This document discusses pharmacology related to the nervous system, specifically focusing on movement disorders and degenerative CNS diseases. It provides details on Parkinson's disease and syndrome, including that it results from degeneration of dopaminergic pathways in the basal ganglia leading to an imbalance between cholinergic and dopaminergic transmission. Common symptoms are described. Treatment aims to increase dopaminergic activity or reduce cholinergic effects, often using levodopa, dopamine agonists, or anticholinergics. Adverse effects of various treatments are also summarized.

1. PHARMACOLOGY
IN THE NERVOUS SYSTEM
(PART 2)
JHONEE BALMEO R.N.
PHARMACOLOGY (NCM 106) INSTRUCTOR

2. MOVEMENT DISORDERS AND DEGENERATIVE
CNS DISEASE
• PARKINSON’S SYNDROME AND ITS TREATMENT
• JAMES PARKINSON FIRST DESCRIBED THE TREMOR, RIGIDITY AND
BRADYKINESIA/AKINESIA THAT CHARACTERIZE THE SYNDROME
KNOWN AS PARKINSON’S DISEASE.
• PARKINSONIAN SYMPTOMS MANIFEST AFTER LOSS OF 80% OR
MORE OF THE NERVE CELLS IN THE SUBSTANTIA NIGRA.

3. PARKINSON’S SYNDROME
• SLOWNESS OF MOTOR MOVEMENTS ( BRADYKINESIA, AKINESIA) .
• - STIFFNESS & RESISTANCE TO PASSIVE MOVEMENTS “ RIGIDITY”.
• - MUSCLE WEAKNESS.
• - TREMORS.
• - SPEECH IMPAIRMENT
• -INCREASED SALIVATION
• - POSTURAL INSTABILITY.

4. PARKINSON’S SYNDROME
• THE ANTAGONISTIC EFFECTS OF DOPAMINE AND ACETYLCHOLINE
WITHIN THE STRIATUM HAVE SUGGESTED THAT PARKINSONISM
RESULTS FROM AN IMBALANCE BETWEEN THESE
NEUROTRANSMITTERS.
• THE THERAPEUTIC BASIS FOR TREATING PARKINSONISM IS TO
INCREASE DOPAMINERGIC ACTIVITY OR TO REDUCE THE EFFECTS
OF ACETYLCHOLINE.

5. PARKINSON’S SYNDROME
• THE FREE-RADICAL HYPOTHESIS HAS RAISED THE WORRYING
POSSIBILITY THAT TREATMENT WITH LEVODOPA (SEE BELOW)
COULD ACCELERATE DISEASE PROGRESSION BY INCREASING FREE-
RADICAL FORMATION AS THE DRUG IS METABOLIZED IN THE
REMAINING NIGRO-STRIATAL NERVE FIBRES.
• THIS IS CONSISTENT WITH THE CLINICAL IMPRESSION OF SOME
NEUROLOGISTS, BUT IN THE ABSENCE OF RANDOMIZED CLINICAL
TRIALS IT IS DIFFICULT TO TELL WHETHER CLINICAL
DETERIORATION IS DUE TO THE NATURAL HISTORY OF THE

6. • ANTAGONISTIC ACTIONS OF THE DOPAMINERGIC AND CHOLINERGIC SYSTEMS IN
THE PATHOGENESIS OF PARKINSONIAN SYMPTOMS.

7. PRINCIPLES OF TREATMENT IN PARKINSONISM
• IDIOPATHIC PARKINSON’S DISEASE IS A PROGRESSIVE DISORDER,
AND IS TREATED WITH DRUGS THAT RELIEVE SYMPTOMS AND IF
POSSIBLE SLOW DISEASE PROGRESSION. TREATMENT IS USUALLY
INITIATED WHEN SYMPTOMS DISRUPT NORMAL DAILY ACTIVITIES.
• INITIAL TREATMENT IS OFTEN WITH A DOPAMINE RECEPTOR
AGONIST, E.G. BROMOCRIPTINE, PARTICULARLY IN YOUNGER (70)
PATIENTS.

8. PRINCIPLES OF TREATMENT IN PARKINSONISM
• A LEVODOPA/DECARBOXYLASE INHIBITOR COMBINATION IS
COMMONLY USED IN PATIENTS WITH DEFINITE DISABILITY.
• OCCASIONALLY, AMANTADINE OR ANTICHOLINERGICS MAY BE
USEFUL AS MONOTHERAPY IN EARLY DISEASE, ESPECIALLY IN
YOUNGER PATIENTS WHEN TREMOR IS THE DOMINANT SYMPTOM.

9. PRINCIPLES OF TREATMENT IN PARKINSONISM
• DRUGS THAT CAUSE PARKINSONISM, NOTABLY CONVENTIONAL
ANTIPSYCHOTIC DRUGS (E.G. CHLORPROMAZINE, HALOPERIDOL)
(SEE CHAPTER 19) ARE WITHDRAWN IF POSSIBLE, OR SUBSTITUTED
BY THE NEWER ‘ATYPICAL’ ANTIPSYCHOTICS (E.G. RISPERIDONE OR
OLANZAPINE), SINCE THESE HAVE A LOWER INCIDENCE OF
EXTRAPYRAMIDAL SIDE EFFECTS.

10. KEY POINTS
PARKINSON’S DISEASE
• CLINICAL DIAGNOSIS IS BASED ON THE TRIAD OF TREMOR,
RIGIDITY AND BRADYKINESIA.
• PARKINSONISM IS CAUSED BY THE DEGENERATION OF
DOPAMINERGIC PATHWAYS IN BASAL GANGLIA LEADING TO
IMBALANCE BETWEEN CHOLINERGIC (STIMULATORY) AND
DOPAMINERGIC (INHIBITORY) TRANSMISSION.
• IT IS INDUCED/EXACERBATED BY CENTRALLY ACTING DOPAMINE
ANTAGONISTS (E.G. HALOPERIDOL), BUT LESS SO BY CLOZAPINE,
RISPERIDONE OR OLANZAPINE.

