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DRUGS THAT RELIEVE PAIN

ASHA RUSSEL
BSN
INSTRUCTOR H

SITES OF DRUG ACTION

Drugs that relieve pain may act at various sites along
the pain pathways :

CLASSIFICATION

They act on brain and spinal cord and reduce the

appreciation of pain (main action of opioid analgesics)
They may suppress conduction in nerves carrying impulses
from the painful area (main action of local anesthetics)

OPIOID
ANALGESICS

NONOPIOID

They may reduce inflammation and other causes of pain in

the painful area (main action of NSAIDs)

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OPIOID ANALGESICS
TYPE
NATURAL

NAME

OPIOID ANALGESICS
Term opioid is applied to any substance which has an

opium-like action

Morphine; Codeine

Also called narcotics or narcotic analgesics, because of

their well-known soporific effects

SYNTHETIC

Diamorphine; methadone;
pethidine; phenazocine;
dextromoramide;
dipipanone; dihydrocodeine;
fentanyl

Mechanism of Action
1)

Chemicals endorphins and encephalins

(bodys own type of opioids)

Two of these, beta endorphins & metencephalin

Nearly all the opioids are potentially drugs of dependence

Mechanism of Action
2) Most important for pain control by opioids

(act on special opioid receptors in the NS)

receptors

If stimulated

Analgesia, euphoria and respiratory depression

(responsible for)
(seen with almost all narcotic analgesics)

Transmission of nerve impulses related to pain are inhibited

Appreciation of pain suppressed

Physical exercise
release of endorphins
for feeling of well-being

responsible

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Mode of Action

OPIOIDS AND RELATED DRUGS

PARTIAL
AGONISTS

AGONISTS

Agonist

Partial Agonist

Antagonist

Morphine
Diamorphine

Buprenorphine
Pentazocine

Naloxone

Stimulation +
blocking of
receptor

Blocking of
receptor

Drug
ANTAGONISTS
Receptor

Stimulation of
receptor

Opioid Agonists
Morphine

Opioid Partial Agonists

Buprenorphine

Diamorphine
Methadone
Pethidine (meperidine)

Meptazinol
Nalbuphine

Codeine
Dihydrocodiene

Tramadol

Dextropropoxyphene

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Opioid Antagonists
Naloxone
Naltrexone

Opioid Agonists

1. MORPHINE

Oral Route

ROUTES :
Can be given as immediate release tablet, that must be given
Oral
SC
IM
IV

every 4 hours
Can also be given as slow-release tablets, needing only twice

a day for long-term control of pain

Repeated doses

gets accumulated

metabolite morphine-6-glucoronide
produce satisfactory analgesia

Infusion via a syringe pump

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Metabolism and Excretion

Injections

After absorption

SC
Continuous SC infusion
IV
Inj. Morphine

* IV

Morphine combined in liver

rapid analgesia

(peak after about 1 hour)

Analgesia starts within 10 mts

lasts for 4 hours

Form several substances

* SC

One is morphine-6-glucoronide

Analgesia starts within 20 mts

Morphine given in small doses by continuous SC inj

in severe fluctuating pain
Dosage in severe pain or in acute LVF depends on
(2) weight and (3) general health of the patient

Excreted by kidneys

useful

If given, repeated doses of morphine

(1) age,

Induce a state of tolerance to drug

Later requires increased doses to produce an effect

CNS depressant actions

CNS Actions
1)

Depressant

Effects
Stimulant

Tolerance

2)
3)
4)
5)
6)

Results
Dependence

7)

Depresses appreciation of pain by the brain and thus act

as powerful analgesic
Relieves all types of pain
Relieves unpleasant nature of pain
Depresses emotional component (anticipation & fear) of
pain. It is euphoric & allays anxiety
Depresses respiration in large doses
Depresses cough centre & damps down the cough reflex
Mild hypnotic & produce drowsiness and sleep

