The physiology and pharmacology of the anococcygeus muscle

TIPS - December I %!M system was studied in the experiments

on

normal rabbits under the elcc~ric stimulation (alternating

current of 60 Hz) of the

posterior limb with a frequency of 2 stimuli per second. each stimulus having a 10 ms The number of stimuli of given

the analgea!;l test the tropanr

compcjund\

were more potent. The

abilit)

to reduce opiate

anal@Gc

effect was found in many tropane derivatives: the character of the lateral chain ~35 of no impon:ance and this property

of the

amplitude causing a flexion of the stimulated limb was recorded. It was found6 in experiments on rats that some derivatives of tropane in the intraperitoneal dose of IS mg kg-‘caused a

compounds

to bc

marked

atropine

duration.

decrease

of

the

pain

reaction

mentioned

determined

by

Therefore.

the

appeared tropane

fragment.

it was of interest to test the role

of this fragment in the anti-morphine action of other agents. With this aim. and cocaine were studied in the

threshold and a reduction of the analgesic

same way and hjth appeared to reduce the

effect of morphine and other analgesicsdif-

influence

fering from morphine

summation

both che,nically and

of

morphine

as to the degree of their analgesic effect

It is noteworthy

including

and

azidomorphine,

idine. In experiments

and

trimepcr-

on rabbits the same

on

fragments

being

tropanc

also have

an antl-

compound: at a dose of 4 mg kg-’ intravenously, restored impulse summa-

responsible for the anti-morphine

tion in the c-ntral

tropine

nervous system reduced

or comple ery suppressed by morphine at a dose of 0.51

mg kg-‘.

were administered

When

the drugs

to the animals prior to

rmpulse

that S-methylpynoliJine

N-methylpiperidine

molecule

the

in the central nervous s!,ctem.

morphine effect. However. derivatives

the) cannclt bc

since

effect of

the

tropine

molecule does not uegrade m the organism. The

experimental

indicate

that

findings

many

tropane

presented derivatives

morphine the latter did not cause a reduc-

have a marked affinity for opiate receplnn

tion of the impulse summation. The same effect was observed with azidomorphine

because

and trimeperidine.

development

The anti-morphine

activitv

of tropane

derivatives was compared wun the activity of

the

classical

nalorphine

and

morphine

antagonists,

naloxone.

impulse summation

Using

the

test it was found that

nalorphine and naloxone are slightly more potent than tropane

derivatives

but with

analgesic

they

not

effects

onl) but

reduce

also

opiate

prevent

the

of the analgesic action of opi-

ates. Another confirmation of the concept that some tropane derivatives are antagonists of narcotic analgesics is provided b> our findings obtained with morphine-libc In our experiments ‘he user! the enkephalin amide analog T! r-Dalapolypeptides.

The physiology and pharmacology of the anococcygeus muscle

TabI,:

I also illuGratcs

the ci~ff~cult~ in

su.qeestmg a lihcl> mhibltcrp ?orn agonist action

transmltfer

On rhc dssisumptlon

rhat it bill tu the time in all species. can&.iates such as dcet>lchnlinr.

John S. Gillespie

raminc. ‘-HT.

GAB.4

dopamine.

dnd &cinc

hi+

idn bc

cu~luded jmcc In the rat ihe> arc crthcr !nrffecti\c or mc’di~ir , L)ntrtictlon Two possibilit.cs arc a pcp11J When the rat anococcygrus

was first intro-

duced as a preparation for pharmacological studies some ten years ago it was suggested that it should prove ‘useful both for teaching and research’*. How far has this proved true? The first preparation was the in vitro rat anococcygeusmuscle. Since then the range has been extended to include ‘an in vivo preparation in the rat and h vitro preparations from the rabbit, cat, dog, and recently, we have made some observations

on the bovine anococc>geus

muscle. All

mall!