11. ANTI-PARKINSONIAN DRUGS
• DRUGS AFFECTING THE DOPAMINERGIC SYSTEM
DOPAMINERGIC ACTIVITY CAN BE ENHANCED BY:
• LEVODOPA WITH A PERIPHERAL DOPA DECARBOXYLASE INHIBITOR;
• INCREASING RELEASE OF ENDOGENOUS DOPAMINE;
• STIMULATION OF DOPAMINE RECEPTORS;
• INHIBITION OF CATECHOL-O-METHYL TRANSFERASE;
• INHIBITION OF MONOAMINE OXIDASE TYPE B.

12. ANTI-PARKINSONIAN DRUGS
• LEVODOPA AND DOPA DECARBOXYLASE INHIBITORS
USE
• LEVODOPA CAN ENTER NERVE TERMINALS IN THE BASAL GANGLIA
WHERE IT UNDERGOES DECARBOXYLATION TO FORM DOPAMINE.

13. LEVODOPA AND DOPA DECARBOXYLASE
INHIBITORS
• LEVODOPA IS USED IN COMBINATION WITH A PERIPHERAL
(EXTRACEREBRAL) DOPA DECARBOXYLASE INHIBITOR (E.G.
CARBIDOPA OR BENSERAZIDE). THIS ALLOWS A FOUR- TO FIVE-
FOLD REDUCTION IN LEVODOPA DOSE AND THE INCIDENCE OF
VOMITING AND DYSRHYTHMIAS IS REDUCED.
• HOWEVER, CENTRAL ADVERSE EFFECTS (E.G. HALLUCINATIONS)
ARE (PREDICTABLY) AS COMMON AS WHEN LARGER DOSES OF
LEVODOPA ARE GIVEN WITHOUT A DOPA DECARBOXYLASE

15. LEVODOPA AND DOPA DECARBOXYLASE
INHIBITORS
ADVERSE EFFECTS (THESE INCLUDE THE FOLLOWING):
• NAUSEA AND VOMITING; •
• POSTURAL HYPOTENSION – THIS USUALLY RESOLVES AFTER A FEW
WEEKS, BUT EXCESSIVE HYPOTENSION MAY RESULT IF
ANTIHYPERTENSIVE TREATMENT IS GIVEN CONCURRENTLY;

16. LEVODOPA AND DOPA DECARBOXYLASE
INHIBITORS
ADVERSE EFFECTS (THESE INCLUDE THE FOLLOWING):
• INVOLUNTARY MOVEMENTS (DYSTONIC REACTIONS) – THESE
INCLUDE AKATHISIA (ABNORMAL RESTLESSNESS AND INABILITY TO
KEEP STILL). INVOLUNTARY MOVEMENTS MAY BECOME WORSE AS
TREATMENT IS CONTINUED, AND MAY NECESSITATE DRUG
WITHDRAWAL;

17. LEVODOPA AND DOPA DECARBOXYLASE
INHIBITORS
ADVERSE EFFECTS (THESE INCLUDE THE FOLLOWING):
• PSYCHOLOGICAL DISTURBANCE, INCLUDING VIVID DREAMS,
AGITATION, PARANOIA, CONFUSION AND HALLUCINATIONS;
• CARDIAC DYSRHYTHMIAS;
• STIMULATION OF GROWTH HORMONE AND SUPPRESSION OF
PROLACTIN.
• SEDATION AND SUDDEN ONSET OF SLEEP.

18. LEVODOPA AND DOPA DECARBOXYLASE
INHIBITORS
DRUG INTERACTIONS
• MONOAMINE OXIDASE INHIBITORS CAN PRODUCE HYPERTENSION
IF GIVEN CONCURRENTLY WITH LEVODOPA. THE HYPOTENSIVE
ACTIONS OF OTHER DRUGS ARE POTENTIATED BY LEVODOPA.

19. INCREASED RELEASE OF ENDOGENOUS
DOPAMINE
AMANTADINE
USE
• AMANTADINE HAS LIMITED EFFICACY, BUT APPROXIMATELY 60%
OF PATIENTS EXPERIENCE SOME BENEFIT. SEVERE TOXICITY IS
RARE.

20. INCREASED RELEASE OF ENDOGENOUS
DOPAMINE
MECHANISM OF ACTION
• ENDOGENOUS DOPAMINE RELEASE IS STIMULATED BY
AMANTADINE, WHICH ALSO INHIBITS REUPTAKE OF DOPAMINE
INTO NERVE TERMINALS.
• RELIEF SYMPTOMS OF PARKINSONISM BY POTENTIATING THE
RELEASE OF DOPAMINE WITHIN THE CN

21. AMANTADINE HYDROCHLORIDE:
• USES:
- INFLUENZA.
- SYMPTOMATIC TREATMENT OF PARKINSONISM ( IDIOPATHIC)

22. AMANTADINE HYDROCHLORIDE:
• DOSE: FOR PARKINSONISM 100 MG BID .
SIDE EFFECTS:
- NAUSEA, VOMITING , ANOREXIA, CONSTIPATION .
- - DEPRESSION , CONVULSION, HALLUCINATIONS, ATAXIA.
- - DIZZINESS, ORTHOSTATIC HYPOTENSION.

23. AMANTADINE HYDROCHLORIDE:
• NURSING CONSIDERATIONS:
- NOTE ANY HISTORY OF SEIZERS.
- DON’T DRIVE A CAR OR WORK IN A SITUATION WHERE ALERTNESS
IS IMPORTANT.
- RISE SLOWLY FORM A PRONE POSITION (TO AVOID ORTHOSTATIC
HYPOTENSION) .
- LIE DOWN IF FEELING DIZZY .
- MONITOR VITAL SIGNS BEFORE & DURING THERAPY

24. MIGRAINE
• MIGRAINE IS COMMON AND FRUSTRATING, YET ITS
PATHOPHYSIOLOGY REMAINS POORLY UNDERSTOOD.
• THE AURA IS ASSOCIATED WITH INTRACRANIAL
VASOCONSTRICTION AND LOCALIZED CEREBRAL ISCHAEMIA.
SHORTLY AFTER THIS, THE EXTRACRANIAL VESSELS DILATE AND
PULSATE IN ASSOCIATION WITH LOCAL TENDERNESS AND THE
CLASSICAL UNILATERAL HEADACHE, ALTHOUGH IT IS UNCLEAR
WHETHER THIS OR A NEURONAL ABNORMALITY (‘SPREADING
CORTICAL DEPRESSION’) IS THE CAUSE OF THE SYMPTOMS.

