Download Pain (Medications and their Prescription) 311 MDS Dr. Hesham Kh

Pain
(Medications and their Prescription)
311 MDS
Dr. Hesham Khalil, BDS, MSc (Distc), MaxProsth certi, MFDSRCS (England), PhD
Definition:
Pain is an unpleasant sensation and emotional experience which is associated with
actual or potential tissue damage or is described in terms of such damage.
Introduction:
Pain is not a simple sensation but rather a complex perception, involving higher
processing of peripheral nerve signals in the context of other factors, such as previous
experience and current mood.
The Gate Control Theory (Melazack and Wall, 1965), which incorporates
psychological mechanism, remains the major working theory about pain despite the
lack of neuro-histological evidence for some of its components.
Pain History:
The nine important aspects when taking a history from a patient complaining of pain
include:
1- Site
The patient is asked to point or describe where the pain is felt. It is important
to ascertain whether the pain is localized or generalized.
2- Radiation
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Assess the spread of pain. Sometimes the pain may be felt away from the
causative lesion. This is called referred pain.
3- Onset and duration
Determine whether the pain is acute or chronic in nature. The patient may the
pain to a certain incident or a particular time.
4- Periodicity
Continuous or intermittent
5- Character
This is best described by the patients own words. It may be sharp, dull,
throbbing, stabbing, shooting etc.
6- Severity
A visual analogue scale could be helpful
7- Exacerbating factors
Hot, cold, sweet, pressure, talking, posture, exercise, etc.
8- Relieving factors
e.g. analgesics
9- Associated symptoms
Swelling, discharge, bad taste, etc.
Pain Mediators:
Many types of dental pain arise as a result of infection or damage to tissue. Both
events initiate an inflammatory response that is intimately linked with pain. The
passage of nociceptive impulses generated in the peripheral nerve fibers depends
on the release of various neurotransmitters. These neurotransmitters act either
peripherally of centrally.
Examples of pain mediators include the following:

Plasma kinins: e.g. bradykinin

Serotonin

Histamine

Prostaglandins

Leukotrienes
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
Cytokines

Neuropeptids
Pain is provoked when a variety of substances are released or injected into the tissues.
These pain-producing substances can be released by trauma, infection, allergenic
reaction, neurogenic reflexes and central changes from cell membranes, mast cells
and nerve endings. This leads t the excitation of free nerve endings which act as
nociceptors or peripheral sense organs that respond to noxious stimulus. This group of
substances include histamine, bradykinin, potassium, acetylcholine, prostaglandins,
leukotrienes, and the neuropeptides. Arachidonic acid is derived from cell membrane
phospholipids by the action of enzyme phospholipase A2. This enzyme is activated by
trauma or infection. Once released, arachidonic acid is acted on by two further
enzyme systems. Cyclo-oxygenase activity results in the formation of prostaglandins,
thromboxane, and prostacycline, whereas lipo-oxygenae activity results in the
production of the leukotrienes.
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The analgesic effect of aspirin and other NSAIDS is believed t be due to inhibition of
cyclo-oxygenase. In addition of their peripheral action, NSAIDS seem to possess a
central analgesic action as well.
Pain transmission:
Free nerve endings which act as nociceptors are present in all orofacial tissues
including the skin, oral mucosa, the temporomandibular joint, periodontium, tooth
pulp, periosteum and muscles. Bone itself has substance P and clacitonin gene-related
peptide containing nerve endings. These become excited by noxious stimuli and the
impulses are transmitted via three major classes of nociceptive fibers:
1- C-polymodal fibers.
2- A-delta fibers
3- A-beta fibers
Analgesics
Aspirin

Acetylsalicylic acid

Weak organic acid

Has been used to treat postoperative pain

Pharmacokinetics:
rapidly absorbed from the gastrointestinal tract
(partially from the stomach and mainly from the upper small intestine). It
is hydrolysed to salicylate by esterase enzymes in the gut wall, blood and
liver. The half life of aspirin is 20-30 minutes, whereas that of salicylate is
2-3 hours. Salicylate is excreted in the urine as salicyluric acid and
glucuronides. In the liver, salicylate is conjugated with glycine and
glucuronic acid.
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
Pharmacodynamics: It can inhibit some of the chemical mediators of pain.
It irreversibly inhibits the cyclo-oxgenase system by acetylating its active
site.

