Transcript Acute Care Nutrition Workshop

Acute Care Nutrition
Workshop
John Hess, Ph.D., D.C.N.
Topics to be Covered
 Herbal Approach vs. Pharmaceutical
– Is there an alternative?
 Joint pain
– Herbal approaches with a history
 Protocols
– Understanding dosing
 Testing your knowledge
– Brief test on herbs covered
Traditional Approach
 Non-steroidal anti-
inflammatory drugs
(NSAID’s)
 Corticosteroids
Almekinders, LC. Efficacy of non-steroidal anti-inflammatory drugs in treatment of ligament
injuries. Sports Med 1993;9(3):137-42
Analgesics
For Pain &
Inflammation
Fries; Journal of Rheumatology stated
NSAIDs: Are the most widely used class of drugs.
•Annually, more than 70 million prescriptions are written,
and more than 30 billion NSAIDs are sold OTC in the
U.S.
•13 million people in the U.S. use NSAIDs regularly.
•The estimated number of annual hospitalizations in the
U.S. for serious GI complications is at least 103,000 with
direct costs exceeding $2 billion.
•There are more deaths annually related to NSAID use
than AIDS-related deaths.
Fries, JF. NSAID gastropathy: the second most deadly rheumatic disease? Epidemiology and risk appraisal. J
Rheumatol 1991; (Suppl 28)18:6-10;
Bland J. Nutritional Management of the Underlying Causes of Chronic Disease,
Seminar Series. Washington:Institute of Functional Medicine; 2000
Side Effects…
 Adverse GI effects of
NSAIDs include
dyspepsia, occult
bleeding, overt bleeding,
and “ulcer disease.”
 2 aspirin= 1 tsp of blood
lost per day.
 Consequences of NSAIDinduced GI toxicity
include anemia,
hospitalization, and death.
Garnett WR. GI effects of OTC analgesics:
implications
for product selection. J Am Pharm Assoc
(Wash)
1996;NS36(9):565-72
. . . the administration of
NSAIDs may lead to loss
of intestinal integrity, and
contribute to persistence
of the disease.
Healthy Gut
Leaky Gut
Auto-Immune Connection
Fries; Journal of Rheumatology, 1991 also stated…
 “. . . it generally has been believed that serious
complications from NSAID use are very rare and
that these familiar drugs are quite safe.”
 “Only recently, however has the overall toxicity
of NSAID’s been accurately quantitated and the
existence of a substantial public health problem
identified.”
Fries, JF. NSAID gastropathy: the second most deadly rheumatic
disease? Epidemioloy and risk appraisal. J Rheumatol 1991; (suppl
28)18:6-10
Understanding Inflammation
http://www.arthritis.co.za/cox.html
Pharmacology of Pain
 Selective COX-2 inhibitors alleviate
inflammation and pain and (in theory) will
not cause the side effects associated with
COX-1 inhibition (gastric damage,
increased bleeding)
 The reality is that COX-2 inhibitors do
possess some activity against COX-1
New Solutions for Herbal Pain
Management
 Why treat pain?
 Is it valid to consider herbs for treating
pain?
 The pharmacology of pain (briefly)
 Key herbs: California Poppy, Corydalis,
Willow Bark
 Some major conditions: dysmenorrhea, low
back pain, arthritic pain
Pharmacology of Pain
 Analgesics are divided into two classes:
opiate (opioid) and non-opiate
 Morphine and other opiate analgesics
stimulate opiate receptors in the CNS and
inhibit the perception of pain
 Non-opiate analgesics inhibit the
manufacture of chemicals that sensitize
and/or stimulate pain fibers
Pharmacology of Pain
Opiate Analgesics
 Opiate analgesics are more effective for the
sharp pain associated with the direct
mechanical stimulation of pain fibers
 They include morphine, codeine and
related drugs
 They are generally used to relieve intense
pain
Pharmacology of Pain
Non-opiate Analgesics
 Non-opiate analgesics are effective for
alleviating the dull throbbing pain
associated with such pathological
processes as inflammation
 They do not relieve the sharp pain
associated with direct mechanical
stimulation of pain fibers
 They are (with the exception of
acetominophen) anti-inflammatory agents
Is there a safer and more effective
approach?
Nutrition can Influence fatty acid metabolism
and eicosanoid synthesis.
