Drugs 2

Question 1

Colchicine Mechanism

Answer 1

depolimerization of microtubules

-required for phagocytosing and movement of WBC (polymorphic neuclotides)

Question 2

Colchicine Application

Answer 2

• effective only against gouty arthritis (ACUTE)

- prophylactic agent against such attacks

Question 3

Colchicine Use

Answer 3

• terminate acute attacks of gout
• prevents recurrence of gouty arthritis
• in familiar Mediterranean fever

Question 4

Colchicine Toxicity

Answer 4

• GI disturbances - given to much

- Blood dyscrasias - chronic

Question 5

Indomethancine Application

Answer 5

-treatment of acute attack of gout

Question 6

Indomethacine Mechanism

Answer 6

• cyclooxygenase inhibitor
• analgesic and antipyretic
• inhibits leukocyte motility

Question 7

Indomethacine Dosing

Answer 7

50mg, 3 times a day (3-5 days)

-give with antacid regimen to prevent ulcer

Question 8

Indomethacine Toxicity

Answer 8

50% of patients

• GI-nausea, vomiting, ulcers
• CNS- sever frontal headache
• Hematopoietic disorders
• antagonize furosemide and HCTZ

Question 9

Allopurinol Mechanism

Answer 9

• 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

Question 10

Allopurinol Effects

Answer 10

• 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

Question 11

Allopurinol Uses

Answer 11

Primary Hyperuricemia of gout due to enzyme abnormalities and in children (enzyme abnormalities)
Secondary Hyperuricemia due to hematologic disorders (like multiple myeloma) or chemo

Question 12

Allopurinol Toxicity

Answer 12

• 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

Question 13

Febuxostat Mechanism

Answer 13

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

Question 14

Febuxostat Uses

Answer 14

• 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

Question 15

Febuxostat Toxicity

Answer 15

-mild, 2-3% of patients had transaminase elevations >3 times the upper limit

Question 16

Probenecid Mechanism

Answer 16

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

Question 17

Probenecid Clinical Effects

Answer 17

• 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

Question 18

Probenecid Toxicity

Answer 18

-salicylates inhibit uricosuric action of probenecid

Question 19

Pegloticase Mechanism

Answer 19

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

Question 20

Pegloticase Effects

Answer 20

• 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

Question 21

Pegloticase Use

Answer 21

• control hyperuricemia in patients with severe gout in whom congenital therapy has failed/contraindicated (~50,000)
• large crystals (tophi) around hands or elbow

Question 22

Pegloticase Toxicity

Answer 22

• 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

Question 23

Duloxetine Mechanism

Answer 23

-for fibromyalgia
inhibit reuptake of serotonin-norepinephrine
(ser more)

Question 24

Duloxetine Pharm

Answer 24

-urinary elimination

_CYP metabolism

Question 25

Duloxetine Toxicity

Answer 25

- increase HR & BP, warning with CV issues - Contraindicated with closed-angle glaucoma - don't give with MAOI's - SIADH - BLACK BOX: suicidal ideation

Question 26

Pregabalin Mechanism

Answer 26

fibromyalgia - inhibit presynaptic alpha-2-delta subunits of L-type calcium channels - inhibit excitatory transmission by glutamate - alleviate neuropathic pain, anxiety, pain syndromes

Question 27

Pregabalin Pharm

Answer 27

renal unchanged elimination

Question 28

Pregabalin Toxicity

Answer 28

rebound symptoms upon withdrawal, dependence | -sedation , depression, suicidal thoughts, dizziness, blurred vision, xerostomia

Question 29

Cyclobenzaprine Mechanism

Answer 29

-skeletal muscle relaxer | central action, at level of brainstem

Question 30

Cyclobenzaprine Pharm

Answer 30

enterohepatic recirculation, hepatic CYP, decreased clearance in elderly

Question 31

Cyclobenzaprine Toxicity

Answer 31

additive depressant with drugs/alcohol drowsiness, xerostomia, dizziness, fatigue, nausea/vomiting (GI) , constipation, blurred vision -increase QT interval

Question 32

Tizanidine Mechansim

Answer 32

-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

Question 33

Tizanidine Pharm

Answer 33

-renal excretion - decrease with age/renal function

Question 34

Tizanidine Toxicity

Answer 34

-hepatocelluar toxicity, require liver tests -tapered cessation-rebount hypertonicity, tachycardia, HTN additive CNS asthenia, xerostomia, dizziness, sedation, hypotension

Question 35

Baclofen Mechanism

Answer 35

-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

Question 36

Baclofen Pharm

Answer 36

renal

Question 37

Baclofen Toxicity

Answer 37

- 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

Question 38

Dantrolene Mechanism

Answer 38

-decreases muscle contraction by directly interfering (ryanodine) with calcium ion release from SR within skeletal muscle FDA: malignant hyperthermia, MS, neuroleptic malignant syndrome, spasticity

Question 39

Dantrolene Pharm

Answer 39

-reconstitution delays administration

Question 40

Dantrolene Toxicity

Answer 40

CNS additive - with CCB Vfib, cv collapse - muscle weakness, drooling, dysarthria, enuresis, myalgias, backache