Pharmacological properties:
1- Analgesic
2- Anti-inflammatory
3- Antipyretic
4- Antithrombotic

Side effects:
1- Gastrointestinal: disturbances, epigastric pain, nausea, gastric erosion.
2- Haemostatic: prolong bleeding time due to impaired platelet
aggregation.
3- Tinnitus: due to rise in labyrinthine pressure.
4- Uricosuric: decrease uric acid secretion, which results in an increase in
plasma level.
5- Kidney: decrease renal blood in case of underlying circulatory
problems such as heart failure and hypertension..
6- Bronchospasm

Drug interactions: aspirin binds firmly to plasma proteins and may
displace other drugs from the binding site, especially warfarin,
methotreaxte, and sulphonylureas.

Reye's syndrome: is a rare disorder occurring in childhood. It involves an
acute encephalopathic illness and fatty degeneration of the viscera,
especially the liver.
Summary (aspirin)
Indications: mild to moderate pain, pyrexia, antiplatelet
Cautions: Asthma, allergy, impaired renal or hepatic function, dehydration,
pregnancy, elderly.
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Contraindications: children under 12 years, breast feeding (Reye's syndrome), GIT
ulceration, haemophilia.
Interactions:

other NSAIDS (increase side effects)

anticoagulats (increase risk of bleeding)

antiepiliptics (enhance the effect of phenytoin and valproate)

cytotoxic (reduce excretion of metotrexate)

Diuretics (antagonism of diuretics effect or reduction in excretion)

Metoclopramide and Domperidone (enhance effect of aspirin by increasing
absorption)
Para-Aminophenols -Paracetmol

The active metabolite is N-acetyl-p-aminohhenol (acetaminophen).

Pharmacological properties:
1- Analgesics
2- No or little anti-inflammatory
3- Antipyretic

Pharmacokinetics: well absorbed from the small intestine after oral
ingestion. Plasma level peaks after 30-60 minutes, and the half life is 2
hours. It is conjugated in the liver and excreted in the urine.

Side effects:
o Safest analgesic!
o Skin rash
o White blood cell disorders
o Hepatotoxicity: at normal dose, paracetamol is broken down in
the liver to metabolites that are normally innocuous. In
overdose, one of the metabolites accumulates and renders liver
cells incapable of synthesizing protein. Acute liver damage can
occur after a single dose of 10-12g.
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Summary (paracetamol)
Indications: mild to moderate pain, pyrexia
Cautions: impaired renal or hepatic function, alcohol dependence.
Interactions:

anticoagulants (enhance warfarin)

Metoclopamide and Domperidone (accelerate absorption of paracetamol).
Non Steroidal Anti-Inflammatory Drugs (NSAIDS)
These drugs share many of aspirin's pharmacological properties. They are antiinflammatory and analgesic because they can inhibit the synthesis of
ecosanoids. Patients who are hypertensive to aspirin often have a similar
reaction when given NSAID.
Propionic acid derivatives:
Examples of these include ibuprofen, naproxen, flurbiprofen, and ketoprofen.
Ibuprofen is rapidly absorbed following oral administration. It binds
extensively to plasma proteins. The drug is broken down in the liver and the
metabolites excreted in the urine.
Ibuprofen and other propionic acid derivatives should be avoided in patients
with
gastrointestinal
disorder, haemostatic problems,
or history of
hypersensitivity to aspirin.
The fenamates:
An example of this group is mefenamic acid (Ponstan). It is rabidly absorbed
after oral dose. The drug is metabolized in the liver. Half of the metabolites
are excreted in the urine and the other half in the faeces.
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Diflunisal:
This is a difluorophenyl derivative of salicylic acid with similar properties of
aspirin. It is main advantage is the long plasma half life and low incidence of
side effects. Of concern in dentistry is the association between diflunisal and
dry socket which could be due to fibrinolysis enhancement.
Diclofenac:
It is a NSAID derived from phenylacetic acid. It possesses analgesic,
antipyretic, and anti-inflammatory properties. Intramuscular perpetration is
popular for the relief of moderate to sever pain but related to abscess
formation.
Interactions of NSAIDS:
Examples of the interactions include the followings