25. • PATHOPHYSIOLOGY
5HT IS A POTENT VASOCONSTRICTOR OF EXTRACRANIAL VESSELS IN
HUMANS AND ALSO HAS VASODILATOR ACTIONS IN SOME
VASCULAR BEDS.

26. DRUGS USED FOR THE ACUTE MIGRAINE
ATTACK
• IN THE MAJORITY OF PATIENTS WITH MIGRAINE, THE
COMBINATION OF A MILD ANALGESIC WITH AN ANTI-EMETIC AND,
IF POSSIBLE, A PERIOD OF REST ABORTS THE ACUTE ATTACK.

27. DRUGS USED FOR THE ACUTE MIGRAINE
ATTACK
• SIMPLE ANALGESICS
• ASPIRIN, 900MG, OR PARACETAMOL, 1G, ARE USEFUL IN THE
TREATMENT OF HEADACHE. THEY ARE INEXPENSIVE AND ARE
EFFECTIVE IN UP TO 75% OF PATIENTS. OTHER NSAIDS CAN ALSO
BE USED.
• DURING A MIGRAINE ATTACK, GASTRIC STASIS OCCURS AND THIS
IMPAIRS DRUG ABSORPTION.
• IF NECESSARY, ANALGESICS SHOULD BE USED WITH
METOCLOPRAMIDE (AS AN ANTI-EMETIC AND TO ENHANCE

28. DRUGS USED FOR THE ACUTE MIGRAINE
ATTACK
• ANTI-EMETICS FOR MIGRAINE
• METOCLOPRAMIDE, A DOPAMINE AND WEAK 5HT ANTAGONIST,
OR DOMPERIDONE.
• METOCLOPRAMIDE SHOULD BE USED WITH CAUTION IN
ADOLESCENTS AND WOMEN IN THEIR TWENTIES.

29. ANALGESICS AND THE CONTROL OF PAIN
• PAIN IS A COMMON SYMPTOM AND IS IMPORTANT BECAUSE IT
BOTH SIGNALS ‘DISEASE’ (IN THE BROADEST SENSE) AND AIDS
DIAGNOSIS.
• FORTUNATELY, PAIN RELIEF WAS ONE OF THE EARLIEST TRIUMPHS
OF PHARMACOLOGY.

30. DRUGS USED TO TREAT MILD OR MODERATE
PAIN
• PARACETAMOL (ACETAMINOPHEN)
USES
PARACETAMOL IS AN ANTIPYRETIC AND MILD ANALGESIC WITH FEW,
IF ANY, ANTI-INFLAMMATORY PROPERTIES AND NO EFFECT ON
PLATELET
IT HAS NO IRRITANT EFFECT ON THE GASTRIC MUCOSA AND CAN
BE USED SAFELY AND EFFECTIVELY IN MOST INDIVIDUALS WHO ARE
INTOLERANT OF ASPIRIN.
CLASS. : NON-NARCOTIC ANALGESIC, PARA-AMINOPHENOL TYPE.

31. DRUGS USED TO TREAT MILD OR MODERATE
PAIN
• PARACETAMOL (ACETAMINOPHEN)
USES
• - PAIN DUE TO HEADACHE, DYSMENORRHEA, ARTHRALGIA,
MYALGIA, MUSCLUOSKLETAL PAIN, IMMUNIZATION, TEETHING,
TONSILLECTOMY.
• - TO REDUCE FEVER DUE TO BACTERIAL & VIRAL INFECTION . - AS
A SUBSTITUTE FOR ASPIRIN WHEN CONTRAINDICATED .

32. DRUGS USED TO TREAT MILD OR MODERATE
PAIN
• PARACETAMOL
ADVERSE EFFECTS
THE MOST IMPORTANT TOXIC EFFECT IS HEPATIC NECROSIS
LEADING TO LIVER FAILURE AFTER OVERDOSE, BUT RENAL FAILURE
IN THE ABSENCE OF LIVER FAILURE HAS ALSO BEEN REPORTED AFTER
OVERDOSE.
THERE IS NO CONVINCING EVIDENCE THAT PARACETAMOL CAUSES
CHRONIC LIVER DISEASE WHEN USED REGULARLY IN THERAPEUTIC

33. DRUGS USED TO TREAT MILD OR MODERATE
PAIN
• PHARMACOKINETICS, METABOLISM AND INTERACTIONS
ABSORPTION OF PARACETAMOL FOLLOWING ORAL ADMINISTRATION
IS INCREASED BY METOCLOPRAMIDE, AND THERE IS A SIGNIFICANT
RELATIONSHIP BETWEEN GASTRIC EMPTYING AND ABSORPTION.
PARACETAMOL IS RAPIDLY METABOLIZED IN THE LIVER.
DOSE: TAB. 500 MG Q4 HRS OR UP TO 1G Q6 HRS.

34. DRUGS USED TO TREAT MILD OR MODERATE
PAIN
• NURSING CONSIDERATIONS:
1- SUPPOSITORIES SHOULD BE STORED BELOW 27C .
2- LIVER FUNCTION STUDIES FOR LONG TERM THERAPY.
3- NOTE SIGNS OF MET-HEMOGLOBINEMIA: BLUISH DISCOLORATION
OF GUM & FINGERNAILS.
4- TEACH PATIENT SIGNS OF TOXICITY TO BE REPORTED
IMMEDIATELY.

35. DRUGS USED TO TREAT MILD OR MODERATE
PAIN
• ASPIRIN (ACETYLSALICYLATE)
• USE
ANTIPLATELET USES OF ASPIRIN WILL BE DESCRIBED ON OTHER
TOPIC. AS AN ANTIPYRETIC AND MILD ANALGESIC IT HAS SIMILAR
EFFICACY TO PARACETAMOL.
VARIOUS PREPARATIONS ARE AVAILABLE, INCLUDING REGULAR AS
WELL AS BUFFERED, SOLUBLE AND ENTERIC-COATED FORMS.

