Pain Management Flashcards
Why is pain considered the 5th vital sign?
Due to unsatisfactory pain relief
No reliable marker for pain
What is the most common sx prompting patients to seek medical attention?
Pain
What type of pain is described as a transient pain in response to a noxious stimulus at nociceptors that are located in cutaneous tissue, bone, muscle, connective tissue, vessels, and viscera
Nociceptive pain
What type of pain is described as when tissue damage occurs; pain hypersensitivity occurs to prevent contact or movement of injured part until healing is complete?
Inflammatory pain
What type of pain is described as Spontaneous pain and hypersensitivity to pain associated with damage to or pathologic changes in peripheral nervous system
Neuropathic pain
What type of pain is described as pain sensitivity due to an abnormal processing or function of CNS in response to normal stimuli?
Functional pain
What is involved in stimulation of the pathophysiology of nociceptive pain?
injury results in release of bradykinins, potassium, PROSTAGLANDINS, histamine, leukotrienes, serotonin, and substance P which sensitize or activates nociceptors
What is involved in transmission of the pathophysiology of nociceptive pain?
Impulse transmitted along sparsely myelinated A-δ fibers (responsible for sharp well localized pain) and unmyelinated C fibers (producing dull, aching, burning and diffuse pain). Fibers synapse in dorsal horn of spinal cord releasing variety NT (Glutamate, substance P)
What is involved in perception of the pathophysiology of nociceptive pain?
Transmission continues along spinal cord to thalamus where pain is precieved
What is involved in modulation of the pathophysiology of nociceptive pain?
complex process; endogenous opiate system
What is involved in inflammation pathophysiology?
The changes that occur in response to tissue injury or insult- leading to pain, redness, heat, swelling, and +/- loss of function.
Produced by interactions w/ inflammatory mediators derived from leucocytes or damaged tissues. Ex: Histamine, Kinins (bradykinin), Neuropeptide (substance P), Cytokines (interleukins), Arachidonic acid metabolites (eicosanoids)
What are inflammatory mediators derived from leucocytes or damaged tissues?
Histamine Kinins (bradykinin) Neuropeptide (substance P) Cytokines (interleukins) Arachidonic acid metabolites (eicosanoids)
What are the alterations of local blood vessels and what do these changes result from?
Result from alterations in local blood vessels (trauma) or antigens (viral, bacterial, etc)
Dilation of blood vessels
Increased permeability
Increased receptiveness for leukocytes- leukotriene- chemotatic response : accumulation of inflammatory cells (polymophonuclear neutrophil, leukocytes, macrophages, lymphocytes, basophils and eosinophils also accumulate depending on the type of inflammation)
Arachodonic acid
Disturbance of the phospholipids of the cell membrane metabolizes arachidonic acid by the enzyme phospholipase
Metabolized further by cyclooxygenase to produce prostaglandins, thrombozane, and prostacyclin (prostanoids)
and by lipoxygenase to produce leukotrienes
Disturbance of the phospholips of the cell membrane mobilized arachidonic acid by what enzyme?
Phospholipase A2
Arachidonic acid is metabolized by cyclooxygenase to produce what?
Prostaglandins
Thromboxane
Prostacyclin (collectively knowns as prostanoids)
Arachidonic acid is metabolized by lipoxygenase to produce what?
Leukotrienes
What are the 2 enzyme isoforms of cyclooxygenase?
Cox-1 and Cox 2
Cox-1
In most tissues- platelets, gastric mucosa, renal vasculature
Involved in physiological cell signaling
Most adverse effects w/ NSAIDs occur because of inhibition of cox-1
Cox-2
Induced at sites of inflammation & produces the prostanoids involved in the inflammatory responses
Analgesic and anti-inflammatory effects of NSAIDs are largely a result of inhibition of Cox-2
Eicosanoids
Involved in most inflammatory reactions
inflammatory therapy is based on the manipulation of their biosynthesis
Polyunsaturated fatty acids produced by arachidonic acid
What are the prostanoids eicosanoids?
Prostaglandinds (PGD2, PGE2, PGF2)
Thomboxane A2 (TXA2)
Prostacyclin (PGI2)
What is the action of inflammation for the prostaglandins?
