metoclopramide - 花蓮慈濟醫院 hualien tzu chi hospital · 2017. 6. 7. · (a) metoclopramide...

Metoclopramide

與 EPS 案例分析

東基廖若華藥師

103-0607

The Pathophysiology of N/V

NEJM 2005;352:817-825

1

2

3

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(A) Metoclopramide promotes gut motility by inhibiting

presynaptic and postsynaptic D2 receptors as well as presynaptic

5-HT4 receptors.

(B) Metoclopramide also produces antiemetic effects by

inhibition of D2 and 5-HT3 receptors in the CTZ. CTZ: Chemoreceptor trigger zone ; GI: Gastrointestinal.

Mechanism of action of

metoclopramide

Extrapyramidal symptom (EPS)

Extrapyramidal

symptom (EPS)

引起 EPS 的藥物治療 EPS 的藥物

Acute dystonias

Benzatropine

Diphenhydramine

Acute akathisia β-blockers

Parkinsonism Anticholinergic medication

Tardive dyskinesia

Benzodiazepines,

Dopaminergic drugs,

Dopamine depleters

(Reserpine,Tetrabenazine),

Tocopherol Pierre JM. Extrapyramidal symptoms with atypical antipsychotics:

incidence, prevention and management.

Drug Saf. 2005; 28: 191-208.

Basic Data

--------------------------------------------------------------------------------

Marital status: married

Race/ethnicity: Taiwanese

Occupation/personal description: other no

Relevant past history/active medical problems: with a history of old CVA

with left side weakness, bilateral renal stone s/p ESWL, HIVD s/p

Admitted/transferred from: admitted from the Emergency Department

Source of information: family member

Reliability of source: good

Adverse drug reaction : Aspirin (97/07/03)

Ambulatory status on admission: bed-bound

Chief Complaints

--------------------------------------------------------------------------------

turbid urine recently days and consciouness since this morning.

Present Illness

--------------------------------------------------------------------------------

This 74-year-old female is a patient of 1). old CVA with left side

weakness 2). DJD s/p laminectomy 10 years ago. 3).left renal stone s/p

ESWL and right renal atrophy. She had regular medical control at MMH.

This time, she has bedridden for about 4 month. This time, she has

suffered from turbid urine for about 3 days and consciouness drowsy

since this morning. Therefore, she was brought to our ER for help. She

denied fever, cough and abdominal pain.

At ER, BT 37.1 degrees, pyuria and turbid urine was noticed.

Laboratory revealed WBC 21250/ul with seg 93%, Hb 7.3, BUN 58.5,

Cr 3.1. Thus, under the impression of urinary tract infection, she was

admitted to our ward for the further management.

Past Medical History

-----------------------------------------------

[ Past Medical History ]

Operation: Yes

1. DJD s/p laminectomy 10 years ago.

2. left renal stone s/p ESWL and

right renal atrophy

[最近一個月本院門診有效用藥]: 無

[外院用藥]

Mgo 1# bid

Rivotril (0.5) 1# hs

Piracetam 1#qd

Arcoxia (60) 1# qd

[其他療法]: 無

Family History

--------------------------------------------

[ Family History ]

1.Diabetes mellitus: Unknown

2.Hypertension: Unknown

3.Myocardial infarction: Unknown

4.Malignancy: Unknown

5.Stroke: Unknown

6.Sudden Death: Unknown

7.Others: No

[ Hereditary Disease ]

1.G6PD deficiency: Unknown

2.Thalassemia: Unknown

3.Others: No

Personal and Social History

--------------------------------------

[ Personal and Social History ]

1.Alcohol (喝酒) : No

2.Tobacco (吸菸) :No

3.Betel Nut (檳榔) :No

4.Street drug/IV drug :No

Review of Systems

-----------------------------------------------------------------------

General conditions:

fever(-),chills(-),change of appetite(-),◆fatigue(+),body weight loss(-),

Urogential: ◆Foley tube: turbid urine (+),

frequency(-),urgency(-),dysuria(-),hematuria(-),oliguria(-)

Physical Exam

-----------------------------------------------------------------------

General appearance: acute ill looking

GCS E4M5V4

Abd : soft, distension(-), tenderness(-), no rebounding pain

shifting dullness(-)

Hepatomegaly(-),◆ turbid urine (+),

bowel sound: normoactive

Radiology

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檢查類別: RT 一般Ｘ光 (2013-01-23 09:17:31)

臨床診斷:

*chief complaints:

Conscious disturbance this morning

Recurrent UTI

Old CVA. lacunar infarction

結果描述:

chest PA:

S/P IF of T-L spine.

tortuous T-aorta.Cardiomegaly.

mild infiltration,RLL & LLL.

