Analgesic Drugs 1 Flashcards
What effect do opiods/opiates have?
- Analgesia
- A state of impaired conciousness/ sedation
**there is a significant difference within individuals
WHat types of pain can opioids treat?
After severe to moderate pain
- Nociceptive Pain (tissue damage)
- Inflammatory Pain (due to inflam. mediators)
These pains are opioid sensitive, however Neuropathic pain (due to nerve damage) is stubborn and uneffected by opiods.
What are the routes of administraion of opioid
- Oral
- Parenteral: intramuscular, intravenous, intermittent, continuous, Patient controlled
- Trans-mucosal
- Transdermal
Where do you even get opium from and what does it contain?
It’s the dried latex from opium poppies containing
- *Narcotic alkaloids:**
- morphine (can be processed chemically → herion)
- codeine
Non-narcotic alkaloids:
Whats the difference between an opiate vs an opiod?
Opiate: naturally derived from an opium poppy, no chemical synthesis.
Opiods: Synthetic narcotic that mimics the poppy plant, is chemically manufacuted
What are the most commonly used Opioids/opiates
- Morphine***
- Pethidine
- Fentanyl
- Codiene
- methadol
On a cellular level, how do opioids work at opioid receptors to cause an effect?
O.R’s are essentially presynaptic; type of G-protein coupled receptors.
Opiods then….
- @ Presynaptic neuron: Activate Gi proteins → inhibition of adenylate cyclase enzyme → lowers Ca2+ channels permeability (→ block transmitter release)
- @ Postsynaptic neurons: Increase K+ conductance → hyperpolarization of post-synaptic neuron → decreased response
Where do you find opioid receptors and what types are there?
All over the CNS.
- *Mu Receptors:** Spinal cord >brainstem > thalamus > cortex.
- They are divided into M1, 2 and 3*
Kappa (k) Receptors: Limbic system, hypothalamus, brainstem and spinal cord
k 1 , 2 and 3
Delta Receptors: also within the CNS
d 1, 2 and 3
How are opiod receptors synthesized?
- Mediators from damaged tissues will stimulate the dorsal root ganglion to manufacture these receptors.
- These receptors then migrate in the axon and the dorsal cord.
- This can be stimulated by both exogenous and endogenous opiods!
Different opiod receptors produce different response.
Compare Mu-1 to Mu-2 and Kappa receptors!
Although all three can cause analgesia, Mu-2 has many other effects and kappa can also cause dysphoria.
Just know there are differences!
Give an example and the action on opiod receptors for an
AGONIST
Activate all receptor subclasses but at different affinities.
eg morphine, fentanyl, pethidine
Give an example and an action on opiod receptors for an
ANTAGONIST
Devoid of activity in all receptor classes
eg; Naltrexone, Naloxone
Give an example and the action on opiod receptors for an
AGONIST-ANTAGONIST
Agonist activity on one receptor type, antagonist on another
eg; nalorphine, pentazocine
Give an example and the action at an opiod receptors for a
PARTIAL AGONIST
Activity at 1 or more, but NOT all receptor types
eg; Bup-re-norphine
Draw the graph of pain relief treatment (with pain intensity over time)
- Mild Pain: no opiods
- Moderate Pain: oral opiods
- Severe Pain: injected opiods
What are some of the adverse effects of opiods?
- Respiratory depression (@Mu-2)
- Somnolence drowsiness
- Constipation/Ileus
- Itching
- Nausea & Vomiting
- Vagally mediated bradycardia
- Hypotension morphine
Who should be using opiods with caution?
- Those with sleep apnea
- COPD patients
- eldery/young kids
Type 1- natural opiates
- Morphine (pill and fluid)
- Codeine (pill)
Type II- semisynthetic opiods?
Created from the natural opiate
- Bup-re-norphine (partial agonist)
- Oxycondone
- Di-acetyl morphine (heroin)
Type III- fully synthetic opiods
- Fetanyl (v common)
- Pethidine
- Tramadol
Type IV: endogenous opiods peptides?
Opiods produced naturally in the body
- Endorphins (Mu-opiod receptors)
- Endomorphins (mu agonist)
- Dynorphins (kappa-opiod receptors)
- Enkephalins (delta-opiod receptors)
What needs to be considered when using/ administering opiods?
- The best/most comfortable route of administration
- Round the clock for severe-moderate pain
- Consider inter-patient variability
- use adjuvants for enhancing opiods analgesia and reducing side effects eg; NSAIDS
What effect of opiods can lead to it being a drug of abuse?
Their euphoric effect.
What are symptoms of opiod withdrawal!
How do you manage opiod withdrawal?
Very slow approach.
Addictive opiod is replaced with another opiod with a lower euphoric effect (eg methadone or bup-re-norphine), and then slowly wean the patient off the drug!
Also give adjunctive drugs to reverse symptoms
Clonidine → autonomic withdrawal effect
Promethazine → nausea, vomiting
Antidiarrheal → diarrhea
What is Rapid Opiate Detoxification Treatment?
Techniue of detoxification under general anaesthesia to rapidly (~2hours) induce detox, whilst blocking the sever withdrawal symptoms
- Under GA the patient isn’t subject to withdrawal
- High doses of Naltrexone (antagonist) is used and is used immediately post op to reduced relapse
What are the potency of morphine, methadone, pethidine and fentinyl? How does this relate to dosing?
Morphine: 1
Methadone: 1x
Pethidine: 0.1x (has to give 100x the dose to achieve the same effect)
Fentanyl: 50-100x (give in very very small doses!)
What does morphine do?
- Powerful analgesic
- Sedation
- Cough suppresant
- Miosis (pin point pupil)
- Altered mood (euphoria/tranquility)
- Large VoD (1/3 bound to plasma proteins)
- t1/2 ~3hours
What are morphines routes of administration?
Due to its low lipid solubility, so it has a slow onset and long duration.
- Orally (but only 25% bioavailability sue to hepatic first pass)
- IV: bolus, cont. IV infusion, PCA (patient controlled analgesia)
- IM
- Intrathecal/epidural
What is morphine metabolised to in the liver?
Morphine 3-glucuronide (M3G): 70%, no analgesic property
Morphine 6-glucuronide (M6G): 1/2 as potent as morphine, w longer t1/2
Excretion mainlly in urine
What is pethidine and how is it administered?
Synthetic drug that has some similar effects to anticholinergic (blocks PNS).
-less miosis, dry mouth, tachycardia, less biliary spasm
ROA: Tablets, 50% oral bioavailability, highly lipid soluble (fast acting)
How is pethidine metabolised?
In the liver, but what you need to worry about is one of the two bi-products, ‘Norpethidine’ (long t1/2 8-21 h) thatcan accumulate in patient with renal failure.
This can lead to hallucinations, seizures.
What drugs can pethidine interact with?
Anti-depressants → coma, convulsions, labile circulation, hyperpyrexia.