36. DRUGS USED TO TREAT MILD OR MODERATE
PAIN
• USES:
- THE ANTIPYRETIC EFFECT IS DUE TO AN ACTION ON THE
HYPOTHALAMUS THAT RESULTS IN HEAT LOSS BY VASODILATION
OF PERIPHERAL BLOOD VESSELS & PROMOTING SWEATING.
- - THE ANTI-INFLAMMATORY EFFECTS PROBABLY BY DECREASING
PROSTAGLANDIN SYNTHESIS & OTHER MEDIATORS OF THE PAIN
RESPONSE.
- - THE ANALGESIC ACTION IS NOT FULLY KNOWN BUT MAY BE DUE
TO IMPROVEMENT OF THE INFLAMMATORY CONDITION .

37. DRUGS USED TO TREAT MILD OR MODERATE
PAIN
• CLASSIFICATION: NON-NARCOTIC ANALGESIC, ANTIPYRETIC,
ANTI-INFLAMMATORY, ANTIRHEUMATIC, ANTIPLATELET, NSAID
• DOSE:
• - IN MINOR CONDITIONS: 325-600 MG Q4 HOURS.
• - MAY REACH UP TO 6 GRAMS/DAY IN DIVIDED DOSES IN
ARTHRITIS AND RHEUMATIC CONDITIONS.

38. DRUGS USED TO TREAT MILD OR MODERATE
PAIN
• SIDE EFFECTS:
- REYE’S SYNDROME (LINKED TO
ASPIRIN)
- - HEARTBURN, NAUSEA, ANOREXIA,
OCCULT BLOOD LOSS..
- - GI BLEEDING, POTENTATION OF
PEPTIC ULCER.
- - BRONCHOSPASM.
- - ANAPHYLAXIS
- - SKIN RASHES.

39. DRUGS USED TO TREAT MILD OR MODERATE
PAIN
• IBUPROFEN
• IBUPROFEN HAS AN APPROXIMATELY SIMILAR ANALGESIC POTENCY
TO PARACETAMOL AND, IN ADDITION, HAS USEFUL ANTI-
INFLAMMATORY ACTIVITY, SO IT IS AN ALTERNATIVE TO ASPIRIN
FOR PAINFUL CONDITIONS WITH AN INFLAMMATORY COMPONENT
(E.G. SPRAINS AND MINOR SOFT TISSUE INJURY).

40. DRUGS USED TO TREAT MILD OR MODERATE
PAIN
• IT IS ALSO USEFUL IN DYSMENORRHOEA. IT CAUSES LESS GASTRIC
IRRITATION THAN ASPIRIN AND OTHER NSAIDS AT NORMAL
DOSES, AND IS AVAILABLE OVER THE COUNTER IN THE UK AND IN
MANY OTHER COUNTRIES.

41. DRUGS USED TO TREAT MILD OR MODERATE
PAIN
• ADVERSE REACTIONS
COMMON TO THE NSAIDS, INCLUDING REVERSIBLE RENAL IMPAIRMENT IN PATIENTS
WHO ARE ELDERLY OR HAVE CIRRHOSIS, NEPHROTIC SYNDROME OR HEART FAILURE.
DRUG INTERACTIONS:
IT REDUCES THE EFFICACY OF ANTIHYPERTENSIVE MEDICATION AND OF DIURETICS
BY BLOCKING FORMATION OF VASODILATOR AND NATRIURETIC PROSTAGLANDINS
IN THE KIDNEY.

42. DRUGS USED TO TREAT MILD OR MODERATE
PAIN
• TOPICAL NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
• SEVERAL NSAIDS (INCLUDING IBUPROFEN AND PIROXICAM) ARE
AVAILABLE AS TOPICAL PREPARATIONS.
• SYSTEMIC ABSORPTION DOES OCCUR, BUT IS MODEST.
• THEIR EFFECTIVENESS IN SOFT TISSUE INJURIES AND OTHER
LOCALIZED INFLAMMATORY CONDITIONS IS ALSO MODEST.
• THEY OCCASIONALLY CAUSE LOCAL IRRITATION OF THE SKIN, BUT
ADVERSE EFFECTS ARE OTHERWISE UNCOMMON.

43. KEY POINTS
THE MAIN DRUGS FOR MILD PAIN ARE PARACETAMOL, ASPIRIN AND IBUPROFEN.
• THESE WORK BY INHIBITING PROSTAGLANDIN SYNTHESIS, AND ARE AVAILABLE
OVER THE COUNTER.
• PARACETAMOL:
– IS ANALGESIC;
– IS ANTIPYRETIC BUT NOT ANTI-INFLAMMATORY;
– LACKS GASTRIC TOXICITY, AND CAN BE USED SAFELY IN CHILDREN;
– DOES NOT CAUSE BLEEDING;
– IS DANGEROUS IN OVERDOSE BECAUSE OF PRODUCTION OF A TOXIC
METABOLITE

44. KEY POINTS
• ASPIRIN:
– IS ANTI-INFLAMMATORY, ANALGESIC AND ANTIPYRETIC;
– IS UNIQUELY USEFUL FOR ITS ANTIPLATELET EFFECT;
– IS A COMMON CAUSE OF INDIGESTION AND SEVERE GASTROINTESTINAL
BLEEDING
– ESPECIALLY IN THE ELDERLY;
– IS ASSOCIATED WITH REYE’S SYNDROME IN CHILDREN AND SHOULD NOT BE
PRESCRIBED FOR CHILDREN 12 YEARS OF AGE;
– IS DANGEROUS IN OVERDOSE (SALICYLATE TOXICITY).

45. KEY POINTS
• IBUPROFEN:
• – IS SIMILAR AS AN ANALGESIC TO ASPIRIN, BUT IS PREFERRED BY SOME
PATIENTS (E.G. FOR DYSMENORRHOEA);
• – IS NOT PROVEN TO HAVE A CLINICALLY USEFUL ANTIPLATELET EFFECT.
• TOPICAL NSAIDS (E.G. PIROXICAM GEL):
– HAVE MODEST EFFICACY (AT BEST);
– HAVE LOW TOXICITY.

