chapter 19 narcotic analgesics l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
CHAPTER 19 Narcotic Analgesics PowerPoint Presentation
Download Presentation
CHAPTER 19 Narcotic Analgesics

Loading in 2 Seconds...

play fullscreen
1 / 62

CHAPTER 19 Narcotic Analgesics - PowerPoint PPT Presentation


  • 699 Views
  • Uploaded on

CHAPTER 19 Narcotic Analgesics. I General Consideration. 【action mechanism】 ligands opioids receptor Gi inhibiting adenylate cyclase increasing potassium ion efflux or reducing calcium ion influx impeding neuronal firing and transmitter release . 1.Ligands

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'CHAPTER 19 Narcotic Analgesics' - eli


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
i general consideration
I General Consideration

【action mechanism】

ligands

opioids receptor

Gi

inhibiting adenylate cyclase

increasing potassium ion efflux or reducing calcium ion influx

impeding neuronal firing and

transmitter release

slide3

1.Ligands

(1)endogenous:

  • endorphins from pituitary

β-endorphin

dynorphin

  • enkephalins from brain

M-enkephalin

L-enkephalin

(2)exogenous: drugs

slide4

2.Receptor

(1)classification of opioid receptors

μ, κ, σ,δ

analgesic effect: mediated by μ,κreceptors

(2)location of opioid receptors:

  • CNS
  • nerve terminals in periphery
  • cells of gastrointestinal tract

.

slide5

【analgesic characteristics】

  • relieving pain without affecting other senses and consciousness.
  • high potency of analgesia.
  • dependence.

【clinical use】

intense pain.

slide6

【classification of drug】

1.origin

  • natural opiates

morphine, heroin, codeine, thebaine, paraverine

  • synthetic analgesics

meperidine, methadone, fentanyl, anadol, etorphine, pentazocine.

2.potency

  • strong agonist

morphine,heroin,meperidine,methadone,fentanyl

  • moderate agonist

codeine, propoxyphene.

  • mixed agonist-antagonist

buprenorphine, pentazocine

  • antagonist: naloxone, naltrexone
natural opiates
Ⅱ Natural Opiates

Morphine

【mechanism of action】

  • Morphine activates opiate receptor to produce analgesic effect like endogenous opiate peptides.
  • high affinity for μ receptors
  • varying affinities forδandκreceptors
  • low affinity for σ receptors in CNS and gastrointestinal tract.*
slide8

Sensory neuron second neuron

sp

sp sp

E

E

Enkephalin sp=substence P

Neuron E=enkephalin

slide9

【pharmacokinetics】

  • good absorption from gastrointestinal tract
  • significant first-pass effect
  • subcutaneous injection is commonly used.
  • rapidly entering to all body tissues, including fetuses of pregnant women.
  • not used for analgesia during labor.
  • duration of action is 4 - 6 h.
slide10

【pharmacologic effects】

1. effects on CNS

(1) analgesia and sedation: prominent effect.

characteristics:

  • strong analgesia
  • effective on various pains

chronic dull pain, colic andacute sharp pain.

  • no effect on other senses and consciousness.
  • sedation

relieving anxiety and stress accompanied with severe pain.

  • analgesia with euphoria in partial patients.
slide11

(2) emesis by direct stimulation of CTZ to cause nausea and vomiting.

(3) respiratory depression by reducing response of respiratory centers to blood CO2.

(4) suppression of cough by direct inhibition of cough center.

(5) miosis by stimulating Edinger-Wesphal nucleus, pinpoint pupils are indicative of toxic dosage.

slide12

2.cardiovascular effects

(1)peripheral vasodilation to cause orthostatic hypotension

  • inhibition of vasomotor center.
  • promotion of histamine release from mast cells.

(2)cerebral vasodilation to increase intracranial pressure

  • depression of respiration to increase blood CO2.
slide13

3. gastrointestinal effects

(1)relieves diarrhea or causes constipation

  • reducing peristalsis and stomach mobility
  • increasing spasmodic nonpropulsive contraction
  • decreasing biliary and pancreatic secretions to cause indigestion.

(2)increasing biliary pressure by constriction of

Oddi's sphincter to induce biliary colic.

slide14

4.other effects

  • bronchoconstriction by histamine.
  • retention of urine by increasing sphincter tone of bladder.
slide15

【therapeutic uses】

1. analgesia.

  • acute sharp pain(intense pain)
  • anginal pectoris by analgesic, sedative and vasodilation
  • biliary and kidney colic etc., combined with atropine

2. acute pulmonary edema

  • vasodilation
  • sedative
  • inhibiting respiration

3. severe diarrhea.

slide16

【adverse effects】

1.common side effects

  • nausea, vomiting, constipation, biliary colic,
  • respiratory depression,
  • dysphoria,
  • hypotension,
  • acute urine retention.