A-P

has little

t>: .X1‘P

Ljr-

t fft I ,lthcr than .L

have in common a motor adrcncrgic inncr-

urah cunrraction dt high L. ,lc::ntrstiuns. In

vation and inhibiton

the

mitter

remains

innervation

nerves whew

unknown.

While

is similar, the proper&

transthc!r of I hr

presence

prostaglaridin

oi

indomc ~r:m 16.1mhiblt

synthesis. h,ttic\er.

~[?iztiefrtct

to inhibition and (In thts ha515 it

is re\rrxd

muscle fibres themselvesdiffer wideI) from

has been suggested as the inhibiton

the rat anococcygeuswith no spontaneti)us tone and few receptor types through the dog muscle which is also atonic but now possessesinhibitory &adrenoceptors and motor HI-histamine receptors, to the rabbit which has considerable spontaneous

mitt&.

Wb).

tin. AI‘P powerfully

tram-

in the absence of indomrta-

released from rltrvcs sh&d inhibitor?

u Me

be

exogenous

ATP is ineffective or motor. remains a problem which ma! be c..plained b> acvess to different

receptors. CI nvincing identifi-

TIPS

454 TABLE 1. Speciesdifferences in postsynapticrecepws -_ Receptor a-Adrenoceptors ~Adrenocepton !hpmine Muscarioe HJ3istamine &Histamine WIT ATP Prostaglandin5. B ProstagiandinFD Bradykinin SobstanceP Vasopressin

Dog

Rabbit

Cat

Motor 0 Motor Motor 0 0 Motor ? Motor Motor Inhibitor Inhibitur Motor

Motor Inhibitor Not tested Motor

Motor Inhibitor Not tested Inhibitor Motor Inhibitor Motor Inhibitor Not tested Not tested Inhibitor Not tested Not tested

Motor lnhibttor Not tested Inhibitor 0 0 Motor Inhibitor Inhibitor Inhibitor Not tested Not tested lnhibitor

M0h3r

Not tested Motor Not tested Not tested Nut tested Not tested Not tested Not tested

the inhibitory transmitter believe. the most fascinating aspect of this preparation. What use has been made of the preparation? In teaching, several pharmacology departments in the U.K. have introduced the rat anococcygeus into their laboratory classes as an example of adrenergic nervesmooth muscle transmission. The rat muscle is universally preferred for several reasons; it is cheap, easily isolated and robust in student hands. The absence of spontaneous tone is an advantage in providing a constant base-line for measuring responses. With this preparation direct and indirect sympathomimetic effects are readily and reproducibly obtained, pxesynaptic inhibition by agonists such as clonidine can be demonstrated together with their reversal by selective antagonists such as yohimbine, and, finally, various forms of drug supersensitivity involving either a shift in the dose-response curve or an increase in the maximum response can be demonstrated. A particular convenience in these experiments is the fact that muscarinic agonists also cause contraction and provide a useful control for the selectivity of the effect on adrenergic responses. In research, as in teaching the rat muscle has overwhelmingly been preferred. Many brie used the tissue as a substitute for the vas deferens free from the controversy which surrounds the motor transmitter in the vas. Indeed, some have taken advantage of the difference and used the preparations to complement one another, the vas deferens to measure presynaptic inhibition free from the complications of postsynaptic excitation and the anococcygeus to measure postsynaptic effecti. From the literature the research uses fall into three groups: (1) Studies on the structure, physiology and pharmacology of these muscles and thez innervation. Much of our own efforts cation

remains,

of

Rat

I

0s Motor Inhibitor Not tested Not tested Motor Not tested Not tested Not tested Inhibitor Inhibitor Not tested Not tested No,1twted

have been in this area; Kohyi and his colleagues have described the dog muscle and Garrett the histochemistry of cholinesterase. (2) Studies on neurotransmission. Drugs affecting both adrenergic motor and inhibitory transmission have been examined by groups including Ambache and Zar; Doxey and his colleagues; Doggrell, Woodruff and Paton; Drew; Leighton and his colleagues; and McGrath and his colleagues. (3) Studies on drug supersensitivity. Most work on this has been done by Gibson and Pollock.

