Analgesics Flashcards
Pain acute/nociceptive
short-term pain, with an easily identifiable cause. A warning of present damage to tissue or disease which responds well to medication.
Pain chronic/neuropathic
pain which persists. Is constant or intermittent and has “outlived its purpose” since it no longer help the body to prevent further injury.
Pain allodynia
pain from a stimulus that does not normally cause pain
Pain parasthesis
painful feelings (e.g. pins & needles) with no apparent stimulus
Pain management - general considerations
Assessments Type of pain (nociceptive versus neuropathic) Form of pain (acute versus chronic) Severity of pain Route of administration
Objectives
Best analgesic for the individual
Lowest effective dose
Least invasive route - topical, oral, sublingual, i.v., i.m., i.p., i.t., epidural
Opioids – Mechanism of Action
Act at the level of the spinal cord and the CNS:
Decrease neurotransmitter release
Block postsynaptic receptors
Activate inhibitory pathways
Opioids – side effects
Dose-related; from nausea, vomiting, constipation, drowsiness, to respiratory depression, hypotension, sedation, dependency
opioids cautions/contradictions
Acute respiratory depression, acute alcoholism, head injury
opioids interactions
alcohol - hypotensive and sedative effects
MAOI - CNS excitation/inhibition
SSRI / TCA - sedation
carbamazepine -plasma conc. of methadone
cimetidine (ulcer healing) - inhibit opioids metabolism
SSRI
Selective serotonin reuptake inhibitor
TCA
Tricyclic antidepressants
Opioids neuropharmacology
-Mimic Our Endogenous Ligands “enkephalins”
β-Endorphin; Leu-enkephalin;
Met-enkephalin; dynorphin
-Signal Transduction
G-protein coupled receptors
-Integrated Physiology
“act as suppressors..”
-Act as Agonists at Opioid Receptors
Three types of receptors: m, k, d
Six sub-types: m, k1,2,3: d1,2
Opioid receptor - delta
CNS & Peripheral Sensory Neurons
May contribute to analgesia
opioid receptor - μ
CNS, Spinal Cord,
Peripheral Sensory Neurons, GI Tract
Responsible for most of the analgesic effects
Responsible for side effects
Most analgesic opioids are μ-receptor agonists
opioid receptor - kappa
CNS, Spinal Cord, Peripheral Sensory Neurons
Sedation & dysphoria, but few side effects
Does not contribute to dependence
Opioids Pharmacodynamics
Pure Agonists
Typified by morphine-like drugs
Have high affinity for μ-receptors; low affinity for δ & κ
Opioids Pharmacodynamics
Partial agonists & Mixed Agonist-Antagonists
e. g. nalorphine: mixed effects on μ-receptors
e. g. pentazocine & cyclazocine: (-) at μ-, but partial (+) on δ- & κ-
Opioids Pharmacodynamics
Antagonists
Block the actions of opiates
e.g. naloxone and naltrexone; treatment of heroin/morphine overdose
Morphine
Oral; i.v.; Intrathecal; subcutaneosly Acute & Chronic pain pharmacokinetic t1/2=3-4 h side effects: Sedation, Respiratory depression, Constipation, Nausea, vomiting, Itching, Tolerance, Dependence, Euphoria
Diamorphine
Oral;i.v.
Acute & chronic pain
Pharamacokinetic - More rapid than morphine; metabolised to morphine. Has a greater solubility
side effects:
Sedation, Respiratory depression, Constipation, Nausea, vomiting, Itching, Tolerance, Dependence, Euphoria
Hydromorphone
Oral; i.v. Acute & chronic pain Pharamacokinetic -t 1/2= 2-4 h side effects: same as morphine but less sedative, despite being 6 fold more effective
Methadone
Oral; i.v. chronic pain Pharamacokinetic - Long t1/2= > 24 h Slow onset side effects same as morphine but ↓ euphoric
Pethidine
Oral; i.v.; intramuscular Acute Intense pain t1/2= 2-4 h Rapid acting side effects same as morphine but anticholinergic effects Risk of excitement and convulsions
Buprenorphine
i.v. Sublingual, Intrathecal, transdermal,
Moderate to severe. Acute or chronic. Peri-operative analgesia. iv; postoperative pain
t1/2= ~ 12 h Slow onset.
side effects
same as morphine but less pronounced. Respiratory depression not (-) by naloxone
Pentazocine
Oral; i.v.
Moderate to severe pain.
t1/2= 2-4 h
Dysphoria; Irritation at injection site.
Fentanyl
i.v.; Epidermal; Transdermal patch
acute pain
t1/2= 2-4 h
side effects same as morphine
Codeine
Oral mild pain Prodrug and metabolised to morphine side effects: Mainly constipation; No dependence liability
Tramadol
Oral i.v.