2.tolerance and physical dependence

withdrawal symptoms:

autonomic, motor and psychological responses (insomania, dysphoria, headache, sweating, vomiting, diarrhea, tremor, collapse).

slide17

【contraindication】

1.women in delivery and lactation.

2.patients with bronchial asthma and pulmonary

heart disease.

3.patients with cranial injury and high cranial

pressure.

slide18

Codeine

1.codeine is 3-methyl ether of morphine.

2.pharmacologic effects are similar to morphine,

but its analgesic potency is 1/12 of morphine,

cough depressant potency is 1/4 of morphine.

3.analgesic effect is strongr than aspirin. 30mg of codeine is equivalent to 600mg of aspirin.

4.less sedation, respiratory depression and fewer gastrointestinal effects.

5.use: mild to moderate pains and severe cough by oral administration.

6.physical dependence in long administration.

synthetic analgesics
Ⅲ Synthetic Analgesics

Pethidine (Meperidine,Dolantin)

1.activating opioid receptors, particularlyκreceptors.

2.pharmacologic effects are similar to morphine

  • less potency and shorter duration in analgesis,

sedative and respiratory depression.

  • no effect on cough, bronchial and gastrointestinal smooth muscles.
slide20
3.use
  • to replace morphine to relieve intense pains,
  • to treat acute pulmonary edema,
  • to induce artificial hibernation.
  • not useful for diarrhea or cough.

4.mild adverse effects similar to morphine

5.tolerance: being cross with the other opioids.

dependence: in long use.

slide21

Methadone

1.analgesic effect is equal to morphine in potency and action duration, but more effective in oral

administration than morphine.

2.use:

  • analgesia
  • suppression of withdrawal syndrome
  • treatment of heroin user.
  • orally administered, methadone is substituted for injected opioids and patient is then slowly weaned from methadone.

3.physical dependence occurs slowly and withdrawal syndrome is mild.

slide22

Fentanyl

1.effects

analgesic effect is 80-100 times as effective as morphine with short duration(15 to 30 min) and rapid onset.

2.use

anesthesia or anesthesic adjunct.

slide23

Alfentanil

  • effects

Alfentanil has a more rapid onset of action and shorter duration of narcotic effect than fentanyl.

  • uses

adjunct to general anesthetics

anesthetic inducing agent.

slide24

Ⅳ Opioid Receptor Antagonists

1.partial antagonists

to precipitate a withdrawal syndrome in opioid addicts (nalorphine, pentazocine, butorphanol, nalbuphine, buprenorphine).

2. full antagonists

naloxone and naltrexone.

naloxone may reverse the acute poisoning effects of opioid agonists and precipitate a withdrawal syndrome in opioid addicts.

slide25

Summary for this chapter

  • effects and uses of morphine and dolantin
  • contraindication of morphine
  • dependence
  • characteristics of other analgesics
  • drug name of opiate receptor antagonists
chapter 20 central stimulants
CHAPTER 20 Central Stimulants

【classification of drugs】

1. cerebral stimulants: caffeine.

2. respiratory stimulants: nikethamide, lobeline.

3. spinal cord stimulants: strychnine.

slide27

I Cerebral Stimulants

Caffeine

【mechanism of action 】

caffeine→ blocking adenosine receptors, inhibiting PDE → breakdown of cAMP↓ → central actions and some of peripheral actions.

slide28

【pharmacologic effects】

1.CNS

small dose stimulating cerebral cortex

vigorous

loss of sleepiness

medullary bulb

respiratory--- hyperpnea

vasomotor centers--- BP ↑

large dose spinal cord---convulsion

slide29

2.cardiovascular system

(1)direct effects: cardiac excitement and vascular dilation.

(2)indirect effects: cardiac inhibition and vascular contriction by stimulating vasomotor center and vagal center.

In overall, little changes in heart rate and blood pressure in normal cardiovascular state, increasing heart rate and blood pressure in cardiovascular hypofunction.

3.other systems: relaxing bronchial smooth muscle, diuretic effect and stimulating secretion of gastric acid.

slide30

【therapeutic uses】

1. central inhibition

2.headache in combination with aspirin, migraine in combination with ergotamine.

【adverse effects】

CNS excitement: insomnia, agitation, convulsion etc..

slide31

II Respiratory Stimulants

Nikethamide(coramine)

1.stimulating respiration: short and modest effect.

direct stimulation of respiratory center

reflex-mediated stimulation of respiratory center

by stimulating chemoreceptor in carotid body

increasing sensitivity of respiratory center to CO2

2.use: central respiratory depression,

no effective for peripheral respiratory depression.