In each new species the original description has of necessity included physiol?gical information such as the presence of spontaneous tone and the nature of the innerva,tion as well as a pharmacological descrip Con of receptlors (see Table I). Subsequent research, for example on the ultrastructure and the electrical and ionic basis of excitation and inhibition, has been almost entirely on the rat and most of what follows applies to that species. The rat muscle is composed of parallel bundles of smooth muscle fibres unusually .arising in a true tendon from the coccygeal vertebrae. In all species some of these fibres end by merging with the longitudinal muscle of the colon. In some, such as the rabbit, there is little or no extension beyond the colon but in the rat. dog and ox some muscle fibres in the male continue, to end either in the perineum or by forming the retractor penis muscle. As a consequence the anowccygeus is heavier and stronger in the male than the female and if thii is not taken into account an unnecessarily large variance is introduced into dose-response curves. Each muscle bundle contains between two and eight fibres with numerous gap junctions between fibres

-December

1980

possibly representing regions of electrical continuity. In the narrow tissue ctefts between bundles run the autonomic nerves within Schwann cell sheaths. Many of these are adrenergic as shown by their formaldehyde fluorescence, by the presence of dense-cored vesicles within their varicosities. by the ability to enhance these dense cores with 5-hydroxydopamine and their disappearance after chronic treatment with &hydroxydopamine or reserpine. In the first description of the fine structure no other nerve profiles attributable to the inhibitory nerves were seen’. More recently varicosities containing larger. electron-opaque vesicles have been described contributing up to 40% of the total and most probably representing the inhibitory nerves5. A third type of varicosity with mainly clear vesicles accounted for less than 5% of the nerve profiles and may represent a true cholinergic innervation. If so, this does not seem an importunt neural control since neither motor nor inkibitory responses to nerve stimulation are influenced by a&opine. The origin of these motor and inhibitory nerves in the spinal cord has been identified: the motor are characteristically sympathetic arising in the upper lumbar outflow; the inhibitory equally characteristic, arising from the sacral cord between LS and SY. Both are interrupted by ganglia as judged by the action of ganglion blocking drugs in ho. The organization is, therefore, that of the autonomic nervous system with the inhibitory fibres conforming anatomically to the parasympathetic division. The localization of the ganglion synapses, however, is not entirely clear. In vitro the responses to extnnsic nerve stimulation are insensitive to hexamethonium up to a concentration of 3 X X0-’ M suggesting the fibres are postganglionic with the ganglion relay some distance from the muscle. Indirect support for this conclusion was the observation in wivo that it was possible to stimulate postganglionic sympathetic fibres via an electrode in the vertebral canal several centimetres cranial to the muscle, consisteut with a postganglionic location in the ganglion chain close to the vertebral column. Ganglion cells, however, are present on and just beneath the surface of the muscle’ and recently it has been reported that (+)-tubocurarinc reduces and cho!inesterase inhibitors potentiate the motor response to extrinsic nerve stimulation but not to field stimulation with the implication that some of the extrinsic motor fibres are preganglionic’. There was no effect on the response to inhibitory nerve stimulation. These are puzzling results. One would have

TPS

- December

1980

-1.55

cxp~ctecl the inhibitory parasympathetic

fibres. if these arc

in organization,

than the sympathetic

rather

motor fibres to have

ganglion cells close to the tissue, though the alrangcmcnt

could bc comparable

to the

traction and a fall for relaxation.

then in the

rat. spike potentials contribute

httlc IO the

former and hypcrpolarization

is unlibely IO

be the direct cause of the latt,:r. Tran+ membrane

movement of calcium as a conof depolarization

Nhether

their

sequence

do synapse close to the muscle. More work

cause of contraction in the rar though even

a-receptor.