ACE inhibitors and angiotensin-II antagonists (antagonism of
hypotensive effect, increased risk of renal impairment, increased
risk of hyperkalemia

Other analgesics (with other NSAIDS thee is increased risk of side
effects)

Antacids (reduce absorption of diflunisal)

Antibacterials (some NSAIDS increase the plasma level of
gentamycin, possible risk of convulsions with quinolones)

Anticoagulants
(some
NSAIDS
enhance
the
effect
of
anticoagulants, risk of hemorrhage)


Antidepressants (they enhance the effect of NSAIDS)
Hypoglycemic drugs (some NSAIDS enhance the effect of
sulphonylureas)

Antiepileptics (some NSAIDS enhance the effect of phenytoin)

Other interactions
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Doses of some analgesics:
Analgesic
Aspirin
Diflunisal
Paracetamol
Ibuprofen
Flurbiprofen
Ketoprofen
Naproxen
Mefenamic acid
Diclofenac
Adult dose
600- 1200 mg 4 times a day
500 mg every 12 hours
500-1000 mg every 4 hours
200-600 mg every 4-6 hours
50 mg every 6 hours
25-75 mg every 6 hours
250-500 mg every 12 hours
250 mg every 6 hours
25-75 mg every 8 hours
Child dose
Nil
Nil
120-250 mg every 4 hours
100 mg every 6 hours
Nil
Nil
125 mg every 12 hours
50 mg every 6 hours
Nil
You should consult your drug reference for all doses of any drug .
Opioid analgesics
Opioids analgesics exert their action within the central nervous system by modifying
neural activity associated with pain, so they are sometimes referred as centrally acting
analgesics.
Examples of these analgesics include
-
Morphine
-
Codeine
-
Pethidine
Opioid analgesics are used in treating moderate-to-severe postoperative pain. They
are metabolized by the liver and excreted by the kidneys. Opioid-induced adverse
effects include nausea and vomiting, constipation, decreased respiratory rate and tidal
volume, drowsiness, dry mouth, histamine reactions (e.g., urticaria, sneezing, asthma
exacerbation, and pruritus), sedation, and mental confusion. Opioids cause slowing of
bowel function, thus constipation should be expected whenever opioids are
administered.
Although rare (incidence is less than 1%), the most worrisome adverse effect of
opioids is clinically significant respiratory depression. However, this can be prevented
when with close monitoring of patients every 2 hours for the first 24 hours of opioid
therapy. Opioid toxicity can occur (rare) in patients receiving chronic opioid therapy
and may present as agitation, confusion, nightmares, hallucinations, visual defects,
and jerking motions. Usually a reduced dose or change to a different opioid is
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effective in reducing these symptoms. Because older patients tend to have slower
metabolism and excretion of drugs, they are more sensitive to the sedative and
respiratory effects of opioids. They are also more likely to have urinary retention, and
constipation.
These drugs are controlled and prescribed by specialists. In case of overdose naloxone
(opioid antagonist) is used to reveres their action.
Analgesics and hypertension
There are several postulated mechanisms by which analgesics, particularly NSAIDs,
could increase blood pressure. These include acute and chronic effects on the kidney
(which could lead to salt and fluid retention) and direct vascular effects. NSAIDs also
may interact with antihypertensive medications, resulting in increases in blood
pressure
Principles of prescribing:
Good prescribing practice:

