Pharm: Analgesics & Anti-Inflammatories (10/24a) [Biomedical] Flashcards
Sources of Opioids
Opium poppy
Endogenous opioids
- endorphins, enkephalins, dynorphins
Opioid Receptors
µ (mu) — analgesia, euphoria, respiratory depression, addiction, fastest pain relief, strongest side effects
k (kappa) — analgesia, euphoria, sedation, psychotropic
∂ (delta) — analgesia, sedation
Opioid Classification
Strong agonists
- used to treat severe pain
- EX: morphine, meperidine
Mild-to-moderate agonists
- EX: codeine, oxycodone
Mixed agonist-antagonists
- EX: nalbuphine, buprenorphine
Antagonists
- used to treat opioid overdose and addiction
- EX: naloxone
Opioid Mechanism of Action - Spinal Effects
inhibition of nociceptive pathways
Presynaptic — decrease release of substance P
Postsynaptic — hyperpolarization
Opioid Mechanism of Action - Brain Effects
influence descending pain pathways, norepinephrine and serotonin, which inhibit pain pathways
Opioid Mechanism of Action - Peripheral Effects
decrease excitability of sensory neurons
Opioid - Mechanism of Action
Pain stimulus is sent from the periphery and relayed by afferent to dorsal horn in spinal cord
Presynaptic — at each junction the opioid binds to the receptors and blocks calcium channels, release of pain substances blocked
Postsynaptic — opioid binds to the nerve and creates opening of K+ channel and K+ flows out, causes that part of the synapse to become hyperpolarized and action potential can’t be triggered
Opioid Clinical Considerations
Treatment of moderate-to-severe pain that is consistent
Alter perception of pain rather than eliminating painful sensation
Oral vs parenteral route of administration
Dosing schedule
- Patient controlled analgesia
- Fentanyl and other delivery vehicles (more localized)
Opioid Adverse Effects and Rehab Concerns
Sedation aka narcosis (most common)
Mood changes — dysphoria
Confusion
Respiratory depression — responsible for fatalities
Orthostatic hypotension
GI effects — decreased GI motility, nausea, vomiting
Tolerance and dependence
What causes opioid tolerance
Receptor downregulation and desensitization, G protein uncoupling
Opioid Addiction Treatment - Methadone
strong opioid agonist, similar in potency and efficacy to morphine
Mild withdrawal, Low success rate
Opioid Addiction Treatment - Buprenorphine
mixed agonist-antagonist which partially stimulates mu receptors while acting as strong antagonist at kappa receptors
Opioid Addiction Treatment - Naloxone (Narcan)
nasal spray, used as rescue strategy
antagonist to all receptors but has high affinity for mu
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Used in the treatment of mild-to-moderate pain and inflammation
NSAIDs - 4 primary therapeutic effects
Analgesia (pain)
Anti-inflammatory
Antipyretic (fever)
Anti-coagulation
How do NSAIDs work
Work by prostaglandin production inhibition
Prostaglandins — local hormones that regulate cell function
- inflammation, pain, fever, thrombus formation
NSAIDs - Overall Mechanism of Action
When the cell is injured, cyclooxygenase break downs arachidonic acid→ leads to inflammation, pain, thrombus formation, etc
NSAIDs are responsible for cyclooxygenase (COX) inhibition
NSAIDs Mechanism of Action - COX1 Inhibition
Protect stomach lining from gastric acid
Thromboxanes-platelet aggregation
NSAIDs Mechanism of Action - COX2 Inhibition
Mediates:
local erythema & edema
pain, by increasing sensitivity of receptors
fever
Risk Factors for NSAIDs — GI Complications
Typically no warning of severe complication
Risk factors:
- Age (>65), peptic ulcer, other drugs, multiple anti-inflammatories, systemic illness, cigarette smoking and alcohol
Clinical signs — silent mostly but can have pain, heartburn, nausea, melena (blood in stool), fatigue, severe is internal bleeding
NSAIDs Adverse Effects
Gastrointestinal problems
Cardiovascular problems
- Increase blood pressure
- Increase blood clotting (COX2)
Hepatic and renal problems
NSAID toxicity — confusion, cranial nerve damage, tinnitus
Inhibit bone healing
Inhibit tissue healing?
NSAIDs - COX2 Selective Inhibitors (Coxibs)
Inhibit synthesis of inflammatory prostaglandins produced by COX-2, while sparing the production of beneficial COX-1 prostaglandins that help regulate normal physiological function
Lower incidence of GI irritation
Preferred by patients at risk for prolonged bleeding and bruising (thromboxanes not inhibited)
Risk of heart attack and stroke
EX: Celecoxib (Celebrex), Etoricoxib (EFLAM, ETO, etc)
NSAIDs - Aspirin
the prototypical NSAID, represents the major form of a group of drugs known as salicylates
Treatment of:
- Pain and inflammation
- Fever
- Vascular disorders
- Prevention of cancer (colorectal)
Acetaminophen
Compared to NSAIDs
- similar analgesic and antipyretic effects
- no anti-inflammatory or anticoagulant effects
- no upper GI tract irritation
Mechanism of action
- might only act in CNS (COX-3?)
Adverse effects — hepatotoxicity (liver damage at low doses)
Often combined with other meds (EX: cold meds)
Topical Agents
Ointments
- Contain menthol or capsaicin
- EX: Bengay, Icy Hot, Tiger Balm
- Adverse Effects — burning sensation
Sprays, creams and patches
- Contain aspirin or other NSAIDs
- EX: aspercreme, salonpas
- Adverse Effects — rash
2 types of anti-inflammatory drugs
NSAIDs — requires higher dose to get anti-inflammatory effects
Glucocorticoids
Glucocorticoids
used in moderate to severe inflammation
ends in “-one” (EX: dexamethasone, hydrocortisone)
inhibits phospholipase, also immunosuppressant
Glucocorticoids - Adverse Effects
Impaired tendon, ligament, bone, wound healing — due to effect on collagen
Catabolic effects
Adrenocortical suppression
Salt/water retention
Increased infections
Peptic ulcers
Hyperglycemia
Systemic vs localized administration
- max 3-4 injections per joint per year