3. wide margin of safety. tachycardia and blood pressure increase in the large dose.

slide32

Lobeline

1.stimulating respiratory center by stimulation of chemoreceptors in carotid and aortic bodies.

2.short effect and wide margin of safety. hardly producing convulsion in large dose.

3.use:

asphyxia in the newborn

CO toxication

respiratory failure caused by infectious diseases in

children.

slide33

Summary for this chapter

1.Clinical uses of caffeine.

2.Action mechanisms, uses of nikethamide and lobeline.

3.Pay attention of dosage of caffeine, nikethamide and lobeline in clinical uses.

slide35
I General Consideration
  • Inflammation is a protective response to tissue injury.
  • Inflammation is triggered by the release of chemical mediators from injured tissues and migrating cells.
  • Specific chemical mediators include histamine, 5-HT, PGs, LTs, brandykinin, interleukin-1.
  • nonsteroidal anti-inflammatory drugs(NSAID) or non-narcotic analgesics.
  • effects: antipyretic, analgesic and anti-inflamatory activities.
  • differences: they all exert antipyretic and analgesic actions, most also produce antiinflammatory action.
  • mechanisms of actions: reduction of PG biosynthesis by inhibition of cyclooxygenase.*
slide36

Phospholipids

↓ PLA2

AA

↓cyclooxygenase (-)

PGG2/PGH2↓

PGs↓

(PGD1, PGD2, PGE1, PGE2, PGFα, PGI2 etc.)

slide37

COX

COX-1: gastrointestinal tract, kidney, platelet

COX-2: EC etc.

slide38

1. antipyretic effects:

Effect:

  • reduction of body temperature in patients with fever
  • no effect on normal body temperature

Mechanism:

reduction of PGs biosynthesis via inhibition of cyclo-oxygenase to lower body temperature in patients with fever. *

slide39

pathogens or toxins

↓(+)

PMNs

pyrogen release

↓(+)

hypothalamus

PG E2 synthesis and release

↓(+)

body temperature-regulating center in hypothalamus

set point for body temperature↑

heat production↑and heat dissipation↓

body temperature↑(fever)

slide40

Use: high fever.

Differences in 2 aspects:

effect

action mechanism

  • Phenothiazides decrease both normal and high body temperature by direct inhibition of temperature-regulating center in CNS.
  • Antipyretics decreases only high body temperature by inhibition of PGs biosynthesis and has no effect on normal body temperature.
slide41

2. analgesic effect

Effect:

  • weak, only effective on mild to moderate dull pain
  • little effect on colicky pain and sharp pain (intense pain)
  • no narcotic.

Mechanism:

  • relieving pain via inhibition of PGs biosynthesis*
slide42

injured or inflammatory tissue

PGs release autocoid release

(+) (e.g.bradykinin)

(+) (+)

pain receptors

pain

slide43

Use:

  • common dull pains.

e.g. headache, toothache, neuralgia, muscular pain, arthralgia and dysmenorrhea etc.

Differences:

  • narcotic analgesics:

potency: strong analgesic effect

action site: CNS

mechanism: activation of opiate receptors

use: mainly for sharp pain

  • non-narcotic analgesics:

potency: weak analgesic effect

action site: peripheral tissue

mechanism: inhibition of PGs biosynthesis

use: mainly for dull pain

slide44

3. anti-inflammatory effect

Effect:

relieving inflammatory symptoms

(pain and swelling).

Mechanism:

inhibition of PG synthesis.*

slide45

prostaglandins

vasodilation autocoids release

histamine

serotonin

kinin  increased vascular permeability

edema

pain, swelling

slide46

Use: rheumatic and rheumatoid arthritis etc..

Differences: NSAID---weak

SAID---strong

4.antiplatelet effect

slide47

【classification I】

1. salicylates

aspirin

2. aminophenol derivatives

acetaminophen

3. pyrazolon

phenylbutazone

4. other organic acids

indomethacin etc.

slide48

【classification II】

1. non-selective COX inhibitors: aspirin etc.

antipyretic

analgetic

antiinflammatory

antiplatelet

2. COX-2 selective inhibitors: celecoxib,etoricoxib,meloxicam

antipyretic

analgetic

antiinflammatory

salicylates
Ⅱ Salicylates

Acetylsalicylic acid (ASA, aspirin)

【pharmacokinetics】

  • metabolized in liver by the hydrolyzation to salicylate and acetic acid by esterases .
  • in oral small dose,metabolized in first-order kinetics and half life is 3.5 h,

in large dose (1g/time,>4g/day), metabolized in zero-order kinetics because hepatic metablic pathway becomes saturated, which prolong t1/2 of aspirin to 15 h or more to lead to toxication.

slide50

【pharmacologic effects】

  • Aspirin is rapidly deacetylated by esterases in body, producing salicylate which has anti-inflammatory, analgesic,and antipyretic effects.
  • Aspirin irreversibly acetylates cyclooxygenase to inhibit the enzyme activity.