Vasodilation, vascular permeability, edema, stimulation of other inflammatory mediators
What is the action of inflammation for the thomboxane A2 (TXA2)?
Platelet aggregation and vasoconstriction
What is the action of inflammation of prostacyclin (PGI2)?
Inhibition of platelet aggregation and vasodilation
What are the leukotriene eicosanoids?
LTB4
LTC4
What are the actions of inflammation of leukotrienes?
Increase vascular permeability, promote leukocyte chemotaxis, contraction of bronchial smooth muscle.
What is acute pain usually result from?
An injury or surgery and is usually self limited
What does poorly treated acute pain result in?
Tachypnea Tachycardia Pallor Diaphoresis Pupil Dilation Psychological Stress
What is chronic pain?
Pain that persists beyond expected normal time for healing and serves no physiologic purpose
It can be maladaptive
What are the types of chronic pain?
Malignant- associated with life threatening disease and lasting more than 6 months
Non-malignant- not associated with life threatening disease and lasting more than 6 months (Neuropathic- involving disease of CNS and PNS)
What does PQRST stand for in pain assessment?
Pallative/provactive Quality Radiation Severity Temporal
What is the pain algorithm for acute mild/moderate pain?
- NSAIDS or APAP
2. Opioids
What is the pain algorithm for acute sever pain
- Opioids
2. Add NSAIDs or APAP
What is the pain algorithm for chronic visceral pain?
- Opioids for sever
2. Add adjuvants (TCA- tricyclic antidepressant or AED-antiepilectic drugs)
What is the pain algorithm for chronic inflammatory pain?
- APAP or NSAIDs
2. Long acting opioids
What is the pain algorithm for chronic neuropathic pain? Central and peripheral?
Central- clonidine or baclofen
Peripheral- TCA or AED, lidocaine, SSRI or SNRI, Long acting opiods
What is pain algorithm for chronic functional pain?
- TCA or Tramadol
2. SSRI/SNRI or preganalin
Nonsteroidal anti-inflammatory agents- MOA
Inhibition of cyclooxygenase and resulting inhibition of prostaglandin synthesis, producing three major clinical actions- analgesia, anti-inflammatory, antipyretic
What nonsteroidal anti-inflammatory agents have irreversible inhibition?
Aspirin which causes acetylation of the active site
What is nonsteroidal anti-inflammatory agents have competitive inhibition?
Ibuprofen which acts as a competitive substrate
What is the mechanism of action of the clinical action of Analgesic?
- Peripheral effect due to the inhibition of prostaglandins synthesis at the site of pain and inflammation
- Prostaglandins do not produce pain directly, but sensitize nerve endings to other inflammatory mediators (bradykinin-substance , histamine, 5-HT) amplifying the pain message.
- NSAIDs are effective where inflammation is involved.
- Small component of analgesic action is a consequence of reducing prostaglandin synthesis in the CNS.
What is the mechanism of action of the clinical action anti-inflammatory action?
- Prostaglandins produce increased vasodilation, vascular permeability & edema of inflammatory reaction-thus inhibition of prostaglandins reduces this part of the inflammatory reaction.
- NSAIDS do not inhibit the numerous other mediators involved in an inflammatory reaction
What are the clinical effects of NSAIDs?
Analgesic
Anti-inflammatory action
Antipyretic Action
What is the mechanism of action of the clinical action antipyretic action?
- During fever, leukocytes release inflammatory pyrogens-part of immune response, which act on thermoregulatory center in the hypothalamus to increased body temp.
- Theory-this effect is mediated by an increase hypothalamic prostaglandins (PGEs) causes increase in body temp
- NSAIDs do not affect temp under normal circumstance or in heat stroke.
NSAIDs- Indications
- Musculoskeletal and joint disease (Strains, sprains, rheumatic problems, arthritis, gout)
- Analgesia for mild to moderate pain relief including HA, dysmenorrhea, sunburn
- Symptomatic relief of fever
NSAIDS- GI effects
-Prostacyclins and prostaglandins inhibit gastric acid secretion and increase the synthesis of protective mucus & bicarbonate in the stomach and small intestine.
-NSAIDs inhibit PG synthesis & produce an increase in gastric acid secretion & diminished mucus and bicarb protection.