Nutrition can modulate the inflammatory
response (suppressing excessively can impair
healing).
Nutrition can reduce pain and inflammation
without eliminating the benefits of the
inflammatory response.
Some Key
Analgesic Herbs
 California poppy and Corydalis can be seen as
opioid-like analgesic herbs. However, their
activity is likely to be very mild.
 Willow bark can be likened to NSAIDs in its uses
 Boswellia, ginger and turmeric are more antiinflammatory and probably have little analgesic
activity
 Cramp bark and wild yam for cramping pain in
hollow organs
A look at natural Anti-Inflammatory
Herbs…
Boswellia Serrata – (Frankincense)
 Boswellia is a
moderate to large
branching tree found
in the dry hilly areas
of India. When the
tree trunk is tapped,
a gummy oleoresin
is exuded. A purified
extract of this resin
is used in modern
herbal preparations.
http://www.virtualhealthinfo.com/herb/boswellia.
htm
Boswellia Complex
 The gum-resin is reported to possess, sedative and
marked analgesic activity. The defatted extract of
the gum exudate (oleo-gum-resin) was found to
possess marked anti-inflammatory and antiarthritic activity against adjuvant arthritis in
experimental animals and was free from toxicity
or any other side effects.
 Boswellia reduces the formation of inflammatory
leukotrienes by inhibiting 5-lipoxygenase.
Celery Seed
 Celery Seed is
http://www.healthandage.com/html/res/com/ConsHe
rbs/CelerySeedch.html
traditionally used for
arthritis, and clears acidic
metabolites from the
kidneys
 Celery has large amounts
of potassium and organic
sodium that help to rid the
body of waste material by
stimulating various sites
such as the skin, bowels
and kidneys. It re-balances
the acid/alkaline in the
system and may help
prevent certain cancers.
www.csdl.tamu.edu
Ginger (Zingiber officinale)
…it has been found that ginger alters
arachidonic acid metabolism by
inhibiting thromboxane synthetase,
a pro-inflammatory eicosanoid.
Backon J. Ginger: Inhibition of thromboxane synthetase and stimulation of
prostacyclin: revelance for medicine and psychiatry. Med Hyp 1986;20:271-8
Turmeric
 Anti-Inflammatory
Activity
http://www.mardi.my/bdc/herba/english/Tumeric.ht
ml
Turmeric
 A long and storied history for
this ginger-looking, brown-onthe-outside, bright-orange-onthe-inside rhizome. It was listed
as a coloring agent in an Assyrian
herbal dating back to 600 BCE.
It was used in sacrificial and
religious rites in ancient India
and China--and is used likewise
to this day. In 1280, Marco Polo
mentioned in his journals that he
saw turmeric growing in the
Fukien region of China, "...a
vegetable that has all the
properties of true saffron, as well
the smell as the color, and yet it is
not really saffron."
Boswellia Complex
“Anti-Inflammatory”
Boswellia Complex
“Natural Anti-Inflammatory”
 Each serving contains:
– Boswellia gum resin 4:1 extract
from Boswellia serrata gum resin 1.2 g
Containing boswellic acids 180 mg
300 mg
–
– Celery Seed fruit 6:1 extract
from Apium graveolens fruit 1.0 g
166.7 mg
– Ginger rhizome 5:1 extract
from Zingiber officinale rhizome 300 mg
60 mg
– Turmeric rhizome 25:1 extract
from Curcuma longa rhizome 2.0 g
Containing curcuminoids 70.4 mg
80 mg

4%*
Boswellia Complex
Indications
• Relief of the pain and inflammation of arthritis,
osteoarthritis, rheumatism, juvenile arthritis, and
gouty arthritis
• Assist in the treatment of leukotriene-mediated
inflammation and hypersensitivity-based disorders
such as asthma, brain tumors
Dosage for Boswellia Complex
2 Tablets every 2 hours until
pain diminishes, then 2 tablets,
3 times per day until bottle is
empty.
A look at analgesic Herbs…
Side Note-Glucosamine Synergy
 While we will discuss the use of Willow
Bark, it must be stated that often
Glucosamine Sulfate has been beneficial in
re-hydrating the chondrocytes of the
cartilage and in giving great pain relief.
 “Glucosamine synergy”
Willow Bark Extract
 The use of willow
bark dates back to
the time of
Hippocrates (400
BC) when patients
were advised to
chew on the bark to
reduce fever and
inflammation.
