ANALGESICS Lector prof. Posokhova K.A.. ANALGESICS I. Opioid (narcotic) analgesics 1. Agonists of opioid receptors – morphine hydrochloride, promedol,

ANALGESICSANALGESICS

Lector prof. Posokhova K.A.Lector prof. Posokhova K.A.

ANALGESICSANALGESICS

I. Opioid (narcotic) analgesics1. Agonists of opioid receptors – morphine hydrochloride,

promedol, omnopon, fentanyl, codein;2. Agonists – antagonists and partial agonists of opioid

receptors – pentasocin, buprenorphine.

II. Nonopioid analgesics and nonsteroidal antiinflammatory drugs - NSAIDs

acetysalycylic acid, paracetamol, analgin, indometacin, butadion, ibuprofen, pyroxicam, diclofenac-sodium,

ketorolac, ketoprofen.

III. Substances with mixed mechanism of action (opioid and nonoioid components)

tramadole

OPIOIDOPIOIDAANALGESICSNALGESICS

The following structures take part in perception of pain: thalamus, hypothalamus, reticular formation, limbic

system, occipital and frontal areas of cortex

System which conducts and perceives pain - nociceptivenociceptive System which protects organism from pain –

antinociceptiveantinociceptive

Visceral painVisceral pain – – from inner organsfrom inner organs

Somatic painSomatic pain – – from bones, muscles, joints, teeth, ligaments, from bones, muscles, joints, teeth, ligaments,

nervesnerves

Opioid systemOpioid systemcontainscontains::

• opioid receptorsopioid receptors • endogenic opioid substancesendogenic opioid substances – –

endorphins, encephalines, dinorphinesendorphins, encephalines, dinorphines

Subtypes of opioid receptorsSubtypes of opioid receptors::

mu, delta, kappa, mu, delta, kappa, epsilonepsilon, , sigmasigma

Subtypes of opioid receptorsSubtypes of opioid receptors

muAnalgesia, depression of breathing, euphoria, addiction

development, sedative effect, depression of contents mocing through digestive tract, miosis

kappaAnalgesia, sedative eefect, psychotomimetic action

deltaAnalgesia, euphoria, behaviour changes

sigmaMania, increasing of breathing frequency, hallucinations,

midriasis

Poppy

1. Papaver

rhoeas L.

2. Papaver

somniferum L.

2211

"Among the remedies "Among the remedies which it has pleased which it has pleased Almighty GodAlmighty Godto give to man to to give to man to relieve his sufferings, relieve his sufferings, none isnone isso universal and so so universal and so efficacious as opium."efficacious as opium."

Thomas SydenhamThomas Sydenham(1624 - 1689) (1624 - 1689)

Morphine was first

isolated by Friedrich Wilhelm Serturner in

1805.

Sertürner named his discovery after

Morpheus, the Greek god of dreams.

Morpheus is the son of Hypnos, the god of

sleep.

Morphine hydrochloride“mosaic action” on central nervous system

Effects of depression• analgesia

• decreasing of frequency and depth of breathing

• depressing of central links of coughing reflexes

• from the side of psychical activity – somnolence, retardness

Effects of stimulation• vomiting (excitation of trigger zone of vomiting center)

• bradycardia (increasing of tone of vagal nerve nuclei)

• miosis (increasing of tone of n. oculomotorius nuclei)

• euphoria (condition of full psychological wellness with pleasant emotional feelings and feelings of physical comfort)

• increasing of activity of spinal cord intermediate neurons

ADMINISTRATION OF OPIOID ADMINISTRATION OF OPIOID ANALGESICSANALGESICS

• prophylaxis and treatment of pain shock • traumas• burns• acute myocardium infarction• premedication for potentiation of action of narcosis drugs,

analgesia in postoperative period• colics • to relieve sufferings of oncologic patients of 4th clinical group

(can’t be treated radically)• acute abdomen (strong pain in abdominal cavity, caused by

perforation of ulcer, acute appendicitis, acute intestinal impassability etc.) – only from the moment then diagnosis becomes clear

Morphine Morphine

preparationspreparations

MORPHINE MORPHINE HYDROCHLORIDEHYDROCHLORIDE

routes of administrationroutes of administration• subcutaneously and intramuscularly (analgesic action after 10-15 min)• after oral administration – presystemic elimination ( 20-60 % enters general blood circulation)• sublingually – quick absorption• into epidural, subarachnoidal• into brain ventricles