46. DRUGS USED TO TREAT MODERATE TO
SEVERE PAIN
(NARCOTIC ANALGESICS)
OPIOIDS  SUBSTANCES THAT ACT ON OPIOID RECEPTORS
OPIUM IS DERIVED FROM THE DRIED MILKY JUICE EXUDED BY INCISED
SEED CAPSULES OF A SPECIES OF POPPY, PAPAVER SOMNIFERUM.
OPIUM IS A COMPLEX MIXTURE OF ALKALOIDS, THE PRINCIPAL
COMPONENTS BEING MORPHINE, CODEINE AND PAPAVERINE. THE
MAIN ANALGESIC ACTION OF OPIUM IS DUE TO MORPHINE.
PAPAVERINE IS A VASODILATOR WITHOUT ANALGESIC ACTIONS.

47. NARCOTIC ANALGESICS
• UNTIL 1868, OPIUM COULD BE PURCHASED WITHOUT
PRESCRIPTION FROM GROCERS’ SHOPS IN THE UK. MUCH WORK
HAS GONE INTO SYNTHESIZING MORPHINE ANALOGUES IN THE
HOPE OF PRODUCING A DRUG WITH THE THERAPEUTIC ACTIONS
OF MORPHINE, BUT WITHOUT ITS DISADVANTAGES.

48. NARCOTIC ANALGESICS
• NARCOTIC ANALGESICS:
- IT INCLUDE OPIUM SUCH AS MORPHINE, CODEINE & OPIUM
DERIVATIVES SUCH AS MEPERIDINE.
- THESE SUBSTANCES HAVE SIMILAR PHARMACOLOGICAL
PROPERTIES.
- MEPERIDINE (DEMEROL) IS THE BEST KNOWN.
- THE RELATIVE ACTIVITY OF ALL NARCOTIC ANALGESICS IN
MEASURED AGAINST MORPHINE.

49. NARCOTIC ANALGESICS
• DEPENDENCE & TOLERANCE:
- REMEMBER THAT ALL DRUGS OF THIS GROUP MAY LEAD TO
ADDICTION.
- PSYCHOLOGICAL & PHYSICAL DEPENDENCE & TOLERANCE DEVELOP
EVEN WHEN USING CLINICAL DOSES.
- TOLERANCE USUALLY DEVELOPS BECAUSE THE PATIENT REQUIRES
SHORTER PERIODS OF TIME BETWEEN DOSES OR LARGER DOSES FOR
RELIEF OF PAIN.

50. NARCOTIC ANALGESICS
• EFFECTS OF NARCOTIC ANALGESICS:
1- ON CNS: - ALTERATION OF PAIN PERCEPTION (ANALGESIA)
- EUPHORIA - DROWSINESS - CHANGE IN MOOD
-MENTAL CLOUDING - DEEP SLEEP
2- DEPRESS RESPIRATION: OVER DOSE LEADS TO RESPIRATORY ARREST
 DEATH.
3- DEPRESS COUGH REFLEX: CODEINE IN SMALL DOSES IS USED AS
ANTITUSSIVE.

51. NARCOTIC ANALGESICS
• 4- NAUSEA & EMETIC EFFECT
• 5- MORPHINE  VASODILATION  HYPOTENSION.
• 6- PUPILLARY CONSTRICTION ( THE MOST OBVIOUS SIGN OF
DEPENDENCE) .
• 7- DECREASES THE PERISTALTIC MOTILITY  CONSTIPATION
(SOME TYPES USED IN DIARRHEA).

52. NARCOTIC ANALGESICS
ACUTE TOXICITY:
CHARACTERIZED BY RESPIRATORY DEPRESSION, DEEP SLEEP ,
STUPOR, COMA, PINPOINT PUPIL, R.R 2-4M , CYANOSIS,
HYPOTENSION, DECREASED URINARY OUT PUT, DECREASED
TEMPERATURE, CLAMMY SKIN, AND FINALLY DEATH (DUE TO
RESPIRATORY FAILURE).
TREATMENT OF ACUTE OVERDOSE:
• 1- INDUCE VOMITING OR GASTRIC LAVAGE.
• 2- ARTIFICIAL RESPIRATION.

53. NARCOTIC ANALGESICS
• CHRONIC TOXICITY:
THE PROBLEM OF CHRONIC DEPENDENCE ON NARCOTICS IS WELL
KNOW & IS NOT ONLY THE PROBLEM OF THE STREET BUT IS ALSO
FOUND OFTEN AMONG THOSE WHO HAVE EASY ACCESS TO
NARCOTICS “PHYSICIANS, NURSES… PHARMACISTS”. NARCOTIC
ANALGESICS SOMETIMES USED FOR NON-THERAPEUTIC PURPOSES.

54. NARCOTIC ANALGESICS
• - SIGNS & SYMPTOMS:
-CONSTRICTED PUPIL, CONSTIPATION, SKIN INFECTIONS, NEEDLE
SCAR ABSCESSES & ITCHING ON THE ANTERIOR SURFACE OF THE
BODY.
- WITHDRAWAL SIGNS APPEAR WHEN DRUGS IS WITHHELD FOR 4-12
HRS. & CHARACTERIZED BY INTENSE CRAVING FOR THE DRUG,
INSOMNIA, YAWNING, SNEEZING, VOMITING, DIARRHEA, TREMORS,
SWEATING, MENTAL DEPRESSION, MUSCULAR ACHES, PAIN, CHILLS &

55. NARCOTIC ANALGESICS
• ACTION OF NARCOTIC
ANALGESICS:
- NARCOTIC ANALGESICS
ATTACH TO SPECIFIC RECEPTOR
IN THE CNS RESULTING IN
ANALGESIA- ACTION
- ACTION EXACTLY IS UNKNOWN
BUT MAY BE BY DECREASING CELL

56. NARCOTIC ANALGESICS
• CONDEINE SULFATE:
CLASS. : NARCOTIC ANALGESIC, MORPHINE TYPE.
ACTION:
- RESEMBLES MORPHINE PHARMACOLOGICALLY BUT PRODUCE LESS
EFFECT ON RESPIRATORY SYSTEM, LESS NAUSEA & LESS VOMITING.
- IN HIGH DOSES (MORE THAN 60 MG), IT WILL IRRITATE THE COUGH
CENTER, BUT IN LOWER DOSES, IT IS A POTENT ANTITUSSIVE AND
IS AN INGREDIENT IN MANY COUGH SYRUPS

57. NARCOTIC ANALGESICS
• USES:
- IT HAS BEEN USED FOR MANY YEARS AS AN ANALGESIC FOR
MODERATE PAIN, AS A COUGH SUPPRESSANT AND FOR
SYMPTOMATIC RELIEF OF DIARRHOEA.
DOSE:
- ANALGESIC: 15-60 MG 4-6 HRS.
- ANTITUSSIVE: 10-20 MG 4-6 HRS.