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CNS stimulant actions

Stimulates the CTZ in the brainstem causing nausea &

vomiting (seen in 30% of mobile patients)

Pupils of the eyes are constricted due to an effect on the

Peripheral Actions
Constipation
Increase in biliary pressure

nucleus of the third nerve

Urinary retention
Stimulates the vagus nerve & cause undue slowing of the

pulse & lowering the BP (troublesome if morphine is used

for pain of coronary thrombosis)

Tolerance to Morphine
Tolerance : the phenomenon whereby successively

Histamine release (can lead to bronchoconstriction)

Common uses of Morphine

Pain control

more of a drug is needed to produce the same effect

Cough
Occurs due to long-term use
Diarrhea

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Pain control

Signs of over dosage & Treatment

Drowsy or unconscious

Used in pain control in:

Surgical emergencies

Cyanosis of skin & sweating

Post operative period

Following injury

Respiratory depression

Controlling severe pain in terminal cancer on a regular basis

Acute failure of LV with pulmonary edema
Morphine is one of the best analgesics for severe pain of
temporary nature
Useful after a coronary thrombosis, as it acts by its
widespread sedative effect on the CNS and by dilating veins &
relieving congestion of the lungs

Pin point pupils

Treatment :
Immediate endotracheal intubation to aid respiration
Administration of an opioid antagonist

2. DIAMORPHINE (HEROIN)
Obtained by chemical modification of morphine
When given by injection, enters nervous system more

rapidly than morphine & action starts little sooner

Thereafter changed to morphine in the body
More soluble than morphine & useful when large doses are

required by injection
More popular than morphine among addicts

Adverse effects of morphine & diamorphine

Allergy
Bradycardia
Confusion
Constipation
Dependence
Dry mouth
Hallucinations and nightmares (especially at night)
Hypersensitivity
Nausea
Sedation
Urinary retention

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Hypersensitivity
Certain patients are very sensitive
The most important of these group are patients with:

Dependence
Occurs rapidly when used in a social context

1) Chronic bronchitis

Rare with therapeutic use

2) Emphysema
3) During an asthmatic attack

Their use in chronic painful non-fatal disorders should

4) Liver damage

be avoided

5) Impaired renal function

6) Very old people
7) Very young people

Give only small doses

3. METHADONE

Allergy :
Chemically abase and bases are known to cause

allergic reactions
Pregnancy :
Will cross placenta and affect the fetus

It is a synthetic analgesic
Powerful analgesic as that of morphine, but less

euphoric and tranquilizing effect

Cough depressant, but effect on respiratory centre is

not so marked
Drug of dependence especially if given by injection

Drug interactions :
Increase the effect of other central depressants

(eg: MAOIs dangerous with pethidine)

Oral &subcutaneous inj

well absorbed and less

vomiting
Action longer-lasting than morphine and not be given
more than twice daily to avoid accumulation

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Therapeutic uses

Pain :
Used as a substitute for morphine in severe pain

Pain
Cough :
In smaller doses useful as a cough sedative in terminally ill

Cough

patients

Heroin withdrawal

Heroin withdrawal :
Used in the treatment of drug dependence
Prevents the severe symptoms of withdrawal from heroin
Rarely required more frequently than every 12 hours in the

management of opioid withdrawal

Nursing Point
Opioid antagonists (naltrexone) added to the oral
formulation of methadone because patients treated
with oral methadone for treatment of heroin
dependence, have known to crush the tablets and
attempt to inject them IV, to produce euphoric effect
This is because antagonist is ineffective if taken orally,
but if injected would immediately precipitate
withdrawal symptoms, which all heroin addicts fear

4. PAPAVERETUM (OMNOPON)
It is a mixture of morphine and other opioids
Its action is same as morphine
No more used

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Therapeutic uses

5. PETHIDINE
It is a synthetic substance chemically related to

atropine
Well absorbed after oral and subcutaneous injection
(1)Less powerful than morphine, (2)less effect in
therapeutic doses on cough or in respiratory centre,
(3)does not cause constriction of pupils and (4) causes
some spasm of muscles of the bile duct
Used in head injuries where observation of pupil
size is important
Can develop dependence

