Opioid (narcotic) analgesics and antagonists. Non-opioid (non-narcotic) analgesics

Август 9, 2022

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Opioid (narcotic) analgesics and antagonists. Non-opioid (non-narcotic) analgesics

Содержание

3. 1. FULL AGONISTS: Morphine hydrochloride Tab. 0.01 g; amp. 1% -1 ml Omnopon – amp. 1%
4. 3. Antagonists: Naloxone – amp. 0.04% - 1 ml Naltrexone – Tab. 0.01 ; 0.05 g
5. 1. Phenantrenes: Morphine Codeine Omnopon Aethylmorphine 2. Isoquinolines: Papaverine hydrochloride OPIATES (Opium Alkaloids)
7. μ-Rs: Supraspinal Analgesia, Euphoria / Sedation, Respiratory Depression, ?GIT Motility, Smooth Muscle Spasm, Miosis κ-Rs: Spinal
8. MECHANISM OF ACTION: Stimulation of Opioid Receptors through Gi-Proteins => inhibition of Adenylyl Cyclase => ?K+
9. CNS: Euphoria, Drowsiness, Apathy, Mental Confusion, Nausea and Vomiting Respiratory: ?Tidal Volume ?Respiratory Rate Antitussive effects:
10. GIT: Inhibition of peristalsis => Constipation Sphincter of Oddi spasm, nausea ⭣Gastric, Biliary, and Pancreatic Secretions
11. Clinicall uses of MORPHINE ⮟ ANALGESIA: Renal or Biliary Colic Myocardial Infarction Acute Trauma Postoperative Pain
12. OVERDOSE with MORFINE Respiratory and CNS Depression, Miosis ?BP ?HR ? t° Skin is bluish and
13. Treatment of overdose with Morphine Narcotic antagonist: NALOXONE 0.4 mg/ml IV bolus 0.8-2 mg (2-5 ml)
14. Promedole amp. 1% -1 ml, Tab. 0.025 g, a synthetic opioid, Piperidine Compound Binds to opioid
15. Fentanyl amp. 0.005%-1 ml ∙ is chemically related to Promedole, ∙ has 80 times the analgesic
16. Pentazocine amp. 3%-1 ml,Tab. 0.05 agonist - κ-Rs and σ-Rs antagonist - μ and δ-Rs Activates
17. TRAMADOL caps. 0.05 g; amp. 5%-1 ml a centrally acting weak synthetic opioid with μ agonist
18. Naloxone amp. 0.04%-1 ml - a pure Antagonist. antagonizes most of the opioid effects: respiratory depression,
19. Naltrexone - Tab. 0.05 g (50 mg) T1/2 = 10 hours. A single oral dose of
20. Drugs from other groups with analgesic activity α2 – Adrenomimetics: Clopheline Tricyclic antidepressants: Amitriptyline Imizine Antiepileptic
21. NON-OPIOID ANALGESICS 1.Para-Aminophenol Compounds Paracetamol (Acetaminophen, Panadol) Phenacetin 2. Salicylates – Salicylic Acid Compounds Acetylsalicylic Acid
22. 4. Antranil Acid Compounds Mephenamic Acid 5. Indole-Acetic Acid Compounds Indometacin 6. Phenyl-Acetic Acid Compounds Diclofenac-Sodium
24. COX-2 inhibitors: Meloxicam Celecoxib Nimesulide COX-1 is structural and responsible for PROTECTIVE PROPERTIES of GIT. COX-2
25. Para-Aminophenol Compounds: ● Paracetamol ● Phenacetin Mechanism of action: inhibition of COX-3 1) Antipyretic action: Inhibition
26. ADVERSE EFFECTS Hemologic: hemolytic anemia, neutropenia, leukopenia, thrombocytopenia Hepatic: Liver Damage (toxic doses), Rash, Hypoglycemia ?Hepatic
27. Large doses of Paracetamol ( 7-10 g) => Hepatocellular damage with central lobular necrosis Renal tubular
28. Aspirin is a weak organic acid that is unique among the NSAIDs in irreversibly acetylating (inactivating)
29. MECHANISM OF ASPIRIN ASTHMA DEVELOPMENT ARACHIDONIC ACID COX Inhibitors
30. THERAPEUTIC USES of SALICYLATES 1. Antipyretics and analgesics: Gout, Rheumatic Fever, Rheumatoid Arthritis. headache, arthralgia, and
31. ADVERSE EFFECTS of SALICYLATES 1. GIT: nausea, vomiting, bleeding, ulceration 2. Blood: ?Prothrombin Aspirin should not
32. SALICYLISM - a condition of mild salicylate intoxication: nausea, vomiting, hyperventilation, headache, mental confusion, dizziness, tinnitus
33. Analgin (Metamizole) Tab. 0.5 g, amp. 25%-2 ml Antipyretic action - by direct action on the
34. Analgin is a major cause of AGRANULOCYTOSIS Phenylbutazone (Butadion) Diclofenac-natrium Indometacin can cause APLASTIC ANEMIA. =>
35. Indomethacin - is more effective in relieving inflammation with acute gouty arthritis, osteoarthritis of the hip,
36. Diclofenac-Natrium (VOLTAREN) Tab. 0.025 g; amp. 2.5%-3 ml a Potent COX inhibitor with Antiinflammatory, Analgesic, and
37. Ketorolac Tab. 10 mg (0.01 g), amp. 3%-1 ml IM, ophthalmic drops: 0.5% solution Effective Analgesic
38. Selective COX-2 inhibitors Meloxicam Tab. 0.015 g Celecoxib Caps. 0.1 g Advantage: fewer Gastric Ulcers and
39. Слайд № из 40 Mechanism of Cardiovascular Disorders Development Thrombus ARACHIDONIC ACID COX-1 COX-2 TXА2 Prostacyclin
40. Rofecoxib, Valdecoxib, Nimesulide – have been withdrawn from the pharmaceutical market: Rofecoxib and Valdecoxib have been
42. Скачать презентацию