Willow Bark
 Many Salix species are used
therapeutically especially Salix alba, S.
daphnoides and S. purpurea
 They all contain derivatives of salicylic
acid, mainly salicin
 Recent clinical trials have found that a high
potency willow bark extract has significant
analgesic activity, but with fewer side
effects than conventional NSAIDs
The Differing Pharmacologies
of the Salicylate Derivatives
Salicin
 Salicin effectively delivers salicylic acid into the
bloodstream, but it does this in a unique way
 Salicin is carried unchanged (and hence is
stomach friendly) to the distal ileum or colon
where gut flora remove the sugar and convert it
into salicyl alcohol
 The salicyl alcohol is absorbed and oxidized in
the blood, tissue and liver to give salicylic acid
The Differing Pharmacologies
of the Salicylate Derivatives
Aspirin
 Aspirin is a potent inhibitor of COX-1 and
COX-2
 The acetyl group causes irreversible
acetylation of COX which inactivates it
 Aspirin therefore has potent analgesic and
anti-inflammatory activities (COX-2) but
also can cause gastric damage and inhibits
platelet function (COX-1)
The Differing Pharmacologies
of the Salicylate Derivatives
 Platelet function is inhibited by the
inhibition of production of thromboxane A2
(a prostaglandin) by COX-1
 Because aspirin irreversibly inactivates
COX by acetylation and because platelets
cannot make new proteins such as COX
(no nucleus) the effect of aspirin persists
for the life of the platelet (7 to 10 days)
Willow Bark:
Salicin vs Aspirin
COOH
COOH
CH2OH
HO
OH
O
CH3
O
O
Salicylic Acid
Aspirin
Salicin
OH
OH
O
CH2OH
The Differing Pharmacologies
of the Salicylate Derivatives
Salicylic Acid
 Unlike aspirin, salicylic acid has virtually
no inhibitory effect on isolated COX-1 or
COX-2
 However it can inhibit PG synthesis in
intact cells
 This means that salicylic acid or sodium
salicylate will have little antiplatelet (blood
thinning) effects – they lack the acetyl
group
The Differing Pharmacologies
of the Salicylate Derivatives
 Recently, it has been reported that aspirin
and sodium salicylate equipotently
suppress COX-2 induction at therapeutic
concentrations
 Also salicylates appear to have direct
analgesic effects in the CNS by unknown
mechanisms
Willow Bark
More Than Just Salicylate
 A study involving 10 healthy volunteers found
that a dose of a high potency willow bark extract
(providing 240 mg/day of salicin) resulted in
blood salicylate levels of around 1.4 g/mL
 In contrast, blood salicylate levels of 35 to 50
g/mL have been reported after taking just 500
mg of aspirin
 Clearly the clinically-observed analgesic effects
from willow bark (see later) must come from
more than just the effects of salicylate
Willow Bark
 Based on research on willow bark and related herbs
it has been suggested that lipoxygenase and
hyaluronidase inhibition and free radical
scavenging effects, all from other components in
willow bark, contribute to the overall analgesic
effect
 This means that many of the side effects,
interactions and contraindications for aspirin, such
as interactions with methotrexate, spironolactone
and frusemide, are unlikely to apply for willow
bark
Willow Bark
Clinical Trials
Osteoarthritis
 In 78 patients with OA of knee and/or hip
 Potent willow bark extract (containing 240 mg of
salicin per day) versus placebo under doubleblind conditions
 The WOMAC pain index, (Western Ontario
McMaster Universities Osteoarthritis Index ),
was used as the outcome after 2 weeks
 It dropped by 14% for willow bark versus an
increase of 2% for placebo (difference, p<0.05)
Willow Bark
Clinical Trials
Chronic Low Back Pain
 This was a landmark study completed by
191 patients (there were an additional 19
dropouts, mostly in the placebo group)
 Under double-blind conditions two doses
of willow bark extract (containing 120 or
240 mg of salicin per day) were compared
against a placebo
 Tramadol was the rescue medication
Willow Bark
Clinical Trials
 After 4 weeks the number of pain-free
patients was an amazing 39% for the
higher dose group and 21% for the lower
dose group, versus only 6% for placebo
 A significant response in the higher dose