Used in the treatment of moderately severe pains

(viscera)

oral or IM inj

Olden times, used in later stages of labor as it is short-

acting, thus avoiding prolonged depression of the infants

respiration immediately after birth
Has good evidence that though being a sedative, it is

ineffective analgesic in these circumstances, it is being

replaced by epidural analgesia
Action lasts 2-3 hours

6. FENTANYL
Very powerful opioid & short-acting
Used largely in the intraoperative period to help anesthetic

induction
Use requires care, as severe respiration depression is a risk
Fentanyl patch (apply to dry, non-hairy skin) allow slow

absorption for upto 72 hours in the relief of terminal pain

Even after removal of patch, their action may continue for
24 hours due to its complex distribution in the body
Nursing Point:
increases absorption from fentanyl patches
leads to symptoms of over dose

7. CODEINE
Is obtained from opium
Mild analgesic (only one seventh power of morphine)
Given orally
Most useful action
morphine)

depress cough centre (half power as

Decreases peristalsis of the intestine

Fever

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Therapeutic uses
Cough : Widely used in various cough mixtures (dont give

8. DIHYDROCODEINE
Similar to codeine and is used as a mild analgesic

to diabetics)
Causes (1) constipation, (2) occasionally dizziness, (3) low
Mild analgesia : It is combined with aspirin or

blood pressure and (4) nausea

paracetamol as a mild analgesic

Administered by IM inj or as tablets
Diarrhea : It controls diarrhea

Nursing Points
Increasing the dose of codeine or dihydrocodeine

above normal dose will not enhance analgesic effect

These drugs when given alone are ineffective in post-

operative dental pain

9. DEXTROPROPOXYPHENE
Similar to methadone but much weaker analgesic
Combined with paracetamol as the compound tablet
co-proxamol (distalgesic)
Uses :
Distalgesic useful in treating pain that does not respond to aspirin
or paracetamol alone
Adverse Effects :
Slightly addictive and can cause vomiting
Over dosage :
Over dosage can be dangerous, not only because paracetamol can
cause liver damage, but also because dextropropoxyphene can
cause respiratory depression and collapse

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Partial Agonist
Are powerful analgesics but are (1) less addictive, (2) less

likely to depress respiration and are (3) less euphoric

Partial Agonist

Examples :
1) Buprenorphine
2) Meptazinol
3) Nalbuphine
4) Tramadol

1. BUPRENORPHINE

Therapeutic use

Is as powerful as morphine
Given by injection or sublingually, but orally undergoes

large first-pass metabolism

6-8 hours (longer than morphine)
(1) Less likely to depress respiration & (2) risk of
dependence is low but can occur
It shows ceiling effect, so that increasing the dose above
the usual range will not improve its efficacy
In therapeutic dose, it slightly reduces the analgesic
action of other opioids when they are combined
In higher doses, the antagonist action will become
apparent if combined with opioid agonists

Used to treat moderate and severe pain

Longer action

Given by injection for post-operative pain (but slow

to take effect)
Given sublingually every 6-8 hours for various forms of

chronic pain

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2. TRAMADOL

Adverse Effects

It is relatively a new analgesic

Troublesome vomiting (requires drug to be stopped)

Action : It is a weak opioid and reduces pain appreciation

by interfering pain pathways through the spinal gate

Respiratory depression (not so marked as with

morphine) only partly reversed by naloxone

Routes : Oral and systemic, as powerful as pethidine and

action lasts up to 6 hours
Uses :
To treat moderate severe pain (Eg: Post-operatively)
Orally given to treat chronic pain

Advantages :
Respiratory depression not usually marked
Its addiction potential is low