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1. FULL AGONISTS:
Morphine hydrochloride Tab. 0.01 g; amp. 1% -1 ml
Omnopon

– amp. 1% solution - 1 ml
Promedole (Trimeperidine)-amp. 1% - 1 ml, Tab. 0.025 g
Fentanyl – amp. 0.005% - 1 ml
2. PARTIAL AGONISTS, or Agonists-Antagonists:
Pentazocine – amp. 3%-1 ml, Tab. 0.05 g
Tramadol – caps. 0.05; amp. 5%-1 ml
Nalorphine – amp. 0.5%-1 ml and 0.05%-0.5 ml
Buprenorphine – Tab. 0.0002

OPIOID AGONISTS and ANTAGONISTS

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3. Antagonists:
Naloxone – amp. 0.04% - 1 ml
Naltrexone – Tab. 0.01

; 0.05 g

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1. Phenantrenes:
Morphine
Codeine
Omnopon
Aethylmorphine
2. Isoquinolines:
Papaverine hydrochloride
OPIATES (Opium Alkaloids)

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μ-Rs: Supraspinal Analgesia,
Euphoria / Sedation,
Respiratory Depression,

?GIT Motility,
Smooth Muscle Spasm, Miosis
κ-Rs: Spinal Analgesia,
Sedation / Dysphoria, Miosis
σ-Rs: Dysphoria, Psychotomimetic effects, Respiratory and Vasomotor Stimulation, Mydriasis
δ-Rs: Euphoria, Convulsive activity
ε-Rs: β-endorphine-like Analgesia

OPIATE RECEPTORS

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MECHANISM OF ACTION:
Stimulation of Opioid Receptors through Gi-Proteins =>
inhibition

of Adenylyl Cyclase =>
?K+ Efflux (Hyperpolarization)
?Ca2+ Influx
=> impeding Neuronal Firing and
Transmitter Release

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CNS: Euphoria, Drowsiness, Apathy,
Mental Confusion, Nausea and Vomiting
Respiratory:
?Tidal Volume ?Respiratory

Rate
Antitussive effects: a direct suppression of
the Cough Reflex Center
Cardiovascular: Peripheral Vasodilation
?Total Peripheral Resistance
Histamine Release =>
Flushing, Red Eyes, Sweating

