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complications of

treatment

Sunsanee Pongpakdee MD.

Bhumibol Adulyadej hospital

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topics

1. a deadly headache

2. medication-overuse headache

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A deadly headache

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!"#$%&'()$* +,- 35 . /0$'1,$ +,02 3,$+,%,1

• !"#!$%&'( !$%&)*% 1 +,-(,.%/012&%3%$

• )4%,(, 02. 12/09/58

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!"#"$

• 1 ! )5(, -(,.% 02. (22/08/58) !"#607893 : ;%,, ?@BCD,?E(%)F&, ?!G(

&%H%IA%,%&:

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!"#"$

• 4 [!#%\ -(,.% 02. (2 [!#%\](.%) ^_I!"#!$%&

'(!$%&)*%`1 2 4%1 a".b3B(%I%0c% H,!$%&'(

!$%&)*%)=,d@"1Ce f1.%g0"HZ 02.

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!"#"$

• Zh$&I00. g0"H23 purple mottling skin appearance

on both foot (right > left) with poikilothermia and

paresthesia

• femoral/popliteal pulse 1+ & absent both dorsalis

paedis pulse i1[& acute arterial occlusion f1jk,(,

02.

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!"#"$

• 08>l%1 admit (2-8/09/58)

• Heparin 5000 unit IV bolus then 10000 unit IV drip

!J3 aPTT g%. heparin chart

•

(%I%0!"# c% )m, d@"1Ce

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!"#"$ • 3 +,-(,.% 02. (09/09/58) ^_I!"#!$%&'( !$%&)*%.%I ?@)o&"?@Ce ?@c% ?@)m, ?@?;jp&%JI7%

• 1 +,-(,.% 02. (11/09/58) !"#6078)>'(,)q. pain score6/10 a".b3B(%I%0!"#!$%&'(!$%&)*%.%IT, f1P,&%XY !"#6078)N#d)>r(1 Cs1$8 1 )N# )p% I$%1+, )m, (%I%0

!"#?@ST,• 7 M"/.1 -(,.% 02. (12/09/58) !"#!$%&'( !$%&)*%.%IT,)t(& : !$%&'( !$%&)*%)!u&,)=,d@"1Ce f1.%g0"HZ ER

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%$&'(!)*

• /0C!08vw" HIV infection xyHz&{ 2555 JI7%Z

02.|0%},0%~0 J3!08K%,&%i•)i.(

• Lopinavir / ritonavir

• Lamivudine (150) 1 tab oral q 12 hrs

•

Efavirenz (600) 1 tab oral od

• Tenofovir (300) 1 tab oral od

• Atorvastatin (40) 1 tab oral hs

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*$+,-".#"/

• Vital signs: BT 37c, BP 120/90 mmHg, HR 100/min,

RR 18/min

• Systemic and neuro examinations are

unremarkable

• no sclerodactyly, no digital pitting scar, no

mechanic hands

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*$+,-".#"/

• Extremities: paresthesia, poikilothermia

• violaceous and mottling skin of both hands and feet

• Pulse: Right Left

• Brachial 2+ 2+

• Radial* 1+ 1+

• Femoral 2+ 2+• Poplitial 2+ 2+

• Dorsalis pedis* 1+ 1+

• Posterior tibial 2+ 2+

see pictures

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Ergotismas a complication of

drug interaction

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Ergotism

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What is ergot?

• fungal infection of Rye

• Claviceps Purpureas

• produce Ergot alkaloids

• cause vasoconstriction andhallucination

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Claviceps PurpereasRye ergot

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Ergot alkaloids

• derivatives: dihydroergotamine, bromocriptine

• structures similar to catecholamine, serotonin,

dopamine

• half life 2-4 hr

• but vasoconstrictive effect may last 24 hr.

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metabolism

• by CYP3A4

• drug interaction:

• Protease inhibitor: ritonavir

• Macrolide: erythromycin, clarithromycin

• Azole anti fungal

• caffeine increase absorption of ergot

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Ergotism

• fungal infected rye consumption

• female smoker and migraineur taking ergotamine

• overdosage

• drug interaction!