58. NARCOTIC ANALGESICS
• MEPERIDINE HYDROCHLORIDE “PETHEDINE
HYDROCHLORIDE”:
TRADE NAME: DEMEROL
CLASS. : NARCOTIC ANALGESIC, SYNTHETIC.
ACTION: SIMILAR TO OPIATES.
- IT HAS NO ANTITUSSIVE EFFECT
- THE DURATION OF ACTION IS LESS THAN THAT OF OPIUM.

59. NARCOTIC ANALGESICS
• USES:
- SEVER PAIN.
- RENAL & HEPATIC COLIC.
- OBSTETRIC PREANASTHETIC MEDICATION (WITH CAUTION)
- IN MINOR SURGERIES.
- SPASM OF GI TRACT, UTERUS.
- PRIOR SOME DIAGNOSTIC PROCEDURES E.G. CYSTOSCOPE.
- POST OPERATIVE PAIN.

60. NARCOTIC ANALGESICS
DRUG INTERACTIONS
• WHEN PETHIDINE IS GIVEN WITH MONOAMINE OXIDASE
INHIBITORS, RIGIDITY, HYPERPYREXIA, EXCITEMENT, HYPOTENSION
AND COMA CAN OCCUR.
• PETHIDINE, LIKE OTHER OPIATES, DELAYS GASTRIC EMPTYING,
THUS INTERFERING WITH THE ABSORPTION OF CO-ADMINISTERED
DRUGS.

61. NARCOTIC ANALGESICS
• ADD. CONTRAINDICATIONS:
- HYPERSENSITIVITY.
- CONVULSIVE STATES.
- CHILDREN LESS THAN 6 MONTHS.
- HEAD INJURIES.
- DIABETIC ACIDOSIS.
- ADD. SIDE EFFECTS:
TRANSIENT HALLUCINATIONS, HYPOTENSION.

62. NARCOTIC ANALGESICS
• DOSE:
• DRUG CAN IS AVAILABLE IN THE FORM OF TABLETS, SYRUP, I.M,
S.C.
• DOSE IS 50-100 MG Q 3-4 HR.
IT CAN BE GIVEN AS I.V. CONTINUOS INFUSION ON A
CONCENTRATION OF 1 MGML. IT ALSO CAN BE GIVEN IV
SLOWLY, AND SHOULD BE DILUTED IN A CONCENTRATION OF
10MG/ML.

63. NARCOTIC ANALGESICS
ALFENTANYL, FENTANYL AND REMIFENTANYL
• USE THESE ARE DERIVATIVES OF PETHIDINE.
• THEY ARE MORE POTENT BUT SHORTER-ACTING AND ARE USED TO
TREAT SEVERE PAIN OR AS AN ADJUNCT TO ANAESTHESIA.
• FENTANYL IS AVAILABLE AS A TRANSDERMAL PATCH WHICH IS
CHANGED EVERY 72 HOURS.

64. NARCOTIC ANALGESICS
• METHADONE HYDROCHLORIDE:
METHADONE HAS VERY SIMILAR ACTIONS TO MORPHINE, BUT IS
LESS SEDATING AND LONGER ACTING.
METHADONE IS ALSO BECOMING MORE WIDELY USED IN THE
TREATMENT OF CHRONIC OR TERMINAL PAIN PATIENTS
CLASS.: NARCOTIC ANALGESIC, MORPHINE TYPE.

65. NARCOTIC ANALGESICS
• ACTION:
- PRODUCE ONLY MILD EUPHORIA, WHICH IS THE REASON IT IS USED
AS A HEROIN WITHDRAWAL SUBSTITUTE & FOR MAINTENANCE
PROGRAM.
- IT PRODUCES PHYSICAL DEPENDENCE BUT THE ABSTINENCE
SYNDROME DEVELOPS MORE SLOWLY UPON TERMINATION OF THE
THERAPY.

66. NARCOTIC ANALGESICS
- ACTION:
- WITHDRAWAL SYMPTOMS ARE LESS INTENSE BUT MORE
PROLONGED THAN THOSE ASSOCIATED WITH MORPHINE.
- IT IS NOT EFFECTIVE FOR PREOPERATIVE OR OBSTETRIC
ANESTHESIA.
- IT DOESN’T PRODUCE SEDATION OR NARCOSIS.

67. NARCOTIC ANALGESICS
• USES:
1- SEVER PAIN.
2- DRUG WITHDRAWAL.
ADDITIONAL CONTRAINDICATIONS:
- PREGNANCY SINCE IT DEPRESSES RESPIRATION OF NEONATE.
- I.V. USE.
- LIVER DISEASE.

68. NARCOTIC ANALGESICS
ADDITIONAL SIDE- EFFECTS:
CONSTIPATION,
AND PULMONARY EDEMA.
DOSE: CAN BE GIVEN ORAL, I.M., S.C. AT A DOSE OF 2.5 – 10 MG Q
3-4 HRS.

69. NARCOTIC ANALGESICS
• MORPHINE
IS ACTIVE WHEN GIVEN BY MOUTH AND A MORE RAPID EFFECT CAN
BE OBTAINED IF IT IS ADMINISTERED INTRAVENOUSLY, BUT THE
POTENTIAL FOR ABUSE IS ALSO GREATLY INCREASED. SOME
ANAESTHETISTS GIVE SYNTHETIC HIGH POTENCY OPIOIDS, SUCH AS
FENTANYL, EITHER INTRAVENOUSLY OR EPIDURALLY, FOR
OBSTETRIC SURGERY (E.G. CAESAREAN SECTION).+

70. NARCOTIC ANALGESICS
• USE
• • THE MOST IMPORTANT USE OF MORPHINE IS FOR PAIN RELIEF.
THE EFFECTIVE DOSE IS HIGHLY VARIABLE. PREVIOUS ANALGESIC
REQUIREMENTS (IF KNOWN) SHOULD BE TAKEN INTO ACCOUNT
WHEN SELECTING A DOSE.
• • MORPHINE MAY BE GIVEN AS AN INTRAVENOUS BOLUS IF RAPID
RELIEF IS REQUIRED (E.G. DURING MYOCARDIAL INFARCTION).

