinemia, non-pregnancy related A-G syndrome),
(parkinsons disease), 2 (non-insulin dependent diabetes mellitus, diabetes mellitus type 2)

neuroleptic malignant syndrome

(levodopa)
neuroleptic malignant syndrome (NMS)

NMS
1-4

(standard) 28

65-95
(Bromocriptine Quick Release; Bromocriptine QR)
1-3 55-65

11


90-96 6 (volume
of distribution; Vd) 61 1
2-6 93
450 3 4 (Cytochrome P450 3A4) 5-6

1.

(Hyperprolactinemia)

(prolactinoma)
(female infertility of pituitary hypothalamic origin hyperprolactinemia) (non-pregnancy woman with A-G syndrome)

2. (Acromegaly)

3. (Parkinsons Disease)

(dopamine receptor agonist)

4. 2 (Diabetes mellitus type 2) (Bromocriptine QR)

(metformin)

5. Neuroleptic malignant syndrome (NMS)

1.

2. (ergotamine)

3.

4.

5.

6.

12

(withdrawal) Neuroleptic malignant syndrome

7-8

1.

2.

(myoclonus)

3.

(20-30 )

1.

(prednisolone)

(cafergot) (sumatriptan)
(Serotonin Syndrome)

2.

450 3 4 (Cytochrome P450 3A4)

450 3
4 (Cytochrome P450 3A4 inhibitor) (ritonavir)
450 3 4 (Cytochrome P450 3A4
substrate) (clarithromycin)

450 3 4 (Cytochrome P450 3A4 inducer) (carbamazepine)

13

1. (Hyperprolactinemia)

(prolactinoma) 1.25-2.5
2.5 2-7
2.5-15

2. (Acromegaly) 1.25-2.5

1.25-2.5 3-7
20-30 100

3. (Parkinsons Disease) 1.25 2

2.5 14-28
2.5-40 100

4. 2 (Diabetes mellitus type 2)

Bromocriptine QR 0.8 1
2 0.8
1.6-4.8

5. Neuroleptic malignant syndrome 2.5-

15 3 10
48-72
9

(Bromocriptine mesylate)

2.5 5
(Bromocriptine QRquick release) 0.8

2 4

14


1. Cuellar FG. Bromocriptine mesylate (Parlodel) in the management of amenorrhea/galactorrhea associated with
hyperprolactinemia. Obstetrics and gynecology. 1980 Mar;55(3):278-84. PubMed PMID: 6987580.
2. Dhib-Jalbut S, Hesselbrock R, Mouradian MM, Means ED. Bromocriptine treatment of neuroleptic malignant
syndrome. The Journal of clinical psychiatry. 1987 Feb;48(2):69-73. PubMed PMID: 3804991.
3. Rosebush PI, Mazurek MF. Bromocriptine and neuroleptic malignant syndrome. The Journal of clinical
psychiatry. 1991 Jan;52(1):41-2. PubMed PMID: 1988419.
4. Mahajan R. Bromocriptine mesylate: FDA-approved novel treatment for type-2 diabetes. Indian journal of phar
macology. 2009 Aug;41(4):197-8. PubMed PMID: 20523873. Pubmed Central PMCID: 2875741.
5. Holt RI, Barnett AH, Bailey CJ. Bromocriptine: old drug, new formulation and new indication. Diabetes, obesity
& metabolism. 2010 Dec;12(12):1048-57. PubMed PMID: 20977575.
6. Kanto J. Clinical pharmacokinetics of ergotamine, dihydroergotamine, ergotoxine, bromocriptine, methysergide,
and lergotrile. International journal of clinical pharmacology, therapy, and toxicology. 1983 Mar;21(3):135-42.
PubMed PMID: 6133838.
7. Reimer J, Kuhlmann A, Muller T. Neuroleptic malignant-like syndrome after rapid switch from bromocriptine
to pergolide. Parkinsonism & related disorders. 2002 Dec;9(2):115-6. PubMed PMID: 12473402.
8. Wu YF, Kan YS, Yang CH. Neuroleptic malignant syndrome associated with bromocriptine withdrawal in
Parkinsons disease--a case report. General hospital psychiatry. 2011 May-Jun;33(3):301 e7-8. PubMed PMID:
21601731.
9. Verhoeven WM, Elderson A, Westenberg HG. Neuroleptic malignant syndrome: successful treatment with
bromocriptine. Biological psychiatry. 1985 Jun;20(6):680-4. PubMed PMID: 3995115.

15


(Cyproheptadine)

(Cyproheptadine) piperidine H1-antagonist serotonin
receptor (5-HT1A 5-HT2A receptor) Cushings syndrome,
vascular headache, anorexia serotonin syndrome

conjugated metabolite
1-4 6-9 8


H1-antagonist histamine receptor


serotonin receptor antagonism
appetite center hypothalamus
serotonin (third-line therapy) serotonin
toxicity monoamine oxidase inhibitor (MAOI)1 serotonin syndrome
benzodiazepine (external cooling)
serotonin toxicity2-4 serotonin syndrome5

serotonin syndrome
hyperthermia serotonin toxicity (mild to moderate
manifestations)6

16



1. Angle-closure glaucoma

2. Bladder neck obstruction

3. Elderly, debilitated patients

4.

