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Narcotic (Opioid) Analgesics

‫ تزتذدم فً الجوات القضائيى يعنً المخاكم وغيره عسان تسير الً كل انواع المذدرات السرعيى‬Narcotic ٌ‫كلم‬
‫والػير سرعيى‬

‫ عادي فً ما يفيد االنزان‬Opioid ‫ بتزتذدم فً الطب عادي عسان بتسير ألزتذدام ال‬Opioid ٌ‫اما كلم‬

√ CNS depressants, potent analgesics for all types of pain

√ Without loss of consciousness

√ Prolonged use leads to addiction

Classification
1) Opioid Agonists

a) Natural Phenanthrene Alkaloids of Opium

i. Morphine ii. Codeine

b) Semisynthetic Morphine (Phenanthrene) Derivatives

i. Heroin {Diacetylmorphine} ii. Dihydromorphinone

iii. Dihydrocodeinone

c) Synthetic (Non-Phenanthrenes) Morphine Substitutes

i. Meperidine ii. Fentanyl iii. Fentanyl Derivatives

iv. Methadone v. Tramadol

2) Mixed Agonist – Antagonist Narcotic Analgesics

i. Pentazocine ii. buprenorphine

iii. nalbuphine iv. butorphanol

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3) Natural Opium Alkaloids

a) Phenanthrene Opium Alkaloids

Narcotic Analgesic

Addictive Spasmogenic on smooth muscles

● Morphine “Main constituent”, 10% of opium

● Codeine 1% of opium

b) Benzyl- isoquinoline Opium Alkaloids

Not narcotic = Antitussive )necrosis ‫ يبقً بيعمل‬Narcotic ‫مضاد للقئ ( مش عسان ازمى‬

Not analgesic

No addiction ‫ اشال‬CNS ‫طبيعً انى مش بيعمل ادمان ألنى مش بيعدي ال‬

Spasmolytic on smooth muscles Used with abdominal colic

Negligible CNS action

Papaverine: Spasmolytic Narcotine: Antitussive

: ‫فً مجاميع تانيى زياده عن الكتاب بس هتوضخلك الدنيا اللً جايى برده زي مثال‬

● Semisynthetic morphine derivatives

- Heroin Not used as medication since 1910

● Synthetic morphine substitute ( Agonist )

: ‫ زي مثال‬Function ‫ فً ال‬Morphine ‫دي ادويى سبى ال‬

i. Meperidine ii. Methadone

iii. Tramadol iv. Fentanyl

! ‫ عسان مش عايزين نزرع النبات اشال‬Morphine ‫السركات بتخاول تشنع ادويى سبيوى لل‬

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● Mixed agonist – antagonist narcotic analgesia ( Partial agonist )

‫ادويى مره تستػل كده ومره تستػل كده‬

● Antagonist

Toxicity ‫ عسان نقدر نعالجوا لو خشل‬Antagonist ‫كل عيلى الزم يكون ليوا‬

i. Naloxone ii. Naltrexone

Morphine
Pharmacokinetics

Absorption

i. Orally → Low oral bioavailability {25 – 30%}

ii. Better absorbed after SC and IM injections

iii. Shock → Slow diluted IV injection (As it causes bradycardia and hypotension)

Distribution

i. All over the body

ii. Passes BBB

iii. Passes placental barrier

iv. Pregnancy → Addiction of fetus ( Respiratory center depression )

v. Labor → Neonatal asphyxia

Treat by naloxone:

a. IM to mother before labor

b. Intraumbilical to baby after labor

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Metabolism

i. Extensive (70-75%) hepatic first pass metabolism

ii. Conjugated with glucuronic acid by hepatic microsomal enzymes ► Deficient in

extremities of age → Supersensitivity

→ Active morphine-6-glucuronide {10%}

► More active than morphine

→ Inactive morphine-3-glucuronide {90%}

Excretion

i. Saliva → Test for racing horses

ii. Stomach → Stomach wash in all cases of poisoning

iii. Bile → Enterohepatic circulation

iv. Milk → Affect suckling baby

v. Urine → Major route of excretion t1/2→ 2 – 3 hours

Duration of Action → 6 – 8 hours

Pharmacodynamics
Mechanism of Action

A. Direct

Stimulation of opiate receptors in CNS {brain & spinal cord} and periphery {gut and
adrenal medulla}