-May produce epigastric distress, ulceration and/or hemorrhaging. Avoid in peptic ulcer dz
MISOPROSTOL- PGE analog used to tx NSAID induced GI damage
What is misoprostol used for?
Dilation of the cervix
NSAIDS- Kidney effects
- Prostaglandin synthesis normally antagonized intrarenal effects of vasoconstrictors
- This can lead to: retention of sodium and water, edema and hyperkalemia, and high doses should be avoided if heart or renal problems.
NSAIDS- adverse effects
GI bleeds
Tinnitus
Edema and hyperkalemia
Pts w/ CHF, hepatic cirrhosis, and renal insufficiency may already have a decrease in renal blood flow and GFR-> unopposed to vasoconstriction
NSAID- contraindictations
GI bleeds
Hypersensitivity to NSAIDS
Caution- in patients w/ asthma, renal impairment and thrombocytopenia.
Avoid at least one wk prior to surgery
Aspirin-MOA
- Rapidly hydrolyzed to salicylic acid in the plasma, both agents responsible for the pharmacologic effects of inhibiting cyclooyenase
- Anti-coagulant (Antiplatelet) effect due to inhibition of thromboxane A2 (1st step in thrombus formation) production in platelets leading to ineffective platelets for clotting.
Aspirin- Therapeutic uses
CV- prophylactially to decrease in incidence of TIAs, MIs, unstable angina
Antipyretic & analgesic
Colon cancer prevetion w/ chronic use
Anti-inflammatory
Aspirin- Adverse Effects
Salicylism- poisoning w/ salicylates- N/V, hyperventilation, HA, mental confusion, dizziness, & TINNITUS. W/ larger doses restlessness, delirium, hallucinations, convulsions, coma, respiratory & metabolic acidosis
- Respiratory: therapeutic dose = increased alveolar ventil -> increased CO2 and respirations. Higher dose= hyperventilation leads to resp alkalosis; compensated by kidney. Toxic dose=central respiratory paralysis->resp acidosis cue to continued CO2 production.
- REYE’s SYNDROME- ASA w/ viral infections led to hepatitis and cerebral edema-often fatal
- Hypersensitivity=urticaria, bronchoconstriction, angioedema
What is salicylism?
poisoning w/ salicylates- N/V, hyperventilation, HA, mental confusion, dizziness, & TINNITUS. W/ larger doses restlessness, delirium, hallucinations, convulsions, coma, respiratory & metabolic acidosis
What is Reye’s Syndrome?
ASA w/viral infections led to hepatitis and cerebral edema-often fatal.
Aspirin- drug interactions
- Increased hemorrhage w/ heparin and oral anticoagulants
- Decreased urate excretion w/ probenecid (contraindication in gout pts)
- Antacids decrease rate of absorption
- Ibuprofen inhibits antiplatelet effect of low dose ASA
Diflunisal (Dolobid)
Diflurophenyl derivative of salicylic acid (not metabolized to salicylic acid -> no salicylate intoxication
More potent than ASA
No antipyretic activity, doesn’t cross BBB
Name the NSAIDs we should know for this class?
