Adjuvant Analgesics. Drugs used to treat Gout. Centrally-Acting Muscle Relaxants Flashcards
(28 cards)
Adjuvant Analgesics
Background Information
Are drugs that lack analgesic effect but reduce neuropathic pain
Effective only in neuropathic pain
Neuropathic Pain
Caused by damage to peripheral or central pain pathw.:
Polyneuropathy
Traumatic nerve lesion
Spinal cord injury
Damage at level: middle brain/thalamus/cortex
Types Phantom Limb Pain Diabetic Neuropathy Postherpetic Neuralgia Trigeminal Neuralgia Pain post Stroke
Symptoms
Spontaneous pain (often paroxysmal)
Mechanical heat/cold hyperalgesia
Allodynia (pain caused by non noxious stimuli)
Even opioids have limited effect
Adjuvant Analgesics
Drug Groups
TCA
Anti-epileptics
Na Channel Blocking Agent
Capsaicin
Can also use
Glucocorticoids
Cannabis preps
Alpha 2 R agonist: clonidine
Adjuvant Analgesics
TCAs
Amitiyptyline, Nortriptyline, Imipramine, Clomipramine
First generation
NA and 5 HT reuptake inhibitors
Significant first pass metabolism (dose should be increasing), lipid soluble, large Vd
Metabolism: N demethylation–> active metabolite, hydroxylation–> glucuronide conjugation (inactive)
Side Effects:
Antagonism of M1 R: anticholinergic (dry mouth, urinary retention, blurred vision)
Antagonism of H1 R: sedation/ weight gain
Antagonism on alpha R: orthostatic Hypotension
Direct membrane effects: convulsion/ arrhythmias
Toxicity: the “3 Cs”: coma, convulsions, and cardiotoxicity
Drug interactions:
− Hypertensive crisis with MAO inhibitors
− Serotonin syndrome with SSRIs, MAO inhibitors, and meperidine
− Prevent antihypertensive action of α2 agonists
!!! TCAs potentiate the sedative effect of ethanol !!!
Adjuvant Analgesics
Na Channel Blocking Agent
Lidocaine
Non ionised from crosses axonal membrane
From within: ionised from blocks inactivated Na channel
Slows recovery and prevent AP propagation
Order of sensitivity
B and C > Adelta > Abeta > Agamma > Aalpha
Recovery follows reverse order
Coadminister with alpha 1 agonists to decrease absorption into systemic circulation; prolong effects; reduce toxicity
Adjuvant Analgesics
Capsaicin
Local as transdermal patch
Desensitised (irreversibly damages) nociceptive nerve endings
–> Herpes zoster; diabetes
Adjuvant Analgesics
Anti-epileptics: Phenytoin
Blocks axonal Na channels in their inactivated state
Prevents seizure propagation
Variable absorption
Nonlinear kinetics
Inducer of CYP450
Elimination: Zero order of kinetics
SE CNS depression Gingival hyperplasia Hirsutism Osteomalacia (decerase Vit D) Megaloblastic Anaemia (decrease folate)
Adjuvant Analgesics
Anti-epileptics: Carbamazepine
Blocks axonal Na channels in their inactivated state
Prevents seizure propagation
Inducer of CYP450
SE
Osteomalacia (decerase Vit D)
Megaloblastic Anaemia (decrease folate)
CNS Depression
Adjuvant Analgesics
Anti-epileptics: Valproic Acid
Blocks axonal Na channels in their inactivated state
Also inhibits GABA transaminase (degrades GABA)
Blocks T type Ca channels
Inhibits CYP450
SE
Hepatotoxicity
Thrombocytopenia
Pancreatitis
Adjuvant Analgesics
Anti-epileptics: Gabapentin
Affects calcium channels and NT release
GABA effects too
Adjuvant Analgesics
Anti-epileptics: Lamotrigine
Blocks Na and glutamate Rs
SE
Steven Johnsons
Gout
Breakdown of purines
GMP and AMP–>hypoxanthine–>xanthine–>uric acid
Enzyme: Xanthine Oxidase
Disorders of Uric Acid
Consequences
Hyperuricemia: disturbance of uric acid metab. and excretion
Primary (inherited)
Defect of uric acid sectretion (99%)
Overproduction of uric acid (1%)
Secondary
Malignant tumor, chemo, radio-> urate overproduction
Renal failure/drugs-> reduced urate excretion
Gout
Drug Categories
Prototype
Uricosuric Drugs
Acute Gouty Arthritis Drugs
Gout
Allopurinol
Orally used
Analogue of hypoxanthine-> alt substrate for xanthine oxidase
Allopurinol converted–> oxipurinol (first pass in gut wall and liver)–> inhibition of urate formation
Formed oxipuranol is non competitive inhibitor of xanthine oxidase
Allopurinol T1/2: 1 hr
Oxipurinol T1/2: 24 hrs
Decreases uric acid production = uricostatic
Accumulating hypoxanthine and xanthine have good water solubility
Also: Slight decreases de novo purine synth
SE
Increased risk of acute attacks during first 2 weeks–>
can combo with colchicines or NSAIDs
GIT disturbance
Rash/ allergic reaction
Dose should be reduced in renal failure
Interactions
(slight) CYP inhibitor
Decreased metab. of mercaptopurine
Via xanthine oxidase inhibitin: coumarin, theopyliine:
decreased metab.