Adverse Effects :
Nausea
Vomiting
Dizziness
Dry mouth

Morphine Antagonists

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Morphine Antagonists
Used to treat over dosage by opioids
Most widely used are :
Naloxone

1. Naloxone

It is a pure antagonist

Action : It reverses the effects of both natural and

synthetic opioids
Routes : Rapidly effective if given subcutaneously or
intravenously

Naltrexone
Uses : Used to terminate the action of narcotic drugs in the
post-operative period
Relatively short action (about 1 hour) and if used to reverse

the effects of longer acting opioids, repeated doses may be

needed

2. Naltrexone
Is an orally active opioid antagonists

Uses :

ANALGESICS FOR ACUTE PAIN

Used in special clinics in the treatment of opioid

withdrawal

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1. The Pain Relief Programme (PRP)

Causes for acute pain

A. Important factors taken into account for the

programme :
Surgery

Patients vary in their sensitivity to pain and response to

Trauma

The PRP for an individual patient will depend on the

analgesics, so the programme should be individualized

Medical illnesses such as MI or some form of colic

B. General Rules Followed :

The programmes must be flexible and aim is to keep
the patient free of pain
Many programmes have a continuous background of
analgesia with facilities for a top-up (perhaps with a
more powerful analgesic) if the pain breaks through
A combination of drugs and treatments should always
be considered as this can be very successful
Anxiety markedly exacerbates the perception of pain.
Explanation and reassurance are powerful tools which
help to reduce anxiety and therefore the perception
and distress of pain

severity, nature and cause of the pain. It includes a

wide range of analgesics and in addition, local
anesthetics and drugs that are specific for certain types
of pain (eg: colchicine for gout)

2. Patient-Controlled Analgesia
Pain in post-operative and some terminally ill patients

can be effectively controlled by the self administration of

analgesia via a syringe pump
A number of PCA devices are available, all designed so
that dose, rate and frequency of administration can be
controlled and pre-set
A number of drugs have been used successfully
including morphine and pethidine
Part of the success of PCA is related to the feeling of
control it gives patients and the confidence that they will
not have to wait for the nurse to give an injection to
relieve pain

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Principles of PCA
Nursing time is saved, as it eliminates the time needed to

prepare and administer injections

However, nurses still have a responsibility for monitoring

the adequacy of analgesia and the appearance of sideeffects such as nausea or respiratory depression
Patient must be taught how to use the device before they

need it

A patient can self-administer a bolus of analgesic on

demand
The machine is programmed to allow self-dosage only

at pre-set intervals between lock-out time

Continuous low-level dosage can be programmed
The syringe is securely locked into a case
The programming panel is securely locked and the key

kept secure

Pain in terminal disease

Pain is a prominent feature of terminal disease,

ANALGESICS IN PATIENTS WITH

TERMINAL DISEASE

particularly cancer
The use of drugs are only a part of the management of

the dying, but the correct use of analgesics play a

very important part in the care of these patients

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Causes of pain in terminal disease

The concept of total pain

Related directly to the spread of the cancer

Physical pain

The result of therapeutic measures such as surgery or

wound procedures

Total
pain

Due to secondary deposits, particularly in bone

Due to some unrelated cause
Due to a combination of these factors

Anxiety
Anger
Fear

General feelings
of illness

Adjusting the dose of analgesic to keep the

patient pain-free

Mild Pain

The nurse has a fundamental role in the assessment of the

Weak analgesics such as paracetamol may be adequate

patients pain
Co-proxamol or dihydrocodeine are useful if given
Nursing interventions may include regular administration

of analgesia and also active listening to the patients

worries & anxieties
The nurse is critically important in the titration of the

drug against the pain

regularly are better than paracetamol

Pain arising from secondary deposits in bone, anti-

inflammatory analgesics such as aspirin or naproxen

are very effective either alone or combined with
opioids

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Moderate-to-Severe Pain
Should be treated by giving opioid analgesics regularly, titrated

against the patients pain

The most effective drugs are morphine and diamorphine
Diamorphine is more soluble than morphine and is thus better
for injection, if a small volume is required
The opioids should be prescribed regularly and given regularly
For the average person, immediate release oral tablets are
satisfactory
Lower doses required for
(1) elderly patients, (2) very ill
patients and (3) patients with impaired liver or renal function
Higher doses necessary for
(1) who are already on or (2) have
recently been on opioids