5. MAOI

6.

7.

8. Prostatic hypertrophy, symptomatic

9. Pyloroduodenal obstruction

10. Stenosing peptic ulcer

1. monoamine oxidase inhibitor (MAOI)
anticholinergic ( )
7-9

2. selective serotonin reuptake inhibitor
(SSRI) fluoxetine, paroxetine 10-12

3. bupropion

4. anticholinergic morphine oxymorphone
13

5. donepezil reversible acetylcholinesterase inhibitor


6. belladonna anticholinergic

1. 12 2 2
serotonin syndrome 1 32

2. 0.25 // 6 12 14

1. anticholinergic effect

2. FDA category B

17


1. Boyer EW, Shannon M. The serotonin syndrome. The New England journal of medicine. 2005;352:1112-20.
Epub 2005/03/24.
2. Sprouse JS, Aghajanian GK. (-)-Propranolol blocks the inhibition of serotonergic dorsal raphe cell firing by
5-HT1A
selective agonists. European journal of pharmacology. 1986;128:295-8. Epub 1986/09/09.
3. Gerson SC, Baldessarini RJ. Motor effects of serotonin in the central nervous system. Life sciences.
1980;27:1435-51. Epub 1980/10/20.
4. Himei A, Okamura T. Discontinuation syndrome associated with paroxetine in depressed patients: a retro
spective analysis of factors involved in the occurrence of the syndrome. CNS drugs. 2006;20:665-72. Epub
2006/07/26.
5. Nisijima K, Yoshino T, Yui K, Katoh S. Potent serotonin (5-HT)(2A) receptor antagonists completely prevent
the development of hyperthermia in an animal model of the 5-HT syndrome. Brain research. 2001;890:23-31.
Epub 2001/02/13.
6. Stork C. Serotonin Reuptake Inhibitors and Atypical Antidepressants. In: Hoffman R, Howland M, Lewin N,
Nelson L, Goldfrank L, editors. Goldfranks Toxicologic Emergencies. 10 ed. New York: McGraw-Hill; 2015.
7. Gupta V, Karnik ND, Deshpande R, Patil MA. Linezolid-induced serotonin syndrome. BMJ case reports.
2013;2013. Epub 2013/03/21.
8. Clark DB, Andrus MR, Byrd DC. Drug interactions between linezolid and selective serotonin reuptake inhibitors:
case report involving sertraline and review of the literature. Pharmacotherapy. 2006;26:269-76. Epub 2006/02/10.
9. Graudins A, Stearman A, Chan B. Treatment of the serotonin syndrome with cyproheptadine. The Journal of
emergency medicine. 1998;16:615-9. Epub 1998/08/08.
10. Feder R. Reversal of antidepressant activity of fluoxetine by cyproheptadine in three patients. The Journal of
clinical psychiatry. 1991;52:163-4. Epub 1991/04/01.
11. Goldbloom DS, Kennedy SH. Adverse interaction of fluoxetine and cyproheptadine in two patients with bulimia
nervosa. The Journal of clinical psychiatry. 1991;52:261-2. Epub 1991/06/01.
12. Christensen RC. Adverse interaction of paroxetine and cyproheptadine. The Journal of clinical psychiatry.
1995;56:433-4. Epub 1995/09/01.
13. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Rockville MD2004.
14. Cantrell F. Cyproheptadine In: Olson KR, editor. Poisoning & Drug Overdose. 6th edition. New York: McGrawHill; 2012. p. 471.
18


(Dantrolene)

(Dantrolene) (muscle relaxant)

malignant hyperthermia

70 3-6
5-hydroxy dantrolene
6-9
15.5
(volume of distribution) 36.4 1

ryanodine ryanodine receptor type1

myoplasmic calcium
cardiac ryonide receptor (RYR-2)

48

19

1. malignant hyperthermia

2. neuroleptic malignant syndrome

(hepatitis) (cirrhosis)

1.

2.

3. thrombophlebitis tissue necrosis

central vein

4. (thrombocytopenia)

5. anaphylaxis (urticarial)

6.

