Narcotic Analgesics CS 18

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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 (body’s 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)

µ 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 infant’s 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 (don’t 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 patient’s 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 patient’s 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 patient’s 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% O₂ + 50% NO₂) 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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