group was evident after only one week of
treatment
Willow Bark
Clinical Trials
Percentage of Painfree Patients
50
40
30
20
10
0
1
Placebo
2
3
4
2 Willow Bark tablets per day
5
6
weeks
4 Willow Bark tablets per day
Willow Bark
Clinical Trials
Versus Vioxx in Low Back Pain
 An open, randomized, controlled trial compared
willow bark extract (containing 240 mg/day
salicin) and rofecoxib (Vioxx, 12.5 mg/day)
 114 patients experiencing acute exacerbations of
chronic low back pain
 After 4 weeks there was no difference observed
between the results of the two products in terms
of pain, requirement for additional analgesics or
side effects
Willow Bark - Matching the Trial
Results
 In all the trials a high potency willow bark
extract was used
 The amount of extract was around 400 mg
per tablet, standardized to 15% salicin
 2 to 4 tablets per day were prescribed
(containing 120 to 240 mg/day salicin)
 400 mg of extract containing 15% salicin
corresponds to 6 to 8 g of willow bark,
depending on the species used
Willow Bark - Matching the Trial
Results
 So to match the remarkable results of the
clinical trials, we need to match these
doses
 But this will not be enough, since other
components in willow bark also contribute
to the analgesic effect
 So the full phytochemical profile of the
willow bark extract chosen should match
the profile of the extract used in the trials
 This is known as phytoequivalence
Phytoequivalence
120
120
2: 270 n m , 4 n m
2: 270 n m , 4 n m
S a l i c i n As s a l i x R 0 0 4 2 5 0 . 7 6 8 9 0 g / 2 5 0 m L 1 ta b l e t
Salicin B ru cia R 00795 0.10695g /25m L
r d w i l l o w b a r k 0 1 s e p t. 1 0 2
r d w i l l o w b a r k 0 1 s e p t. 1 0 3
100
100
60
60
40
40
20
20
m AU
80
m AU
80
0
0
0
5
10
15
20
25
30
35
40
45
50
M in u t e s
Brown trace - “Clinical Trial Material” Green trace - “MediHerb Saligesic”
MediHerb Saligesic
 A high potency willow bark extract in
tablet form phytoequivalent to the extract
proven in clinical trials
 Each tablet contains 400 mg of extract with
60 mg of salicin, corresponding to 8 g of
bark
 Dose is 2 to 4 tablets per day
MediHerb Saligesic
Saligesic Treatment for 6 weeks
16
Before Treatment
3 weeks
14
6 weeks
12
10
8
6
4
2
0
Pa
Ba
in
s
ler
Ki l
dP
un
ai n
gro
ck
P
ute
Ac
ai n
Saligesic
Saligesic Dosage
2 tablets twice daily for 1
month. (Then it is possible to cut the
dosage in half)
Some Major Conditions
Involving Pain
 Dysmenorrhea
 Osteoarthritis
 Low back pain
Dysmenorrhea
Background
 Dysmenorrhea can be classified as
spasmodic (with intermittent crampy pain)
or congestive (with constant, dull dragging
pain)
 The former occurs immediately around
menstruation, the latter is more extended
 Dysmenorrhea can also be classified as
primary (no organic cause) or secondary
(e.g. linked to endometriosis)
Dysmenorrhea
 The pain of primary dysmenorrhea is
caused by uterine cramping and local
ischaemia due to release of endometrial
PGs
 The estrogen-primed endometrium requires
progesterone to enhance the production of
PGs
Dysmenorrhea
Herbal Treatments
 Hormone-regulating herbs in extreme and
protracted cases to be taken throughout the
cycle:
– Chaste tree (only if dysmenorrhea occurs with
PMS)
– False unicorn, dong quai
Dysmenorrhea
 Short-term treatment (commenced shortly
before menstruation) with analgesics, antiinflammatories and smooth muscle
relaxants:
– Corydalis and willow bark are analgesic
– Ginger and willow bark are anti-inflammatory
– Cramp bark, wild yam and raspberry leaf
relax non-gravid uterine muscle
A New Innovation
Cramplex for Primary Dysmenorrhea
 I find that compliance with a short-term
herbal treatment for dysmenorrhea can be
difficult for patients
 This is because of the large doses of herbs
needed and the fact that the patient often
feels nauseous and has difficulty taking
liquid herbs
 Therefore I felt the need for a high potency
herbal tablet for dysmenorrhea
Cramplex
 Each tablet contains:
– Corydalis
– Wild yam
– Raspberry leaf
– Cramp bark
– Ginger
600 mg
400 mg
400 mg
400 mg
400 mg
 Dosage is 2 tablets every 4 hours, 3 to 4
times a day. Best to start a few days before
menstruation.
