Drugs 2 Flashcards
Colchicine Mechanism
depolimerization of microtubules
-required for phagocytosing and movement of WBC (polymorphic neuclotides)
Colchicine Application
- effective only against gouty arthritis (ACUTE)
- prophylactic agent against such attacks
Colchicine Use
- terminate acute attacks of gout
- prevents recurrence of gouty arthritis
- in familiar Mediterranean fever
Colchicine Toxicity
- GI disturbances - given to much
- Blood dyscrasias - chronic
Indomethancine Application
-treatment of acute attack of gout
Indomethacine Mechanism
- cyclooxygenase inhibitor
- analgesic and antipyretic
- inhibits leukocyte motility
Indomethacine Dosing
50mg, 3 times a day (3-5 days)
-give with antacid regimen to prevent ulcer
Indomethacine Toxicity
50% of patients
- GI-nausea, vomiting, ulcers
- CNS- sever frontal headache
- Hematopoietic disorders
- antagonize furosemide and HCTZ
Allopurinol Mechanism
- competitive inhibitor of xanthine oxidase (prevents uric acid synthesis) - reversible
- metabatolized to oxypurinol which is a non-competitive inhibitor of X.O. - irreversible
SUCIDE INHIBITOR
Allopurinol Effects
- reduces plasma levels and urinary excretion of U.A.
- increases plasma levels and urinary excretion of oxypurine precursors such as Xanthine and hypoxanthine - very H2O soluble
- facilitates dissolution of uric acid crystals in the joints and kidneys
- prevents formation of uric acid kidney stones
Allopurinol Uses
Primary Hyperuricemia of gout due to enzyme abnormalities and in children (enzyme abnormalities)
Secondary Hyperuricemia due to hematologic disorders (like multiple myeloma) or chemo
Allopurinol Toxicity
- increased incidence of acute gout
- hypersensitivity rxns, dermatitis (2%), exfoliative dermatitis
- effects on liver function
- interactions w/6-mercaptopurine (decrease 25%)
- ampicillin and related antibiotics are contraindicated
Febuxostat Mechanism
Xanthine Oxidase Inhibitor (direct)
- potent inhibitor of both oxidized and reduced forms of xanthine oxidase, and the enzyme-inhibitor complex is highly stale
- structurally unrelated to allopurinol
- lowers urate concentrations by decreasing urate levels
Febuxostat Uses
- more potent than allopurinol in lowering UA levels, less side effects (80mg)
- lower ureate levels in patients who display adverse symptoms to allopurinol like hypersensitivity
- can be used in patients with mild to moderate renal impairment
Febuxostat Toxicity
-mild, 2-3% of patients had transaminase elevations >3 times the upper limit
Probenecid Mechanism
Increase Urinary Excretion or Uric Acid - URICOSURIC AGENT
- inhibits transport of organic (anions) across epithelial barriers
- interferes with U.A. reabsorption (by competing) by the organic acid transporter in the brush border of proximal tubule
Probenecid Clinical Effects
- Indicated to increase U.A. excretion in patients who excrete less than 1g or UA a day
- dissolution of uric acid crystals in joints
- given with adequate hydration to patients with good renal function
Probenecid Toxicity
-salicylates inhibit uricosuric action of probenecid
Pegloticase Mechanism
new class - Bio-uricolytic agents (uricase enzyme)
humans don’t have, but all other animals do
-enzyme urate oxidase with polyethlyene glycole
give IV in patients that all other drugs have failed
-breaks uric acid into allontoin, which is then excreted and it’s more water soluble
-recombinant Pig enzyme
Pegloticase Effects
- rapidly lowers serum levels of uric acid and reduces the urinary excretion of uric acid
- increases serum levels of allantoin and the urinary excretion of allantoin, which is 5 times more soluble than UA
Pegloticase Use
- control hyperuricemia in patients with severe gout in whom congenital therapy has failed/contraindicated (~50,000)
- large crystals (tophi) around hands or elbow
Pegloticase Toxicity
- gout flares (b/c crystals dissolve) give Colchicine, NSAIDS, steroids prophylactly
- pegylated formulation of urate oxidase in order to increase elimination half-life of enzyme (would be 8 hours)
- IV every 2 weeks, expensive $30,000 per year
- 89% developed abs against PEG moiety of pegloticase, so need decreased dose
Duloxetine Mechanism
-for fibromyalgia
inhibit reuptake of serotonin-norepinephrine
(ser more)
Duloxetine Pharm
-urinary elimination
_CYP metabolism
Duloxetine Toxicity
- increase HR & BP, warning with CV issues
- Contraindicated with closed-angle glaucoma
- don’t give with MAOI’s
- SIADH
- BLACK BOX: suicidal ideation
Pregabalin Mechanism
fibromyalgia
- inhibit presynaptic alpha-2-delta subunits of L-type calcium channels
- inhibit excitatory transmission by glutamate
- alleviate neuropathic pain, anxiety, pain syndromes
Pregabalin Pharm
renal unchanged elimination
Pregabalin Toxicity
rebound symptoms upon withdrawal, dependence
-sedation , depression, suicidal thoughts, dizziness, blurred vision, xerostomia
Cyclobenzaprine Mechanism
-skeletal muscle relaxer
central action, at level of brainstem
Cyclobenzaprine Pharm
enterohepatic recirculation, hepatic CYP, decreased clearance in elderly
Cyclobenzaprine Toxicity
additive depressant with drugs/alcohol
drowsiness, xerostomia, dizziness, fatigue, nausea/vomiting (GI) , constipation, blurred vision
-increase QT interval
Tizanidine Mechansim
-skeletal muscle relaxer
agonist of pre-synaptic alpha-2 receptor agonist, decreased activation of polysynaptic spinal cord motor neurons with concomitant reduction in muscle tone, but not strength
FDA: MS, spasticity, spinal cord trauma
Tizanidine Pharm
-renal excretion - decrease with age/renal function
Tizanidine Toxicity
-hepatocelluar toxicity, require liver tests
-tapered cessation-rebount hypertonicity, tachycardia, HTN
additive CNS
asthenia, xerostomia, dizziness, sedation, hypotension
Baclofen Mechanism
-GABAb agonist at multiple levels of the spinal cord, inhibitory signal or hyperpolarizing and reducing excitatory polysynaptic pathways
-pain relief by inhibit substance P
FDA: MS, muscle spasm, spasticity, spinal cord trauma
Baclofen Pharm
renal
Baclofen Toxicity
- renal failure drug accumulation: encephalopathy, abdominal pain, seizures, respiratory depression
- BLACK BOX: rebound-seizures, confusion, hallucinations, psychiatric
- additive CNS depresison
- hypotension with MAOIs
- antidibetic: baclofen
- drwosiness asthenia, confusion, dizziness, fatigue, headach
Dantrolene Mechanism
-decreases muscle contraction by directly interfering (ryanodine) with calcium ion release from SR within skeletal muscle
FDA: malignant hyperthermia, MS, neuroleptic malignant syndrome, spasticity
Dantrolene Pharm
-reconstitution delays administration
Dantrolene Toxicity
CNS additive
- with CCB Vfib, cv collapse
- muscle weakness, drooling, dysarthria, enuresis, myalgias, backache
