gastro-intestinal system

35 Pages·2008·0.46 MB·English

© palliativedrugs.com Ltd.
1: GASTRO-INTESTINAL SYSTEM
Antacids ........................................................ 1 Guidelines:Managementof
Compoundalginateproducts ................ 2 opioid-inducedconstipation ............... 24
Simethicone ................................................ 3 Guidelines:Bowelmanagement
Antimuscarinics inparaplegiaandtetraplegia ............... 24
(anticholinergics) ..................................... 3 Psylliumhusk(Ispaghulahusk) ........... 26
Guidelines:Managementof Contact(stimulant)laxatives .............. 27
deathrattle ................................................ 9 Docusatesodium ................................... 28
Propantheline .......................................... 10 Lactulose .................................................. 30
Prokinetics ................................................ 11 Polyethyleneglycol ................................ 30
H -receptorantagonists ..................... 13 Magnesiumsalts ..................................... 31
2
Misoprostol ............................................... 16 Rectalproducts ...................................... 32
Protonpumpinhibitors ...................... 17 Productsforhemorrhoids ................ 34
Loperamide .............................................. 21 Pancreatin ................................................. 34
Laxatives .................................................... 22
ANTACIDS AHFS 56:04
Antacidstakenbymouthtoneutralizegastricacidinclude:
. magnesiumsalts
. aluminumhydroxide
. hydrotalcite/aluminummagnesiumcarbonate(notUSA)
. calciumcarbonate
. sodiumbicarbonate.
Magnesiumsaltsarelaxativeandcancausediarrhea;aluminumsaltsconstipate.Mostproprietary
antacidscontainamixtureofmagnesiumsaltsandaluminumsaltssoastohaveaneutral
impactonintestinaltransit.Withdosesof100–200mL/24hormore,theeffectofmagnesium
saltsincreasinglyoverridestheconstipatingeffectofaluminum.
Thesodiumcontentofsomeantacidsmaybedetrimentalinpatientsonsalt-restricteddiets,
e.g. those with hypertension or heart failure; Gaviscon.R liquid and magnesium trisilicate
mixture USP both contain 1.14mEq/10mL compared with 0.13mEq/10mL in Maalox.R
Antacid/AntiGas.R. Regular use of sodium bicarbonate may cause sodium loading and
metabolicalkalosis.Calciumcarbonatemaycausereboundacidsecretionabout2haftereach
dose,andregularusemaycausehypercalcemia,particularlyiftakenwithsodiumbicarbonate.
Aluminum hydroxide binds dietary phosphate. It is of benefit in patients with hyper-
phosphatemiainrenalfailure.Long-termcomplicationsofphosphatedepletionandosteomalacia
arenotanissueinadvancedcancer.
Hydrotalcite(notUSA)bindsbilesaltsandisofspecificbenefitinpatientswithbilesalt
reflux,e.g.aftercertainformsofgastroduodenalsurgery.
In post-radiation esophagitis and candidosis which is causing painful swallowing, an
aluminum hydroxide-magnesium hydroxide suspension containing oxethazine
(Mucaine.R; not USA), a local anesthetic, can be helpful. Give 5–10mL (without fluid)
15mina.c.&atbedtime,andp.r.n.beforedrinks.
This should be regarded as short-term symptomatic treatment while time and specific
treatmentoftheunderlyingconditionpermitshealingofthedamagedmucosa.Alternatively,
plainbenzocainesuspension150mg/mLcanbeused.
HPCFUSA 1
© palliativedrugs.com Ltd.
© palliativedrugs.com Ltd.
COMPOUNDALGINATEPRODUCTS
Thefollowingshouldbeborneinmind:
. the administration of antacids should be separated from the administration of EC tablets; direct
contact between EC tablets and antacids may result in damage to the enteric coating with
consequentialexposureofthedrugtogastricacid,andofthestomachmucosatothedrug
. apartfromsodiumbicarbonate,antacidsdelaygastricemptyingandmaytherebymodifydrug
absorption
. someproprietaryproductscontainpeppermintoilwhichmasksthechalkytasteoftheantacid
andhelpsbelchingbydecreasingthetoneoftheloweresophagealsphincter
. mostantacidtabletsfeelgrittywhensucked;somepatientsdislikethis
. someproprietaryproductsarefruit-flavored,e.g.Tums.R(chewabletablet)
. the cheapest products are magnesium trisilicate mixture USP and aluminum
hydroxidegelUSPgivenaloneorasamixture
. someantacidscontainadditionalsubstancesforuseinspecificsituations,e.g.sodiumalginate
(seebelow),simethicone(seep.3).