effect of LSD

is needed to clarify these conflicting obser-

here

vntions but at the end of the day I believe

depolarizations

tte

calcium may bc more important. at least for

large majority

of fibres close to the

The electrical

properties

of the muscle

and its response to nerve stimulation have been examined in the rat and the rabbit with very different resting membrane

results. In the rat the potential

is high. about

611 mV. and stable, corn spending to the alrsence of spontaneous

such small release of

Ic w, 48 mV in the atonic muscle and falling

truly

phcntolamme

the

amt. rhcreftlrc. invrll\c\ For example.

t&

cxcitatc,r?,

was still preen:

in muscle

from reserpinized

animals1o kct hdd previ

arc

common and might be the immc.Jiate cause

adrenalme by LSD but nor by eyulcontrac-

of calcium entry equally the large

tile doses of l3aClt \uggcst\ that at least part ot the ehcct of LSD is a true mdnect \yrn-

response.

depolarizations

cancelling

In the rabbit

large

with spike potentials and contraction hyperpolarization\

this calcium

entry

and bb

could

b.2

directly responsible for inhibition.

pathomimctic

action.

N hy indirect

\yrn-

pathomimetic effects are x) readily seen in This tissue is unclear The explanation

mechanirzal activ-

it 1. In the rabbit the memorane potential is

rnsldc of acta In I\

ou4ly been completely absent in muscle\ treated uith h-h~drox~dopaminc” !Uorc recently an mcreawd release
the twitch

muscle will be found to be postganglionic.

produce

that intracellular

M’rth LSD and

through ncuronal noradrrn~lmc rclea\c even though their action i\ ah&shed h>

virs deferens where the sympathetic nerves

single stimuli

may be the

sldcrcd an indrrec~ agoni\f

cocaine thcrc i5 an element elf dtruht as 1~1

Drugs alrectirlg neurotrMsmisskM

thouId

Table II illustrates two points: first. the

lie either

m a high density

e*cen lower when tone is present. and with

preponderance

SI ‘perimposed rhythmic

adrenergic side compared with the povett? of information on the inhibitory innerva-

or a high postsvnaptic receptor xnsitivit\

tion.

sion

ization with frequent tl eir peak. Nerve

waves of depolarspike potentials

stimulation

at

in the rat

p.oduccs graded depolarizations

without

When

of work

on the

the inhibitory

identified

and

agonist

motor.

transmitter and

is

antagonist

of

adrenergic nerve\ an dvld neurona) uptake. a particularly narro% synaptic CM to noradrenaline. Perhaps thn i. one OCAfor a multifactor:al explandtion smci’ all four factors are fake urab!e though ntl

spike potentials and these give rise to g.aded contractions. Guanethidine blocks

analogues are made available this disparit! will no doubt quickly disappear in a wave of

single one uniquely hi@. The tinal unusual feature concerns the ~t~ons of dnpamint

tlae adrenergic

new work. Second. the drugs have been arranged in groups to underline the suita-

As an agonist dopamme is highl; effectrvt.. almost as effective as norddr~rlahns. and both it WIT apr~morphme are rntaponizcd

nerves.

depolarises

the

n uscle and raises tone. Nerve stimulation n rw produces

mechanical

inhibition

but

Ir:tle or no hyperpolarization. These responses are quite unlike the large hyperp rlarizations in the guinea-pig taenia from s imulating

the

non-cholinergic

non-

a jrenergic nerves in that tissue, sugesting t rat the transmitter might also be different. 1 was a surprise, therefore.

to find in the

r rbbit responses to inhibitory nerve stirluk&ion almost identical to those in
on

as well as mechanical inhibition. Pasr ive tisplacement of the membrane potenrial 2 ltered the magnitude of both the dcpolari ration associated with adrenergic

motor

bility of the preparation for the stud!: of almost all aspects of adrcncrgic transmission. Pre- and post-synaptic a-agonists and

neuronal uptake have all been successful)>

ever. is ineffertivcr hut dcts a5 .i prcferenrlal of noraJrenalm< as &WX antagonist pimozide su_gge+ing vlme interactmn\

demonstrated.

