CNS P3 ( Opiod - Genral and local anastia ) Flashcards
DF and classification of opioids
-DF: drug that relieve or decrease the pain sensation
— Classification:
1- Full agonist:
1-1 Morphine
1-2 Fentanyl
1-3 Trimeperidine
1-4 Codeine
—
2-Partial agonist-antagonist
2-1Buprenorphine
2-2 pentazocine
—
3-analgesics mixed mechanism of action :
3-1 Tramadol
—
4-full antagonist:
4-1 naloxone
4-2 naltrexone
explain the Endogenous ligand , receptors , effect associated with the receptors .
-Endogenous ligand : are ligands found naturally in the body and they are 3:
1-Endorphins = muo , delta receptors
2-enkephalins = muo , delta receptors
3-Dynorphins = kaba receptor
——
- receptors and there effect when they are triggered :
1- Muo : analgesic, Rc depression,Euphoria,meiosis,sedation,
suppression of Gi motility , addiction , bradycardia
2-delta : Rc depression, suppression of Gi motility
3- kaba : dysphoria , meiosis,sedation, suppression of Gi motility,addiction
explain the mechanism of All opioids
1- molecular mechanism:
-opiate receptor stimulation > Gi > inhibit of adenylate cyclase (AC) > decrease the cAMP which inactivation of Ca2 and activate Channel K+ which lead to Hyperpolaraization
2-mechanism of Spinal analgesia
-the receptor m,d,k located in the post horn of the spinal cord so when the drug enter and stimulate these receptors it’s decreasing the SGR ( substnsia of gluntosa of Rolando ) and decrease glutamate which lead to Disinhibition of the descending Anti-nociceptive pathway
3-mechanism of Supraspinal analgesia
the opeite receptor also located in the brain when it’s stimulate they lead to activate the Descending inhibitory pain control which lead to inhibit the of the sensation comes from the spinal
4- NA mechanism :
also these drugs are responsible for decreasing the NA release which lead to decrease the emotional pain
( ex tramadol )
expain the prototype of opioids
-Drug : Morphine A1%-1ml IV or IM
—Pharmacokinetics:
1- oral absorption: good ( bioavailability 25%) dup to significant first pass
2- T half life :4-5 h
3-metabolism: in the liver by conjugation leading to inactive metabolites
4- Execration : Renal 90% bile ( 10% as conjugated morphine )
- mechanism: mentioned earlier but its act more on Muo receptor more then D,K
—pharmacological effect :
—CNS—
1- analgesic: Dose dependent (morphine can treat all types of pain exempt Itching
2-Euphoria : large dose cause Dysphoria
3-Rc depression: duo to stimulation of M receptor over dose lead to Co2 retention and cerebral VD > increase ICP
4-cough suppression
5-vegal stimulation
6- Vomating and nausea: Duo to CTZ stamulation
—CVS—
1-bradycardia
2-orthostatic hypotension
—Smooth Mc—
1- bronchi construction: duo to vegal stamulation , histamine release
2-Constpation : duo to spasmodic non-propulsive contraction of insistent
3-spasm of sphincter of oddi : sphincter of bile
4-uterus : prolongation of labor by
uclear mechanism
— therapeutic uses :
1-analgesia: for sever pain , Mi acute , post surgery
2- Pulmonary edema : bcs
2-1 decrease stress of patient
2-2 vasodilation ,decreasing the VR preload, decreasing pulmonary congestion
3- sever colic : but not hepatic colic ( billary colic )
—addvers effect :
1- CNS : tolerance and physical dependance
2-CVS : posturla hypotintion
3-RC : Rc depression, bronchi construction
4-GIT : constapation , urin retention
5- Ginto : labor prolongation
6- Eye miosis ( clearn in addiction patient PPP)
—risk of dependence: high
— Contra indication :
1- head truma
2-biallry colic , gallstones
3- hepatic damage: increase the risk of Encephalopathy
4- hyperthyroidism: duo to multiple effect then normal
— treatment of toxicity:
- mansifstion : Coma with Rc depression
- treatment: 1- patient im ventilator and give the patient Opioids blocker (ex Naloxone ) in case the patient not addicted
explain the Full agonist - Codeine
-Drug : Codeine Tab 0,015
-mechanism : Same as morphine act on Muo receptor more then others
- pharmacokinetics: has greater bioavailability (60%) duo to less first pass metabolism
- pharmacological effect :
same as morphine but it has little effect on Euphoria , - as analgesic has 20% potency of morphine
- rusk of depends: middle
- therapeutic uses :
1- analagisc for modren or milde pain usually mixed with paracetamol
2- As central Antitussive
explain the Full agonist-Fentanyl