7. (thrombocytopenia) aplastic anemia

1. calcium channel blocker verapamil , amlodipine , cinnarizine

hyperkalemia cardiovascular collapse

2. carbamazepine carbamazepine

3. benzodiazepine, opioid (respira-

tory depression)

4. methotrexate methotrexate

20

malignant hyperthermia 2-3 /

intravenous bolus 2-3 / 15 hypermetabolism

10 / skeletal muscle
hypermetabolism 30 hypermetabolism
1 / 6 . 24

neuroleptic malignant syndrome 1 /

5-10 10 /

sterile water 60

1. Krause T, Gerbershagen MU, Fiege M, Weisshorn R, Wappler F. Dantrolene--a review of its pharmacology,
therapeutic use and new developments. Anaesthesia. 2004;59(4):364-73.
2. Olson KR. Poisoning and Drug Overdose. 6th edition. New York: McGraw-Hill Professional; 2012.
3. FACMT MWSMMFFF, FACMT SWBMMF, MD MB. Haddad and Winchesters Clinical Management of
Poisoning and Drug Overdose. 4 edition. Philadelphia: Saunders; 2007. p1584.
4. Lewin N, Howland MA. Goldfranks Toxicologic Emergencies. 9th edition. New York: McGraw-Hill
Professional; 2010. p1968.

21


(Naloxone)

opioid agonists

agonist, antagonist, partial agonist-antagonist (naloxone)

..19601 opioids

pure antagonist affinity opioid receptors opioid agonist

displace opioid agonist reversible2

Opioid receptors 3 mu, kappa delta opioid receptors, affinity

mu receptor receptor analgesia, sedation, miosis, euphoria, respiratory depression

decreased gastrointestinal motility opioids1

Onset of action : intravenous (IV) 1-2 , subcutaneous (SC) 5.5 , intralingual

30 , intranasal (IN) 3.4 , inhalation 5 , intramuscular (IM) 6 , endotracheal 60

(bioavailability) 6, distribution half-life 5 ,

(volume of distribution) 0.8-2.64 1 , elimination half-life 60-90

2-3 , duration of action 20-90
glucuronide1

narcotic depression respiratory depression opioids

(severe respiratory depression) opioids3

22



opioids acute
opioid overdose2

(intravenous; IV)

opioids fetus
cardiac irritability3

opioids 4

- (withdrawal symptoms) opioids

30-60 opioids

- (seizures)

opioid

- (cardiac arrest)

- (tachycardia) opioids

- (pulmonary edema) neurogenic pulmonary

edema centrally mediated massive catecholamine response shift blood

volume pulmonary vascular bed hydrostatic pressures

alveoli

- flushing, hot flashes, hypo- or hypertension, hallucination

23

(SC)

(IM)5 (IN) endotracheal tube

2 opioids
opiates

respiratory

depression

opioids
opioids (to have adequate respiration, but avoid opioid withdraw)

- opioid non-dependence 0.4

- opioid dependence 0.04

(titrate) 0.4 respiratory depression

2 , 4 8-10 10

1

maintenance dose mainte-

nance infusion 30-90

opioid methadone 24

- Maintenance dose 2 3 adequate respiration

dose drip titrate

bolus dose dose adequate respiration

titrate 1

24

- IV infusion opioids

dose methadone sustained

release drip 12-24
2
2 opioids respiratory depression
2
1

DBL Naloxone Hospira injection vial

1 0.4 5 vials3

1. Howland MA, Nelson LS. Antidotes in depth (A6): Opioid antagonists. In: Nelson LS, Lewin NA, Howland MA,
Hoffman RS, Goldfrank LR, Flomenbaum NE, eds. Goldfranks Toxicologic Emergencies. 9th edition. China:
The McGraw-Hill Companies, Inc.; 2011:579-585.
2. Barnett V, Twycross R, Mihalyo M, Wilcock A. Opioid antagonists. J Pain Symptom Manage. 2014;47(2):341352. doi:10.1016/j.jpainsymman.2013.12.223.
3. MIMS Thailand. DBL Naloxone. http://www.mims.com/Thailand/drug/info/DBL Naloxone/?type=brief. Accessed
September 14, 2015.
4. Wermeling DP. Review of naloxone safety for opioid overdose: practical considerations for new technology
and expanded public access. 2015. doi:10.1177/2042098614564776.
5. Clarke S, Dargan P. Towards evidence based emergency medicine: best BETs from the Manchester Royal
Infirmary. Intravenous or intramuscular/subcutaneous naloxone in opioid overdose. Emerg Med J. 2002;19(3):249.

25


(Sodium Nitroprusside)

(Sodium nitroprusside; SNP)

(ultra-short acting)
(hypertensive emergency)
(arterial vasoconstriction) ergotism

SNP (metabolized) smooth muscle cell nitric oxide (NO) active

metabolite NO guanylate cyclase cyclic GMP SNP

peripheral vascular resistance
venous return sodium nitroglycerin (NTG) NO NTG

SNP NTG

SNP

30
2 3 continuous intravenous drip
SNP NO cyanide cyanide
thiocyanate thiocyanate 3

26

1. hypertensive emergency

2. ergotamine peripheral arterial spasm

1. (compensatory hypertension)

coarctation of aorta

2. cyanide

cyanide

1.