bet\reen

antagonists, neurone blockers, indirect sympathomimetics and drugs blocking It

is unnecessary

to

Soradreuafine

sensitivity

of

a-receptors

to agonists. Several

pre-

and

post-synaptic

have studied this either in GO

nerves, the posts! naptic a-receptors

\~ay which suggested a reversal potential of

rather

.-20 mV for the former and -80

clonidine

potentials.

close

to

Measurement

these

of input

tance through the microelectrode excitation or inhibition

reversal resis-

measurement

is slmrlar to other adrensrrK

high sensitivity and guanfacine

have a

so that only

for

is it possible to

show depression of the nerve response free from postsynaptic excitati
during

noradrenaline

1sIo\r. to measure prrsy nap

failed to show any

tic inhibition

and the anococcygeus

convincing change but the more sensitive of meinbrane

conductance

for

postsynaptic excitation. A srcnnd unusilal feature is the east with w hich indirect s),%

by passing longitudimll current through the

pathomimetic

muscle and measuring

only is the list of indirect sqmpathomime-

electrotonic

did show a fall in membrane

decay

resistance in

tics in Table

actions are produced. II long (but

?;ctt

by no means

the rabbit, though a much smaller fall in the

exhaustive).

rat’.

neurone blockers and other drugs such as

These results sug:est intracellular

that if a rise in

calcium I.Sresponsible for con-

uptake and drug

One problem brought out in Table I is that while the sensirivity of the presynaptic a-receptors

potential

n0radrcnalmc

workers

nerve stimulation

rium

an,’

or in vi~ros.

and the hyperpolariza-

the latter. Such results suggest an increase in permeability to some ion with an equilib-

dopamme

receptors.

supersemiitivity

r erve stimulation

mV for

gu

through each of these groups in detail Three slightl) unusual features arc perhaps worth commenting on. First. the rrlari\e

t on of inhibitory

in a

by haloperidol su_uesting an .lctiorl on rru? dopaminc receptors. Eirnmocriprine. ht)u-

cocaine, and TEA.

it also includes

labetolol,

the peptide

all of the ekdoism

none of which is commonly

COW

once again 11sneuronal locatton. Frnm these results one UCXAIL~rxpct

the

456 TABLE

11. Somr drUgS

acrivc In the ml anoroccygcus muscle prepafatiim. Mcuor effects Postsynaptic

Presynap:ic Adremcepfor agonisU Noradrenaline Clonidi*e Guanhtciire ~~yrneta~~~line Tetrah~drozoline Naphazoline Merhoxamine Fhenyle~phrinr Admwrptor amqqorrixs Phen~~olamiine Phenoxybenzaminc Yohinbme Piperoxan Prazostn

IO*-IX* M inhibits twitch + noradnnahne release IV-2 x ltJ% inhibits twitch + noradrenaline release Ct.4eg kg-’ inhibits twitch Z x 10”~ inhi!Jitstwitch + ntIrad~naline rclcaa 5 x ii) ‘M itlhibits twitch + noradrenaline release R x IO ‘M inhibits twitch f noradrenaline release 10.4 M no elfect 10-Y *Joel?&

IO-a-IO-*M contraction 8 x LO‘* M ctmtractinn 144 pg kg+ contraction h x it1 *ht ~ntract~tl 9 x IW•Mcontraction 2 x IO* ktcontractton I! x 10-‘ktcontractton 3 x 10.‘ktcontractton

5 x 10 * M irtcre.ws noradrenalinc release 3 * 10’ ‘M s~cre~sesnoradrenaline relea~l lO_’ M mcrcwsnoradrenaline release * twitch f W’M mcn‘,~s noradrenali~ release

:! x IO*M inhibits twitch + noradrenaline 2 x ItJ+t+t inhibits twitch + noradrenaline S x 10“~ inhibits twitch + nutadrenaline I 0”’

Minhibits noradrenaline

Contraction IO-* g ml-’ contraction ItI4 g ml“ inhibits DA and noradrenaline Inhibits noradrenaline Inhibit> noradrenaline