Duration of analgesic action – 4-6 hoursMaximum single dose of morphine is 0,02 g,

maximum daily dose – 0,05 g

Other cases of morphine Other cases of morphine administrationadministration

• acute left-ventricular cardiac insufficiency

(morphine promotes depression of tone of vaso-motor centers with dilation of arterioles and venules and decreasing of heart load)

• traumas of thorax accompanied by cough (morphine depresses central links of coughing reflexes)

Side effects of morphineSide effects of morphine

• addiction• vomiting (excitation of starting zone of vomiting

center)

• bradycardia (increasing of tone of n. vagus nuclei)

• spasm of sphincters of gastro-intestinal tract accompanied by constipations

• increasing of tone of smooth musculature of urinary and bile-excreting tracts (retentions of urination, bile stasis)

• Bronchial spasm

• tolerance

CONTRAINDICATIONS FOR CONTRAINDICATIONS FOR ADMINISTRATION OF MORPHINEADMINISTRATION OF MORPHINE

• pain that accompanies chronicchronic diseases. In exceptional occasions it is introduced (not more than 1-2 injections) in case of pain which threatens development of pain shock, for, example, acute attach of ulcer disease

• children before the age of 22 years years

• for aged from 2 to 6 years and elderly the drug should be administered very carefully (breathing depression is possible)

• pregnancy and lactation

• anesthesia during child delivery (fetus breathing depression)

• skull traumas, brain hemorrhages (increasing of intracranial pressure)

• depression of function of breathing center, damage of respiratory organs, bronchial asthma

OMNOPONOMNOPON

• contains mixture if opium alkaloids (48-50% morphine)

• does not cause spasms of smooth musculature, as it contains alkaloids of isoquinoline raw

• is used for analgesia according to all the indications of morphine hydrochloride, for example, colics

Promedol Promedol • duration of analgesic action - 3-4 hours• moderate spasmolytic influence on smooth

musculature of internal organs• stimulation of rhythmic contractions of uterus • does not depress breathing • can be used for analgesia and stimulation of

child delivery • in case of pain syndrome connected with

spasms of smooth musculature

Phentanyl Phentanyl • synthetic opioid analgesic of short action

• analgesic activity is 300 times higher than of morphine

• analgesic effect after intravenous introduction – after 1-3 min, lasts for 15-30 min

• used with a neuroleptic droperidol (complex drug – “talamonal”) for neuroleptanalgesia – a variant of general anesthesia

PhentanylPhentanyl

Codeine Codeine • opium alkaloid• analgesic action is not strong, but

anticough effect is considerable• administered as an anticough drug of

central action• analgesic with weak activity combined

with non-opioid analgesics (paracetamol) for potentiation of the effect

PARACETAMOL+CODEINEPARACETAMOL+CODEINE

Pentazocin Pentazocin • agonist-antagonist of opioid receptors

• comparatively with morphine, it is a bit less dangerous in the aspect of addiction development

• indicated in case of pain of medium intensity in such conditions like other opioid analgesics. In case of strong pain its administration is limited as in case of increasing of dose of the drug excitation appears

• it can cause increasing of blood pressure and tachycardia that’s why it’s not advised to use in case of acute myocardium infarction

• if it is administered for people with narcotic addiction manifestations of abstinence develop

Buprenorphine Buprenorphine • Partly agonist of mu-opioid receptors • Acts longer than morphine (approximately 6 hours) • Analgesic activity is higher than of morphine, that’s why

it’s used in doses of 0,3-0,6 mg• In case of breathing depression, which it causes, naloxon is

less effective since buprenorphine is slowly released from the connection with mu-receptors

• Indicated for pain decreasing in the same situations as other narcotic analgesics

• May be used for detoxication and supporting treatment of individuals who is addicted to heroine

BuprenorphineBuprenorphine

Acute poisoning with opioid analgesics

It is often observed in drug addicts death – from breathing depression

SYMPTOMSdizziness nausea, vomiting (rarely), heavy sweating general weakness, somnolence, which after transfers into deep dream and coma pale and cyanotic skin, decreased body temperature weak pulse, decreased blood pressurerare and superficial breathing