Nowadays,antacidsaregenerallyonlyusedp.r.n.foroccasionaldyspepsia;H-receptorantagonists
2
(seep.13)andPPIs(seep.17)areusedwhencontinuousgastricacidreductionisindicated.
COMPOUND ALGINATE PRODUCTS AHFS 56:04
Includedforgeneralinformation.Alginateproductsaregenerallynotrecommendedasantacidsin
palliativecarepatients.
Class:Alginate.
Indications: Acidreflux(‘heartburn’).
Pharmacology
Alginatespreventesophagealrefluxpainbyforminganinertlow-densityraftonthetopoftheacidic
stomachcontents.Bothacidandairbubblesarenecessarytoproducetheraft.Alginateproductsmay
thus be less effective if used with an H-receptor antagonist or a PPI (reduces acid) and/or an
2
antiflatulent(reducesairbubbles).Gaviscon.R,asodiumalginateproduct,isaweakantacid;mostof
theantacidcontentadherestothealginateraft.Thisneutralizesacidwhichseepsintotheesophagus
aroundtheraftbutdoesnothingtocorrecttheunderlyingcauses,e.g.laxloweresophagealsphincter,
hyperacidity,delayedgastricemptying,obesity.Indeed,sodiumalginateproductsarenobetterthan
simethicone-containingantacidsinthetreatmentofacidreflux.1Sodiumalginateproductshavebeen
largelysupersededbyacidsuppressionwithH-receptorantagonistsandPPIs.
2
Onsetofaction55min.
Durationofaction1–2h.
Cautions
RegularstrengthGaviscon.RliquidandtabletscontainNaþ1.7mEq/15mLandNaþ0.8mEq/tablet
respectively, and Gaviscon.R Extra Strength liquid and tablets contain Naþ 2.7mEq/15mL and
Naþ1.3mEq/tabletrespectively.Theyshouldnotbeusedinpatientsrequiringa salt-restricted
diet,e.g.thosewithfluidretention,heartfailureorrenalimpairment.
Doseanduse
Severalproductsareavailablebutnoneisrecommended.ForpatientsalreadytakingGaviscon.R
and who are reluctant to change to Maalox.R Antacid/AntiGas (or similar option), prescribe
Gaviscon.R2–4tabletsorGaviscon.Rliquid15–30mLp.c.&atbedtime,andp.r.n.
Supply
Gaviscon.RproductsaregenerallyavailableOTC.
1 PokornyCetal.(1985)Comparisonofanantacid/dimethiconemixtureandanalginate/antacidmixtureinthetreatmentof
oesophagitis.Gut.26:A574.
2 www.palliativedrugs.com
© palliativedrugs.com Ltd.
© palliativedrugs.com Ltd.
SIMETHICONE
SIMETHICONE AHFS 56:10
Class:Antifoamingagent(antiflatulent).
Indications:Aciddyspepsia(includingacidreflux),gassydyspepsia,bloating,flatulence,†hiccup
(ifassociatedwithgastricdistension).
Pharmacology
Simethicone (silica-activated dimethicone or dimethylpolysiloxane) is a mixture of liquid
dimethicones with silicon dioxide. It is an antifoaming agent present in several proprietary
antacids, e.g. Maalox.R Antacid/AntiGas. By facilitating belching, simethicone eases flatulence,
distensionandpostprandialgastricdiscomfort.Simethicone-containingantacidsareaseffectiveas
Gaviscon.R in the treatment of acid reflux.1 Maalox.R Antacid/AntiGas should be used in
preferencetoGaviscon.Rliquidbecauseitischeaperandcontainsmuchlesssodium.
Onsetofaction55min.
Durationofaction1–2h.
Cautions
AlthoughMaalox.RAntacid/AntiGascontainsbothaluminumandmagnesium,athigherdoses
(e.g.30–60mLq.i.d.ormore)thelaxativeeffectofmagnesiumwilloverridetheconstipating
effectofaluminum.2
Doseanduse
. StartwithMaalox.RAntacid/AntiGasregularstrengthsuspension10mLp.r.n.,or10mLq.i.d.&
p.r.n.
. ifnecessary,doubledoseto20mL.
Supply
Simethicone(generic)
Tabletschewable80mg,[email protected].¼$9.
MylantaGas.R(JohnsonandJohnson/Merk)
Tabletschewable40mg,80mg,125mg,[email protected].¼$18.