Leading to: Inhibits release of substance P and modulate release of several

neurotransmitters

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 B. Indirect

Release of natural endogenous opioid peptides {endorphins, enkephalins and

dynorphins} (pleasure substances that increase during stress)

Types of opiate receptors ( Find all over the body )

i. Mu (μ):

Supraspinal analgesia, euphoria, RC inhibition, miosis and constipation

ii. Kappa (κ):

Spinal analgesia, miosis, less sedation and less RC inhibition

CNS → Mixed stimulation and depression

1. Stimulation: 2. Depression

i. Euphoria i. Analgesia ► All types of pain, WITHOUT

affecting other sensations;
ii. Increased cerebrospinal fluid EXCEPT itching ➢ Due to histamine release
iii. 3rd cranial nerve ► Miosis “Pin point pupil ii. Narcosis
”
iii. RC► Hypoventilation and Hypoxia
iv. Vagal center“CIC”► Bradycardia
iv. Cough center ► Antitussive
v. CTZ (Chemoreceptor trigger zone)“Small
dose” ► Nausea and vomiting v. VMC ► Hypotension

vi. Antidiuretic hormone (ADH) ► Edema + vi. HRC ► Hypothermia

Oliguria vii. ACTH – FSH - LH
vii. Monosynaptic {Sensory neuron synapse viii. Polysynaptic {Interneurons between
directly onto motor neuron} spinal reflexes sensory and motor nerves} spinal reflexes
{Stretch reflex} {Withdrawal reflex}

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viii. Lower seizure threshold ► Epilepsy

ix. Hippocampal pyramidal cells ► Truncal

rigidity

→ Impairs thoracic compliance and ventilation:

Administer neuromuscular blockers

‫ بس للتوضيح بس‬Analgsia for all type of pain except itching ‫ ال‬Mechanism ‫هشرح‬

Grey and white matter ‫ من‬Spinal cord ‫ده قطاع فً ال‬

ً‫ بييج‬Nerve ‫ اي‬Posterior and anterior horn ‫طالع منى‬

Sensory + Motor divisions ‫بيتقزم ل‬

‫ ويروح يمزك فً منطقى ازموا‬Post. horn ‫ هيقابل ال‬sensory ‫ال‬

collection of neurons ‫ دي عباره عن‬substania gelatinosa

Higher centers ‫بتزتقبل اسارات االخزاس وتزمد لوا بالمرور الً ال‬

Dorsal spinothalamic tract ‫عن طريق‬

‫ ولما ال‬Dorsal horn ً‫ بيكون تركيزها كبير ف‬M&K receptors ‫ دي مليانى‬SG ‫لقوا بقً ان منطقٌ ال‬
‫ ف متطلعش لل‬Pain transmitter ‫ بتاع ال‬Substance P ‫دي بتستػل بتوقف دذول او وشول ال‬receptor
Pain sense ‫ وتكون وقفت ال‬Higher centers

‫ عند مزتوي ال‬Sense of pain ‫ بيوقف ال‬Morphine ‫ يعنً ال‬Spinal analgesia ‫وده بيكون ازمى‬
Spinal

Supraspinal analgesia ‫ تانً ازمى‬Mechanism ً‫ف‬

‫ يروح ليوم هيعمل‬Morphine ‫ ولما ال‬M&K receptors ً‫ هنالق‬Higher centers ‫هنروح ع طول لل‬

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 ‫ اللً طالع عن‬Pain sensory ‫ ودي هتقابل ال‬activate to descending inhibitory pain control
Higher ceters ‫ وتمنعى يطلع ال‬Spinal cord ‫طريق ال‬

Oculumotor nerve = 3rd cranial nerve ‫ ازمى‬Nerve ً‫ ف ف‬Miosis ‫بالنزبى لل‬

4 – 6 Muscles that control eye movement ‫بيبقً مزؤول عن‬

‫ يعمل خاجى ازموا‬Stimulation ‫يعملى‬Morphine ‫فلما ال‬

Sever miosis bilateral

)Pin point eye( ‫ بيتعرف من عينى بيبقً عنده‬Morphine ‫عسان كده اللً بياذد‬

‫ ازموا‬Medulla ‫ بيروح ينبى منطقى فً ال‬Morphine ‫ ف ال‬Neusea and vomiting ‫بالنزبٌ بقً لل‬
Chemoreceptor trigger zone