KUB:

lumbar spondylosis & scoliosis.

A stone of GB. ASVD of abdominal aorta.

intestinal ileus.

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Specific Findings

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turbid urine

pyuria

Conscious disturbance

Tentative Diagnosis

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1. Urinary tract infection

2. old CVA with left side weakness

3. acute on chronic renal failure

4. anemia

Plan and Goals of Management and Treatment

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< Patient's medical needs >

1. antibiotic with Cefazolin

2. f/u blood culture and urine culture

3. IVF support

4. f/u stool OB due to anemia

01/23--01/26

01/23--01/30

01/23--01/30

02/02--02/04

Radiology

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檢查類別: CT 電腦斷層 (2013-01-30 03:52:48)

結果描述:

CT scan of brain without contrast enhancement with 5 & 10mm intervals:

Multiple oval small low attenuation(cystic) spots(<5mm) on bil.basal

ganglia,suggestive of enlarged perivascular spaces.

No intracranial hemorrhage,infarct or occupied lesion.

No significant brain swelling.

No deviation of midline structure.

Diffused cerebral atrophy.

Cavum septum pellucidum with cavum vergae is evident.

IMP: 1.PVSs,bil.basal ganglia.

2.Cerebral atrophy.

3.Cavum septum pellucidum with cavum vergae.

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Discharge Medications

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Iwell 1# TID PO X 14day 共 42 tab

Sennosides (12mg/tab) 2# HS PO X 14day 共 28 tab

Hospital Course

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Patient received Foley catheterization and hydration. Cefmetazole 1.0gm iv q12h was also

given. N/S 500ml iv drip and Na supplement by oral. PRBC 2 u iv drip was done due to

chronic anemia. However, EPS after primperan medication was noted during hospitalization.

Patient's condition was getting better gradually. So, she was discharged on 102-02-05.

Discharge Diagnosis

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1. Urinary tract infection

2. Hyponatremia

3. Aute on chronic renal failure

4. Lumbar spodylosis s/p Laminectomy

5. EPS, caused by primperan medication

Complication

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EPS by primperan 1 # Tid

東基 ADR 登錄

-------------------------------------------------------------------------- 發生日期: 2013/01/28 登錄日期: 2013/02/01 通報者: 內科NSP

藥品名稱: Metoclopramide (Primperan) [中度]

症狀描述: EPS and focal seizure

不良反應結果: 延長住院時間 ; 停藥 [並投與解藥]

ADR類型 : Nervous system disorders

處置方式: 停藥 [並投與解藥]

通報事件描述: 在服用 Primperan 後,出現右臉及右上肢抽慉

------------------------------------------------------------------ [ Subject Finding ]

Epigastric/upper abdominal pain since 7days, had before few

times, slow onset,

associated w nausea(+), vomitting x1 , stools x1/days, Appettite OK

smoker(5cig/day), OH(heavy drinking rice wine 3/30 to 4/1), betel(-)

cough(-), sputum(-), dyspnea(-), fever(-)

PHx:

[ Object Finding ]

Seems well, minimal distress, BT 36.8 ℃

palmar erythema(+) clubbed(-) x2wspider nevi

Abdo: mild non local tenderness epig(+), guarding(-), rebound(-), L

(-), S(-), K(-), K(-), no distension, normalBS

chest: clear TML AE&PN R=L

CVS: S1S2NB, edema(-), JVP(-),

----------------------------------------------------------------------------------

535.00 Y N Acute gastritis, without mention of hemorrhage

--------------------------------------------- [ Subject Finding ]