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clinical presentations

• gangrenous: limb burningpain, ischemia

• convulsive: pins & needles,

hallucination, convulsion

St. Anthony

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• gangrenous: limb burning

pain, ischemia

• convulsive: pins & needles,

hallucination, convulsion

dancing mania 1642

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management

• stop vasoconstrictive

• volume expansion

• vasodilators

• anticoagulant

• thrombolysis / angioplasty

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medication-overuse

headache

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medication-overuse headache

• prevalence 1-2%

• 3:1 female to male

• common in midlife

• higher in low economic status, higher BMI


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• prevalence 1-2%

• 3:1 female to male

• common in midlife

• higher in low economic status, higher BMI


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• middle-aged lady with long history of migraine*/

tension type headache

• history of overuse for 4-5 years

• more frequent headache

• pain - tension type/ migraine/ others


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• often have episodic headache history

• taking acute medication > 2 days per week

• gradual transformation (severity, frequency)

• headache characters vary


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• usually morning (from nocturnal withdrawal)

• variable location; neck pain > 2/3

• autonomic: rhinorrhea, nasal congestion/ drip

• comorbid depression, anxiety


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diagnosis

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8.2 MOH Diagnostic criteria

A. Headachea present on "15 days/month fulfilling criteria C and D

B. Regular overuseb for "3 months of one or more drugs that can be

taken for acute and/or symptomatic treatment of headachec

C. Headache has developed or markedly worsened during medication

overuseD. Headache resolves or reverts to its previous pattern within 2 months

after discontinuation of overused medicationd

EFNS guideline 2011 International classification of headache disorders, 2nd edition

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Subtypes of MOH

8.2.1 Ergotamine-overuse headacheErgotamine intake on "10 days/month on a regular basis for >3 months

8.2.2 Triptan-overuse headache

Triptan intake (any formulation) on "10 days/month on a regular basis for

>3 months

8.2.3 Analgesic-overuse headache

Intake of simple analgesics on "15 days/month on a regular basis for >3 months

8.2.4 Opioid-overuse headache

Opioid intake on "10 days/month on a regular basis for >3 months

8.2.5 Combination analgesic-overuse headacheIntake of combination analgesic medicationsa on "10 days/month on a regular

basis for >3 months


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Subtypes of MOH

8.2.6 MOH attributed to the combination of acute medications

Intake of any combination of ergotamine, triptans, analgesics, and/or opioids on"10 days/month on a regular basis for >3 months without overuse of any single

class aloneb

8.2.7 Headache attributed to other medication overuse

Regular overusec for >3 months of a medication other than those described

earlier

8.2.8 Probable MOH

A. Headache fulfilling criteria A, C, and D for 8.2 MOH

B. Medication overuse fulfilling criterion B for any one of the subforms 8.2.1–82.7

C. One or other of the following:1. Overused medication has not yet been withdrawn

2. Medication overuse has ceased within the last 2 months, but headache has

not so far resolved or reverted to its previous pattern


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a

The headache associated with medication overuse is variable and often has a peculiar pattern with characteristics

shifting, even within the same day, from migraine like to those of tension-type headache.

b

Overuse is defined in terms of duration and treatment days per week. What is crucial is that treatment occurs bothfrequently and regularly, i.e., on 2 or more days each week. Bunching of treatment days with long periods without

medication intake, practised by some patients, is much less likely to cause MOH and does not fulfill criterion B.

c

MOH can occur in headache-prone patients when acute headache medications are taken for other indications.

dA period of 2

months after cessation of overuse is stipulated in which improvement (resolution of headache,

or reversion to its previous pattern) must occur if the diagnosis is to be definite. Prior to cessation, or

pending improvement within 2 months after cessation, the diagnosis 8.2.8 Probable MOH should be applied. If

such improvement does not then occur within 2 months, this diagnosis must be discarded.

a

Combination typically implicated are those containing simple analgesics combined with opioids, butalbital, and/or

caffeine.

b

The specific subform(s) 8.2.1–8.2.5 should be diagnosed if criterion B is fulfilled in respect of any one or more

single class(es) of these medications.

c

The definition of overuse in terms of treatment days per week is probably to vary with the nature of the medication.

International classification of headache disorders, 2nd editionEFNS guideline 2011

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A.Headache >15 d/month

B.Regular overuse for >3 months of >1 acute/symptomatic

treatment drugs:

1.Ergotamine, triptans, opioids, or combination analgesic

medications on >10 d/mo on a regular basis for >3 months

2.Simple analgesics or any combination of ergotamine,

triptans, or analgesics opioids on >15 d/mo on a regular

basis for >3 months without overuse of any single class alone

C.Headache developed or markedly worsened during medication

overuse

International classification of headache disorders, 2nd edition (revised)continuum 2012

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8.2 medication- overuse headache

(A) Headache occurring 15 or more days per month in a

patient with a preexisting headache disorder

(B) Regular overuse for more than 3 months of 1 or more drugs

that can be taken for acute and/or symptomatic treatment of

headache

(C) Not better accounted for by another ICHD-3 diagnosis

International classification of headache disorders, 3rd, 2013

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medication-overuse headacheSub-entities of Medication Overuse Headache