Combinationproducts
Maalox.RAntacid/AntiGas(Novartis)
Oral suspension regular strength (simethicone 20mg, dried aluminum hydroxide 200mg,
magnesiumhydroxide200mg/5mL),[email protected].¼$17;lowNaþ.
Oralsuspensionmaximumstrength(simethicone40mg,driedaluminumhydroxide400mg,
magnesiumhydroxide400mg/5mL),[email protected].¼$17;lowNaþ.
1 PokornyCetal.(1985)Comparisonofanantacid/dimethiconemixtureandanalginate/antacidmixtureinthetreatmentof
oesophagitis.Gut.26:A574.
2 MorrisseyJandBarrerasR(1974)Antacidtherapy.NewEnglandJournalofMedicine.290:550–554.
ANTIMUSCARINICS (ANTICHOLINERGICS) AHFS 12:08
Indications: Smooth muscle spasm (e.g. bladder, intestine), prevention of motion sickness
(scopolamine hydrobromide TD), prevention of opioid-induced nausea and vomiting
(scopolamine hydrobromide TD), adjunctive treatment of peptic ulcer, reduction of GI
motility to aid diagnostic procedures (hyoscyamine and propantheline), pancreatitis
(hyoscyamine and propantheline), symptomatic treatment of Parkinson’s disease (PO
hyoscyamine and scopolamine hydrobromide, including sialorrhea and hyperhidrosis for
POhyoscyamine),dryingsecretions(includingsurgicalpremedicationtodecreasesalivationand
airwaysecretions,†sialorrhea,†drooling,†deathrattleand†inoperableintestinalobstruction),
†paraneoplasticpyrexiaandsweating/hyperhidrosis.
HPCFUSA 3
© palliativedrugs.com Ltd.
© palliativedrugs.com Ltd.
ANTIMUSCARINICS(ANTICHOLINERGICS)
Contra-indications:Seeindividualmonographs.
Pharmacology
Antimuscarinicsareclassifiedchemicallyastertiaryaminesorquaternaryammoniumcompounds.
The naturally-occurring belladonna alkaloids, atropine, hyoscyamine (l-atropine) and
scopolamine hydrobromide, are all tertiary amines, whereas the numerous semisynthetic
and synthetic derivatives fall into both categories. Thus, dicyclomine, oxybutynin and
tolterodine are tertiary amines, and glycopyrrolate, propantheline and scopolamine
butylbromide(notUSA)arequaternaryammoniumcompounds.
Apart from scopolamine, which causes CNS depression at therapeutic doses, the tertiary
aminesstimulatethebrainstemandhighercenters,producingmildcentralvagalexcitationand
respiratory stimulation. At toxic doses, all the tertiary amines, including scopolamine
hydrobromide, cause CNS stimulation resulting in agitation and delirium. Synthetic tertiary
aminesgenerallycauselesscentralstimulationthanthenaturally-occurringalkaloids.Quaternary
ammonium compounds do not cross the blood–brain barrier in any significant amount, and
accordinglydonothaveanycentraleffects.1TheyarealsolesswellabsorbedfromtheGItract.
Peripheralantimuscariniceffectsareaclasscharacteristic(Box1.A),andhavebeensummar-
izedas:
‘Dryasabone,blindasabat,redasabeet,hotasahare,madasahatter.’
However,atleastfivedifferenttypesofmuscarinicreceptorshavebeenidentified,2andnewer
drugs tend to be more selective in their actions. Thus, oxybutynin and tolterodine are
relativelyselectiveformuscarinicreceptorsintheurinarytract(seep.405).
Box1.A Peripheralantimuscariniceffects
Visual )
Mydriasis
blurredvision(andthusmayimpairdrivingability)
Lossofaccommodation
Cardiovascular 9
Tachycardia,palpitations >=
alsorelatedtonorepinephrinepotentiationanda
Extrasystoles
Arrhythmias >; quinidine-likeaction
Gastro-intestinal
Drymouth
Heartburn(relaxationofloweresophagealsphincter)
Constipation
Urinarytract
Hesitancyofmicturition
Retentionofurine
Skin
Reducedsweating
Flushing
Except when a reduction of oropharyngeal secretions is intended, dry mouth is an almost
universal undesirable effectwith this class of drugs. Thesecretionof saliva is mainlyunder the
controloftheautonomicnervoussystem.Foodinthemouthcausesreflexsecretionofsaliva,and
so does stimulation by acid of afferent vagal fibers in the lower esophagus. Stimulation of the
parasympathetic nerves causes profuse secretion of watery saliva, whereas stimulation of the
sympathetic nerve supply causes the secretion from only the submaxillary glands of small
quantitiesofsalivarichinorganicconstituents.3Iftheparasympatheticsupplyisinterrupted,the
salivaryglandsatrophy,whereasinterruptionofthesympatheticsupplyhasnosucheffect.The
muscarinicreceptorsinsalivaryglandsareveryresponsivetoantimuscarinicsandinhibitionof
4 www.palliativedrugs.com
© palliativedrugs.com Ltd.