Seen ER 4/4 w gastritis, today jaw and arm feel tight and

cannot unclench muscle

smoker(5cig/day), OH(heavy drinking rice wine 3/30 to 4/1),

betel(-), cough(-), sputum(-), dyspnea(-), fever(-)

PHx: on meds Psych OPD from VGH Taitung for Anxiety

[ Object Finding ]

Seems well, minimal distress, BT 37 ℃

clenched jaw muscles

clenched forearm muscles

palmar erythema(+) clubbed(-) x2wspider nevi

Abdo: mild non local tenderness epig(+), guarding(-),

rebound(-), L(-), S(-), K(-), K(-), no distension, normalBS

chest: clear TML AE&PN R=L

CVS: S1S2NB, edema(-), JVP(-),

A: r/o EPS vs Anxiety

improved after vena, advised to stop metoclopramide tabs

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333.99 Y N Other extrapyramidal diseases and abnormal movement disorders

東基 ADR 登錄 -----------------------------------------------------------

發生日期: 1020405 登錄日期: 2013/04/05

通報者: 急診醫師

藥品名稱: Metoclopramide (Primperan) [輕度]

症狀描述: spasms forearm and jaw

不良反應結果: 其他 ( Diphenhydramine IM )

ADR類型 : Nervous system disorders

處置方式: 停藥 [並投與解藥]

通報事件描述: spasms forearm and jaw

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小於1歲 1~18歲 19~30歲 31~40歲 41~50歲 51~64歲大於65歲

EPS 相關通報案件

案

件

數

年齡分布 Drug Safety Newsletter 2012 December vol. 40

EPS 通報個案基本資料(n=565)

項目 No. 項目 No.

Drug Safety Newsletter 2012 December vol. 40

1歲以下 EPS 個案基本資料


18歲以下 EPS 個案基本資料(n=59)

項目 No. 項目 No.


18歲以下EPS個案不良反應分析


器官系統分類 / 症狀 No.

Extrapyramidal Reactions Populations most at risk for extrapyramidal reactions include young women, children, the elderly, diabetics, patients with

neurologic disorders and patients taking concurrent neuroleptic medications.[61,62] Genetic factors may also play a role

as polymorphisms of CYP2DG have been demonstrated to decrease themetabolism of metoclopramide and increase the

risk for extrapyramidal reactions.[63] The incidence of these reactions also increases in patients receiving higher

intravenous doses. In 479 reports of metoclopramide-related extrapyramidal reactions in the UK from 1967–1982, 455

were for acute dystonias, 20 for parkinsonism and four for TD.[64]

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62







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Acute Dystonic Reactions Acute dystonic reactions are the most frequent extrapyramidal side effects (EPS) from metoclopramide and typically

occur within 24–48 h of initiating treatment, thus affecting approximately 0.2–6% of patients taking metoclopramide and

the incidence increases with higher doses.[64] Dystonia consists of spasmodic or sustained involuntary muscle

contractions resulting in twisting, repetitive movements or abnormal postures. It can present as facial spasm, torticollis,

oculogyric crisis, trismus, tortipelvic (abdominal rigidity) or opisthotonic (spasm of the entire body). Acute dystonic

reactions typically resolve with discontinuation of the drug.[65]

65

Akithisia Akithisia presents with subjective feelings of inner restlessness as well as objective findings of motor restlessness.

Incidence ranges from 10 to 25% depending on the mode of metoclopramide administration.[66,67] Oral and

intramuscular formulations have a lower rate of akithisia compared with intravenous administration. Furthermore, the

speed of administration of intravenous metoclopramide also appears to influence the risk of akithisia. In one report,

akithisia was reduced from 11.1 to 0% when 10 mg of metoclopramide were administered intravenously

over 2 versus 15 min.[68]

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Drug-induced Parkinsonism Prolonged therapy with metoclopramide can result in Parkinsonian-like symptoms, including bradykinesia, tremor and

rigidity. Incidence is unknown, but one series found a fourfold increased risk of developing drug-induced Parkinsonism in

those taking metoclopramide compared with controls.[65] Another series found that patients on metoclopramide had a

threefold increased risk of starting anti-Parkinsonian therapy compared with nonusers.[69] Parkinsonian symptoms

generally resolve within 2–3 months of discontinuation of metoclopramide.