2. cyanide (10-15 / /)

1 (lacticacidosis)
sodium thiosulfate sodium thiosulfate 10 1
sodium nitropusside

3. thiocyanate

3 / / 48
1 / / disorientation,
delirium, muscle twitching psychosis hemodialysis thiocyanate

4. methemoglobinemia SNP 10 /

1. 50 SNP 3 5% D/W

5% D/W 250, 500 1000 200, 100 50 /

aluminum foil

27

2. 0.3 //

3 //

SNP 50 (lyophilized powder)

1. Chu J. Antimigraine medications. In: Robert S. Hoffman MAH, Neal A. Lewin, Lewis S. Nelson, Lewis
R. Goldfrank, ed. Goldfranks Toxicologic Emergencies. 10th ed. China: McGraw-Hill Companies; 2015.
2. NL B. Ergot Derivatives. In: Olson KR ed. Poisoning & Drug Overdose. 6th ed. New York: McGraw-Hill;
2012:202-204.
3. Baldwin ZK, Ceraldi CC. Ergotism associated with HIV antiviral protease inhibitor therapy. Journal of vascular
surgery. Mar 2003;37(3):676-678.
4. Michel T, Hoffman BB. Chapter 27. Treatment of Myocardial Ischemia and Hypertension. In: Brunton LL,
Chabner BA, Knollmann BC. eds. Goodman & Gilmans The Pharmacological Basis of Therapeutics, 12e. New
York, NY: McGraw-Hill; 2011.
5. Benowitz NL. Antihypertensive Agents. In: Katzung BG, Trevor AJ. eds. Basic & Clinical Pharmacology, 13e.
New York, NY: McGraw-Hill; 2015.

28

29

30


(Common toxidromes)

(neurotransmitter) toxidrome
serotonin syndrome, sympathomimetic, opioid toxidrome
neurotransmitter (receptor) toxidrome sympatholytic
neuroleptic malignant syndrome toxidrome
Serotonin syndrome

Serotonin syndrome serotonin tramadol,

Selective serotonin re-uptake inhibitor (SSRI), MDMA (3,4-methylenedioxy-methamphetamine; ecstasy)

dextromethrophan
serotonin receptors central peripheral receptors 5HT-2A receptor1

serotonin syndrome

6
1 serotonin
syndrome

serotonergic drugs

myoclonus, tremor, hyperreflexia

31

 1 serotonin syndrome2
Symptom Cluster

Altered Mental Status

Neuromuscular Abnormalities

Autonomic Hyperactivity

Symptomatology
Agitation
Anxiety
Disorientation
Restlessness
Excitement
Tremors
Clonus
Hyperreflexia
Muscle rigidity
Bilateral Babinski signs
Akisthesia
Hypertension
Tachycardia
Tachypnea
Hyperthermia
Mydriasis
Diaphoresis
Dry mucous membranes
Flushed skin

criteria 2 criteria
1. Hunter criteria
Hunter Serotonin Toxicity Criteria: Decision Rules
In the presence of a serotonergic agent:
1. IF (spontaneous clonus = yes) THEN serotonin toxicity = Yes
2. ELSE IF (inducible clonus = YES) AND [(agitation=yes) OR (diaphoresis = yes)] THEN serotonin
toxicity = YES
3. ELSE IF (ocular clonus = yes) AND [(agitation = yes) OR (diaphoresis = yes)] THEN serotonin
toxicity = yes
4. ELSE IF (tremor = yes) AND (hyperreflexia = yes) THEN serotonin toxicity = yes
5. ELSE IF (hypertonic = yes) AND (temperature> 38oC) AND [(ocular clonus = yes) OR (inducible
clonus = yes)] then serotonin toxicity = YES
6. ELSE serotonin toxicity = No

32

2. Sternbachs criteria3
1.Recent addition or increase in a known serotonergic agent
2.Absence of other possible etiologies (infection, substance abuse, withdrawal, etc.)
3.No recent addition or increase of a neuroleptic agent
4.At least three of the following symptoms:

Mental status changes (confusion, hypomania)

Agitation

Myoclonus

Hyperreflexia

Diaphoresis

Shivering

Tremor

Diarrhoea

Incoordination

Fever

Hunter criteria (sensitivity) (specificity) Sternbachs

criteria (84 75 ), (97 96 )4

serotonin syndrome 6-24 5
serotonin syndrome

serotonin

cyproheptadine nonspecific serotonin antagonism

4-8 1-4
32 /
0.25 / 1 / 6
12 /

33

extrapyramidal syndromes (EPS)

EPS dopamine receptor

Acute dystonia

5 acute dystonia 2-5

acute dystonia

Benztropine

- 2 IV/IM

- 0.05 / 1 2

- 50 IV/IM

Diphenhydramine

- 1 / 1 50

- 0.1 / 1 IV

Diazepam
Akathisia

acute dystonia
benzodiazepines
Parkinsonism

parkinsonism Parkinsons disease akinesia,

rigidity postural instability

Tardive dyskinesias

orobuccal masticatory movement disorder

typical
antipsychotics

34

Neuroleptic Malignant Syndrome (NMS)