© palliativedrugs.com Ltd.
ANTIMUSCARINICS(ANTICHOLINERGICS)
salivationoccursatlowerdosesthanrequiredforotherantimuscariniceffects.4Thisreducesthe
likelihood of undesirable effects when antimuscarinics are given to reduce salivation. In some
patients,areductioninexcesssalivaresultsinimprovedspeech.5
Toreducetheriskofundesirableeffects,e.g.thedevelopmentofanagitateddelirium(central
antimuscarinicsyndrome),theconcurrentuseoftwoantimuscarinicdrugsshouldgenerallybe
avoided(Box 1.B). Likewise, the concurrent use of an antimuscarinic and an opioid should be
avoidedasfaraspossible.Bothcauseconstipation(bydifferentmechanisms)and,ifusedtogether,
willresultinanincreasedneedforlaxatives,andmayevenresultinaparalyticileus.Ontheother
hand, morphine and glycopyrrolate are sometimes purposely combined in terminally ill
patientswithinoperableintestinalobstructioninordertopreventcolicandtoreducevomiting.6
Scopolamine hydrobromide TD patches are also approved for the prevention of opioid-
inducednauseaandvomiting.
Box1.B Drugswithantimuscariniceffectsassociatedwithpalliativecare
Analgesics Antipsychotics(typical)
meperidine(notrecommended) phenothiazines,e.g.
nefopam(mostlypostoperative;notUSA) chlorpromazine
Antidepressants methotrimeprazine(notUSA)
TCAs prochlorperazine
paroxetine(SSRI) Antisecretorydrugs
Antihistamines,e.g. belladonnaalkaloids
chlorpheniramine atropine
cyclizine(notUSA) scopolamine
dimenhydrinate hyoscyamine(l-atropine)a
promethazine glycopyrrolate
Antiparkinsonians,e.g. Antispasmodics,e.g.
orphenadrine dicyclomine
procyclidine(notUSA) mebeverine
Antipsychotics(atypical) oxybutynin
olanzapine propantheline
tolterodine
a.becausethed-isomerisvirtuallyinactive,hyoscyamineistwiceaspotentasracemicatropine.
Antimuscarinicsusedasantispasmodicsand/orantisecretorydrugsdifferintheirpharmacokinetic
characteristics(Table1.1).Availabilityandfashionareprobablythemaininfluencesinchoiceofdrug.
Table1.1 Pharmacokineticfeaturesofantimuscarinicdrugsusedfordeathrattle
Bio-availability Plasmahalflife Durationofaction
(antisecretory)
Atropine readilyabsorbed 4h nodata
Hyoscyamine(I-atropine) readilyabsorbed 3–5h nodata
Scopolaminehydrobromide 60–80%SL 5–6h 1–9h
Glycopyrrolate 55%PO 1.7h 7h
Cautions
Concurrenttreatmentwithtwoantimuscarinicdrugswillincreasethelikelihoodofundesirable
effects, and of central toxicity, i.e. restlessness, agitation, delirium. Children, the elderly, and
patients with renal or hepatic impairment are more susceptible to the central effects of
antimuscarinics.
Various drugs not generally considered antimuscarinic have been shown to have detectable
antimuscarinic activity by means of a radioreceptor assay, including codeine, digoxin,
dipyridamole,isosorbide,nifedipine,prednisolone,ranitidine,theophylline,warfarin.7
Theoretically,thesedrugscouldexacerbatetoxicity,particularlyindebilitatedelderlypatients.
HPCFUSA 5
© palliativedrugs.com Ltd.
© palliativedrugs.com Ltd.
ANTIMUSCARINICS(ANTICHOLINERGICS)
The increased GI transit time produced by antimuscarinics may allow increased drug
absorption from some formulations, e.g. digoxin and nitrofurantoin from tablets and
potassiumfromSRtablets,butreducedabsorptionfromothers,e.g.acetaminophentablets.
DissolutionandabsorptionofnitroglycerinSLtabletsmaybereducedbecauseofdecreased
salivaproduction.
Becauseantimuscarinicscompetitivelyblockthefinalcommon(cholinergic)pathwaythrough
whichprokineticsact,8concurrentprescriptionshouldbeavoidedifpossible.
