Unit 2: Analgesics Flashcards
Drugs for pain: - NSAIDs - opioids
What is pain?
An unpleasant sensory-emotional experience associated with, or resembling, tissue damage—typically signalling injury or illness.
Occurs through the activation of nociceptors (pain sensors)
Severity ranges from mild and dull (barely noticeable) to explosive and sharp (debilitating)—sensations include:
- prick
- tingle
- pressure
- sting
- burn
- ache
Types of Pain
Acute: short-duration (lasting minutes to 3 mo)
Chronic: long-duration, sometimes life-long—can be constant or intermittent
Neuropathic Pain: nerve/nervous system damage—typically chronic—often described as:
- pins and needles
- stabbing/burning
- hot/cold
eg: carpal tunnel, paralysis
Nociceptive Pain: damage to body tissue (skin, muscles, organs, joints, tendons/ligaments, bones) caused by external injury—can be acute or chronic
- sharp
- achy
- throbbing
eg: twisted ankle, scrapped knee
Radicular Pain: occurs when the spinal nerve is compressed or inflamed—radiates from the back and hips into the legs
- steady
- tingling
- numb
- muscle weakness
eg: sciatica
What activates nociceptors?
Perception of pain comes from many situations:
- extreme temperature (hot/cold)
- mechanical stretching
- mechanical pressure
- capsacin (chili pepper)
- tissue damage/infection—releases chemicals like prostaglandins, activating nociceptors
Classes of Analgesics (pain meds)
Local Anaesthetics: drugs that stop all action potentials by blocking voltage-gated sodium channels of all nociceptive neurons
- eg: lidocaine
NSAIDS: non-steroidal anti-inflammatory drugs—block the production of prostaglandins
- eg: ibuprofen, aspirin, naproxen
Acetaminophen: mechanism of action = unknown—does not affect prostaglandin production
- aka tylenol
Opioids: opiates are derived from poppy, and activate the mu opioid receptor (mediates pain relief)
- eg: opium, morphine, codeine, heroin, fentanyl…
Non-Steroidal Anti-Inflammatory Drugs (NSAIDS)
Target: cyclooxygenase (COX2)
Mechanism: antagonist of prostaglandins (PGE2)
Therapeutic Effects: reduces
- pain
- swelling (inflammation)
- redness (inflammation)
- fever
- blood-clotting (low dose aspirin)
Side Effects: (if used excessively/at high doses)
- stomach/GI ulceration—prostaglandins protect the stomach/intestinal lining
- reduced kidney function
- exacerbated asthma
- allergy
How do NSAIDs work?
NSAIDs reduce inflammation by suppressing the signaling function of prostaglandins (PGE2), (which cause swelling and increased blood flow in response to injury), by inhibiting the cyclooxygenase (COX2) enzymes and thereby reducing prostaglandin synthesis. Limiting the levels of prostaglandins will reduce the firing rate of nociceptive neurons in the ascending pathway
Ligands (Endogenous and Exogenous)
Ligands: biologically active molecules that bind to cell receptors, causing biochemical/physiological changes/effects
Endogenous ligands: naturally-occurring molecules (within the body)
Exogenous ligands: molecules that originate from an external source (outside of body)
Mu Opioid Receptors (MOR)
Mu Opioid Receptors (MOR): mediates pain relief; located in brain regions that control pain sensation and emotional response to pain
When MORs on a neuron are bound by an agonist, the result is inhibition (less firing of that neuron)
Opioid Potency
Class: analgesic; depressant
Target: mu opioid receptors (MORs)
Mechanism: agonist of MORs
_Prescribed Opioids (potency compared to morphine)
Morphine
- active ingredient in the poppy plant
- source for many semi-synthetic opioids
- genetic differences dictate metabolic speed
Codeine:
(0.1X as potent)
- converted to morphine in the liver (active drug)
- tylenol-3 = acetaminophen + codeine
- semi-synthetic
Hydrocodone (Vicodin)
(0.6x as potent)
- moderate to moderately severe pain
- cough suppressant
- semi-synthetic
Oxycodone (Oxycontin)
(1.5X more potent)
- percocet = acetaminophen + oxycodone
- semi-synthetic
Hydromorphone (Dilaudid)
(5X more potent)
- moderate to severe pain
- semi-synthetic
Methadone
(5X more potent)
- used for chronic pain and opioid use disorder
- synthetic
Diamorphine (Heroin)
(10X more potent)
-semi-synthetic
Fentanyl
(100X more potent)
- synthetic
Opioids: Acute Effects
Opioids have a narrow therapeutic window—meaning that the adverse effects occur at or near the therapeutic dose.
Opioid acute (short-term) effects:
CNS
- euphoria
- alert/drowsy
- histamine release — allergic response = common
Mouth
- dryness
Skin
- warm/flushed
Respiratory
- slowed breathing
Muscular
- weakness
GI
- constipation
Opioids: Long-Term Effects
Chronic use of opioids will cause the body to make adaptive changes, downregulating the amount of mu opioid receptors
Long-Term Effects
CNS
- tolerance—more drug required for same analgesic and euphoric effects
- dependence—drug is required for functioning; otherwise, experiences withdrawal symptoms
- addiction—compulsion to use despite adverse consequences
Heart
- infection of lining and valves
Respiratory
- pneumonia
Circulatory
- collapsed veins
Liver
- decreased function
Systemic
- abscesses
Receptor Desensitization
The decreased responsiveness that occurs with repeated or chronic exposure to agonist, causing the receptor to internalize into the neuron and stop the signal
A feature of all G-protein coupled receptors, including ones for vision, smell, taste and the MORs that mediate analgesia.
Methadone Treatment
Methadone is a synthetic opioid (5X more potent than morphine) that activates MORs
It is given in tapered doses to lessen withdrawal from heroin; however, methadone withdrawal is just as aversive
Not effective to reduce heroin use/relapse rates unless paired with other interventions (eg. counselling)
Buprenorphine Treatment
Buprenorphine is another semi-synthetic opioid (25-100x more potent than morphine), but is a partial agonist of MORs, meaning that is doesn’t full activate the mu opioid receptor, thus is unable to produce the same euphoric high.
It is used in tapered doses to lessen heroin withdrawal symptoms–less rewarding and causes a less aversive withdrawal than methadone
Not effective in reducing heroin use/relapse rates unless accompanied by other interventions (eg. counselling)
Opioids:
Target, Mechanism of Action, Therapeutic Use
Target: mu opioid receptors (MORs)
Mechanism: agonist of mu opioid receptors; bind to MORs in central and peripheral nervous systems to hyperpolarize nociceptive neurons, eliciting analgesia
Drug Class: analgesic (painkiller); narcotic
Structure: similar to hormone endorphin (peptide) that blocks perceptions of pain and increases feelings of well-being
Therapeutic Effects:
reduces
- moderate to severe pain
- coughing (hydrocodone)
- diarrhea (loperamide)