NMS serotonin syndrome NMS
dopamine (central nervous system; CNS)
serotonin syndrome 2
altered mental status, muscle rigidity autonomic dysfunction muscle rigidity
lead pipe rigidity
2 neuroleptic malignant syndrome6
Feature
Altered mental status
Motor symptoms
Hyperthermia
Autonomic instability

Potential Manifestations
Delirium, lethargy, confusion, stupor,
catatonia, coma
Lead pipe rigidity, cogwheeling, dysarthria
parkinsonian syndrome, akinesia, tremor
dystonic posture
Body temperature > 38 oC
Tachycardia, diaphoresis, sialorrhea,
hypertension or hypotension, cardiac
dysrhythmias

Neuroleptic Malignant Syndrome

dantrolene 1
/ 1 IV 5-10
10 / 1 dantrolene bromocriptine
dopamine agonist 2.5-10 3-4
Sedative-hypnotic toxidrome

gamma aminobutyric acid (GABA) receptors

chloral hydrate, gamma-hydroxybutyrate (GHB), benzodiazepines,

Z-drugs ( zolpidem, zopiclone ) GHB
7 amnesia

35

Sympathomimetic toxidrome

Sympathomimetic toxidrome

sympathetic beta alpha receptors

sympathetic hypertension, tachycardia, hyperthermia
rhabdomyolysis

methamphetamine, MDMA methcathinone8
sympathetic benzodiazepine sympathetic
beta blocker

1. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005 Mar 17;352(11):1112-20.
2. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J. 2013 Winter;13(4):533-40.
3. Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991 Jun;148(6):705-13.
4. Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple
and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003 Sep;96(9):635-42.
5. Christodoulou C, Kalaitzi C. Antipsychotic drug-induced acute laryngeal dystonia: two case reports and a mini
review. J Psychopharmacol. 2005 May;19(3):307-11.
6. Juurlink Dn. Pychotropic medications. In: Nelson LS, Hoffman RS, Lewin NA, Goldfrank LR, Howland MA,
Flomenbaum NE, editors. Goldfranks toxicologic emergencies. 9 ed. New york: McGraw-Hill; 2011. p. 1003-15.
7. Busardo FP, Jones AW. GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood
and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome. Curr Neuropharmacol. 2015
Jan;13(1):47-70.
8. Glennon RA, Yousif M, Naiman N, Kalix P. Methcathinone: a new and potent amphetamine-like agent.
Pharmacol Biochem Behav. 1987 Mar;26(3):547-51.

36


(Case study: Rodenticide poisoning)

34

18

1

1.

20-40

2.

24

3.

-
3-4

4.

1
rhabdomyolysis
spinal seizure 30-60

37





bromadiolone superwarfarin

warfarin superwarfarin

enzyme vitamin K epoxide reductase enzyme vitamin K

quinone reductase vitamin K active form vitamin K dependent coagulation
factor (factor II, VII, IX, X) active form 2,3 ( 1)

coagulation factor activity 25% coagulation

factor half-life factor VII 4-6 coagulation factor active

form 18 (3-4 half-life factor VII)
prothrombin time INR 24-48 2,3

24-48 prothrombin
time INR
superwarfarin warfarin

superwarfarin broadifacoum, bromadiolone, difenacoum

1-2 warfarin 35 superwarfarin potency

warfarin 100 4-7

prothrombin time INR 24 48

2,3
38

1/1 3

complete blood count, prothrombin time, INR

fresh frozen plasma15-20./ 1

prothrombin complex concentrate, factor eight inhibitor bypass activity (FEIBA),
recombinant factor VIIa vitamin K1 10 . 5 8-10

vitamin

K1 warfarin warfarin8,10
( 4)

superwarfarin prolong prothrombin time INR

vitamin K1 25-50 ./ 3-4 prothrombin time INR 8-12

vitamin K1
prothrombin time INR vitamin K1
vitamin K1 6-7
()

partial thromboplastin time, prothrombin time, INR 20

Partial thromboplastin time 32 (22-33), Prothrombin time > 200 (10.5-13.5), INR >17
vitamin K1 40 . 4
prothrombin time, INR prothrombin time INR
12 vitamin K1: Prothrombin time 144.4 (10.5-13.5), INR 13.71
24 vitamin K1: Prothrombin time 47.6 (10.5-13.5), INR 4.42
48 vitamin K1: Prothrombin time 14.3 (10.5-13.5), INR 1.22
vitamin K1 40 . 4
vitamin K1