Cramplex
Clinical Anecdote
A Naturopath in Melbourne
 Normally gets severe pain associated with
periods as well as nausea, migraines and
general debility.
 Took 2 doses of Cramplex at start of period
(double dose), and by afternoon had total
relief of all symptoms.
 “God Bless Cramplex”
Arthritic Pain
 The cause of the arthritis should be treated as
well as treatments for pain relief
 Diet is an important part of the treatment of both
OA and RA, and RA requires a comprehensive
approach (beyond the scope of this presentation)
 Celery is a valuable herb for arthritic pain
because I believe it addresses some of the
underlying pathological processes as well as
providing pain relief and dampening
inflammation
 Other key anti-inflammatory herbs are ginger,
Boswellia, nettle leaf and turmeric
Arthritic Pain
 Counter-irritation should be exploited
wherever possible
 Willow bark is the major oral analgesic
herb
Case History:
Arthritic Pain
A Case of Small Joint OA
 This disorder can be very difficult to treat
and is quite stubborn, presumably because
of its hereditary aspect
 The following 58-year-old female patient
has quite advanced disease with large
deformities on all of her fingers, marked
stiffness and moderate pain
Case History:
Arthritic Pain
 She was initially prescribed the following liquid:
Ginger
1:2
Celery
1:2
Nettle leaf 1:2
15 mL
50 mL
35 mL
100 mL
Dose 8 mL with water twice a day
 Boswellia Complex tablets at 2 per day were also
included. Progress was steady but not dramatic.
Case History:
Arthritic Pain
 In the past 6 months she has also taken 2
Saligesic tablets per day and reported a big
improvement in her pain and stiffness,
despite being more active than usual
Chronic Low Back Pain
Low Back Pain
 Again the cause needs to be addressed, be it




injury, muscular, disc prolapse or arthritis etc
If the cause is OA or inflammation then the
guidelines previously discussed are relevant
I have found St John’s wort to be very useful
where sciatica is involved
Herbs for the microcirculation such as grape
seed, bilberry and Ginkgo can help damaged
discs to heal
Willow bark is the key analgesic herb
Case History:
Low Back Pain
Michelle Rawnsley, Naturopath, Brisbane
Male 41 years
 Presented with chronic lower back pain
following a fall in 1984
 Medication since 1993: considerable use of
pain relieving agents including
acetominophen and codeine
Case History:
Low Back Pain
Initial Consultation
 He suffered pain mostly in morning (on
rising) and at night
 The pain markedly decreased his quality of
life
 He was prescribed Saligesic, 2 tablets bid
 Sleep improved within 4 days
 Pain decreased significantly after 1 week
Case History:
Low Back Pain
 3 weeks after the initial consultation, he
advised of only slight pain in the morning.
He has stopped other pain medication.
 12 weeks after the initial consultation, the
improved picture was much the same.
Sleep was good, provided he took the
Saligesic before bed. No conventional
painkillers used for more than 2 months.
 That patient experienced no side effects
from taking the Saligesic.
Case Study: Low
Back Pain
 A female patient aged 62 has severe low
back pain and sciatica. The sciatica is of
recent onset.
 She was a heavy smoker and has signs of
arterial disease
 X-ray investigations indicate L3/4 disc
bulging and degenerative arthritis of the
lower back
 Outline your herbal protocol with products
and doses
Conclusions
 Although herbal clinicians do not have access to
strong herbs such as opium, clinical trial results
and practical experience show that there is still a
valid role for herbs in modern pain management
 However, the phytotherapist will always want to
treat the cause as well
 In recent years there have been several significant
advances in understanding the use of herbs in
pain control, the most significant has been for
willow bark
Acute/Chronic
Think of “Boswellia Complex” for
inflammation. (Ligaplex I and II
for nutrition support)
Think of “Saligesic” for Chronic
low back, hip and joint pain
Ligaplex I - Acute Trauma
Ligaplex II –
ChronicMuscular/Skeletal Conditions
Some Key
Analgesic Herbs
 California poppy and Corydalis can be seen as
opioid-like analgesic herbs. However, their
activity is likely to be very mild.
