3. Analgesics Flashcards
Chronic pain is pain greater than how many months?
Exhibit reactive __ and increased/decreased function
3-6 months
Depression
Decreased
Prostaglandins are lipid mediators derived from ___ that play roles in the pathogenesis of what three symptoms?
- Arachidonic acid
2. Inflammation, fever, pain
Why do we not give ASA to asthmatics?
Leukotriene will buildup in the lungs and trigger asthma
Effects of COX-1 activated sites on PGHS-1/2 molecules (3)
- Promotes platelet aggregation (through thrombin A2 production)
- Promotes kidney blood flow in compromised kidney
- Promotes protection of the stomach and intestine line
Effects of COX-2 activated sites on PGHS-1/2 molecules
- Promotes fever
- Promotes inflammation
- Promotes hyperalgesia
Acetaminophen - MoA
- Acts primarily in CNS to inhibit synthesis of what?
- Inhibits this synthesis by inhibiting a specific site on what?
- It also acts as a reducing co-substrate at the ___ site
- Inhibits synthesis of prostaglandins
- Inhibits site on PGHS2 (prostaglandin H synthase 2)
- POX2 site
What is the secondary theory for acetaminophen’s MoA
Acetaminophen leads to increased levels of endogenous cannabinoids
Acetaminophen max dose for an adult >50 kg?
3000 mg/day
Acetaminophen is primarily metabolized where?
- At what dosage do you get cell necrosis?
- Acetaminophen toxicity is the most common cause of?
Liver
4000 mg acetaminophen
- Acute hepatic failure in the US
Mechanism of acetaminophen toxicity? (Creation of what?)
Creation of a toxic metabolite (cytochrome P450 oxidation)
Overdose leads to creation of excess NAPQI which leads to toxicity
ASA - MoA (3)
- Inhibits enzyme cyclooxyrgenase active site (COX) irreversibly
- Prostaglandin-indepedent actions
- Inhibition of neutrophil activation and response
A high dose of ASA (4-8g/day) has what two effects?
- Anti-inflammatory
2. Limited due to toxicity, tinnitus, gastric issues (GI issues are a COX-1 side effect)
Three use of ASA? (dental, medical, prophylaxis)
- Dental: Treatment of post-op pain
- Medical: Treatment of pain/fever
- Prophylaxis of myocardial infarction and transient ischemic episodes
Side effects of ASA? (7)
- Increased bleeding time
- GI issues (ulcers, bleeding)
- Reye syndrome
- Pregnancy (ductus arteriosus pre-mature closure)
- Caution breast-feeding
- Renal function
- At high levels, tinnitus, confusion, N/V, thirst, headache, ab pain, diarrhea
ASA interactions (3)
Hypotensive effect reduced
- Beta blockers
- ACE inhibitors
- Diuretics
Increased INR (for anti-coagulants and thrombolytics)
Aspirin and alcohol leads to GI ulcers and bleeding
What is Cycloxygenase enzyme responsible for forming?
- Prostaglandins
- Prostacyclins
- Thromboxanes
NSAIDs (cox-1 and cox-2) moa?
Reversibly block COX enzyme and reduce prostaglandins throughout body (this affects the stomach)
COX-2 inhibitor - MoA
Inhibit prostaglandin synthesis by decreasing activity of COX-2 enzyme (decreased formation of prostaglandin precursors)
- Anti-pyretic, analgesic, and anti-inflammatory properties
Cox inhibitors - Adverse effects
- Cardiovascular - increased risk of what three events?
- May limit cardio-protective effects of aspirin by antagonizing aspirin’s what?
- Heart attack, stroke, thrombosis
2. Aspirin’s irreversible platelet inhibition
Cox inhibitors reduce the efficacy of which hypertensive medications?
BAD (beta blockers, ace inhibitors, diuretics)
Cox inhibitors increase the potency of coumadin due to what?
Protein bumping
- Bind serum albumin and leads to free Coumadin. This leads to increased anti-coagulation effect
NSAIDs - Side effects
- Skin reactions
- CV: Increased risk of thrombotic events
- GI irritation and ulcers
- CNS: Dizziness, drowsiness, blurred vision
- Platelet adhesion/aggregation may be decreased
NSAIDs - Respiratory system adverse effects
- Blocking cyclooxyrgenase can shunt arachidonic acid towards the formation of the bronchoconstricting ___
- Estimated that 10% of patients with ___ experience a decline in their respiratory function
- Leukotrienes
2. Asthma
Opioids: MoA
Raise pain threshold and alter brain’s perception of pain (bind to Mu and Kappa receptors) and emotional response to pain - Inhibits flow of pain sensations
What does binding to Mu receptor do? (Opioids)
- Analgesia, decreased GI motility, respiratory depression, sedation, physical dependence
What does binding to Kappa receptor do?
- Analgesia, decreased GI motility, mitosis, sedation
What are the major concerns with opioids? (2)
- CNS depression
2. Respiratory depression
Common side effects of opioids (4)
- Constipation (due to decreased GI motility)
- Dizziness/nausea
- Loss of apatite
- Respiratory depression
Tramadol (Ultra) - MoA
Bind to opioid receptors to cause inhibition of pain pathways and block re-uptake of nor-epi. (More mu receptor selective)
Opioids - Interactions
- Combining the follow drugs with opioids can result in marked toxicity (2) and especially one other drug
- MAOI’s
- Matulane
(Especially meperidine)