8.2 Medication-overuse headache

8.2.1 Ergotamine-overuse headache

8.2.2 Triptan-overuse headache

8.2.3 Analgesic-overuse headache

8.2.3.1 Paracetamol (acetaminophen)-overuse headache

8.2.3.2 Acetylsalicylic acid overuse headache

8.2.3.3 Other non-steroidal anti-inflammatory drug (NSAID)-overuseheadache

8.2.4 Opioid-overuse headache

8.2.5 Combination analgesic-overuse headache


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medication-overuse headacheSub-entities of Medication Overuse Headache

8.2 Medication-overuse headache

8.2.6 Medication-overuse headache attributed to multiple drug classes notindividually overused

8.2.7 Medication-overuse headache attributed to unverified overuse of multipledrug classes 8.2.8 Medication-overuse headache attributed to other medication

8.3 Headache attributed to substance withdrawal

8.3.1 Caffeine-withdrawal headache

8.3.2 Opioid-withdrawal headache

8.3.3 Oestrogen-withdrawal headache

8.3.4 Headache attributed to withdrawal from chronic use of other substance


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risks

• headache frequency

• acute medication overuse

• white race

• less education

• previous marriage

• obesity

• DM.

• arthritis

• caffeine use

• stressful life

• head injury

• snoring


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chronification

• Butalbital 5 day use/month

• Opioid 8 day use/month

• NSAIDs 10-15 day use/month

• Triptans 10 day use/month


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chronification

• using acute medication for other indication in

patient with history of EM (episodic migraine)

• frequency of headache (esp.>10 days/month)


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prevention

• headache diary

• treatment for sustained pain-free response

• limit pain and acute treatment to < 10/month

• preventive medication if indicated


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treatment

1. wean off overused medications

2. established prevention (drug / non-drug)

3. provide acute medications (prevent further overuse)

4. educate patient and family


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withdrawal

• abrupt withdrawal / tapered withdrawal

• add preventive drug

• some use steroid during withdrawal

• relapse 30%


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summary 1

• Ergotism: vasoconstrictor, hallucinogenic

• complete clinical history

• aware of drug interaction!

• Education!


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summary 2

• Medication-overuse headache: not uncommon

• risks: headache frequency, acute medication (type,overuse)

• proper preventive medication in Episodic primary

headache

• Education!


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thank you

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" George Orwell , 1984

“Of pain you could wish only one thing: that it

should stop. Nothing in the world was so bad

as physical pain. In the face of pain there are noheroes.”

http://www.goodreads.com/author/show/3706.George_Orwell

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chronic daily headache

1. transformed (chronic) migraine + MOH.

2. chronic tension type headache + MOH.

3. new daily persistent headache + MOH.

4. hemicrania continua + MOH.

MOH= medication overuse headache Silberstein-Lipton Chronic daily headache classification system, 1994

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chronic migraineA. headache >15 d/m for 3 months

B. at least 5 prior migraine attacks

C. >8 days/month for 3 months with migraine headache C1 and / or C2

C1) unilateral

• throbbing

• moderate or severe

• aggravate by physical activity

• nausea and/or vomiting

• photophobia and photophobia

C2 ) relieved by triptans or ergot

D. no medication overuse/ other causes

International classification of headache disorders,2nd edition

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chronic tension-typeA.at least 10 episodes of B-E, >15 d/m, >3 months

B. headache last hours/continuous

• pressing/tightening (nonpulsatile) quality

•

mild or moderate

• bilateral

• no aggravation by walking stairs or similar routine physical activity

C.both of

•

no more than one of photophobia, phonophobia or mild nausea

• no moderate or severe nausea and no vomiting

D.use of analgesic/other

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new daily persistentA. headache within 3 days onset fulfil B-D

B. present daily, unremitting > 3 months

C. at least 2 of

• bilateral location

• pressing / tightening (nonpulsating) quality

• mild to moderate intensity

• not aggravated by routine physical activity

D. both of

• no more than one of photophobia, phonophobia or mild nausea

• neither moderate or severe nausea nor vomiting

E. no other causes

International classification of headache disorders,2nd edition

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Hemicrania Continua A. Unilateral headache fulfilling criteria B-D

B. Present for > 3 months, with exacerbations of moderate or greater intensity

C. Either or both of the following

1. at least one of the following symptoms or signs, ipsilateral to the headache

a) conjunctival injection and/or lacrimationb) nasal congestion and/or rhinorrhoea

c) eyelid edema

d) forehead and facial sweating

e) forehead and facial flushing

f) sensation of fullness in the earg) miosis and/or ptosis

2. a sense of restlessness or agitation, or aggravation of the pain by movement

D. Responds absolutely to therapeutic doses of indomethacin

E. Not better accounted for by another ICHD-3 diagnosis

2016 04 29 rcpt headache

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