 Willow bark can be likened to NSAIDs in its uses
 Boswellia, ginger and turmeric are more antiinflammatory and probably have little analgesic
activity
 Cramp bark and wild yam for cramping pain in
hollow organs
For More Severe Pain…
California Poppy
California Poppy
 Eschscholtzia californica is a member of the
poppy family and contains some typical alkaloids
of this family
 But the main alkaloids californidine and
eschscholtzine are fairly unique to this species
 According to Davis (of Parke-Davis) in the 1890s
it was “an excellent soporific and analgesic,
above all harmless” and “the effect produced . . .
is the same as morphine . . .”
California Poppy
 Pharmacological studies have shown
analgesic, sedative and anxiolytic activities
 An extract formulation containing 80%
California poppy and 20% Corydalis cava
interacted with opiate receptors in vitro
 High doses are needed for clinical
analgesic activity
Corydalis
Corydalis
 Corydalis tuber (Corydalis ambigua) is
commonly used in Chinese medicine for pain
relief, especially organ pain
 It contains around 20 alkaloids, but the most
potent analgesic is tetrahydropalmatine (THP)
 Analgesic potency is 1 to 10% of opium,
depending on the study
 THP does not interact with opioid receptors and
appears to interact with the dopaminergic system
Corydalis
 Clinical studies on THP have demonstrated
analgesic effects in neuralgia,
dysmenorrhea and headaches
 Use of extracts of the whole Corydalis
tuber require repeated and high doses for
analgesic effects
 THP is toxic in overdose, but use of
Corydalis tuber is generally safe
Lifestyle Modifications
 Reduce high meat consumption
 Reduce refined sugars
Testing your Knowledge
Name the 4 herbs in Boswellia
Complex?
–Boswellia
–Celery Seed
–Ginger
–Turmeric
Which herb has been compared
to Vioxx
“White Willow Bark” –
(Saligesic)
Is there a concern with using
Coumadin, (a blood thinner),
with Willow Bark – “Saligesic”?
NO!, there is mild action on
platlet activity with White
Willow Bark Extract.
What are the contraindications
for Willow Bark?
 Willow bark is contraindicated in those
with allergy or sensitivity to salicylates
 Possible Reyes syndrome, an acute
sepsis-like illness encountered
exclusively in children below 15 years
of age. Cause is unknown, but
salicylates have been implicated.
What is the activity of Boswellic
Acids?
Anti-Inflammatory
Inhibits 5-lipoxygenase activity
What is the herb Celery Seed
used for in Boswellia Complex?
Traditionally used for Arthritis
and Clearing acid from the
kidneys.
What is the Acute Dosage
protocol for Boswellia Complex?
2 Tablets every 2 hours until
pain diminishes, then 2 tablets,
3 times per day until bottle is
empty.
Case Study: Severe
Dysmenorrhea
 A female patient aged 17 has severe
dysmenorrhea which lasts for about 2 days. She
cannot function on these days
 Her doctor wants to put her on the OCP, but her
mother decided to try your treatment first
 On taking her history you note no complicating
issues (such as endometriosis or PMS)
 Outline your herbal protocol with products and
doses
Cramplex
 Cramplex 2 every 2 hours, then 2 TID
Case Study
A man 36 years of age presents
with low back pain that has
been chronic in nature over a
period of 5 years.
–He is now in an acute flare-up.
What 3 products might be used
successfully here?
Case Study
Ligaplex II - 9 per day
Boswellia Complex - 2 tablets
every 2 hours
Saligesic - 2 tablets twice per day,
long term for pain.
Case Study
A girl 19 years old and a
gymnast, presents with a
twisted ankle and low back
pain.
What 2 products might be
effectively used?
Case Study
Boswellia Complex – 2 tablets
every 2 hours until pain is
diminished, then 2 3 times per
day.
Ligaplex I – 9 tablets per day.
Case Study
A women in her 30’s presents
with Fibromyalgia and wishes
to seek an alternative to COX-2
inhibitors. Which herb might be
used and at what dosage?
Case Study
“White Willow Extract”
(Saligesic) – 2 tablets twice per
day, until pain relief achieved.
Then dosage might be able to
be cut in half.
The End!