Ibuprophe (Motrin) Oxaprozin (Daypro) Naproxen (Naprosyn,aleve) Indomethacin (Indocin) Sulindac (Clinoril) Diclofenae (voltaren) Etodolac (Lodine) Nabumatone (Relafen) Piroxicam (Feldene) Meloxicam (Mobic) Aspirin
Propionic acid derivatives
All possess anti-inflammatory, analgesic, and antipyretic activity
Gi effects less intense than ASA
Side effects- dyspepsia -> bleeding; CNS: HA, tinnitus, dizziness
Indomethacin (Idoncin)- Therapeutic use
Idoleacetic Acid
Very potent anti-inflammatory agent, more effect than ASA or other NSAIDs, but side effects limit indomethacins use
Use- GOUTY ARTHRITIS, osteoarthritis of the hip
Indomethacin (Idoncin)- pharmacokinetics
Idoleacetic Acid
Rapidly & almost completely absorbed
Metabolized by the lier
Cleared by bile and urine
Indomethacin (Idoncin)- adverse effects and Drug interactions
Adverse effects- dizziness, more GI compaints- N/V/D anorexia
CNS effects- HA, dizziness, vertigo, mental confusion
Hepatic and pancreatic effects
Drug interactions- decreased effects of ACEI, furosemide, thiazides and beta blockers
Sulindac (clinoril)
Idoleacetic Acid
Less potent than indomethacin
Etodolac (lodine)
Idoleacetic Acid
Gi problems maybe less
Fluid retention, kidney and liver function abnormalities have been reported
Interacts w/ digoxin, lithium, MTX, & enhance nephrotoxicity of cyclosporine
Diclofenac (Voltaren)
Idoleacetic Acid
Approved for RA, OA, and ankylosing spondilitis
MOre potent than indomethacin or naproxen
AN OPTHALMIC PREPARATION IS AVAILABLE
Can elevate hepatic enzymes
Nabumatone (Relafen)
Idoleacetic Acid
Prodrug
As potent as aspirin for tx of RA and OA
Fewer side effects
Piroxicam (Feldene) and Meloxicam
Oxicam Derivatives
Meloxicam COX-2 selective at low-moderate doses; nonselective at high doses
High incidence of GI ADRs
Once daily dosing
Drug interaction- interfere w/ renal excretion of lithium
Ketorolac (Toradol)
Pyrrolizine Carboxylic Acid derivative
Only injectable NSAID (IM, IV) also an oral tablet, ophthalmic solution
High rate of GI bleed- administer for 5 days max
What is the only cox-2 inhibitor still on the market?
Celecoxib (Celebrex)- black box warning
Cox-2 inhibitors
Newest generation of NSAIDs
Specifically block cox-2, very little cox-1 involved, with fewer side effects. Fewer GI bleeds, still need to use w/caution in pts w/ CHF and renal disease. May need ASA as adjunct, lack antiplatelet effects of their predecessors
Acetaminophen (Tylenol)- MOA
Inhibits prostaglandins in the CNS but has minimal effect on cyclooxygenase in periphery
Analgesic, antipyretic, weak anti-inflammatory effet, no anti-platelet effects
Acetaminophen (Tylenol)- Pharmacokinetics
Rapidly absorbed from the GI
1st pass metabolism
Conjugated to inactive glucuronidate metabolie and sulfated metabolites
Hydoxylated to N-acetyl benzoquinoneimine (reactive metabolite)
Excreted in the urine
Acetaminophen (Tylenol)- overdose
Glutathione becomes depleted
N-acetyl benzoquinoneimine binds sulfhydryl groups of hepatic proteins causing hepatic nercrosis
Renal tubular necrosis can also occur
DO NOT EXCEED 3.2 TYLENOL/24H
What is a drug used to counteract acetaminophen overdose by creating sulfhydryl groups for toxic metabolite to bind?
N- Acetylcysteine (Mucomyst)
What is associated with opioids?
Physical Dependence Tolerance Addiction Pseudoaddiction Withdrawal
What is the effect of drug defined by the occurrence of an abstinence syndrome following administration of an antagonist drug, abrupt dose reduction, or discontinuation?
Physical dependence
What is diminution of drug effect over time as a consequence of exposure to the drug?
Tolerance
What is a behavioral pattern characterized as loss of control over drug use, compulsive use, and continued use of drug despite harm?
Addiction
What is the iatrogenic syndrome resulting from inadequate pain management. As a result, patients engage in relief seeking behaviors as though they are drug-seeking, as commonly seen with addiction. The relief seeking behaviors resolve upon institution of effective analgesic therapy?
Pseudoaddiction
What is any time tolerance is developed and you disrupt this medication there will be a withdrawal?
Withdrawal
What class of drugs is illegal to prescribe refills?
Class II
What class drug can be signed for at the pharmacy?
Class V
What class drug has low risk for abuse and can refill for 6 months?
Class IV
What class drug has moderate risk for abuse, and can refill for 6 months? Ex- Hydrocodone
Class III
What class drug is high risk for abuse and a new Rx is needed every month? Ex- morphine, oxycodone, methadone, meperidine
Class II
What class drugs are illegal agents and have a very high risk for abuse? Ex-heroin, cocaine
Class I
How many pharmacologically active alkaloids does opium consist of?
20
What are the 3 endogenous peptide-neurotransmitters that opiate drugs mimic?
