opioids Flashcards
Classify therapeutically useful opioid analgesics based on their receptor selectivity.
- Agonist at Mu,Kappa,Delta
* Morphine, codeine, pethidine, oxycodone, dextropropoxyphene - Agonist at mu, delta
* Fentanyl - Agonist at Mu
* Methadone, tramadol - Mixed agonist-antagonists and partial agonists
* Pentazocine – antagonist at μ receptor, agonist at κ and δ receptors
* Buprenorphine – partial agonist at μ receptor, antagonist at κ and δ receptors
Explain the mechanism of action of opioids.
Opioid agonists bind to opioid receptors (G-protein coupled receptors) and produce the following actions:
* Inhibit adenylate cyclase →
↓ intracellular cAMP → decrease in cell excitability (through μ & δ receptors)
* Activation of potassium channels → increase in K+ efflux → hyperpolarization of neurons → decrease in neuronal excitability (through μ & δ receptors)
* Suppress N-type voltage-gated calcium channels → reduced intracellular Ca2+ → decreased release of neurotransmitters from presynaptic neurons (through κ receptors)
Explain the pharmacological actions of morphine.
map in notes
List pure opioid antagonists.
Pure antagonists at mu (μ), kappa (κ) and delta (δ) receptors include
* Naloxone
* Naltrexone
* Nalmefene
Tell the role of drugs used in opioid dependence.
mediated through μ receptors.
1)Psychological dependence
-The patient believes that optimal state of well being is achieved only through the action of the drugs.
-The euphoria that individuals feel and the easing of pain during use of opioids.
-Presence of strong emotional cravings to the drug.
2)Physical dependence
-Continued presence of drug needed to maintain physiological equilibrium.
-Abrupt stoppage of opioid results in withdrawal symptoms.
-Pain, hyperventilation, cough, vomiting, diarrhoea, mydriasis, dysphoria, agitation, piloerection and drug seeking behaviour.
Apply the pharmacological aspects of methadone to provide basis for its use in the management of opioid
dependence
- Methadone
- agonist at μ receptor
-long acting.
-opioid in use is substituted by methadone.
- spare the addict from undesirable withdrawal symptoms because the opioid receptors remain occupied for a longer duration. Later methadone can be withdrawn by tapering the doses over a period of weeks.
Methadone is preferred because -
* Tolerance and physical dependence develop more slowly with methadone
* The withdrawal signs and symptoms occurring after abrupt discontinuance of
methadone are milder
* It has longer duration of action
* It is orally effective
- Buprenorphine
* It is a partial opioid agonist used as an alternative to methadone. - Naltrexone
* It is a long acting, orally effective pure opioid antagonist.
* Used in addicts who are completely withdrawn from opioid (after methadone therapy)
* Used to block pleasurable effects leading to relapse - Clonidine
* It is a centrally acting sympatholytic agent
* Used to detoxify the patient and to prevent relapse
* Reduces the severity of withdrawal effects of opioids
endogenous opioids peptide
-Enkephalins, endorphins and dynorphins.
-released within the body in response to pain and bind to opioid receptors to relieve pain.
Morphine depressant effects:Analgesic*
Mediated mainly through mu (μ), kappa (κ) and delta (δ) receptors
* Reduce both the sensory as well as the affective components of the pain
* Increases pain threshold, ↓ pain transmission, ↓ emotional reaction to pain
* More effective against dull, continuous pain such as deep-seated visceral pain than a sharp
intermittent integumentary pain
* Neuropathic pain may respond poorly to opioid analgesics
Morphine depressant effects: Euphoria, dysphoria
- Produces a sense of well-being (μ)*
- Distress and anxiety associated with pain are reduced
- Patients in distress due to pain may complain of dysphoria (κ)* characterized by restlessness and
malaise
Morphine depressant effects:Sedation
- Mediated through μ and κ receptors
- Drowsiness and mental clouding of judgement can be seen
- Disrupts normal REM sleep pattern
Morphine depressant effects: Respiratory depression
- Mediated through μ receptors
- Respiratory depression is the most common cause of death in opioid poisoning.*
- This is dose dependent and can occur at therapeutic doses
- Inhibition of the respiratory center in the medulla → ↑pCO2
- Causes suppression of neurogenic, hypercapnoeic and later hypoxic drives to the respiratory center
- Produces indifference towards breathing, but the patient may start breathing if commanded
- The increased pCO2 → causes cerebrovascular dilation → ↑ blood flow → increased intracranial pressure
Morphine depressant effects:Vasomotor center depression
Seen at higher doses, may cause bradycardia and fall in BP.
Morphine depressant effects:Cough suppression
Causes suppression of cough center in medulla and cough reflex at sub-analgesic doses
- do not give for productive cough (flam)
Morphine stimulant effects:
- Miosis
* Mediated through μ and κ receptors
* Pinpoint pupil due to stimulation of Edinger Westphal Nucleus
* Useful in diagnosis of opioid poisoning - Nausea and Vomiting
Directly stimulate the Chemoreceptor Trigger Zone → emesis - Convulsions
May be seen in high doses
Peripheral effects of morphine: CVS*
larger dose of morphine can cause postural hypotension & bradycardia. This is due to:
* Release of histamine from mast cells and histamine will cause vasodilatation
* Depression of vasomotor centre in the medulla. Vasomotor centre regulates blood pressure and
depression of vasomotor centre causes the loss of vasomotor tone of blood vessels, resulting in
vasodilatation → hypotension
* Direct action decreasing tone of blood vessels