Dopaminc Apt?rrWphine Haloperidol Bromocriprine Pimoride

IUVM inhibits twitch i~‘~-ltJF’ M inhibits twitch I OS’c(mhih,itstwitch inhibits twitch fndim-r s~~~i~s fyramine Amphetamine Guanethidine LSD LrbSolol Cocame TEA Eled0isitl

I tJ_ M contraction. releases noradrenaline lO* Mcontraction 1W’v contraction. reletis noradrenaline IV-ltJ’%tconvaction It?’ w contr mion 3 * IO‘*Mcontraffion. rekases noradrenaline IO-’ u amtraction IlIP-IO-‘g ml-’ contraction

I;oradredine upi& blockem Cocaine Sortqptiline ltolryptthne Desipramme fmipramme .4rnit~~t~i~ Gtmnethidine

10-u potentiares twitch + noradrenaline IO-M prevents [‘H]noradrenaline uptake 6 x 10“ M prevents (*Hjnoradrenaline uptake 4 x Ii)* N prevents ~‘HJnoradrenaline uptake 3 x JtJ-’ M prevents {‘H]noradrenaline uptake 3 x ID* kt prevrnts IaH]~~drena~e uptake 10~wpotentiatesnoradrenaline

Other acnic

Drugs

AcltyIcbolinr CarbacboI Xemliimine 5-m Bat% KC2 Rescrpioe Tri!, PGf%

IO-* hfcontraction 3 x 10- kt contraction IO-‘M potent&es ACh IO+ .*icontraction 3.8 x IO-‘t.t contraction S x i O-’ M contractron

SK) fig kg’

depletes nD~~en~~~

90%

lo“ M inhibitshvitch response IO-‘-3 Y IO* M inhibits twitch

inhjbi~~ TEA KCl Ethallol PCS B~kinin papavcri= sodiwnnitroprumide Sodimn nitrite

effects

IO“ ht potentiates inhibitory response 5 x lO-‘kr relaxes high tone 200 mkt reducesinhibitory response lo*-3 x 101~red~inhibitotyresponr

fnhiidwn ~O~-lO~~~hi~t~n IO*-IO-’ M inhibition

TIPS - December IWO preparation to demonstrate at least one form of supersensitivity, that due to loss of neuronal uptake and confined to agonists subject to neuronal uptake. This is so; the noradrenaline supersensitivity produced by cocaine, Ghydroxydopamine or some neurone blocking drugs does not extend to either oxymetazoline. which is not subject to neuronal uptake, or to carbachoP. Two other forms of supersensitivity have been demonstrated by the same workers. First is a non-selective increase in Sensitivity produced by chronic resetpine or thyroxine treatment which causes a supersensitivity to acetylcholine and KCI as well as to noradrenaline, a situation similar to that produced by chronic denervation in other tissues. The mechanism here. as in other tissues, is obscure. Second, an increase in the maximum contractile response with no change in the dose-percentage response is produced by morphine withdrawal, by single doses of reserpine or by corticosterone. The common link in these apparently dissimilar situations may be an increase in plasma corticosterone since the supersensitivity following morphine withdrawal or reserpine is absent when steroid synthesis is inhibited by metyrapone or when the adrenals have been removed, and the mechanism may be to alter the tissue distribution of sodium since either blocking the sodium-potassium pump with ouabain

or raising cxtracellular sodium levels will similarly raise the maximum response. In addition to these major forms of drug supersensitivity other minor effects have been reported. Morphine withdrawal causes some hypersensitivity to ACh apparently from inhibition of cholinesterase by corticosterone and an even more puzzling observation is a specific hyprsensitivity to ACh produced by the antidepressant mianserin. In conclusion. the years since its introduction seem to confirm thr anococcygeus as a useful oreparation for mth teachirg and research. So far its usefulnesshas been mainly in the study of adrenergic neurotransmission. This situ&m will screly be transformed when more is known of thinhibitory nerves and transmitter.