39


1. Burkhart KK. Rodenticides In Brent J, Wallace KL, Burkhard KK, Phillips SD, Donovan JW; editor. Critical Care
Toxicology Diagnosis and Management of the Critically Poisoned Patient. Pennsylvania. Elsevier Mosby, 2005
(ISBN: 0815143877, 9780815143871); 963-73.
2. Suchard JR, Curry SC. Oral Anticoagulant. In Brent J, Wallace KL, Burkhart KK, Phillips SD, Donovan JW;
editor. Critical Care Toxicology Diagnosis and Management of the Critically Poisoned Patient. Pennsylvania.
Elsevier Mosby, 2005 (ISBN: 0815143877, 9780815143871); 695-9.
3. Chen BC, Su M. Antithrombotics. In Robert S. Hoffman, Mary Ann Howland, Neal A. Lewin, Lewis S. Nelson,
Lewis R. editors. Goldfranks Toxicologic Emergencies, Tenth Edition. McGraw-Hill Education, 2015; 814-35.
4. Olmos V, Lpez CM. Brodifacoum poisoning with toxicokinetic data.Clin Toxicol (Phila). 2007 Jun-Aug;45(5):487-9.
5. Kruse JA, Carlson RW. Fatal rodenticide poisoning with brodifacoum. Ann Emerg Med. 1992 Mar;21(3):331-6.
6. Gunja N, Coggins A, Bidny S. Management of intentional superwarfarin poisoning with long-term vitamin K
and brodifacoum levels. Clin Toxicol (Phila). 2011 Jun;49(5):385-90.
7. Hong J, Yhim HY, Bang SM, Bae SH, Yuh YJ, Yoon SS, et al. Korean patients with superwarfarin intoxication
and their outcome.J Korean Med Sci. 2010 Dec;25(12):1754-8.
8. Garcia DA, Crowther MA. Reversal of Warfarin: Case-Based Practice Recommendations. Circulation. 2012;
125: 2944-2947
9. Koutrouvelis A, Abouleish A, Indrikovs A, Alperin J. Case scenario: emergency reversal of oral anticoagulation.
Anesthesiology. 2010 Nov;113(5):1192-7.
10. Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, et al.; American College of Chest Physi
cians. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of
Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest.
2012 Feb;141(2 Suppl):e152S-84S.

40


(Case study: Ergotism)

31
HIV Kaletar (lopinavir+ritonavir), lamivudine, tenofovir
3
1 2
2 2

: Vital signs: BT 36.5oC, PR 60 bpm, BP 116/70 mmHg, RR 20/min

HEENT: not pale conjunctiva, no icteric sclera

Lung: no crepitation, no wheezing

Heart: normal S1,S2, no murmur

Extremities: cold and clammy skin all distal extremities

Pulsation
Upper extremities

Right

Left

Axillar artery
Brachial artery
Radial artery
Lower extremities

Positive
Negative
Negative

Positive
Positive
Negative

Positive
Positive
Negative

Positive
Negative
Negative

Femoral artery
Popliteal artery
Dorsalis pedis artery

acute peripheral arterial occlusion both extremities ergotism

41

 ergotism

2
(acute limb ischemia)

2
ergots ergotamine ergotism
drug interaction protease inhibitor ergotamine
Ergotism 1
Ergotism

ergot alkaloids ergotamine, methysergide, dihydroergotamine, ergonovine

serotonin receptors central sympatholytic action
neuronal firing rate stabilize cerebrovascular smooth musculature
alpha adrenergic receptor
ergotamine

(cyanosis)
(gangrene)3 pulse pressure
renal artery
Ergotism
ergot alkaloids cytochrome 450 3A4 (CYP3A4)
inhibitor CYP3A44 protease Inhibitors (PI) (lopinavir, ritonavir, atazanavir)
statins (atrovastatin, simvastatin) immunosuppressives (tacrolimus, cyclosporine) azole (itraconazole, ketoconazole) macrolide antibiotics (erythromycin, clarithromycin)5
drug interaction (DI) ergot alkaloids ergotism
ergot alkaloids
Kaletar(lopinavir+ritonavir) protease Inhibitors CYP3A4
inhibitor ergotamine CYP3A4
42

 ergotamine ergotism
ergotism6
ergot alkaloid 1
(activated charcoal) drug interaction
ergot alkaloids CYP3A4 inhibitors
sodium nitroprussside 0.3
//
/ nifedipine 10 8 7
heparin low molecular weight
heparin
morphine

1. Chu J. Antimigraine Medications. In: Robert S. Hoffman MAH, Neal A. Lewin, Lewis S. Nelson, Lewis R.
Goldfrank, ed. Goldfranks Toxicologic Emergencies. 10th ed. China: McGraw-Hill Companies; 2015.
2. Baldwin ZK, Ceraldi CC. Ergotism associated with HIV antiviral protease inhibitor therapy. Journal of vascular
surgery. Mar 2003;37(3):676-678.
3. Marine L, Castro P, Enriquez A, et al. Four-limb acute ischemia induced by ergotamine in an AIDS patient
treated with protease inhibitors. Circulation. Sep 20 2011;124(12):1395-1397.
4. Eadie MJ. Clinically significant drug interactions with agents specific for migraine attacks. CNS drugs.
2001;15(2):105-118.
5. Ausband SC, Goodman PE. An unusual case of clarithromycin associated ergotism. The Journal of
emergency medicine. Nov 2001;21(4):411-413.
6. NL B. Ergot Derivatives. In: Olson KR, editor. Poisoning & Drug Overdose. 6th ed. New York: McGraw-Hill;
2012:202-204.
7. Kemerer VF, Jr., Dagher FJ, Pais SO. Successful treatment of ergotism with nifedipine. AJR. American
journal of roentgenology. Aug 1984;143(2):333-334.