Endorphins
Enkaphalins
Dynorphins
What are the four type of opiate receptors
Mu (μ) Kappa (к) Delta (δ) Sigma (σ Binding capacity correlates w/ analgesia
What is the biological response to stimulation of the Mu (μ) receptor?
Respiratory depression, physical depression, tolerance, constipation, euphoria, miosis-primary analgesia response
What is the biological response to stimulation of the Kappa (к) receptor?
Spinal-level analgesia and sedation, w/out respiratory depression, miosis
What is the biological response to stimulation of the Sigma (σ) receptor?
Vasomotor stimulation, psychotomimetic effects, miosis, binds non-opiod agents
What is the biological response to stimulation of the Delta (δ) receptor?
Enkephalins more selective w/ the delta receptors in the periphery.
What is the action of the brainstem?
Respiration, cough, N/V pupillary diameter, control of stomach secretions, maintenance of blood pressure
What is the action of the medial thalamus?
Mediates deep pain that is poorly localized and emotionally induced
What is the action of the spinal cord?
Receipt & integration of incoming sensory information leading to the attenuation of painful afferent stimuli
What the is action of the hypothalamus?
Receptors affect neyroendocrine secretion
What is the action of the limbic system?
No analgesic effects but some emotional behavior effects
What is the action of the periphery?
May have anti-inflammatory effects due to the inhibition of the Ca++ dependent release of excitatory, proinflammatory substances from the sensory nerve endings
What is the action of immune cells?
Role unknown for response to painful stimuli
What meant by opioid pure agonists?
Bind to μ receptors to produce analgesia that increased with dose without a ceiling effect
Ex- morphine-like, meperidine-like, methadone-like, different types of drugs due to allergies
What is meant by opioid partial agonist/antagonist?
Partially stimulate μ receptors and antagonize κ receptors.
Reduced analgesic efficacy w/ a ceiling dose in opiod naive pts
Reduced side effects at the μ receptor, psychotomimetic effects due to κ antagonism
Possible withdrawal sx in patients who are dependent on pure agonists
Tolerance and dependence can ensue w/ prolonged use
Phenanthrenes
Strong agonist
Morphine
Hydromorphone (Dilaudid)
Phenylheptylamines
Strong agonist
Methadone
Phynylpiperidines
Strong agonist
Meperidine (Demerol), fentanyl (sublimaze); most widely used phenylpiperidines.
Morphine-MOA
Highest affinity for(μ) receptors, varying affinity for (δ) & (к) receptors and low affinity for (σ) receptors
MOA- interact w/ sterospecific opiate receptors especially in the CNS and GI
-Inhibit pain reflexes through inhibition of neurotransmitter release
-Inhibit actions on neurons converying pain information to higher brain centers
-Modulates pain perception in the spinal cord
Morphine- Actions (analgesia, euphoria, respiratory, depression of cough reflexes, miosis)
Analgesia- raise pain threshold, alter brains perception of pain
Euphoria- contentment, well-being
Respiratory- respiratory depression by reducing the sensitivity of respiratory center neurons to CO2
Depression of cough reflexes- antitussive effects by receptors other than those for analgesia. Other drugs like codeine are used
Miosis- stimulation of μ and к receptors, littler tolerance to effect seen in addicts.
Morphine- Actions (Emesis, GI, CV, histamine release)
Emesis- stimulates chemoreceptors trigger zone that causes vomiting
GI- relieves diarrhea and dysentery, decrease motility of smooth muscle increased GI tone and anal sphincter tone, constipation ensues.
CV- high dose causes bradycardia &/or HPOTN, can increase CSF pressure- contraindicated w/ severe brain injury.
HIstamine release- Urticaria, sweating and vasodilation, bronchoconstriction
Morphine- Actions (Hormonal)
Inhibits release of gonadotropin releasing hormone and corticotrophin releasing hormone (can have effects in the body in a chronic picture, if you admin over long periods of time but usually not short periods)
Decrease concentration of luteinizing hormone, follicle-stimulating hormone, adrenocorticotropic hormone, & β-endorphin.
decrease testosterone and cortisol levels.
Increases prolactin & growth hormone released by diminishing dopaminergic inhibition. (Can cause sx in patients but will typically only occur w. abuse and long term use. Increased prolonged Prolactin will cause lactation)
Increase of antidiuretic hormone leads to urinary retention.