Use with caution in myasthenia gravis, conditions predisposing to tachycardia (e.g. thyro-
toxicosis, heart failure, b-adrenergic receptor agonists), and bladder outflow obstruction
(prostatism).Use in hotweatheror pyrexiamay lead toheatstroke. Likely toexacerbateacid
reflux.Narrow-angleglaucomamaybeprecipitatedinthoseatrisk,particularlytheelderly.
Doseanduse
Antispasmodic
Antimuscarinicsareusedtorelievesmoothmusclespasminthebladder(seeoxybutynin,p.405)
andrectum(opiumandbelladonnasuppositories).
Antispasmodic andantisecretory
Antimuscarinicsareusedtoreduceintestinalcolicandintestinalsecretions,particularlygastric,
associatedwithinoperableorganicintestinalobstructioninterminallyillpatients(Table1.2).
Table1.2 Antisecretoryandantispasmodicdrugs:typicalSCdoses
Drug Statdose CSCIdose/24h
Atropine 400microgram 1,200–2,000microgram
Scopolaminehydrobromide 400microgram 1,200–2,000microgram
Hyoscyamine(l-atropine) 200microgram 600–1,000microgram
Glycopyrrolate 200microgram 600–1,200microgram
Antisecretory
Sialorrheaanddrooling
Indicatedparticularlyinpatientswithmotorneurondisease(amyotrophiclateralsclerosis/ALS),
advancedParkinson’sdiseaseorwithvariousdisordersoftheheadandneck.Severalregimens
havebeenrecommended,including:
. glycopyrrolatePO,solutionandtablets(seep.455)
. scopolaminehydrobromide1mg/3daysTD9
. hyoscyamine drops 125microgram/mL, 2mL SL q4h p.r.n. but the relatively large volume
makesthislesspreferable
. hyoscyamineSLtablets125–250microgramq4hp.r.n.
. atropine1%ophthalmicsolution,4dropsSLq4hp.r.n.(Note:dropsizevarieswithapplicator
andtechnique,doseperdropmayvaryfrom200–500microgram,i.e.800microgram–2mg/dose).
Aregimenofatropine1%500microgram(1drop)b.i.d.hasbeenreported10butacontrolled
trialfound500microgram(2drops)q.i.d.nobetterthanplacebo.11
When antimuscarinics are contra-indicated, not tolerated or ineffective, botulinum toxin
injections (with ultrasound guidance) into the parotid and submandibular glands offer an
alternativeapproach.Generallyeffectivein<1–2weeks,withbenefitlasting3–4months.12–16
Deathrattle
ManycentersuseantimuscarinicsSLfordeathrattle, therebyavoidingtheneedforinjections.
Treatmentregimens,alloff-label,arebasedmainlyonlocalclinicalexperience:
. atropine1%ophthalmicsolution,4dropsSLq4hp.r.n.(Note:dropsizevarieswithapplicator
andtechnique,doseperdropmayvaryfrom200–500microgram,i.e.800microgram–2mg/dose)
. hyoscyaminedrops125microgram/mL,2mLSLq4hp.r.n.butrelativelylargevolumeandthus
lesspreferable
. glycopyrrolate100microgramSLq6hp.r.n.
6 www.palliativedrugs.com
© palliativedrugs.com Ltd.
© palliativedrugs.com Ltd.
ANTIMUSCARINICS(ANTICHOLINERGICS)
However, with some patients injections may be preferable (Table 1.2; also see Guidelines for
managementofdeathrattle,p.9).17
Paraneoplasticpyrexiaandsweating
Antimuscarinicdrugsareusedinthetreatmentofparaneoplasticpyrexia(Box1.C).
Box1.C Symptomaticdrugtreatmentofparaneoplasticpyrexiaandsweating
Prescribeanantipyretic:
. acetaminophen500mg–1gq.i.d.orp.r.n.(generallylesstoxicthananNSAID)
. NSAID,e.g.ibuprofen200–400mgt.i.d.orp.r.n.(orthelocallypreferredalternative).
IfthesweatingdoesnotrespondtoanNSAID,prescribeanantimuscarinicdrug:
. amitriptyline 25–50mg at bedtime (may cause sedation, dry mouth and other anti-
muscariniceffects)
. scopolaminehydrobromide1mg/3daysTD18
. glycopyrrolateupto2mgPOt.i.d.19
Ifanantimuscarinicfails,otheroptionsinclude:
. propranolol10–20mgb.i.d.–t.i.d.