43


(Case study: Opioid poisoning)

39
CC: 1
PI: 3 PTA:

1 PTA:

PH: Major depressive disorder migraine

PE: A Thai female patient, coma
BP 90/50 mmHg, PR 64 bpm, RR 4 bpm, BT 36.4oC, O2 saturation (room air) 90 %, capillary
blood glucose 98 mg/dL
HEENT: not pale, not icteric
Lungs: rhonchi both lungs.
Heart: normal S1S2, no murmur
Abdomen: soft, not tender, liver and spleen not palpable
Extremities: no pitting edema
Neuro: E1V1M1, pupils 1 mm both eyes, stiff neck negative, deep tendon reflex 1+ all , Babinskis
sign dorsiflexion both feet

44


Alteration of consciousness: coma
Bradyspnea with low oxygen saturation
Miosis
History of Major depressive disorder and migraine

1. opioids opioid
opioid toxidrome (CNS depression)
(respiratory depression) (miosis pinpoint pupils)
opioid meperidine

opioids

2. barbiturates phenobarbital
(coma) (hypothermia)
3. isopropanol
4. clonidine centrally acting antihypertensive methyldopa
(CNS depression)
(hypothermia)
5. ethanol ethanol (CNS
depression) (respiratory depression) (coma)
6. (brain stem) pontine hemorrhage

tricyclic antidepressants (TCA)
anticholinergic toxidrome
sodium channel blockade
potassium channel blockade (Electrocardiography, ECG)

45

 benzodiazepines

1.
O2 saturation pulse
oximeter

2. (capillary blood glucose)
glucose thiamine
3. (
< 12) opioids naloxone
opioids 1,2 naloxone 0.4 (
opioids 0.04
) naloxone
/ 2 2-3
2-4 naloxone 10

0.9% NSS naloxone

(0.4 ) 1 vial 3 vials

2-3

morphine syrup 50
alprazolam (0.5 ) 10
46


1. Boyer EW. Management of opioid analgesic overdose. N Engl J Med. 2012 Jul 12;367(2):146-55
2. Nelson LS, Olsen D. Opioids. In: Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR, editors.
Goldfranks Toxicologic Emergencies. 10th edition. New York:McGraw-Hill;2015.p.877-903

47

 1
(Case study 1: Snake bites)

1
CC: 5
PI:

- 5 .

- 2 . 1 .

- 1 .

. 5%D N/3 .

PH: 9
SH:

PE:

VS: BT 36.3oC, PR 158/min, RR 40/min (ventilator), BP 127/79 mmHg

GA&Neuro: unconscious, no spontaneous movement or breathing

pupils 2 mm. not react to light

Ext: right foot laceration wound 3 mm at dorsal side, swelling and redness right foot to mid-leg

Others: within normal limits

1.

2.

48

tetrodotoxin saxitoxin

1, 2

10 vials 100 .

Progress note:
Treatment
- ventilator support, 5%D N/3 IV rate 30 mL/hr
- Penicillin 100,000 U/kg/day
- Antivenom for cobra 100 mL drip in 2 hours
Progress

antivenom 6
extubation

2
Co-amoxiclav

49

1.

2.

ambu bag

3.

4.

5.

30

6. Co-amoxiclav penicillin

1. Rojnuckarin P, Suteparuk S, Sibunruang S. Diagnosis and management of venomous snakebites in Southeast

Asia. Asian Biomedicine 2012; 6 (6): 795-805
2. , . . ,
, . .
2555: 24-32

50

 2
(Case study 2: Snake bites)

20
CC: 2
PI: 2 ( 8:00 .)

PE:

VS: BT 37.1oC, PR 92/min, RR 20/min, BP 130/80 mmHg

Ext: fang marks 1 cm apart at right thumb with edema up to wrist
Others: within normal limits

1, 2

1.

2.

3. 20WBCT, CBC, prothromibin time, INR

4. 3

5.

6.

7.

- (systemic bleeding)

- Unclotted 20WBCT INR > 1.2

- Platelet count 50,000/cu.mm.

- compartmental syndrome

8.

9. prophylactic antibiotic

10. (tetanus prophylaxis)

51

Progress note:
CBC, Prothrombin time 20WBCT - clotted
paracetamol
3

PE: GA: no ecchymosis, no petechiae

Ext: more swelling of right hand, palpable digital pulse, no ulcers, no blebs

: platelet count 100,000, 20WBCT unclotted, Prothrombin time: INR 1.0

unclotted 20WBCT

INR 1.1

unclotted 20WBCT (sensitivity) 85.7%

(specificity) 95.8% INR > 1.2 85.7% 95.6%

3 1 / (gold standard)
2

20WBCT
2 1. 2.