Gillespie. .I S. (lY72) BI J Phurmacol 45. 404-416 Bumstock. G.. Cwks. T and Crow. R (1978) Br. 1. Pharmncol. 64. 13-3) Duxey.J. C.. Smith. C. F. C and Walker. I. St. (1977) Br. J. fhormucol. 60. Yl-96 Gillespie. 1. S. and Liillmann-Rauch. R. !W1) Cellriue Rer. 149.91-IO4 G&bins. I. L. and Hailer. C J ( I Y79) Cell IWW Res. ZOO.257-2 7 I Gi’lrspie. J. S. and McGrath. J. C. tlY73) 1. %ysiol. (London) ‘30, h5VAT McKirdy. H. C. and Muir. T. C (1978) Br J Pham7zKol. 64,173-I 84

The clinician’s role in patient compliance Lois A, Maiman and Marshall H. Becker Depanmenr ofPed&trics, School of Menkute. Univerriry of Rochester, 601 Elmwood Avenue. Rochesrr~ Gr Yor& 14642, U.S.A. and DqwunemofH& Behviorand H&h Ekatin. Schdof PubhiHearM. Univwsiry ofMichigon. 1420 Worhington Hk&. Ann Arbor, Michipa 41:‘IO9. E’ S A. ._ -

A large number of therapies are currently available which, when used in accordance with I’heestablished details of the regimen. are nNasonablyefficacious in preventing and treating illness. However, as the foctts of medical practice has shifted from acute illnesses to chronic diseases, patients can no longer be only passiverecipients of medical care, but instead, must take an active role in managing their own care (with physician guidance). Thus progress in treatment and in achievement of desired medical outcomes depends heavily upon patient adherence (or ‘compliance’) to recommended or prescribed regimens. An extensive literature existsdocumenting generally low rates of patient com-

pliance. Although thest: rates van for dtfferent conditions. treatments, patients. and settings, reviewers have noted that at least a third of the patients in most studies failed to co-opetate with their p_hysicums’ advice. Moreover, when the med:catio:l regimen is long term, only about 50% of patients are generally found to IX compliant. and this figure can drop to 23% or lower where the C0nditiOii is asymptomatic (as. f0r example, is frequently the casewith a medication regimen for hypertensionj~. ‘Other research efforts have clearly demonstrated that physicians cannot predtct the probab!e degree of their patients’ adherence to regimen at levels of accuracy better than would be attained bv chance; moreover.

thei substanttall~ nlt’reztrmatc the conptiancr rates of their VIII paticnrs. and often express both link dc?re to undsrstanch the prc>Mm and littlc 5!rnpathv for the unto-o;xratrve parlent (,althtwgh. as medical students. their oun drq-tahq hehavL)rs and ci>mplilnce-related attttudes CICIWI~ mtrror th*bq fou;lJ f*)r patient5 in penrral). Nanwmplianse riers

tc, attainment

disrupting

&n&its

patient

irea!‘S

cf

signifiia3t

th~xtpeutic

c>r invalidating

the

har-

petals: h) pw:“tiai

d the rrgtmen. h! exp~sq to ~d&:,0nal mcdtc:d ti‘+

rhr

and alternative therapies u hich rnLt> l-~ dnp licattvc or unnecessa~. and Hhrt-h ma) result in iarrogenic out~omrs. h> mterfcring with the Jwtcw-patient wla~~onzhtp (s.y.

patient

dissdtisfactt0n

rtw!trr?p

from

poor mrdi4 0urc0mt5 iauszcf r! p00T c0mplLincr. and negative rcait!ons b) physicians to ‘problem patients) 2nd b) interfering with attempts to e\alt:a~ the qualitv of the treatment. A c*msidrrable amount of ths resrarcr on noncompliance has examined the I& of the patient’s so&demographic ctiArac terisrics (e.g. age. sex. religion. race. mari r EbWcr!Wc*H”llmd BIImrllki btn IW