PHARMACOLOGICAL EFFECTS

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GIT:
Inhibition of peristalsis => Constipation
Sphincter of Oddi spasm, nausea
⭣Gastric,

Biliary, and Pancreatic Secretions
?Tone in the Biliary Tract => Biliary Spasm
?Amylase and Lipase levels up to 15 times
Urinary tract:
?Smooth Muscle tone and spasms

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Clinicall uses of MORPHINE
⮟ ANALGESIA:
Renal or Biliary Colic
Myocardial Infarction
Acute

Trauma
Postoperative Pain
Terminal Cancer
⮟ PULMONARY EDEMA

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OVERDOSE with MORFINE
Respiratory and CNS Depression, Miosis ?BP
?HR
? t°
Skin is bluish

and cold, face is pale,
Urine Retention, bladder overflowed,
Circulatory Collapse,
Pulmonary Edema, Convulsions,
Shock, Apnea, Cardiopulmonary Arrest

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Treatment of overdose with Morphine
Narcotic antagonist: NALOXONE 0.4 mg/ml
IV bolus 0.8-2

mg (2-5 ml) q2-3 min to a total dose 10 mg
Symptomatic treatment:
Cordiamine, Sulfocamphocaine,
Atropine, Coffeine
⮟ Continued Respiratory Support
⮟ Correction of Fluid and Electrolyte Imbalance
FORCED DIURESIS:
5% Glucose 500-800 ml
0.9% NaCl isotonic solution
4% NaHCO3
FUROCEMIDE 0.1% 4-8 ml

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Promedole amp. 1% -1 ml, Tab. 0.025 g,
a synthetic opioid,

Piperidine Compound
Binds to opioid Rs, particularly κ-Rs
It is preferred for analgesia during LABOR –
Neonatal Respiratory Depression is less marked
and it does not interfere with Uterine Contractility
It is often used in minor procedures like dilatation and curettage.

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Fentanyl amp. 0.005%-1 ml
∙ is chemically related to Promedole,
∙ has

80 times the analgesic potency of Morphine.
has a rapid onset and short duration of action (15-30 min)
FENTANYL + DROPERIDOL
produce a NEUROLEPTANALGESIA

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Pentazocine amp. 3%-1 ml,Tab. 0.05
agonist - κ-Rs and σ-Rs
antagonist - μ

and δ-Rs
Activates Rs in the spinal cord, and is used to relieve moderate pain
In angina:
?Aortic pressure
?Pulmonary AP => ?Heart Work
?Renal plasma flow

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TRAMADOL caps. 0.05 g; amp. 5%-1 ml
a centrally acting weak

synthetic opioid
with μ agonist effect and inhibitory action on
Noradrenaline and Serotonin reuptake in the CNS.
T1/2 = 6 hours
is only partially antagonized by Naloxone.
Adverse reactions: Dizziness, Headache, somnolence, CNS stimulation, euphoria, anxiety, coordination disturbance, seizures, vasodilation, anorexia, dry mouth,
urine retention, respiratory depression.

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Naloxone amp. 0.04%-1 ml - a pure Antagonist.
antagonizes most of the

opioid effects:
respiratory depression, sedation, and hypotension
Duration of action 1-4 hours
Clinical uses:
Treatment of acute opioid overdose
Postoperative narcotic depression
Diagnosing opiate dependence
Septic shock
Adversed effects: ?HR, ?AP, ventricular fibrillation, cardiac arrest; tremors and withdrawal symptoms in narcotic-dependent patients, diaphoresis, seizures, pulmonary edema.

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Naltrexone - Tab. 0.05 g (50 mg)
T1/2 = 10 hours.

A single oral dose of 100 mg (2 tab.) blocks virtually all effects of a dose of heroin for up to 48 hours.
PO 30-50 mg => minimal analgesia, only slight drowsiness, and no respiratory depression.
Psychotomimetic effects, ?AP
Clinical uses:
Adjunct for maintenance of opioid-free state in detoxified individuals;
Alcoholism.