Morphine - therapeutic uses and administration
Therapeutic uses- analgesia (common), diarrhea (rare), cough (rare)
Administered- orally, parentally, inhalation or rectally. Regular release, immediate release, sustained release.
Morphine- pharmacokinetics
Extensive 1st pass effect
Nebulized (inhaled) morphine low bioavailability but rapid onset
Metabolites of morphine Morphine-6-glucoronide-active, potent, concentrations build w/renal failure.
Morphine- ADRS
RESPIRATORY & CIRCULATORY DEPRESSION
Constipation
Pts w/ renal failure are more prone to ADRs
Sedation, dizziness, HPOTN, N/V, sweating
Euphoria, dysphoria, dry mouth, syncope, urinary retention
Morphine-precautions
Pts. w/head injuries, other intracranial lesions, or pre-existing increase in intracranial pressure
Pts. w/acute asthmatic attack, COPD
Pts. w/BPH or urethral stricture
Use w/caution in elderly and neonates
In pts. whose ability to maintain blood pressure is compromised (usually trauma or septic patients)
Morphine -drug interactions
Concurrent use of CNS depressants, such as ETOH, antipsychotics, benzodiazepines
Cimetidine can increase serum concentration because it is an inhibitor of metabolism
Morphine- monitor?
Pain control
Signs of respiratory or CV depression
Meperidine (Demerol)-MOA
Synthetic opiod
MOA- binds to opioid receptor(к)
Action: antimuscarinic activity. Major metabolite (normeperidine) has excitant effects than can precipitate tremors, myoclonus or seizures. Does not cause the miosis that morphine does, rather it causes mydriasis.
Meperidine (Demerol)- Pharmacokinetics
Hydrolyzed and metabolized in the liver to nirmeperidine which is also hydrolyzed
Mostly excreted in the urine
1/2 life increase in liver and renal failure
Usually given post surgically
Meperidine (Demerol)- ADRs
SEIZURES when: Large doses >400-600mg/day Renal failure Hx of seizures Long-term use in cancer patients Drug interactions
Meperidine (Demerol)- contraindications
Pts taking MAOI w/in past 14-21 days
Meperidine (Demerol)- precautions and drug interactions
Precautions- elderly and pts w/ renal or hepatic failure
Drug interactions- MOAI- BP changes, excitatory, rigidity
Barbiturates
Chlorpromazine
Phenytoin
Meperidine (Demerol)- monitor
SIGNS AND SX OF JERKING OR TWITCHING-MAY INDICATE NORMEPERIDINE ACCUMULATION
Evaluate pain scores
DO NOT USE THIS MEDICATION IN PATIENTS W/ CHRONIC PAIN
Methadone- MOA
Synthetic opioid, equal potency to morphine w/ less
MOA- greatest action at the μ receptors
Methadone- place in therapy
analgesic, and is substituted for morphine and heroin for controlled w/drawal. The pt. is then slowly w/drawn from methadone-easier due to methadone’s long half-life; also for long acting chronic pain control
Methadone- pharmacokinetics
PO, IV, SC Slow dosage escalation Long duration of action USE CAUTION: VARIABLE KINETICS Highly protein bound Urinary elimination USE CAUTION; WIDE RANGE OF “DOSE-EQUIVALENTS”- be careful when you switch between different opiates and switching doses
Methadone- ADRs
> risk for toxicity- long half life
nalaxone is given for respiratory depression and you might have to give it more than once due to the long 1/2 life
Methadone-drug interactions
inducers can decrease methadone levels and effects
Inhibitors can increase methadone levels and effects
Methadone- Monitor
Signs of withdrawal- lacrimation, rhinorrhea, diaphoresis, yawning, restlessness, insomnia, dilated pupils.
Fentanyl (Duragesic)- pharmacokinetics
More potent than
IV, Transdermal removed and applied q 72 hours. (for pain)
To change treatment to another opioid d/c patch 12-18 hours prior to start of new opioid.
What are other agents related to fentanyl that are strong powerful opiates?
sufentanil (Sufenta®) 5-7 times more potent than fentanyl
alfentanil (Alfenta®) less potent than fentanyl
Remifentanil (Ultiva®) >potency than fentanyl acts very rapidly w/short duration of action.