71. NARCOTIC ANALGESICS
• USE
• • ALTERNATIVELY, MORPHINE CAN BE GIVEN CONTINUOUSLY BY
AN INFUSION PUMP (E.G. POST-OPERATIVELY), EITHER
INTRAVENOUSLY OR SUBCUTANEOUSLY.
• • MORPHINE IS EFFECTIVE ORALLY, ALTHOUGH LARGER DOSES ARE
NEEDED DUE TO PRESYSTEMIC METABOLISM.

72. NARCOTIC ANALGESICS
• USE
• MORPHINE INHIBITS COUGH, BUT CODEINE IS PREFERRED FOR THIS
INDICATION.
• MORPHINE RELIEVES DIARRHOEA, BUT CODEINE IS PREFERRED FOR THIS
INDICATION.

73. NARCOTIC ANALGESICS
• MECHANISM OF ACTION
MORPHINE RELIEVES BOTH THE PERCEPTION OF PAIN AND THE
EMOTIONAL RESPONSE TO IT.

74. NARCOTIC ANALGESICS
• ADVERSE EFFECTS
• THESE INCLUDE THE VERY YOUNG, THE ELDERLY AND THOSE WITH CHRONIC
LUNG DISEASE, UNTREATED HYPOTHYROIDISM, CHRONIC LIVER DISEASE AND
CHRONIC RENAL FAILURE. OVERDOSE LEADS TO COMA.
• MORPHINE DEPRESSES THE SENSITIVITY OF THE RESPIRATORY CENTRE TO
CARBON DIOXIDE, THUS CAUSING A PROGRESSIVELY DECREASED RESPIRATORY
RATE.

75. NARCOTIC ANALGESICS
• MORPHINE CAUSES VOMITING IN 20–30% OF PATIENTS BY
STIMULATION OF THE CHEMORECEPTOR TRIGGER ZONE.
• MORPHINE INCREASES SMOOTH MUSCLE TONE THROUGHOUT THE
GASTRO-INTESTINAL TRACT, WHICH IS COMBINED WITH
DECREASED PERISTALSIS. THE RESULT IS CONSTIPATION WITH
HARD DRY STOOL.
• DEPENDENCE (BOTH PHYSICAL AND PSYCHOLOGICAL) IS
PARTICULARLY LIKELY TO OCCUR IF MORPHINE IS USED FOR THE

76. NARCOTIC ANALGESICS
• DOSE:
- ORAL: 10-30 MG Q 4 HR. - I.M.: 5-20 MG70 KG Q 4 HR AS
NEEDED.
- I.V.: BOLUS OF 2.5-15 MG FOR A PERSON OF AVERAGE WEIGHT OF
70 KG OVER 4-5 MINUTES (SLOWLY).
- CONTINUOUS INFUSION: 0.1-1 MG ML IN 5% DEXTROSE IN WATER
BY A CONTROLLED INFUSION PUMP.

77. NARCOTIC ANALGESICS
• DIAMORPHINE
• USE DIAMORPHINE IS DIACETYLMORPHINE. ITS ACTIONS ARE
SIMILAR TO THOSE OF MORPHINE, ALTHOUGH IT IS MORE POTENT
AS AN ANALGESIC WHEN GIVEN BY INJECTION.
• DIAMORPHINE HAS A REPUTATION FOR HAVING A GREATER
ADDICTIVE POTENTIAL THAN MORPHINE AND IS BANNED IN MANY

78. NARCOTIC ANALGESICS
• ADVERSE EFFECTS
THE ADVERSE EFFECTS OF DIAMORPHINE ARE THE SAME AS THOSE FOR
MORPHINE.
• PHARMACOKINETICS
DIAMORPHINE CROSSES THE BLOOD–BRAIN BARRIER EVEN MORE RAPIDLY
THAN MORPHINE. THIS ACCOUNTS FOR ITS RAPID EFFECT WHEN
ADMINISTERED INTRAVENOUSLY AND HENCE INCREASED ABUSE
POTENTIAL COMPARED WITH MORPHINE.

79. NARCOTIC ANALGESICS
• TRAMADOL HYDROCHLORIDE
TRADE NAME: ULTRAM, TRAMAL
CLASS. : NARCOTIC ANALGESIC, SYNTHETIC.
ACTION: UNKNOWN. A CENTRALLY ACTING SYNTHETIC ANALGESIC
COMPOUND NOT CHEMICALLY RELATED TO OPIATES. THOUGHT TO
BIND TO OPIOID RECEPTORS AND INHIBIT REUPTAKE OF
NOREPINEPHRINE AND SEROTONIN

80. NARCOTIC ANALGESICS
• INDICATIONS & DOSAGES
TRAMADOL IS WIDELY USED FOR MODERATE TO SEVERE PAIN,
INCLUDING POST-OPERATIVE PAIN. IT CAN BE ADMINISTERED BY
MOUTH, OR BY INTRAMUSCULAR OR INTRAVENOUS INJECTION
ADULTS: INITIALLY, 25 MG P.O. ADJUST BY 25 MG Q 3 DAYS TO 100
MG/DAY (ON DIVIDED DOSES).

81. NARCOTIC ANALGESICS
• ADVERSE REACTIONS
• CNS: DIZZINESS, VERTIGO, HEADACHE, CNS STIMULATION, ANXIETY,
CONFUSION, EUPHORIA, NERVOUSNESS, SLEEP DISORDER, SEIZURES,
MALAISE, VISUAL DISTURBANCES.
• CV: VASODILATION.
• GI: NAUSEA, VOMITING, CONSTIPATION, DYSPEPSIA, DRY MOUTH,
DIARRHEA, ABDOMINAL PAIN, ANOREXIA, FLATULENCE.
• GU: URINE RETENTION, URINARY FREQUENCY, MENOPAUSAL
SYMPTOMS, PROTEINURIA.
• RESPIRATORY: RESPIRATORY DEPRESSION.
• SKIN: PRURITUS, DIAPHORESIS, RASH.