52

Progress note:

tramadol 6

clotted 20WBCT, INR 1.05

1 3
INR 1.0-1.05

1. Rojnuckarin P, Suteparuk S, Sibunruang S. Diagnosis and management of venomous snakebites in Southeast

Asia. Asian Biomedicine 2012; 6 (6): 795-805
2. , . . ,
, . .
2555: 24-32
3. Pongpit J, Limpawittayakul P, Juntiang J, Akkawat B, Rojnuckarin P. The role of prothrombin time (PT) in
evaluating green pit viper (Cryptelytrops sp) bitten patients. Trans R Soc Trop Med Hyg. 2012 Jul;106(7):415-8.

53

54

55

56

 1
3

1
2
3
4
5
6
7
8
9
10
11
12

Dimercaprol inj.
Sodium nitrite inj.
Sodium thiosulfate inj.
Methylene blue inj.
Diphtheria antitoxin inj.

arsenic, gold, mercury, lead, copper

Cyanide poisoning, Hydrogen sulfide
Cyanide poisoning
Methemoglobinaemia, Toxic encephalopathy ifosfamide
Diphtheria toxin

:
:

1.

2. EMCO www.emco.nhso.go.th

3.

4. Download 3

5. Upload .

6. . 5 Upload .

7.

57

7.1

1
2

Sodium thiosulfate inj.

Methylene blue inj.

7.2

1
2
3
4
5
6
7

(Polyvalent Haematotoxin)
(Polyvalent Neurotoxin)

:
1. 1367

2.

3. EMCO www.emco.nhso.go.th

4.

5. Download 3

6. Upload .

7. . 5 Upload .

58

1.
...................................................................................................................................
................. ............................... ...............................................................................
/ .............................................. / ................................................................
......................................... ...............................................................................
2.
PID ......................................................................................................................................................
.......................................................................................................................................
HN........................... AN.................................

.....................

.............................................................................................................................................................
3. ( )

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.

Dimercaprol inj.
Sodium nitrite inj.
Sodium thiosulfate inj.
Methylene blue inj.
Diphtheria antitoxin inj.

59

4.
- ...............................................................................................................................
................................................................. ...................................................
.......................................................... ............................................................................
5.

.................................................. ..........................

60

 2
Antidotes ()
Botulinum antitoxin inj. Diphtheria antitoxin inj.
1.

2553

Botulinum antitoxin inj. Diphtheria antitoxin inj.

2.

1. Botulinum antitoxin inj.

10 Vial

2. Diphtheria antitoxin inj.

2,000 Vial

1.1
1.2 . (.)
2.1
2.2 . .
2.3
2.4 4

61

3.

4.

./

/
/
Geographic Information System (GIS)
.
5.

Botulinum antitoxin Diptheria antitoxin 2

1 2

62

 1 Botulinum antitoxin
.
./.

. ./. .
. /

IF YES
. . Botulinum
antitoxin ./.
./.
./
. .

IF YES



1. .
.
2. .

2 Diphtheria antitoxin
.
./.

. ./. .
. /

IF YES
. Diphtheria antitoxin
./.
./.
.

DAT

IF YES

. . (4.)
GPO

1. .
2. .

GPO DAT
.

: 4 .
.

5.1 Botulinum antitoxin

2
1.

a. . .

63

b. . . . . . .

c. . Botulinum antitoxin . .

d. . .
. . .

e. .

f.

2.

a.

b. Botulinum antitoxin .

c. . .

. .

d. .

e.

5.2 Diphtheria antitoxin

1.

a. . .

b. . . . . . .

c. . Diphtheria antitoxin
. .

d. .

e. . . . .

64

2.

a.

b. Diphtheria antitoxin .

. . .

c. . .

. .

d. .

65

.....................................................................................................................................................

66

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.

Sodium nitrite inj.

Sodium thiosulfate inj.
Succimer cap
Methylene blue inj.
Dimercaprol inj.
Calcium disodium edetate inj.
Botulinum antitoxin inj.
Diptheria antitoxin inj.

Diphenhydramine inj.

3%*10 ml
25%*50 ml
100 mg/cap
10 mg/ml (10 ml)
200 mg/ml,
3 ml in oil
200 mg/ml,
5 ml in oil
Vial
Vial
Vial
Vial
Vial
Vial
Vial
Vial
Vial
Vial

67

. 02-2520161-4 125
8.3016.30 .

Email address: queensaovabha@hotmail.com

Website: www.saovabha.com

4 . 10330

68

. 02-4197007

. 02-4197317-8
24

Website: www.si.mahidol.ac.th/th/division/shtc/Home_shtc.html
: 3 6
2 10700

69

( 30 )
24

Line ID: poisrequest

Email address: poisrequest@gmail.com
Website: www.ra.mahidol.ac.th/poisoncenter/

PoisonCenter.mahidol.ac.th

: 1
6 . 10400

70


..

..

..

..

..

..

..

..

..

..