PAIN KILLERS

SUBJECT- PHARMACOLOGY SUBMITTED TO- DR. RAHUL PEDDAWAD SUBMISSION DATE- 25/09/2016 PRESENTED BY- MS. PAYAL BARIYA

F.Y PHARMA MBA

ROLL NO. – MBAPH016001

WHAT IS PAIN ? ? ?Subjective experienceHard to explainPain is a direct response to an untoward event associated with tissue damage such as Injury Inflammation Cancer, etc.

TYPES OF PAIN ACUTE trauma or injury, CHRONIC conditions for which cures were

unknown, MALIGNANT processes (cancer)

Based on etiology pain is differentiated into two types

1) NOCICEPTIVE PAIN

2) NEUROPATHIC PAIN

Nociceptive Pain:• Result of activation of sensory receptors

(nociceptors) by mechanical, chemical, or thermal stimuli.• Functional, physiologic or “normal” pain.Neuropathic Pain:• Pain resulting from damage to peripheral

nervous or central nervous system tissue or from altered processing of pain in the CNS.

HOW PAIN IS GENERATED ? ?

CONTD……

ANALGESIC DRUGS

PAIN KILLERS

OPIOIDSNSAIDS

OPIOIDS - OPIUMA dark brown, resinous material obtained from poppy plant (Papaver Somniferum; Family: Papaveraceae)capsule. It contains two types of alkaloids.

Phenanthrene derivatives

• Morphine• Codiene• Thebaine

Benzoisoquinoloine derivatives

• Papaverine• Noscapine

CLASSIFICATION OF OPIOIDS

• MORPHINE, CODIENE

NATURAL OPIUM ALKALOIDS

• DIACETYLMORPHINE(HEROIN), PHOLCODIENE

SEMISYNTHETIC OPIATES

• PETHIDINE, FENTANYL, METHADONE, DEXTROPROPOXYPHENE, TRAMADOL

SYNTHETIC OPIATES

MORPHINEMORPHINE IS THE PRINCIPLE ALKALOID IN OPIUM AND WIDELY USED ANALGESIC DRUG.

PHARMACOLOGICAL ACTIONS OF MORPHINE.

ON CNSANALGESIA:- Strong analgesic- High doses-severe pain- Intrathecal injection causes segmental analgesiaSEDATION:- Drowsiness - Inability to concentrate - Extravagant imagination- Larger doses produce sleep- EEG resembles normal sleep.

PHARMACOLOGICAL ACTIONS OF MORPHINE (CONTD.)

DEP

RES

SIO

N • Respiratory centre depression

• Cough centre• Temperature

regulating centre

• Vasomotor centre.

STIM

ULA

TIO

N • Vagal centre• Hippocampal

cells- convulsions (inhibition of GABA release).

Pharmacological actions of morphine contd.MOOD EFFECTS:- Normal person – calming effect, absence of pain- Dysphoria- In addicted persons- KICK- Euphoria NEURO-ENDOCRINE:- Hypothalamic activation is dampened- Hypothalamic influence on pituitary- Thus; FSH, LH and ACTH levels are lowered – only short

term- tolerance develops.- Decrease in levels of sex hormones and corticosteroids, but

no infertility; except in few cases.

PHARMACOLOGICAL ACTIONS OF MORPHINE. (CONTD.)

CVS:- Direct effect on heart- Vasodilation- histamine release, depression of

vasomotor centre.- Postural hypotension and fainting- Decreased cardiac output. GIT:- Constipation- reduced spasm of sphincters and GIT

secretions ANS:- Mild hyperglyceamia

MORPHINE PHARMACOKINETICS ABSORPTION:- Variable orally, IM or IV DISTRIBUTION:- Widely distributed – liver, kidney, spleen, etc.- Enters brain slowly- Crosses placental barrier- dependence in foetus METABOLISM:- In liver by glucoronidation-water soluble metabolites- Morphine-6-glucoronide –analgesic-renal failure-prolong analgesia- Morphine-3-glucoronide –no analgesia- neuroexcitatory. EXCRETION:- Action lasts for 4-6 Hrs- Completely eliminated in 24 Hrs.

MORPHINE- ADVERSE EFFECTSRespiratory depression-Infants and OldVomitingSedation: Mental cloudingHypotensive effectApnoea: newbornUrinary retentionIdiosyncrasy and allergyAcute morphine poisoningTolerance and dependence

MORPHINE – THERAPEUTIC USESANALGESIC1. Long bone fracture2. Myocardial infarction3. Terminal stages of cancer4. Burn5. Postoperative patients6. Biliary colic and renal colic7. Obstetric analgesia8. Segmental analgesia

MORPHINE – THERAPEUTIC USES (CONTD.)OTHERS1.Preanaesthetic medication2.Surgical analgesia3.Cardiac asthma4.Diarrhoea

PETHIDINEMORPHINE Vs PETHIDINE 1/10th as potent as morphine, but efficacy

is same. Same amount of sedation, euphoria and

respiratory depression Rapid but short DOA No antitussive action Safe margin in asthamic conditions Better oral absorption

PETHIDINE – CONTD.PHARMACOKINETICS: Well absorbed orally. Effect produced within 20 mins Parenteral administration- action lasts for 2-3

hrs Metabolized in liver-mepiridinic acid and

norpethidine Norpethidine accumulates on chronic use Excreted In urine

PETHIDINE – CONTD.ADVERSE EFFECTS: Similar to morphine Atropine like effects Overdose- tremors, mydriasis, convulsion

due to norpethidine accumulation.USES: Substitute for morphine Preanaesthetic medication Analgesic during labour- less foetal

respiratory depression.

METHADONE

Chemically dissimilar but pharmacologically similar Action is shown orally and parenterally DOA same as morphine Accumulation – repeated administration Highly bound to plasma proteins 80-90% Metabolized by liver Excreted in urine Abuse potential is low Substitution therapy – 1:4mg and 1:20mg of Morphine and

Pethidine resp. Codiene as a substitute in Methadone addiction.

TRAMADOLAnalgesicLow actionSpinal inhibition of painEffective both orally and by IV Side effects = morphine but less

prominentWell tolerated and low abuse

potential

REFERENCES:Essentials of Medical

Pharmaccology, KD TripathiRang and Dale’s

PharmacologyPharmacology, Vidyakumar

Padmaja