. cimetidine400–800mgb.i.d.20
. olanzapine5mgb.i.d.21
. thalidomide100mgatbedtime.22,23
Thalidomideisgenerallyseenasthelastresorteventhoughtheresponserateappearstobe
high.22Thisisbecauseitcancauseanirreversiblepainfulperipheralneuropathy,andmayalso
causedrowsiness(seep.398).
Overdose
Inthepast,physostigmine,acholinesteraseinhibitor,wassometimesadministeredtocorrect
antimuscarinictoxicity/poisoning.Thisisnolongerrecommendedbecausephysostigmineitself
cancauseserioustoxiceffects,includingcardiacarrhythmiasandseizures.24–26Abenzodiazepine
canbegiventocontrolmarkedagitationandseizures.Phenothiazinesshouldnotbegivenbecause
theywillexacerbatetheantimuscariniceffects,andcouldprecipitateanacutedystonia(seeDrug-
inducedmovementdisorders,p.547).Anti-arrhythmicsarenotadvisableifarrhythmiasdevelop;
buthypoxiaandacidosisshouldbecorrected.
Supply
See individual monographs: glycopyrrolate (p.455), oxybutynin (p.405), propantheline
(p.10),scopolaminehydrobromide(p.199).
Atropinesulfate(generic)
Ophthalmicsolution1%,2mLbottle¼$6,5mLbottle¼$7,15mLbottle¼$6.
Isopto.RAtropine(Alcon)
Ophthalmicsolution1%,5mLbottle¼$4.50,15mLbottle¼$6.
Hyoscyaminesulfate(generic)
Tablets125microgram,28days@125microgramq4h¼$49.
Tabletsorodispersible125microgram,28days@125microgramq4h¼$85.
TabletsSL125microgram,28days@125microgramq4h¼$52.
TabletsSR375microgram,[email protected].¼$29.
Levsin.R(SchwarzPharma)
Tablets125microgram,28days@125microgramq4h¼$126.
TabletsSL125microgram,28days@125microgramq4h¼$122.
Oralsolution125microgram/5mLand125microgram/mL,28days@125microgramq4h¼$210
and$352respectively.
Injection500microgram/mL,1mLamp¼$21.
HPCFUSA 7
© palliativedrugs.com Ltd.
© palliativedrugs.com Ltd.
ANTIMUSCARINICS(ANTICHOLINERGICS)
NuLev.R(SchwarzPharma)
Tabletsorodispersible125microgram,28days@125microgramq4h¼$142.
Levbid.R(SchwarzPharma)
TabletsSR375microgram,[email protected].¼$68.
LevsinexTimecaps.R(SchwarzPharma)
TabletsSR375microgram,[email protected].¼$77.
Cystospaz.R(Polymedica)
Tablets150microgram,[email protected].¼$57.
1 SweetmanSC(ed)(2007)Martindale:TheCompleteDrugReference(35e).PharmaceuticalPress,London.
2 CaulfieldMandBirdsallN(1998)InternationalUnionofPharmacology.XVII.Classificationofmuscarinicacetylcholine
receptors.PharmacologicalReview.50:279–290.
3 GanongWF(1979)ReviewofMedicalPhysiology(9e).LangeMedicalPublications,pp.177–181.
4 Ali-MelkkilaTetal.(1993)Pharmacokineticsandrelatedpharmacodynamicsofanticholinergicdrugs.ActaAnaesthesiologica
Scandinavica.37:633–642.
5 RashidHetal.(1997)Managementofsecretionsinesophagealcancerpatientswithglycopyrrolate.AnnalsofOncology.8:
198–199.
6 Twycross RG and Wilcock A (2001) Symptom Management in Advanced Cancer (3e). Radcliffe Medical Press, Oxford,
pp.113–114.
7 TuneIetal.(1992)Anticholinergiceffectsofdrugscommonlyprescribedfortheelderly;potentialmeansofassessingriskof
delirium.AmericanJournalofPsychiatry.149:1393–1394.
8 SchuurkesJAJetal.(1986)Stimulationofgastroduodenalmotoractivity:dopaminergicandcholinergicmodulation.Drug
DevelopmentResearch.8:233–241.
9 TalmiYPetal.(1990)Reductionofsalivaryflowwithtransdermalscopolamine:afour-yearexperience.Otolaryngologyand
HeadandNeckSurgery.103:615–618.
10 HysonHCetal.(2002)Sublingualatropineforsialorrheasecondarytoparkinsonism:apilotstudy.MovementDisorders.17:
1318–1320.