Side Effects
Constipation
Treated with a stool softener (docusate) combined with a

bowel stimulant (senokot) found very effective

Tolerance
Tolerance usually does not develop with this regimen
A need to increase dose of the drug usually indicates

advance of the disease

Dependence
The risk of dependence is not relevant in the terminally ill

patients

The frequency of administration is commonly fixed at every

4 hours (but needs regular review)

At first the patient may need additional doses as required

when the pain breaks through (incorporated in the regular 4

hourly schedule)
The object is to keep the patient pain-free
Once the correct dose of oral morphine has been established
change to slow release morphine tablets, which are only
required twice daily and are more effective in controlling
pain at night
Dosage schedules should be reviewed every 24 hours and
titrated against the patients pain and well-being

Other Routes of Administration

In very severe pain or when vomiting makes oral administration
impossible, opioids can be given by subcutaneous infusion
Diamorphine is used because of its solubility
The procedure is as follows:
1. A single 4 hour dose is given SC before the syringe pump is set
2. The 24 hour requirement of the analgesic is calculated and dissolved in
water
3. The syringe pump is started at a rate adjusted to give the correct dose
over 24 hours. It should not be delivered at more than 1.4 ml/hour or
absorption may be incomplete
4. Antiemetic can be included in the syringe. Cyclizine, droperidol or
prochlorperazine are effective
5. Careful monitoring of the therapeutic effect and degree of sedation are
necessary and adjustment of the dose as required

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OPIOID NON-RESPONSIVE PAIN

Dextromoramide, because of its short and rapid

action, can be given orally or sublingually before a

painful procedure or for breakthrough pain

Types of pain that responds poorly to opioid analgesics :

Pain due to pressure
Infiltration affecting a nerve
Bone pain due to secondary deposits

Oxycodone suppositories are useful in relieving pain

at night; their action lasts for 8 hours and they are

particularly useful for patients cared at home

Treatment for these opioid non-responsive pain :

Nerve pain : - Steroids

- Anticonvulsant drugs
Bone pain : - Radiotherapy (if possible)

- NSAIDs
- Prevent movements that cause pain

Treatment for opioid non-responsive pain

Entonox (50% O + 50% NO) by inhalation used to

cover painful procedures

Chlorpromazine

increases the effectiveness of

analgesics, in addition it is an antiemetic

Other Methods
Radiotherapy (very effective in treating secondary deposits

in bone)
Nerve block, either at peripheral level or in the spinal cord

Can be temporary or permanent

Amitriptyline is an useful antidepressant to combat

the psychotic depression that sometimes develop in

these patients

(Note: The comfort and tranquility of the patient will depend

on the character and understanding of the nurse)

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Analgesics in non-painful terminal disease

Many patients with (1) malignant disease or (2) dying from

other disease such as renal failure do not have pain, but they
experience considerable malaise and mental anguish
Small doses of opioids are usually required in these cases

Analgesics In Chronic Non-Terminal Pain

(1) controls cough and (2) relieves sensation of dyspnoea

Analgesics In Chronic Non-Terminal Pain

Pharmacological management of pain can be enhanced by

considerable (1) supportive therapy and various other techniques

like (2) psychotherapeutic methods
Alternative methods like (1) nerve block and (2) transcutaneous
electrical nerve stimulation (TENS) that act by closing the relay
gate in the spinal cord, prove helpful in some patients
Depression is often present as obscure chronic pain. In this case,
antidepressants are effective
It is important to avoid drugs with a high-risk of dependence.
Even so-called low-risk analgesics are not entirely safe

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