Medicines should only prescribed when they are essential

Written prescription should include:
o Full name and address of patient
o Full name and address of the doctor
o Age of the patient
o Quantities of 1 gram should be written as 1g
o Quantities f less than 1 gram should be written in mg e.g. 500mg
o Dose and dose frequency should be stated
o The form of the drug
o Names of the drugs and preparations should be clear
o Number of days
o Exact amount to be supplied
o Any blank spaces in the paper should be ruled out.
o Any special instructions
o Date and signature of the doctor
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Common abbreviations in prescription:
 Ac -
ante cibum
before meals
 Bid - bis in die
twice a day
 Gtt -
gutta
a drop
 Hs -
hora somni
at bedtime
 Pc -
post cibos
after meals
 PO -
per os
by mouth
 Q(*)h -quiaque hora
every(*)hours
 Qid - quarter in die
four times a day
 Tid -
three times a day
ter in die
Example of prescription:
Ibuprofen tablets 400 mg
One tablet every 6 hours
Send: 12 tablets
Ibuprofen tablets 400 mg
One tablet Qid
Send: 12 tablets
Prescribing during pregnancy:
Medications can have harmful effects on the foetus at any time during pregnancy.
Drugs should be prescribed in pregnancy only if the expected benefit to the mother is
recognized as being greater than the risk to the foetus, and all medications should be
avoided if possible during the first trimester. Few medicines have been shown
conclusively to produce congenital malformation (teratogenesis) in humans but no
medicine is safe beyond all doubt in early pregnancy.
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Prescribing during breast feeding:
Some medicines may be excreted in the breast milk and may cause toxicity in the
infant if administered to nursing mothers. Some drugs can inhibit lactation or sucking
reflex of the infant.
Prescribing for the elderly:
Old people, especially the very old require special care and consideration when they
are being prescribed medicines. Poor memory, mental confusion and failing eyesight
may lead to poor treatment compliance or medication errors which potentially serious.
Drug metabolism and excretion can also be affected with the risk of toxicity.
Prescribing for children:
When writing prescription for children, it is preferable to state their age. Many of the
liquid preparations, particularly suitable for children, contain sugar. Sugar free
preparations should be used whenever possible.
Prescribing for patient with systemic disease:
Notice the patient history and all medications he or she is taking. Consult the patient's
physician for further advice.
Adverse drug reaction:
If you suspect an adverse reaction to a drug the following actions may be taken:

Drug should be stopped or changed for an alternative

All adverse reaction should be reported

Classification of drug reactions:
o Type A: those reactions which are predicted from the drug's known
pharmacological properties
o Type B: those reactions which are not expected from the drug's known
pharmacological actions
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Anaphylaxis:
Causes:

Drugs: NSAID's, penicillin, anesthetic agents, intravenous colloids

Radiographic contrast media

Blood product

Food

Latex
Pathophysiology:
Release of mediators such as histamine, leukotrienes and prostaglandins from
mast cells and basophils

Vasodilatation

Increase vascular permeability leading to extravasations and edema

Respiratory muscle contraction

Stimulation of autonomic nervous system

Platelet aggregation

Recruitment of inflammatory cells
Clinical features: (may be some or all)

Pruritis

Angioedema

Urticaria

Wheezing

Laryngeal edema

Hypotension

Death !!

Within 5-60 minutes

Delayed for several hours

Biphasic (recurs some hours later)
Onset:
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Management:

Medical emergency (needs immediate attention

Stop offending agent

Administer adrenaline – IM 0.3-0.5 ml of 1:1000

High concentration oxygen

Intravenous cannula

Intravenous fluid

Give intravenous hydrocortisone 100 mg every 6 hours

Give H1 (piriton) and H2 (cimetidine) receptor antagonist by
intravenous injection

Monitor BP, pulse, respiration

Prevent recurrence
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