11 DeSimoneGGetal.(2006)Atropinedropsfordrooling:arandomizedcontrolledtrial.PalliativeMedicine.20:665–671.
12 LippAetal.(2003)ArandomizedtrialofbotulinumtoxinAfortreatmentofdrooling.Neurology.61:1279–1281.
13 ManciniFetal.(2003)Double-blind,placebo-controlledstudytoevaluatetheefficacyandsafetyofbotulinumtoxintypeAin
thetreatmentofdroolinginparkinsonism.MovementDisorders.18:685–688.
14 ElliesMetal.(2004)Reductionofsalivaryflowwithbotulinumtoxin:extendedreporton33patientswithdrooling,salivary
fistulas,andsialadenitis.Laryngoscope.114:1856–1860.
15 JongeriusPetal.(2004)Effectofbotulinumtoxininthetreatmentofdrooling:acontrolledclinicaltrial.Pediatrics.114:
620–627.
16 OndoWGetal.(2004)Adouble-blindplacebo-controlledtrialofbotulinumtoxinBforsialorrheainParkinson’sdisease.
Neurology.62:37–40.
17 BennettMetal.(2002)Usinganti-muscarinicdrugsinthemanagementofdeathrattle:evidencebasedguidelinesforpalliative
care.PalliativeMedicine.16:369–374.
18 MercadanteS(1998)Hyoscineinopioid-inducedsweating.JournalofPainandSymptomManagement.15:214–215.
19 KlaberMandCatterallM(2000)Treatinghyperhidrosis.Anticholinergicdrugswerenotmentioned.BritishMedicalJournal.
321:703.
20 PittelkowMandLoprinziC(2003)Pruritusandsweatinginpalliativemedicine.In:DDoyleetal.(eds)OxfordTextbookof
PalliativeMedicine(3e).OxfordUniversityPress,Oxford,pp.573–587.
21 ZyliczZandKrajnikM(2003)Flushingandsweatinginanadvancedbreastcancerpatientrelievedbyolanzapine.JournalofPain
andSymptomManagement.25:494–495.
22 DeanerP(2000)Theuseofthalidomideinthemanagementofseveresweatinginpatientswithadvancedmalignancy:trial
report.PalliativeMedicine.14:429–431.
23 CalderKandBrueraE(2000)Thalidomidefornightsweatsinpatientswithadvancedcancer.PalliativeMedicine.14:77–78.
24 AquiloniusSMandHedstrandU(1978)Theuseofphysostigmineasanantidoteintricyclicanti-depressantintoxication.Acta
AnaesthesiologicaScandinavica.22:40–45.
25 CaineED(1979)Anticholinergictoxicity.NewEnglandJournalofMedicine.300:1278.
26 NewtonRW(1975)Physostigminesalicylateinthetreatmentoftricyclicantidepressantoverdosage.JournaloftheAmerican
MedicalAssociation.231:941–943.
8 www.palliativedrugs.com
© palliativedrugs.com Ltd.
© palliativedrugs.com Ltd.
ANTIMUSCARINICS(ANTICHOLINERGICS)
Guidelines: Management of death rattle
Deathrattleis a termusedto describenoisyrattlingbreathingwhichoccursin about50% of
patientsneartheendoflife.Itiscausedbyfluidpoolinginthehypopharynx,andarisesfromone
ormoresources:
. saliva(mostcommon)
. respiratorytractinfection
. pulmonaryedema
. gastricreflux.
Rattling breathing can also occur in patients with a tracheostomy and infection. Because the
patientisgenerallysemiconsciousorunconscious,drugtreatmentfordeathrattleismainlyfor
thebenefitofrelatives,otherpatientsandstaff.
Non-drug treatment
. ease the family’s distress by explaining that the semiconscious/unconscious patient is not
distressedbytherattle
. positionthepatientsemipronetoencourageposturaldrainage;butuprightorsemirecumbentif
thecauseispulmonaryedemaorgastricreflux
. oropharyngeal suction but, because it is distressing to many moribund patients, generally
reserveforunconsciouspatients.
Drugtreatment
Saliva
Because they do not affect existing secretions, an antisecretory drug should be given SC (see
Table)orSL(seeBoxA),assoonastheonsetoftherattleisdetected.SLuseisoff-labelandless
wellsupportedbytheliterature.Evenso,SLadministrationisstandardpracticeatmanycenters.