Acute & chronic pain
Rheumatoid arthritis, restless legs syndrome, motor neurone disease, fibromyalgia.
Well absorbed Half-life 4-6 h
side effects
Dizziness; May cause convulsions; No respiratory depression
Antidepressants & Analgesia; Mechanism of Action
Serotonin and noradrenaline mediate descending inhibition of ascending pain pathways in the brain and spinal cord
Serotonin and Noradrenaline Reuptake Inhibitors
SNRI
Highly effective for neuropathic pain, but not in all patients
Actions are independent of their antidepressant effects
Venlafaxine (Effexor, Efexor)
Duloxetine (Cymbalta, Ariclaim, Xeristar, Yentreve, Duzela)
Selective serotonin reuptake inhibitors
SSRI
Not particularly effective analgesics
Appear to work well in the disease environment, e.g. diabetic- or HIV-related neuropathy e.g. paroxetine, citalopram
Paroxetine (Aropax, Paxil, Pexeva, Seroxat, Sereupin)
Citalopram (Celexa,Cipramil)
SNRI/SSRI Mode of Action
Prevent the recycling of neurotransmitters & enhance the signal..
Duloxetine
Prescribed for peripheral neuropathy, particularity diabetic neuropathy.
Side-effects include nausea, somnolence, insomnia, dizziness
Venlafaxine (Effexor, Efexor)
Prescribed for diabetic neuropathy
Side-effects include nausea, sedation, headache and dizziness.
SNRI & SSRI Antidepressants & Analgesia cautions and contradictions
Epilepsy, cardiac disease, diabetes, angle closure glaucoma, pregnancy / breast feeding
SNRI & SSRI Antidepressants & Analgesia interactions
Alcohol - sedation
NSAIDS / aspirin -risk of bleeding
Tramadol - risk of CNS toxicity
Increase in sedative effectiveness when given with opioid analgesics
SSRI’s antagonise anticonvulsant effect of antiepileptics
Antiepileptic Agents – Mechanism of Action
Inhibit of voltage gated Na+ channels Inhibit of voltage gated Ca2+ channels Inhibit Glutamate, g-Aminobutyric Acid (GABA) & Glycine receptors - Inhibit action potential firing - prevent impulse transmission - limit neuronal excitation - enhance neuronal inhibition
Carbamazepine treatment for
glossopharyngeal neuralgia, post herpetic neuralgia, trigeminal neuralgia, and diabetic neuropathies
Carbamazepine side effects
Dizziness, diplopia, drowsiness, fatigue, nausea, hepatotoxicity, renal impairment, skin reactions, anorexia, dyspepsia, tremor
Carbamazepine cautions and contraindictions
hepatic / renal impairment, cardiac disease, skin reactions, glaucoma, pregnancy, history of bone marrow depression.
alcohol - increase CNS side effects of carbamzepine
antagonised by MAOI, TCA, SSRI
Gabapentin treatment for
various neuropathic pain states;
complex regional pain syndrome, deafferentation neuropathy of the face, postherpetic neuralgia, sciatic type pain, neuropathy
Gabapentin side effects
+ anorexia, dyspepsia, tremor
Gabapentin cautions and contraindictions
elderly, renal impairment, diabetes, pregnancy,
MAOI
Monoamine oxidase inhibitors
Local Anaesthetics – Mechanism of Action
Inhibit of voltage gated Na+ channels or NMDA receptors
Prevent nerve-nerve cell communication
- inhibit firing
- prevent impulse transmission
NMDA receptor
glutamate receptor and ion channel protein found in nerve cells. It is activated when glutamate and glycine (or D-serine) bind to it, and when activated it allows positively charged ions to flow through the cell membrane.
Lidocaine (Xylocaine)
Particularly effective for severe intractable or crescendo neuropathic pain: emergency medicine
Na-Channel Blocker
Effective in non-cancer patients
IV
Lidocaine (Xylocaine) side effects
CNS effects (confusion), respiratory depression, convulsions, hypotension, bradycardia
Lidocaine (Xylocaine) cautions and contraindications
epilepsy, hepatic / respiratory impairment, Atrial fibrillation, heart block, heart failure
Ketamine (Ketalar)
Particularly effective for severe intractable or crescendo neuropathic pain: emergency medicine
Blocker of Glutamate Receptors (NMDA Subtype).
injectable but not favourable due to side effects
Ketamine (Ketalar) side effects
Hypertension, tachycardia, tremor, diplopia, myocardial depression
Ketamine (Ketalar) Cautions / Contraindications
Hypertension, angina, heart failure, aneurysms, cerebral trauma, psychotic disorders