Euphoria ‫اما بالنزبى لل‬

‫ بيبقً عامل دماغ وينزً مساكلى ويخس بزعاده‬Opioid ‫فبيقولك اللً بياذد‬

‫ ممكن ازتذدم خاجات تانيى‬Medication ‫ هنا ك‬Morphine ‫لكن مش بزتذدم ال‬

CVS
→ Small therapeutic dose ► No effect

→ Large dose, especially IV ► Hypotension

→ Inhibit VMC + Stimulate vagal center

→ Direct Venodilator → Histamine release ► Vasodilatation

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Respiratory system
1. Decreases sensitivity of RC to CO2

2. Depresses cough center ► Central antitussive

3. Histamine release

► Large dose ➢ Bronchospasm

4. Induces bronchospasm

GIT
1. Spasmogenic ► Increases tone of muscles and spasm of sphincters ➢ Decreases
propulsive peristalsis and inhibits defecation reflex→ Constipation

2. Decreases gastric, biliary, and pancreatic secretions

Biliary tract
Spasmogenic ► Spasm of wall of gall bladder and sphincter of Oddi → Increase
intrabiliary pressure

► Avoid after cholecystectomy and add atropine in biliary colic

Urinary tract
Spasmogenic ► Spasm of ureter → Add atropine in renal colic

Spasm of sphincters → Urine retention

Oliguria → Increased ADH

Uterus → No effect BUT passes placental barrier ► Neonatal asphyxia

Skin → Sweating and Histamine release ► Itching and wheal formation

‘Triple response of Lewis’

Metabolism → Decreases basal metabolic rate

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 ‫ هو‬Morphine ‫ الزم نعرف ان ال‬Bilairy tract ‫ و‬Urinary tract ‫ و‬GIT ‫ و‬RS ‫قبل ما نسرح ال‬
ً‫ فً كل المناطق دي ندذل فً سرخوم بق‬Spasmogenic

GIT Constipation

‫ كده االكل مش هيتخرك من مكان للتانً وكمان‬Dec. propulsive movement ‫ يروح يعمل‬Morphine ‫ال‬
‫ ينسف ف خركتى هتبقً اشعب‬Food ‫ كده ذليت ال‬Water absorbtion ‫بيزود ال‬

Urinary bladder Inc. tone Spasmogenic + spasm of ureter

‫ يعنً المريض يبقً عايز يدذل الخمام بس‬Ureter ‫ وكمان‬Sphincter ً‫ ف‬Spasm ‫ بيعمل‬Morphine ً‫يعن‬
Difficult micturition ‫عنده‬

Biliary tract

Sphincter of oddi ‫ و‬Gall bladder ً‫نفس الكالم اللً فوق ده بيخشل ف‬

N.B

Atropine + Morphine Antispasmogenic ( Spasmolytic )

Tolerance
1. After continued use for 10 – 14 days

2. Decreased endogenous endorphins and enkephalins or, increased adenylate

cyclase expression

3. Affects mainly analgesia and RC inhibition

4. Does not affect pinpoint pupil, constipation, or excitation

5. Followed by psychic and physical dependence, causing addiction

6. Cross tolerance and dependence between narcotic analgesics

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Dosing and Route of Administration
SC {10 mg} IM {10 mg}

IV {5 mg} Oral {30 mg}

‫ او اقل من كده‬5 mg ً‫) يبق‬IV( ‫ فلو هاخده‬hypotension ‫ بيعمل‬Morphine ‫ناخد بالنا ان ال‬

Therapeutic Uses
I. Pain ► Analgesic in severe visceral pain ( Not in mild or moderate pain )