1. antipyretic action: rapid and moderate in potency.

2. analgesic effects: effective for mild, moderate dull pain.

3. antiinflammatory effects: to treat rheumatoid and

rheumatic arthritis, symptomatic relief.

4.antiplatelet effects: to inhibit platelet aggregation and

secondary release of ADP from activated platelets by

inhibition of TXA2 production.*

slide52

5.other effects:

  • increasing alveolar ventilation
  • increasing gastric acid secretion and diminishing mucus protection to cause epigastric distress, ulceration, hemorrhage
  • resulting in retention of sodium and water to cause edema and hyperkalemia
slide53

【therapeutic uses】

DOSAGE

1. hyperpyrexia: middle dose.

2.dull pain: e.g. headache, arthritis, dysmenorrhea etc. middle dose.

3.rheumatic fever and rheumatoid arthritis (first-line drugs) in relatively large dose.

4. prevention of thromboembolism, stroke, myocardial infarction in small dose. decreasing incidence of transient ischemic attack and unstable angina as well as that of coronary artery thrombosis.

5.chronic use of aspirin reduces incidence of colorectal cancer.*

slide55

【adverse effects】

1.gastrointestinal reaction: epigastric distress, nausea, vomiting, gastric ulceration and bleeding.

taking aspirin with meal or with sodium bicarbonate, taking enteric- coated aspirin.

2. hepatic damage: mild, reversible.

3. prolonging bleeding time due to inhibition of platelet functions in small dose and reduction of plasma prothrombin level in large dose.

4.large dose of aspirin uncouples oxidative phosphorylation. Energy normally used for production of ATP is dissipated as heat, which explains hyperthermia caused by salicylates when taken in toxic quantities.

5.hypersensitivity or allergy.

slide56

6.Reye’s syndrome:

  • seen during viral infectionsfatal, especially in children
  • manifestations: fulminating hepatitis with cerebral edema
  • children should use acetaminophen instead.

7.Salicylate toxication (salicylism):

  • mild toxication: headache, mental confusion, drowsiness, difficulty in hearing, vomiting
  • severe toxication: hyperventilation, severe CNS disturbulance, respiration depression and marked alteration in acid-base balance

Medication: discontinuation of salicylates, gastric lavage, relieving symptoms, intravenous infusion of NaHCO3 and dialysis.

aminophenol derivatives
Ⅲ Aminophenol Derivatives

Acetaminophen

Acetaminophen inhibits prostaglandin synthesis in CNS,but less effect on peripheral cyclooxygenase.

  • antipyretic and analgesic effects are similar to aspirin in potency
  • no anti-inflammatory activity.

Use: dull pain and hyperpyrexia., choice for children with viral infections or chicken pox.

Adverse effects: skin rash and drug fever, hypoglycemic coma, renal tubular necrosis and renal failure in long-term administration, acute hepatic necrosis in large dose.

slide58

Ⅳ Other Organic Acids

Indomethacin

【pharmacologic effects】

  • anti-inflammatory, analgesic and antipyretic effects
  • more potent than aspirin as an anti-inflammatory agent
  • inferior to the salisylates at dose tolerated by patients with rheumatoid arthritis.

【therapeutic uses】

rheumatoid and rheumatic arthritis, not routinely for analgesia and antipyresis because of its toxicity and side effects.

slide59

【adverse effects】

35%-50% of patients report some adverse effects and most adverse effects are dose-related.

1. gastrointestinal complains.

2. CNS effects: frontal headache, dizziness, vertigo, mental confusion etc.

3. hematologic effects: neutropenia, thrombocytopenia, inpaired platelet functions, rare aplastic anemia.

4. contraindication: in pregnancy or nursing women, patients with psychiatric disorders, epilepsy, parkinsonism, renal diseases, peptic ulcers and machine operators.

slide60

Ibuprofen

  • anti-inflammatory, analgesic and antipyretic activity.
  • chronic treatment of rheumatoid and osteoarthritis.
  • less intense of gastrointestinal effects than that of aspirin.
slide61

Other drugs

  • Sulindac
  • fenamates (mefenamic acid, meclofenamate)
  • tolmetin
  • propionicacid derivatives (naproxen, fenoprofen, ketoprofen, flurbiprofen)
  • piroxicam
  • nabumetone
  • etodolac, diclofenac, ketorolac
  • in single agent or in the compound preparations.
slide62

Summary for this chapter

  • effects and uses of NSAID
  • mechanism of action of NSAID
  • pharmacological basis of small dose of aspirin for prevention of thromboembolism
  • characterastics of aspirin, acetaminophen, indomethacin and ibuprofen