82. NARCOTIC ANALGESICS
CONTRAINDICATIONS & CAUTIONS
• CONTRAINDICATED IN PATIENTS HYPERSENSITIVE TO DRUG OR
OTHER OPIOIDS, IN BREAST-FEEDING WOMEN, AND IN THOSE WITH
ACUTE INTOXICATION FROM ALCOHOL, HYPNOTICS, CENTRALLY
ACTING ANALGESICS, OPIOIDS, OR PSYCHOTROPIC DRUGS.
• USE CAUTIOUSLY IN PATIENTS AT RISK FOR SEIZURES OR
RESPIRATORY DEPRESSION; IN PATIENTS WITH INCREASED
INTRACRANIAL PRESSURE OR HEAD INJURY, ACUTE ABDOMINAL
CONDITIONS, OR RENAL OR HEPATIC IMPAIRMENT; OR IN PATIENTS

83. NURSING CONSIDERATIONS FOR NARCOTIC
ANALGESICS
• - USE SUPPORTIVE NURSING MEASURES AS RELAXATION TECHNIQUES
TO RELIEVE PAIN BEFORE USING NACROTICS.
• - EXPLORE THE SOURCE OF PAIN, USE NON-NARCOTIC ANALGESIA IF
POSSIBLE.
• - ADMINISTER THE MEDICATION WHEN NEEDED, PROLONGING THE
MEDICATION ADMINISTRATION WILL DECREASE THE EFFECT OF THE
MEDICATION.
• - MONITOR VITAL SIGNS & MENTAL STATUS.
• - MONITOR RESPIRATORY RATE (DRUG MAY LEAD TO RESPIRATORY
DEPRESSION).

84. NURSING CONSIDERATIONS FOR NARCOTIC
ANALGESICS
• MONITOR BLOOD PRESSURE ( HYPOTENSION MAY OCCUR)
• - MONITOR PULSE RARE (IF 60M WITHHOLD THE DRUG).
• - WATCH FOR CONSTRICTED PUPILS. DOCUMENT IT AND NOTIFY THE
PHYSICIAN.
• - MONITOR BOWEL FUNCTION, SINCE DRUG MAY CAUSE
CONSTIPATION .
• - ENCOURAGE CLIENT TO EMPTY BLADDER EVERY 3-4 HRS (SINCE
DRUG MAY CAUSE URINARY RETENTION)

85. • IF CLIENT IS BED RIDDEN, USE SIDE RAILS.
• - INFORM THE CLIENTFAMILY THAT THE DRUG MAY BECOME
HABIT FORMING AND LEADING TO ADDICTION.
• - DOCUMENT ANY HISTORY OF ASTHMA OR OTHER
CONTRAINDICATIONS.
• - HAVE EMERGENCY EQUIPMENT AND NARCOTIC ANTAGONIST
AVAILABLE .
NURSING CONSIDERATIONS FOR NARCOTIC
ANALGESICS

86. OPIOID ANTAGONISTS
• THE NARCOTIC ANTAGONISTS ARE ABLE TO PREVENT OR REVERSE
MANY OF THE PHARMACOLOGICAL ACTIONS OF MORPHINE-TYPE
ANALGESICS & MEPEREDINE AS RESPIRATORY DEPRESSION INDUCED
BY THESE DRUGS WITHIN MINUTES.
• NALOXONE HYDROCHOLRIDE:
• TRADE NAME: NARCAN.
• CLASS.: NARCOTIC ANTAGONIST.

87. OPIOID ANTAGONISTS
• ACTION:
- BLOCK THE ACTION OF NARCOTIC ANALGESIC BY DISPLACING
PREVIOUSLY GIVEN NARCOTICS FROM THEIR RECEPTOR SITES OR
PREVENTING THEM FROM ATTACHING TO OPIATE RECEPTORS.
- THE DURATION OF ACTION OF NALOXONE IS SHORTER THAN THAT
OF THE NARCOTIC ANALGESIC SO THE RESPIRATORY DEPRESSION MAY
RETURN WHEN THE NARCOTIC ANTAGONIST HAS WASHED OFF THE
BODY.

88. OPIOID ANTAGONISTS
• USES:
• - RESPIRATORY DEPRESSION INDUCED BY NARCOTICS. - DRUG OF
CHOICE WHEN THE DEPRESSANT DRUG IS UNKNOWN. - DIAGNOSIS
OF ACUTE OPIATE OVERDOSE.
• SP: NALOXONE IS NOT EFFECTIVE WHEN RESPIRATORY DEPRESSION
IS INDUCED BY HYPNOTIC, SEDATIVE OR OTHER NONARCOTIC
DRUGS.

89. OPIOID ANTAGONISTS
• SIDE EFFECTS:
• - NAUSEA, VOMITING, SWEATING, HYPERTENSION, TREMORS.
• - IF USED POSTOPERATIVELY: TACHYCARDIA, PULMONARY EDEMA,
HYPO OR HYPERTENSION.
• DOSE:
0.4-2 MG I.V., S.C. OR I.M.

90. OPIOID ANTAGONISTS
• NURSING CONSIDERATIONS:
• 1- DETERMINE THE ETIOLOGY OF RESPIRATORY DEPRESSION.
• 2- ASSESS & OBTAIN BASELINE VITAL SIGNS.
• 3- MONITOR RESPIRATION CLOSELY AFTER THE DURATION OF
ACTION.
• 4- HAVE EMERGENCY DRUGS & EQUIPMENT AVAILABLE.
• 5- IF THE PATIENT IS COMATOSED, TURN HIM TO HIS SIDE TO
AVOID ASPIRATION.
• 6- MAINTAIN SAFE ENVIRONMENT (SIDE RAILS & SOFT SUPPORT).

91. THE MUSCULOSKELETAL SYSTEM
THE ANTI-INFLAMMATORY DRUGS AND
TREATMENT OF ARTHRITIS
• TO BE DISCUSSED NEXT WEEK!
• THANKS YOU! 