Analgesic and Antipyretic Drug

UNIVERSITY OF DEVELOPMENT ALTERNATIVE

Presented By –Name Std ID

01 M.M. Maidul Islam (Group leader) 031151039

02 Nasrin Akhter Shova 031151029

03 Md. Asaduzzaman 032121047

04 Ipsita Nag 031151015

05 Md. Kamruzzaman 031151004

06 Faozia Abida Islam 031151047

07 Sumaiya Alam 031151047

08 Shahbaz Hossain Pranto 031151012

First, we should know about Pain and Fever• Pain:Pain is a symptom of inflammation.

• Fever:When temperature is above of 98.6 F. We know, when temperature is 100.4 F , it is called fever.

• Analgesic:A drug that selectively relieves pain by acting on CNS or on peripheral pain mechanisms without significantly altering consciousness. It is a pain relive drug.

• Antipyretic:A drug that reduces fever by lowering the body temperature (Some analgesic drugs have antipyretic activity).

TYPES OF PAINPAIN

According to sourceVisceral

Somatic

Neuropathic

According to chronicityChronic

Acute

PAIN SCALE

1 3 4 6 7 10 Mild Moderate SevereNon opioid analgesics are mostly used for mild to

moderate pain.Opioid analgesic are used for severe pain.

PAIN RECEPTORPain receptor in our bodies are nerves that transmit pain. These are

free nerve endings located in various body tissues that respond to thermal, mechanical, & chemical stimuli.

When tissue becomes injured, they release chemicals called prostaglandins and leukotrienes that make the pain receptor more sensitive and these causing pain.

PHYSIOLOGY of PAIN

BASIC ANATOMY of NOCICEPTION

CENTRAL ANALGESICSOpioids:

Morphine & morphine like drugs

Non-Opoid: NSAIDs Acetaminophen/PCM Flupirtine Ziconotide

DIFFERENCE:OPIOID ANALGESICS NON OPIOID ANALGESICS(ANTIPYRETIC):

Act centrally Act peripherally

Cause addiction Do not cause addiction

Produce CNS depression Do not produce CNS depression

Do not produce gastric irritation Produce gastric irritation

Show no anti inflammatory effect Show anti inflammatory effect. Reduce body temperature.

eg. Morphine, Tramadol, Pethidine etc. Diclofenac, Ibuprofen, Aspirin etc.

OPIOID ANALGESIC“Opium” is a Greek word meaning “juice,” or the exudates

from the poppy.Opium is extracted from poppy seeds (Paper somniforum)“Opioid” is a natural or synthetic drug that binds to opioid

receptors producing agonist effects.Which are present in the central and peripheral nervous

system, can cause numbness and induce a state of unconsciousness.

MECHANISM of ACTIONAll opioid receptors are G-protein coupled receptors and inhibit adenylate cyclase. They are also involved in Postsynaptic hyperpolarization (increasing K+ efflux)Reducing presynaptic Ca++ influxThus inhibits neuronal activity.

OPIOID RECEPTOR:All opioid receptors are linked through G-proteins to inhibition of adenylate cyclase. They also facilitate opening of potassium channels (causing hyperpolarisation) and inhibit opening of calcium channels (inhibiting transmitter release). They are of 4 types:μ receptorσ receptorδ receptorΚ receptor

RECEPTOR BINDING of MORPHINE

Morphine exerts a narcotic action manifested by analgesia, drowsiness, changes in mood, and mental clouding. The major medical action of morphine sought in the CNS is analgesia.Opiates suppress the "cough center" which is also located in the brainstem, the medulla. Such an action is thought to underlie the use of opiate narcotics as cough suppressants.

RECEPTOR BINDING of MORPHINEMorphine activates analgesic receptors in the CNS. Which leads to a reduction in the transmission of pain signal to the brain. There are 3 main types of analgesic or o opioid receptor activated by morphine. Called the mu, kappa, delta receptors. Which are g-protein coupled receptor. Morphine acts a agonist at all three receptors and activation leads to :

Opening of potassium ion channelClosing of calcium ion channels Reduces the pain signalInhibition of Neurotransmitter release

Morphine has high affinity for mu receptor. Activation of the mu receptor results in sedation, which is the strongest analgesic effect. But activation of this receptor also leads to depression, euphoria, and addiction.

PHARMACOLOGICAL ACTIONSAnalgesiaRespiratory depressionCough suppressionVagal stimulation (bradycardia)Sedation & hypnosisHypothermiaItchingPhysical & pshycological dependenceEuphoriaHistamine release , hypotension….etc.

ADVERSE EFFECTS• Morphine can produce a wide range of adverse effects like nausea, vomiting, dizziness, mental

clouding, respiratory depression, constipation, dysphoria, urinary retention, & hypotension, allergic reactions.

• Tolerance- Repeated administration of morphine results in the development of tolerance to some of its effects including respiratory depression, analgesia, sedation, etc .

• Dependence- Opium has been a drug of addiction for many centuries. Its ability to produce euphoria makes it a drug of addiction. Opioids produce both physiological & pshycological dependence. Manifestations are lacrimination, sweating, yawning, anxiety, restlessness..etc.