1. Cardiac pain {Myocardial infarction}

2. Cancer pain {Especially terminal stages}

3. Colic {Add atropine in biliary and renal colic}

4. Bone fractures {Except skull as morphine is contraindicated in head injury}

5. Postoperative {Except biliary and eye operations}

II. Pulmonary edema due to acute left ventricular failure

1. Venodilator: Decreases venous return ► Decreases end diastolic volume →

Decreases preload ► Decreases pulmonary congestion

Lung ‫ يتجمع ويعمل‬Lung ‫ مش قادر يضر الدم ويطلعى ف يبدأ الدم اللً جاي من‬LV ‫● لما بيخشل ان ال‬
Pulmonary edema ً‫ وده هيزببل‬congestion

:‫ عسان يعالح خالى زي دي‬Morphine ‫يعمل ايى بقً ال‬

(1) Venodilator

Histamine ‫ بيزاعد فً افراز ال‬Morphine ‫وده ألن ال‬

‫ بيروح يوزعوا‬histamine ‫ ال‬precapillary sphincter ‫وبعدين ايى اللً يخشل ؟! فً عندنا خاجى ازموا‬

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Venous ‫ ويروح ال‬arterial side ‫ عندنا مقفولى عسان تمنع الدم ييجً من ال‬Capillaries ‫ من ال‬%09 ‫ودي ان‬
side

‫ ف بكده هيقلل ال‬Venous side ‫ يروح ع‬arterial side ‫ف انا لما بوزع البوابات دي يخشل ان الدم يتخرك من‬
Lung ‫ وميخشلش‬Lung ‫ ف يقل ال‬Heart ‫ فكده انت قللت كميى الدم اللً هتطلع من‬Venous return
congestion

2. Sedation: Depress sympathetic ► Arteriodilator → Decreased total peripheral

resistance ► Decreased afterload

3. Slow respiration

inhibition to RS ‫طب ازاي واخنا قولنا انى بيعمل‬

‫ شػيره وبكده مش هتأثر جامد‬Pulmonary edema ‫ده بزبب ان الجرعى اللً بديوا لمريض ال‬

III. Primary neurogenic shock

IV. Preanesthetic medication

To provide analgesia, sedation, and amnesia

Adverse Effects
1. Interfere with proper diagnosis of head injury and acute abdomen

2. Inhibition of respiration 3. Pinpoint pupil

4. Nausea and vomiting 5. Bronchospasm

6. Constipation 7. Urine retention

8. Neonatal asphyxia 9. Itching

10.Tolerance and cross tolerance with other opioids

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Contraindications

i. Head injury

‫ ده زياده‬pressure ‫ فويزود ال‬morphine ‫ عالً ولو ذد‬ICP ‫ بيكون‬head injury ‫ألن اللً عنده‬

1. Miosis → Interfere with proper diagnosis

2. RC Inhibition → Increase CO2 ► Cerebral vasodilatation → Increases synthesis of

CSF → Increases intracranial tension ► More RC inhibition

RS inhibition ‫ هو ال‬adverse effect ‫من ال‬

ً‫ ه‬RS inhibition ‫ اللً بتموت وتعمل‬overdose ‫معلومى ليك فً الحتى دي ان الجرعى ال‬

(100 mg)

ii. Increased intracranial tension

iii. Epilepsy

iv. Respiratory diseases {Asthma – COPD}

v. Acute abdomen

Morphine ► Analgesia → Interfere with proper diagnosis

‫ عسان ممكن يكون مسكلى مختاجى دوا يعالح مش مزكن لأللم‬abdomen ‫ كويس ل‬diagnosis ‫الزم تعمل‬

vi. Pregnancy and Lactation

Addict fetus ► Withdrawal symptoms after labor

vii. Labor → Neonatal asphyxia

viii. Advanced liver disease → Deficient metabolism

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ix. Extremities of age → Deficient metabolism

x. Myxedema

Decrease metabolism ► More CNS inhibition + Decrease basal metabolic rate →

Myxedema coma {Hypotension, bradycardia, hypothermia, hypoventilation}

xi. Alone in biliary and renal colic, also pancreatitis

xii. Allergy to morphine

xiii. History of addiction to morphine or other opiates Poisoning

Acute Morphine Poisoning

Manifestations

1- Pin point pupil 2- Hypothermia

3- Hypotension 4- Hypoventilation

5- Coma

Cause of Death

Respiratory failure

Treatment:

1- Artificial respiration ( First line of treatment )