Fentanyl (Duragesic)- contraindications
Patch for acute or postoperative pain
USE CAUTIOUSLY: ABUSE, LACK OF TITRATION, VARIABLE ABSOPRTION
Fentanyl (Duragesic)- ADRs
No histamine release so maybe perferrred when CV stability is an issue
Fentanyl (Duragesic)- drug interactions
CNS depressants, inhibitors increasing effects of fentanyl and inducers decreasing effects.
Phenantrenes
Mild-moderate agonists of opioids Codeine
Oxycodone (Roxicodone), Hydrocodone
-less efficacious than morphine or have limiting adverse effects formulations: combination with aspirin or acetaminophen
-Codeine- prodrug metabolize to morphine
Phenylheptylamines
Mild-moderate agonists of opioids Codeine
Propoxyphene
-related to methadone low analgesic activity low efficacy: unsuitable for management of severe pain low abuse potential
Phenylpiperidines
Mild-moderate agonists of opioids Codeine
Diphenoxylate; diphenoxylate metabolite (difenoxin)
-management of diarrhea used in combination with atropine
-limited abuse potential
Loperamide
- management of diarrhea
- limited abuse potential
What are the partial agonist/antagonist opioids?
Phenanthrenes- nalbuphine and buprenorphne
Morphinans- Butorphanol (stadol)
Benzomorphans- pentazocine (talwain)
Buprenorphine
Partial agonist/antagonist
20x as potent as morphine in producing analgesia. Partial μ agonist.
Effects are slower developing.
Similar ADRs to morphine but can antagonize the respiratory depression caused by morphine. long acting, potent
Butorphanol
Partial agonist/antagonist
Analgesic equivalent to buprenorphine (Buprenex) and nalbuphine
More sedation
κ agonist- spinal analgesia
Pentazocine (Talwin®)
Partial agonist/antagonist
Originally developed in an attempt to find analgesics w/little or no abuse potential. (lack of euphoria)
Mild μ & к agonist. Σ activity may account for dysphoria. (patients don’t like being on this medication)
What is an opioid antagonist?
Naloxone
Nalaxone
Antagonist- short duration of
High binding affinity for μ receptor also competitive antagonist of к and δ.No effect in normal individuals but precipitates w/drawal in patients taking opioids w/in 30 sec. of administration and lasts 60-100 min..
Used to reverse OD, respiratory depression, & coma
Naltrexone-has longer duration of action-up to 48 hours. Used for opioid dependent maintenance programs.
Tramadol (Ultram)- MOA
weak μ agonist
norepinephrine/serotonin CNS reuptake inhibition
probably acts through active metabolite; analgesic magnitude –similar to propoxyphene
possibly no advantages over older analgesics
How do you appropriately add an opioid to a treatment regimen?
Short acting / combination
Lowest dose / highest dose adjuvant
Prescribe to ceiling of adjuvants (apap / ibu)
Long acting opioids
Start with lowest dose unless opioid tolerant
Provide short acting breakthrough if minimal risk (10-20% of total daily opioid intake)
Skeletal Muscle relaxants- Centrally acting
Goal- to produce decreased muscle tone and involuntary movement w/out loss of voluntary fxn or consciousness.
What do centrally acting skeletal muscle relaxants work on?
Directly—on the contractile mechanism of the skeletal musculature
Or on transmission in spinal cord motor reflex pathways, primarily to elicit varying degrees of skeletal muscle relaxation.
What agents are used to afford a degree of relief from muscle spasms & hyper-reflexia resulting from conditions such as inflammation, stress & other neurologic d/o?
Cyclobenzaprine
Baclofen
Tizanidine
Carisoprodol
Skeletal muscle relaxants- peripherally acting
AKA Neuromuscular Blocking Agents
Succinylcholine
Vecuronium
Used as an analgesic not as a muscle relaxer but rather as an adjunct to anesthetics
What is the MOA of peripherally acting skeletal muscle relaxants?
MOA: Interfere with the transmission of cholinergic impulses between the somatic motor neurons and skeletal fibers at the neuromuscular junction; producing paralysis of the skeletal muscles involved
Used primarily as adjuncts to general anesthetics in minor surgical procedures or shock therapy