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Drugs from other groups with analgesic activity
α2 – Adrenomimetics: Clopheline
Tricyclic antidepressants:

Amitriptyline Imizine
Antiepileptic drugs: Carbamazepine Sodium Valproate
GABA-receptors’ agonists: Baclophene
Hormones: Somatostatin, Calcitonin
Drugs for narcosis: Nitrous oxide (N2O) Ketamine

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NON-OPIOID ANALGESICS
1.Para-Aminophenol Compounds
Paracetamol (Acetaminophen, Panadol)
Phenacetin
2. Salicylates – Salicylic Acid

Compounds
Acetylsalicylic Acid (Aspirin)
Sodium Salicylate
3. Pyrazolone Compounds
Analgin (Metamizole)
Butadione (Phenylbutazone)

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4. Antranil Acid Compounds
Mephenamic Acid
5. Indole-Acetic Acid Compounds
Indometacin
6. Phenyl-Acetic

Acid Compounds
Diclofenac-Sodium
7. Phenyl-Propionic Acid Compounds
Ibuprophen
8. Naphtyl-Propionic Acid Compounds
Naproxen
- oxicams :
Piroxicam

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COX-2 inhibitors:
Meloxicam
Celecoxib
Nimesulide
COX-1 is structural and responsible for PROTECTIVE PROPERTIES of

GIT.
COX-2 is induced and responsible for
PG production by cells involved in INFLAMMATION.
COX-3 is located in the CNS

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Para-Aminophenol Compounds:
● Paracetamol
● Phenacetin
Mechanism of action: inhibition of COX-3

1) Antipyretic action:
Inhibition of COX-3 => ?PG synthesis in the CNS
2) Analgesic action:
is related to an elevation of the pain threshold.
Tab. «Citramon»:
Aspirin 0.2 g
Phenacetin 0.2 g
Caffeine 0.04 g

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ADVERSE EFFECTS
Hemologic: hemolytic anemia, neutropenia, leukopenia, thrombocytopenia
Hepatic: Liver Damage (toxic doses),

Rash, Hypoglycemia
?Hepatic enzymes
dizziness, excitement, disorientation.

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Large doses of Paracetamol ( 7-10 g) =>
Hepatocellular damage with

central lobular necrosis
Renal tubular necrosis
The liver toxicity: due to toxic metabolite
N-acetyl-P-benzoquinonamine, which normally turns harmless by Conjugation with Glutathione.
TREATMENT:
Sulfhydryl SH- compounds:
Acetylcysteine (ACC)
Cystamine
Methionine

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Aspirin is a weak organic acid that is unique among
the

NSAIDs in irreversibly acetylating (inactivating)
COX-1 and COX-2.
NSAIDs have 3 major therapeutic actions:
⮟Antinflammatory
⮟ Analgesic
⮟ Antipyretic

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MECHANISM OF ASPIRIN ASTHMA DEVELOPMENT
ARACHIDONIC ACID
COX
Inhibitors

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THERAPEUTIC USES of SALICYLATES
1. Antipyretics and analgesics:
Gout, Rheumatic Fever, Rheumatoid

Arthritis. headache, arthralgia, and myalgia.
2. External applications:
Salicylic acid is used topically to treat calluses and epidermophytosis
Methyl salicylate –
externally as a cutaneous counterirritant
3. Cardiovascular applications:
Aspirin 170-350 mg
4. Colon cancer

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ADVERSE EFFECTS of SALICYLATES
1. GIT: nausea, vomiting, bleeding, ulceration
2. Blood: ?Prothrombin

Aspirin should not be taken for at least 1 week prior to surgery.
3. Respiration: Respiratory Alkalosis and
true Metabolic Acidosis.
4. Metabolic processes: hyperthermia
5. Hypersensitivity: Urticaria, Bronchospasm,
Lyell's syndrome (Epidermal Necrolysis),
Angioneurotic Edema, Anaphylactic Shock
6. Reye's syndrome:
HEPATITIS with CEREBRAL EDEMA