Table Antimuscarinicantisecretorydrugsfordeathrattle:typicalSCdoses
Drug StatSCdose CSCIdose/24h
Hyoscyamine(l-atropine) 200microgram 600–1,000microgram
Glycopyrrolate 200microgram 600–1,200microgram
Atropine 400microgram 1,200–2,400microgram
Scopolaminehydrobromide 400microgram 1,200–2,400microgram
BoxA Antimuscarinicantisecretorydrugsfordeathrattle:typicalSLdoses
Glycopyrrolate0.01%oralsolution,1mL(100microgram)SLq6hp.r.n.;canbecompounded
fromglycopyrrolatepowder(seeBoxB).
Atropine1%ophthalmicsolution,4dropsSLq4hp.r.n.(Note:dropsizevarieswithapplicator
andtechnique,doseperdropmayvaryfrom200–500microgram,i.e.800microgram–2mg/dose).
Hyoscyaminedrops125microgram/mL,2mL(250microgram)SLq4hp.r.n.
BoxB Compoundedoralsolutionofglycopyrrolate
Dissolve100mgofglycopyrrolatepowder(obtainablefromGallipot)in100mLofsterileor
distilledwater(¼1mg/mLconcentratedsolution).
Thisconcentrateisstableforapproximately28daysifstoredinarefrigerator.
Dilutetherequiredvolumeoftheconcentrate1partwith9partssterileordistilledwater
(i.e.forevery1mLofconcentrate,add9mLofwater).
To avoid microbial contamination, store in a refrigerator and discard any unused diluted
solutionafter1week.
HPCFUSA 9
© palliativedrugs.com Ltd.
© palliativedrugs.com Ltd.
PROPANTHELINE
Guidelinescontinued
Note:
. byinjection,theefficacyofthedifferentdrugsisbroadlysimilar;therattleisreducedin1/2–2/3
ofpatients
. theonsetofactionofglycopyrrolateisslowercomparedwithscopolaminehydrobromide
. scopolamine hydrobromide crosses the blood-brain barrier and possesses anti-emetic and
sedativeproperties,butthereisalsoariskofdevelopingorexacerbatingdelirium
. atropineandhyoscyaminealsocrosstheblood-brainbarrierbuttendtostimulateratherthan
sedate;concurrentusewithmidazolamorhaloperidolismorelikelytobenecessary.
Respiratorytractinfection
Occasionallyitis appropriatetoprescribeanantibioticinanimminentlydyingpatientif death
rattleiscausedbyprofusepurulentsputumassociatedwithanunderlyingchestinfection:
. e.g. ceftriaxone, mix 1g ampule with 2.1mL lidocaine 1% (total volume 2.6–2.8mL), and give
250–1,000mgSC/IMoncedaily
. somecentersuselargervolumesoflidocaine1%(upto4mL)andadministeradivideddoseat
separateSC/IMsitesoncedailyorgiveb.i.d.
Pulmonaryedema
Considerfurosemide20–40mgSC/IM/IVq2hp.r.n.
Note:bewareprecipitatingurinaryretention.
Gastric reflux
Consider metoclopramide 20mg SC/IV q3h p.r.n., but do not use concurrently with an
antimuscarinicbecausethelatterblockstheprokineticeffectoftheformer.
Rattlingbreathing causing distressto apatient
Inasemiconsciouspatient,ifrattlingbreathingisassociatedwithbreathlessness,supplementthe
abovewithanopioid(e.g.morphine)^ananxiolyticsedative(e.g.midazolam).
PROPANTHELINE AHFS 12:08.08
Class:Antimuscarinic.
Indications: Smooth muscle spasm (e.g. bladder, intestine), adjunctive treatment of peptic
ulcer,reductionofGImotilitytoaiddiagnosticprocedures,†urinaryfrequencyandincontinence,
†hyperhidrosis,†gustatorysweatingindiabeticneuropathy,†paraneoplasticsweating.
Contra-indications: Narrow-angleglaucoma(unlessmoribund), myastheniagravis(unless
moribund).
Pharmacology
Propanthelineisaquaternaryantimuscarinic(seep.3);itdoesnotcrosstheblood-brainbarrier
andthusdoesnotcausecentraleffects.Itdoublesgastricemptyinghalf-time1andslowsGItransit
generally.Ithasvariableeffectsondrugabsorption(seeCautions).Propanthelineisextensively
metabolizedinthesmallintestinebeforeabsorption.Iftakenwithfood,theeffectofpropanthelineby
mouthisalmostabolished.2
Bio-availability550%PO(muchreducediftakenafterfood).
Onsetofaction30–60min.
Timetopeakplasmaconcentrationnodata.
Plasmahalflife3–4h.
Durationofaction4–6h.
10 www.palliativedrugs.com
© palliativedrugs.com Ltd.