Gout
Febuxostat
Also inhibits xanthine oxidase
Gout
Rasburicase
Reduces uric acid levels
Is a recombinant urate oxidase–> converts urate to allantoin (water soluble)
Used to prevent tumor lysis syndrome
Gout
Uricosuric Drugs
Probenecid, Benzbromarone
Inhibit urate reab in proximal tubule–> increase excretion
Given p.o.
Significant PPB
Site of action: luminal membrane of proximal tubule
Lower dose: urate retention due to. competitively inhibiting active secretion of urate in proximal tubules
(Benzbromarone doesn’t do this)
Th dose: net increase in renal excretion
SE
Increased risk of acute attacks during first 2 weeks–>
can combo with colchicines or NSAIDs
GIT disturbance
Rash/ allergic reaction
Dose should be reduced in renal failure
CI
Renal insufficienty
Interactions
Inhibit secretion of weak acids: penicillins, cephalosporins
Low dose of aspirin inhibit effect or uricosurics by reducing secretion of urate and drugs
Drugs of Acute Gouty Arthritis
Colchicines
Bind to tubulin and inhibit polymerisation of these into microtubules
Also reduce chemotaxis and phagocytotic activity of neutrophils
Good oral absorption, can also be given IV
Metabolism
Partial via CYP
Partly unchanged into urine and bile
Undergoes enterohepatic circulation
Decrease dose in hepatic or renal failure
SE Hemorrhagic gastroenteritis Hematuria Myelosuppression Diarrhoea, GIT pain Peripheral Neuropathy
Drugs of Acute Gouty Arthritis
NSAIDs
Drugs of choice because have lower SE than
colchicines
Mainly those with lower GIT side effects; meloxicam,
Ibu, diclofenac
Intra-articular Steroids
Centrally Acting Muscle Relaxants
General
Most drugs act on spinal cord
Reduce path increased tone of skeletal muscle without compromising voluntary contractions
Common side effects
Sedation
Muscle weakness
Centrally Acting Muscle Relaxants
Groups according to clinical efficacy
Site of action
Effective in spasticity only
Effective in acute muscle spasm only
Effective in both conditions
Site of action: Spinal Cord
Presyn Inhibition
Inhibition of excitatory transmitter from presyn neuron
Centrally Acting Muscle Relaxants
Indications
Spasticity
Chronic
Impairment of descending corticospinal inhib pathways
regulating stretch reflex
Spasm of antigravity muscles, enhanced stretch reflex,
pain and disability
Acute Muscle Spasms
Reversible, self improving
Trauma or inflammation–> reflex mech–> muscle tone
increase
Centrally Acting Muscle Relaxants
Grouping of Drugs
Centrally acting Muscle Relaxants Effective in Spasticity
only
Centrally acting Muscle Relaxants Effective in Acute
Muscle Spasms only
Centrally acting Muscle Relaxants Effective in Spasticity
and Acute Muscle Spasms
Peripherally acting Agents used in Spasticity