Triad in case poisoning with morphine Acute miosis

pathological breathing of Chain-Stocks’ typesaved tendon reflexes

Treatment of acute poisoning

• NaloxonNaloxon (antagonist of opioid receptors)

intravenously - 0,4-1,2 mg

general dose of naloxon should not overcome 10 mg

• stomach lavage (for morphine enterohepatic circulation is typical) with 0,05-0,1% solution of potassium permanganate and 0,5 % tannin solution

• suspension of 20-30 g of activated charcoal

• salt laxative agents (sodium sulfate)

• forced diuresis

• atropine sulfate

• inhalation of carbogen (5-7 % СО2 and 93-95 % O2)

NaloxonNaloxon

antagonist of opioid receptorsantagonist of opioid receptors

All narcotic analgesics cause

drug addictiondrug addiction – – narcotic dependencenarcotic dependence

Manifestations

psychological dependencepsychological dependence physical dependencephysical dependence

tolerancetolerance abstinence syndromeabstinence syndrome

NON-OPIOID NON-OPIOID ANALGESICSANALGESICS

Types of action of Types of action of non-opioid analgesicsnon-opioid analgesics

• Analgesic

• Antipyretic

• Anti-inflammatory (except paracetamol)

Mechanism of action of non-opioid analgesics

• depression of cyclooxygenases activity

• decreasing of prostaglandins synthesis in peripheral tissues and in central nervous system

• decreasing of sensitivity of nervous endings and depression of transmission of nociceptive impulses on the level of CNS structures

• pain-relieving action of non-opioid analgesics is partly connected with their anti-inflammatory activity

Indications for administration of non-narcotic analgesics

• headache

• toothache

• radiculitis

• neuritis, neuralgias

• myositits, myalgia

• arthritis, arthralgia

• pain, connected with pelvic organs (dysmenorrhea)

for potentiation of their action – combinations

paracetamol with codein,

analgin with dimedrol, analgin with codein

Acetylsalicylic acid

• Blocks cyclooxygenase irreversably

• As antipiretic and analgesic drug – 0,25 and 0,5 g per time

• As an antiinflammatory – 3-4 g per day (for arthritis, myocarditis, pleuritis, bronchitis etc.

• As platelets inhibitor - for prophylaxis of thrombus-formation (in case of ischemic heart disease, thrombophlebitis etc.) – daily dose – 80-100 mg

Analgin (metamizol-sodium)

Baralgin Baralgin ((maxiganmaxigan, , spazganspazgan, , spazmalgonspazmalgon, , trigantrigan))

analgin+pitophenon hydrochloride+pheniverinium bromide

• Ampoules tablets suppositories

• Analgesic and spasmolytic activity

Paracetamol

• analgesic and antipyretic drug

• maximal effect if the drug is introduced orally – after 2 hours, lasts approximately for 4 hours

• in case of durable administration of big doses – damaging of liver and kidneys, production of met-hemoglobin

Paracetamol

• Tablets

• Suppositories

• Syrups

• Soluble tablets

• Capsules

PARACETAMOLPARACETAMOL

Panadol Panadol ((paracetamolparacetamol))

Ketorolak (ketanov)• according to analgesic activity it prevails over

effect of acetylsalicylic acid, indometacin and equals to opioid analgesics

• moderate anti-inflammatory, antipyretic and anti-aggregate effects

• high effectiveness in case of pain in postoperative period, in oncology, during child delivery, traumas, colics

• i. m., i. v. introduction, orally

NOT indicated

for chronic pain syndrome

Ketorolak Ketorolak ((ketanovketanov))

Ketoprophen Ketoprophen ((ketonalketonal))

• strong analgesic, anti-inflammatory and antipyretic agent

• administered in case of arthroses and arthritis, ancilizing spondilitis, pain of different genesis (after surgeries, in case of traumas, painful menstruations etc.)

• administered orally, intramuscularly, in forms of suppositories and ointments

TRAMADOLTRAMADOLAnalgesic activity is similar to the activity of morphine

In case of intravenous administration effect develops

after 5-10 min, if administered orally – after 30-40 min, action lasts for

3-5 hours.

ADMINISTRATION OF TRAMADOLADMINISTRATION OF TRAMADOL

surgery, traumatology, gynecology, neurology, urology, oncology

For all kinds of acute and chronic pain of moderate and considerable intensity, including

postoperative, traumatic pain neuralgias diagnostic and therapeutic interventions oncologic pathology

Provokes dependenceProvokes dependence