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Tardive Dyskinesia The most feared complication of chronic metoclopramide use is TD, which is characterized by involuntary movements of

the face, tongue or extremities. National guidelines[59,70] suggest the prevalence of TD ranges from 1 to 15% after usage

of metoclopramide for at least 3 months and may not reverse even after discontinuation of the medication.[16,65] As a

result, in 2009, the FDA came out with a black-box warning that must be attached to all metoclopramide labeling, which

warns against chronic use except in rare cases. However, a recent review by Rao et al. estimated the risk of TD from

metoclopramide use to be less than 1%, much less than the estimated 1–15% suggested by national

guidelines.[14] Interestingly, the use of metoclopramide and concurrent rise in metoclopramide-induced TD has been

increasing since 2000, which is also the year that Cisapride (Apotex Inc., Ontario, Canada) was withdrawn from the

market.[16]

16

Tardive Dyskinesia The most feared complication of chronic metoclopramide use is TD, which is characterized by involuntary movements of

the face, tongue or extremities. National guidelines[59,70] suggest the prevalence of TD ranges from 1 to 15% after usage

of metoclopramide for at least 3 months and may not reverse even after discontinuation of the medication.[16,65] As a

result, in 2009, the FDA came out with a black-box warning that must be attached to all metoclopramide labeling, which

warns against chronic use except in rare cases. However, a recent review by Rao et al. estimated the risk of TD from

metoclopramide use to be less than 1%, much less than the estimated 1–15% suggested by national

guidelines.[14] Interestingly, the use of metoclopramide and concurrent rise in metoclopramide-induced TD has been

increasing since 2000, which is also the year that Cisapride (Apotex Inc., Ontario, Canada) was withdrawn from the

market.[16]

14

Reference ● Avorn J, Gurwitz JH, Bohn RL, Mogun H, Monane M, Walker A. Increased incidence of levodopa therapy

following metoclopramide use. JAMA 274(22), 1780–1782 (1995).

● Regan LA, Hoffman RS, Nelson LS. Slower infusion of metoclopramide decreases the rate of akathisia. Am. J. Emerg. Med. 27(4), 475–480 (2009).

● Ganzini L, Casey DE, Hoffman WF, McCall AL. The prevalence of metoclopramide-induced tardive dyskinesia and acute extrapyramidal movement disorders. Arch. Intern. Med. 153(12), 1469–1475 (1993).

● Bateman DN, Rawlins MD, Simpson JM. Extrapyramidal reactions with metoclopramide. Br. Med. J. (Clin. Res. Ed.) 291(6500), 930–932 (1985).

● van der Padt A, van Schaik RH, Sonneveld P. Acute dystonic reaction to

metoclopramide in patients carrying homozygous cytochrome P450 2D6

genetic polymorphisms. Neth. J. Med. 64(5), 160–162 (2006).

● Pasricha PJ, Pehlivanov N, Sugumar A, Jankovic J. Drug insight: from

disturbed motility to disordered movement – a review of the clinical benefits

and medicolegal risks of metoclopramide.Nat. Clin. Pract. Gastroenterol.

Hepatol. 3(3), 138–148 (2006).

● Miller LG, Jankovic J. Metoclopramide-induced movement disorders.

Clinical findings with a review of the literature.

Arch. Intern. Med. 149(11), 2486–2492 (1989).

● Shaffer D, Butterfield M, Pamer C, Mackey AC. Tardive dyskinesia

risks and metoclopramide use before and after U.S. market withdrawal

of cisapride. J. Am. Pharm. Assoc. (2003) 44(6), 661–665 (2004).

● Rao AS, Camilleri M. Review article: metoclopramide and tardive dyskinesia.

Aliment. Pharmacol. Ther. 31(1), 11–19 (2010).

● Metoclopramide in the treatment of diabetic gastroparesis.

Expert Rev Endocrinol Metab. 2010;5(5):653-662. ● Drug Safety Newsletter 2012 December vol. 40 ● Taiwan J Oral Maxillofac Surg 21: 53-58, March 2010

metoclopramide - 花蓮慈濟醫院 hualien tzu chi hospital · 2017. 6. 7. · (a) metoclopramide...

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