2- No pure oxygen → Apnea

3- Stomach wash ► Even with parenteral poisoning

4- Potassium permanganate + Charcoal + Magnesium sulfate

5- Specific morphine antagonist: Naloxone 0.4-2 mg IV or Naltrexone

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 ‫معلومى ليك مومى جدا جدا‬

Acute poisoning only ً‫ اال ف‬Naloxone ‫مينفعش استخدم‬

Acute withdrawal ً‫ ده خطأ كبير جدا عشان هيدخلى ف‬chronic ‫لو استخدمتى مع ال‬
‫ اللً هو شغال‬M&K receptors ‫ ممكن ينتحر وهو واقف قدامك ألنك كده قفلتلى ال‬syndrome
‫بيوم بقالوا سنين‬

Artificial ‫ اسيبى يموت ؟! ال طبعا بيبقً عالجى‬with chronic poisoning ‫طب لو جالً مريض‬
respiration only

Addiction = Chronic Poisoning

1. Tolerance 2. Psychic dependence

3. Physical dependence: Caused by decreased endogenous endorphins and

enkephalins

Sudden stop of morphine {symptoms begin 8-10 hours after last dose} or use of
morphine antagonist precipitates withdrawal or abstinence syndrome

Symptoms of Addiction:

1- Pin point pupil 2- Constipation

3- Psychosis {Drug seeking habit} 4- Moral deterioration

Manifestations of Withdrawal {Abstinence} Syndrome:

1. Psychic craving for morphine

2. Anxiety 3. Yawning 4. Lacrimation
5. Rhinorrhea 6. Reversal of all actions of morphine 7. Excitation
8. Severe pain “Aches” 9. Fever 10. Mydriasis
11. Hyperventilation 12. Hypertension 13. Tachycardia
14. Diarrhea 15. Urination 16. Salivation

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17. Sweating 18. Tremors 19. Convulsions
20. Coma

● Symptoms disappear on taking morphine

Management of Morphine Addiction

● Hospitalization and Psychotherapy

● Gradual withdrawal of morphine → Till the stabilizing dose

● Gradual substitution with methadone

As morphine with less withdrawal manifestations

● Gradual withdrawal of methadone

Clonidine → Control many withdrawal symptoms ( stimulate alpha 2 receptor )

{Inhibits sympathetic hyperactivity during withdrawal}

Acupuncture → Increases release of endogenous endorphins and enkephalins

Oral naltrexone → μ antagonist that blocks euphoria, producing dysphoria

Other Opioid Agonists

I. Codeine {Methylmorphine}

1. Phenanthrene opium alkaloid

2. 1% of opium

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3. Pharmacodynamic:

As morphine BUT:

i. Less potent ii. Less addictive

iii. Less RC depression iv. Produces excitation in large doses

4. Therapeutic Uses

i. Analgesic ii. Central antitussive

‫ شغال بطريقتين‬Codeine ‫كده ال‬

‫ ومره تانيى‬Opiate recep. ‫مره مع نفزى يروح ينبى ال‬

Demethylation ‫ عن طريق‬Morphine ‫يتخول ل‬

Under genetic control ً‫لكن مش كل الناس لألزف تقدر تعمل موضوع تخويلى ده ف بيتزم‬

Potency Less Potent ‫طب ايى حكايٌ ال‬

Morphine 100% ‫ايى معنً الجدول؟؟‬
Codeine 10%
Standard dose of morphine is 10mg ‫معناه ان لو‬

100mg ‫ هتكون‬Morphine‫ اللً لو خبيت اديوا للعيان عسان تكون مزاويى لل‬Dose of codeine ‫كده ال‬

‫وده طبعا هيعمل مساكل‬

‫ لكن انت وشلت‬Morphine ‫الن كده هيستػل زي ال‬

‫ بدري جدا وده ذطر كبيير ألن انت متضمنش‬RD ‫لل‬

‫ تقل كل ما يكون امان اكتر‬Dose ‫ عسان كده كل ما ال‬dose ً‫يخشل عند انو‬

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‫سبحان هللا وبحمده سبحان هللا‬
‫العظيم‬
‫تعود علي العادات الحسنه‬
‫وهي سوف تصنعك‪!!..‬‬

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