Non-Opoid Analgesics (NSAID’s)-as Antipyretic DrugNon steroidal anti-inflamatory drugs are aspirine-type or non-

opioid analgesics. In addition, they have anti-inflamatory, anti pyretic & uricosuric

properties without addiction liability.The active principle is salicin, that is converted into salicylic acid

in body.Drugs for antipyretic• Aspirin• Paracetamol / Acetaminophen

CLASSIFICATION

Non selective COX inhibitor

• Salicylic acid derivatives. Eg: aspirine• Para aminophenol derivatives. Eg:

paracetamol• Pyrazolone derivatives. Eg:

Sphenylbutazone• Indole acetic acid derivatives. Eg:

sulindac• Arylacetic acid derivatives. Eg: diclofenac• Propionic acid derivatives. Eg: ibuprofen

• Anthralinic acid derivatives. Eg; flufenamic acid

• Oxicams. Eg: piroxicam• Alkanones. Eg: nabumetone

Selective COX-2 inhibitors• Nimesulidde, celecoxib,

rofecoxib…etc

MECHANISM of ACTIONActivities of antipyretic:• Used to treat fever.• Inhibits the enzyme COX.• Fever release of endogenous pyrogens (e.g., interleukin-1) released

from leucocytes acts directly on the thermoregulatory centers in hypothalamus increase body T°.• This is assoc with increase in brain PGs (pyrogenic).• Aspirin prevents the T°-rising effects of interleukin-1 by preventing

the increase in brain PGs.

MECHANISM of ACTION

Arachidonic acid

COX-1 COX-2

Leukotrienes\Prostaglandin

sProstaglandi

ns

Primarily support platelet function

Primarily protect GI-tract mucosa

Primarily mediate inflamation, fever,

pain

NSAIDs COX-2 inhibitors

ADVERSE EFFECTAnalgesics doses are usually well tolerated but anti-inflammatory doses are usually

associated with adverse effects whed used for a long period.A.G.I tract:- Epigastric distress, nausea, vomiting, erosive gastritis, peptic ulcer, increase occult blood loss in stools are commonB. Allergic reactions are not common and may be manifested as rashes, photo sensitivity..etcC. HaemolysisD. NephrotoxicityE. Reye’s syndromeF. Salicylism G. Acute salicylate intoxication

SIDE EFFECTS of ANALGESICS & ANTIPYRETIC DRUG• Risk of experiencing side effects depends on the type of analgesic what we take,

and how long we take it.• Side effects of analgesics may include:• Constipation• Drowsiness• Dizziness• Upset stomach• Ringing in your ears• Skin itching or rash• Dry mouth

OVERVIEW• Some of analgesic and antipyretic drugs are also called OTC drugs. OTC drugs are

those drugs which are not prescribed by physician, like paracetamal, aspirin, diclophenac sodium, ibuprofen etc. • These drugs are helpful for those person who are not capable for going to

physician. So, they can treat their usual problem. • But these drugs are also have some harmful. These drugs are sometimes abused.

Many people are used these drugs as dope because they are addicted by these drugs. • Actually these drugs are not so costly.but some drugs are costly like

cocaine,morphine,heroine,pathedine etc.These drugs are created addiction.So government should take proper step for these and people should concern about these.

MANAGEMENT OF ANALGESIC ABUSE AND DEPENDENCE• Crisis intervention: Directed at immediate survival by reversing the potentially lethal effects of overdose with an opioid

antagonist.• Harm reduction: Intended to reduce morbidity and mortality associated with use of dirty needles and overdose.• Detoxification/withdrawal: • Aims to remove the opioid of abuse from the patient's body, either through gradual taper and

substitution of a long-acting opioid or through ultra-rapid opioid detoxification.• Maintenance treatment or opioid (agonist) replacement therapy.• Abstinence-oriented therapy: Treatment directed at cure. The patient is tapered off of short-acting opioids during the

detoxification/withdrawal process and may be placed on an opioid antagonist with the goal of minimizing relapse.

All treatment approaches share the common goal of improving health outcomes and reducing drug-related criminality and public

References• The Pharmacological Basis of Therapeutics, Goodman & Gillman 12th ed Ch 18 Pg 481• Foy’s Principles of Medicinal Chemistry 6th ed • http://en.wikipedia.org/wiki/Morphine• nawrot.psych.ndsu.nodak.edu/courses/.../morphine/Page2WP.htm• www.rxmed.com/.../MORPHINE%20SULFATE%20INJECTION%20BP.html• depression.about.com/od/glossaryt/g/toxicity.htm• medical-dictionary.thefreedictionary.com/morphine+poisoning• www.drugbank.ca/drugs/DB00295• http://www.answers.com/Q/What_is_the_antidote_for_morphine• www.optionsbehavioralhealthsystem.com/.../heroin/effects-signs-symptoms• http://www.drugs.com/drug-class/narcotic-analgesics.htm• Slideshare.com/net

SINCERELY,THANk YOU