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SALICYLISM - a condition of mild salicylate intoxication:
nausea, vomiting, hyperventilation,
headache,

mental confusion,
dizziness, tinnitus (ringing in the ears),
tachypnoea and respiratory alkalosis
SEVERE SALICYLATE INTOXICATION :
restlessness, delirium, hallucinations,
convulsions, coma,
Respiratory Alkalosis + Metabolic Acidosis,
Death from respiratory failure.
Treatment: gastric lavage, correction of hyperthermia,
IV fluids
Dialysis (hemodialysis or peritoneal dialysis)
Correction of acid-base and electrolyte balances:
Urinary Alkalinization: normal 0.9% NaCl saline solution
containing 2% glucose solution and
2% Sodium Bicarbonate solution at the rate of 2 liters/hour.

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Analgin (Metamizole) Tab. 0.5 g, amp. 25%-2 ml
Antipyretic action - by

direct action
on the hypothalamic heat-regulating center to block the effects of Endogenous Pyrogens IL1,TNF-α
=> heat dissipation through sweating and vasodilation
T1/2 = 72 hours.
Clinical uses: moderate to severe pain including headache, toothache, neuralgia, and myalgia

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Analgin is a major cause of AGRANULOCYTOSIS
Phenylbutazone (Butadion)
Diclofenac-natrium

Indometacin
can cause APLASTIC ANEMIA.
=> Should be used ONLY when ASPIRIN and other safer NSAIDs are ineffective.

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Indomethacin -
is more effective in relieving inflammation
with acute gouty arthritis,

osteoarthritis of the hip,
ankylosing spondylitis, and uveitis,
postoperative ophthalmic procedures,
Indomethacin can delay labor by suppressing uterine contractions.
Indomethacin has been recommended as
a Tocolytic in Preterm Labour < 32 weeks of gestation.

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Diclofenac-Natrium (VOLTAREN)
Tab. 0.025 g; amp. 2.5%-3 ml
a Potent COX inhibitor

with Antiinflammatory, Analgesic, and Antipyretic properties
more potent than Indomethacin
Adverse effects: 20% of patients -
GIT distress,
Occult GIT Bleeding,
Gastric Ulceration,
? Hepatic Enzyme Levels

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Ketorolac
Tab. 10 mg (0.01 g),
amp. 3%-1 ml IM,
ophthalmic

drops: 0.5% solution
Effective Analgesic in patients with
moderate to severe postoperative pain.
as effective as Morphine, and have fewer side effects, in surgical and chronic cancer pain.
has longer duration of action (T1/2 = 5 hours) and acts like the other NSAIDs
has less antinflammatory activity
Clinical uses: postoperative pain, cancer pain,
topically for allergic conjunctivitis

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Selective COX-2 inhibitors
Meloxicam Tab. 0.015 g
Celecoxib Caps. 0.1 g
Advantage: fewer Gastric

Ulcers and do not inhibit platelet aggregation
Disadvantage: may have prothrombotic effect, leading to a higher incidence of Cardiovascular Events.
Adverse reactions:
Renal Toxicity – ?Renal blood flow, Edema, Hypertension
Interfere with Wound (Ulcer) Healing, Bone Remodeling, Prenatal Renal Development

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Слайд № из 40
Mechanism of Cardiovascular Disorders Development
Thrombus
ARACHIDONIC ACID
COX-1
COX-2

TXА2

Prostacyclin (PgI2)

COX-2
inhibitors

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Rofecoxib, Valdecoxib, Nimesulide –
have been withdrawn from the pharmaceutical market:
Rofecoxib

and Valdecoxib have been reported to be associated with increased incidence of
MYOCARDIAL INFARCTION and STROKE,
Nimesulid - due to its high HEPATOTOXICITY.