-drug : Fentanyl A 0,005%-1ml IV
- mechanism: same as morphine
- pharmacokinetics: its most potant opioid and shorter duration
- risk of depends: high
- analagisc activity: 100 more then morphine
- therapeutic uses :
1- neuroleptianalgisa
2- sever pain ( as skin patch )
explain the Full agonist - Trimeperidine
- Drug : Trimeperidine tab 0.025
- mechanism: same as morphine act on Muo more then D,k
-pharmacological: has an antispasmodic effect on smooth ms ,and promotes the opining of the cervix during labor - risk of depends: middel
-analagisc activity : less then 3 times of morphine - uses :
1-Labor pain Relief
2- Colic
explain the agonist - Loperamid
- Drug : Loperamid capsules 0,002
- mechanism: its opioid agonist act on m,d,k peripherally only dose not pass BBB , so its only act as spinal analgesic
-phamalogicl effect : same as morphine but prephrally and it dosnt make constapation
-therapeutic uses ; to treat Daihrrhia 
explain the drug mixed agonist-antagonist ( Pentazocine )
-drug : Pentazocine tab0,05
-mechanism: its K agonist and M antagonist and work as spinal analgesic
- risk of depends: low
- analagisc activity : less then 3 time of morphine
- uses : chronic pain , cardiac arrhythmia
explain the drug mixed agonist-antagonist ( Buprenorphine )
-Drug :Buprenorphine tab 0,0002
-mechanism: partial M agonist and K antagonist and work as spinal analgesic
-risk of depends: low
-analagisc activity: more then 50time lf morphine
-uses : chronic pain , cardiac arrhythmia
explain the opioid mixed mechanism-tramadol
-Drug : tramadol A5%-2ml
-mechanism: it has 2 mechanisms
1- stimulate M receptor which lead to morphine action
2-inhibit the reuptake of NA and serotonin which lead to accumulation of these transmitters in the synaptic cleft and cause NeuroPsychotric complex
- risk of depends: low
- analgesic activity: 10% of morphine
- uses : sever pain , Post oprative orthopedic surgery
explain the Opioid blockers
- Drug : 1- Naloxone A 0,04%-1ml 1h
2-Naltrexone tab 0,05 48h - mechanism: blockes the Opetes receptor M,d,k
-uses : to treat acute opioids toxicity and prevent the Rc depression - contraindications: the addiction patient
Df of : general anaesthesia , balanced anaesthesia, main goal of anaesthesia, classification of general anaesthesia
- general anaesthesia: its drug that case depression of CNS chrectraized by reversible loss of consciousness, sensitivity of reflex
- balanced anaesthesia: its to create anaesthesia, several drug of diffraction effect used samtinously
- main goal of general anaesthesia: to eliminate consciousness,analgesia, suppression of reflexes , muscles relaxation
— classification of general anaesthesia:
1-inhalation anaesthetic :
1-1 gases : Nitrous oxide
1-2 volatile holagated hydrocarbons : - first generation : halothane ,
-2nd generation : isoflurane , Enflurane
-3rd generation: Sevofulrane , desflurane
2- non-inhalation :
1-thiopental
2-propofol
3-ketamine
mechanism of general anaesthesia
-they are several mechanisms :
1- increase the sensitivity of GABAa receptor to GABA which equal the increase of the cl- inside the cell
2- activation of Two-pore K channel
3-blocking of NMDA receptor which equals blocking of Ca2
4-increase the ability of glycine to activate glycine-regulated chlorine channel
explain the inhlation drugs
- drugs :
1- Volatile liquids : isoflurane,sevoflurane,enflurane,
Desfulrane ( the most speed of induction of them is sevo )
2-Gases : Nitrous oxide ( laughing gas) , Xenon
-pharmacokinetics:
diffuse of the anaesthetic agent from the lung to alveoli then to blood depends on these factors :
1- partial pressure: between the alveoli and blood , the higher the partial pressure of the anaesthetic agent in the inhaled air the faster the induction , induction of the anaesthetic agent is proportionally related to the partial pressure
2-Paritint Coefficient : between the tissue and anaesthetic agent in the blood stream in two forms 1-free form 2-sulable in plasma form , so the more the free form the more effective , the relation betwen them its inversely related with blood / gas , and the partint coefficient Brain/gas the more the sulabe form the more effective
3- COP: increase the Blood flow slowes dwin the induction but accelarte the onset if the Equlberrium
—adverse effect :
1- malignant hyperthermia
2-increase ICP
3- Cardiac arrhythmia
