Opioid

Opioid Analgesic Agents

Opioid Analgesics
Pain relievers that contain opium, derived from the opium poppy or chemically related to opium Narcotics: very strong pain relievers

Pain Transmission

Body has endogenous neurotransmitters Enkephalins Endorphins Produced by body to fight pain Bind to opioid receptors Inhibit transmission of pain by closing gate

Opioids

Opioids are natural or synthetic compounds that produce morphine-like effects. All drugs of this chapter act by binding to specific opioid receptors in the CNS to produce effects that mimic action of endogenous peptide neurotransmitters.

Classification of Opioid Analgesics

Three classifications based on their actions: Agonist (morphine) Agonist-antagonist (Mixed opioid) Pentazocine and partial agonist .(buprenorphine ) Antagonist (Naloxone )



Narcotic analgesics (opiates or opioids)
ll
Drug Classification
Natural - e.g. morphine, codeine
Semi-synthetic - e.g, heroin
Synthetic - e.g. pethidine, methadone
Morphine-like
compounds contain a
phenanthrene ring
system

3
CH
N
O
OH
HO
Morphine

OPIOID CLASSIFICATION

Classify by their potency: 1. strongest (morphine,methadone, meperidine ,Heroin) 2. Mild to Moderate (oxycodone, ,codeine ,, propoxyphene)

Opiates receptor:

1.mu( µ)2.Kappa (ķ)3.Sigma(δ)4.Delta (ơ)

1-Morphine.

Action
1.Analgesia 2.Euphoria 3. Respiration 4. Depression of cough reflex 5. miosis 6. Emesis 7. Gastrointestinal tract 8.Cardiovascular 9.Histamine release 10. Hormonal action

Therapeutic uses:

Main use: 1.analgesia : to relief moderate to severe pain :2.Treatment of diarrhea. 3.Relief of cough (cough center suppression). 4.Treatment of acute pulmonary edema.

Side Effects

Dysphoria Nausea and vomiting Respiratory depression Urinary retention Diaphoresis and flushing Pupil constriction (miosis) Constipation Elevation of intra cranial pressure.

Toxicity and undesired effect

1-Tolerance Although development begin with the first dose of an opioid , tolerance generally dose not become clinically manifest until after 2-3 weeks of frequent exposure to ordinary therapeutic dose Tolerance develops when large doses are given at short interval .


2-Physical Dependence
is a state of physiologic adaptation that is manifested by a drug class–specific withdrawal syndrome that can be produced by abrupt cessation of the drug, rapid dose reduction, decreasing blood content of the drug, administration of an antagonist.Dependence results from adaptation at cellular synaptic.

Physical Dependence The sings and symptom of withdrawal include rhinorrhea , lacrimation , yawning , chills, hyperventilation , hyperthermia, mydrasis, muscular aches , vomiting , diarrhea anxiety and hostility .

Note:

Opioid tolerance and physical dependence are expected with long-term opioid treatment and should not be confused with psychological dependence (addiction).

Psychological Dependence (addiction)

A pattern of compulsive drug use characterized by a continued craving for an opioid and the need to use the opioid for effects other than pain relief

Withdrawal Opioid Syndrome

Manifested as: anxiety, irritability, chills and hot flashes, joint pain, lacrimation, rhinorrhea, diaphoresis, nausea, vomiting, abdominal cramps, diarrhea

Contraindication and caution therapy

1- use of pure agonist (morphine) with weak partial agonist (pentazocine), cause diminishing analgesic or even inducing a state of withdrawal therefore combination should be avoided . 2- use in patient with head injuries respiratory depression result . with elevated intracranial pressure , this may lead to lethal alteration in brain function .

3- use during pregnancy the fetus may become Physical Dependent in utero and manifested withdrawal symptoms in the infant including irritability crying,diarrhea ,or even seizure control of these symptom using such drug as diazepam , methadone .


4- In patient with impaired pulmonary function depressant properties of the opioid analgesic lead to acute respiratory failure 5- in patient with impaired hepatic or renal function because opioids are metabolized in liver and half- life is prolonged In patient with impaired hepatic function lead to accumulation , dosing can decrease in such patient

Meperidin

Is synthetic opioid , it used for acute pain Action: in therapuetic doses(80-100)parnterally ,it produses Analgesia,sedation ,respiratory depression, CNS actions Not cause pinpoint pupil but dilate the pupils(atropin like effect)

USES

Analgesia for severe pain ,it is employed in obstetrics(analgesia during labor) I.M duration is short(3-4 )hours Adverse effects CNS exitation produse Tremors Muscle twitches Rarely convulsions dependence Dry mouth and blurred vision

Methadone

Adverse effects
Like morphine produce pysical dependance and mild with drawal syndrom.

Fentanyle

More potent analgesic (100-fold more than morphine). Rapid onset of action. Short duration of action(15-30)minutes.


USES Used in anesthesia I.V. because provide cardiovascular stability during surgery Epidural used for analgesia post-operatively and during labor Transmucosal preparation used in the treatment of cancer patient Available for rapid onset (sublingual absorption)


Heroin
More potency than morphine Cross blood brain barrier rapidly Exaggerated euphoria No medical use

Moderate analgesic

Codeine Oxycodone Propoxyphen

Codeine

naturally occuring, Less potent analgesic than morphine.analgesic dose 30-60mg orally USES. analgesic and Antitussive use Used with aspirin and acetaminophen for control pain. Less produce euphoria. Lower potential for abuse Rarely produce dependence.

Propoxyphene

Is used an analgesic to relieve mild to moderate pain Used with aspirin or acetoaminophen for analgesia It has antitussive action. Produce nausea ,anorexia , consitipation In toxic:respiratory depression ,convulsion hallucination ,confusion,cardiotoxicity.

Mixed agonist-antagonists

Stimulate one receptor and block another Pentazocine Buprenorphine

Adverse effects

Higher dose causes : Respiratory depression decrease the activity of GIT Increase BP and tachycardia Hallucination Tolerance and dependence on repeated use.


Buprenorphine with naloxone for treatment of withdrawal effects

Other analgesic (TRAMADOL)

Toxicity include 1-seziure (CI in patient with epilepsy)2- nausea vomiting, and dizziness3-no clinically significantly effects on respiratory and cardiovascular system 4- Anaphylactic reaction with repeated use5 –has abuse potential but less than other opioid.

Tramadol is gaining acceptance as an analgesic after dental procedures and is a safe and effective alternative for individuals who cannot tolerate opioids in combination with acetaminophen or nonsteroidal anti-inflammatory drugs.


Tapentadol (approved in 2008)Tapentadol is a compound that is related mechanistically to tramadol and approved more recently for the management of acute pain. In contrast to tramadol, tapentadol has strong μ opioid agonist activity and norepinephrine reuptake inhibition. Its potency is greater than that of tramadol and similar to morphine. The dual mechanism of action may contribute to an improved side-effect profile with diminished nausea and vomiting and constipation,

Opioid Antagonis: (Narcan

Naloxone is a competitive antagonist at µ,ķ,δ receptorsNo produce pharmacological effect in normal individual but it precipitates withdrawal symptoms in opioid abusers.

Naloxone (Narcan)

Used to reverse opioid overdose displaces receptor-bound opioids Good for overcoming respiratory/CV depression Treated acute opioid intoxication.
Opioid Receptor
Naloxone
Morphine
Just beat it!

Naltrexone

Action similar to naloxone Longer duration of action is well absorbed after oral administration but may undergo first pass metabolism , it has half life 10 hours Is employed for rapid opioid detoxification Treating chronic alcoholism