Opioid (narcotic) analgesics and antagonists. Non-opioid (non-narcotic) analgesics

Содержание

1. FULL AGONISTS: Morphine hydrochloride Tab. 0.01 g; amp. 1% -1 ml Omnopon

3. Antagonists: Naloxone – amp. 0.04% - 1 ml Naltrexone – Tab. 0.01

1. Phenantrenes: Morphine Codeine Omnopon Aethylmorphine 2. Isoquinolines: Papaverine hydrochlorideOPIATES (Opium Alkaloids)

μ-Rs: Supraspinal Analgesia, Euphoria / Sedation, Respiratory Depression,

MECHANISM OF ACTION: Stimulation of Opioid Receptors through Gi-Proteins => inhibition

CNS: Euphoria, Drowsiness, Apathy, Mental Confusion, Nausea and Vomiting Respiratory: ?Tidal Volume ?Respiratory

GIT: Inhibition of peristalsis => Constipation Sphincter of Oddi spasm, nausea⭣Gastric,

Clinicall uses of MORPHINE ⮟ ANALGESIA: Renal or Biliary Colic Myocardial Infarction Acute

OVERDOSE with MORFINE Respiratory and CNS Depression, Miosis ?BP ?HR ? t° Skin is bluish

Treatment of overdose with MorphineNarcotic antagonist: NALOXONE 0.4 mg/mlIV bolus 0.8-2

Promedole amp. 1% -1 ml, Tab. 0.025 g, a synthetic opioid,

Fentanyl amp. 0.005%-1 ml∙ is chemically related to Promedole, ∙ has

Pentazocine amp. 3%-1 ml,Tab. 0.05 agonist - κ-Rs and σ-Rs antagonist - μ

TRAMADOL caps. 0.05 g; amp. 5%-1 ml a centrally acting weak

Naloxone amp. 0.04%-1 ml - a pure Antagonist.antagonizes most of the

Naltrexone - Tab. 0.05 g (50 mg) T1/2 = 10 hours.

Drugs from other groups with analgesic activityα2 – Adrenomimetics: ClophelineTricyclic antidepressants:

NON-OPIOID ANALGESICS1.Para-Aminophenol Compounds Paracetamol (Acetaminophen, Panadol) Phenacetin 2. Salicylates – Salicylic Acid

4. Antranil Acid Compounds Mephenamic Acid 5. Indole-Acetic Acid Compounds Indometacin 6. Phenyl-Acetic

COX-2 inhibitors: Meloxicam Celecoxib NimesulideCOX-1 is structural and responsible for PROTECTIVE PROPERTIES of

Para-Aminophenol Compounds: ● Paracetamol ● Phenacetin Mechanism of action: inhibition of COX-3

ADVERSE EFFECTSHemologic: hemolytic anemia, neutropenia, leukopenia, thrombocytopeniaHepatic: Liver Damage (toxic doses),

Large doses of Paracetamol ( 7-10 g) => Hepatocellular damage with

Aspirin is a weak organic acid that is unique among the

MECHANISM OF ASPIRIN ASTHMA DEVELOPMENTARACHIDONIC ACIDCOXInhibitors

THERAPEUTIC USES of SALICYLATES1. Antipyretics and analgesics: Gout, Rheumatic Fever, Rheumatoid

ADVERSE EFFECTS of SALICYLATES1. GIT: nausea, vomiting, bleeding, ulceration2. Blood: ?Prothrombin

SALICYLISM - a condition of mild salicylate intoxication: nausea, vomiting, hyperventilation, headache,

Analgin (Metamizole) Tab. 0.5 g, amp. 25%-2 mlAntipyretic action - by

Analgin is a major cause of AGRANULOCYTOSIS Phenylbutazone (Butadion) Diclofenac-natrium

Indomethacin -is more effective in relieving inflammation with acute gouty arthritis,

Diclofenac-Natrium (VOLTAREN) Tab. 0.025 g; amp. 2.5%-3 ml a Potent COX inhibitor

Ketorolac Tab. 10 mg (0.01 g), amp. 3%-1 ml IM, ophthalmic

Selective COX-2 inhibitors Meloxicam Tab. 0.015 g Celecoxib Caps. 0.1 gAdvantage: fewer Gastric

Слайд № из 40Mechanism of Cardiovascular Disorders Development ThrombusARACHIDONIC ACIDCOX-1 COX-2

Rofecoxib, Valdecoxib, Nimesulide – have been withdrawn from the pharmaceutical market:Rofecoxib

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