Test #1 Flashcards
Uricostatic agents
- allopurinol and febuxostat
Uricosuric agents
- probenecid, salicylate, losartan
- increase the rate of excretion of uric acid
Enzymes for gout treatment
pegloticase
Anti-inflammatory agents for gout
colchicine and indomethacin
Allopurinol
Xanthine Oxidase Inhibitor
- reduces synthesis of urate
- oxypurinol is an active metabolite (long)
Effects
—prevents progression of gouty arthritis
—decrease nephropathy by decreasing stones
—increase acute gout flare
PK
—rapidly absorbed and long lasting (1/day)
—colchicine with to prevent acute flare
Adverse
—probenecid will increase clearance
—with warfarin - increase bleeding risk
—hypersensitivity
Febuxostat
- non-competitive xanthine oxidase Uses ---hyperuricemia with gout Adverse ---bad for liver, nausea
Probenecid
MoA ---inhibits transport of urate across URAT-1 Uses ---gout therapy ---combined with more fluids, bicarb, colchicine Adverse ---GI - peptic ulcer ---Salicylates will reduce efficacy ---blocks penicillin excretion High doses are uricosuric not low doses
Losartan
- moderate uricosuric agent
Pegloticase
- pegylated recombinant porcine uricase Uses ---refractory gout ---not for chronic gout Adverse ---BBW - anaphylaxis and hymolytic anemia
Colchicine
MoA
—anti-mitotic by interfering with microtubules
—prevents activation and migration of neutrophils
PK
—oral and metabolized by CYP3A4
Uses
—acute gout
—prevention while other agents are started
Adverse
—GI - stop if they continue
—Myelosuppression
Indomethacin
NSAID - inhibitor of COX 1/2 Adverse --- narrow therapeutic window --- 50% of SE ----severe frontal headache ---seizures, depression and psychosis
Hydroxychloroquine
Uses ---antimalarial drug ---anti-inflammatory agent and combined for RA PK ---oral daily Adverse ---GI and skin in short term ---retinal damage - get baseline exam ---decreases blood glucose ---don't use with psoriasis or prophyria ---hepatotoxic
Sulfasalazine
Uses ---immune suprressive for RA PK ---oral daily ---metabolized in gut and poorly absorbed Adverse ---GI and diarrhea ---skin rash ---blood dyscarsias/agranulocytosis
Methotrexate
Uses ---RA with folate replacement PK ---oral, SC ---once per week ---take 4-6 weeks for effect MoA ---anti-folate to inhibite purine synthesis ---inhibits AICAR transformylase to increase adenosine ---reduces thymidine levels (pyrimidine) Adverse ---hepatotoxicity with high doses ---teratogenic ---pulmonary toxicity ---alopecia
Leflunomide
MoA ---inhibits dihydro-orotate - inhibits pyrimidine --- inhibits T-cell proliferation Uses ---immunosuppressive agent PK ---oral daily (prodrug to teriflunomide) Adverse --- long half life causes much CYP450 inhibition ---carcinogenic and teratogenic
Minocycline
MoA ---tetracycline antibiotic ---inhibits metalloproteinases to decrease collegen degradation in RA PK ---experimental ---twice daily oral Adverse --- dizziness and hyperpigmentation
Etanercept
- anti tumor necrosis factor alpha MoA ---anti TNF alpha and stops binding to receptor PK ---SC injection weekly with methotrexate ---short duration Adverse ---headaches ---progressive multifocal leukoencephalopathy
Infliximab
MoA ---monoclonal antibody against TNF PK ---IV every 4-8 wks with methotrexate Adverse ---Cause hypotension
Adalimumab
MoA ---Anti-TNF humanized antibiody PK ---SC injection per 2 weeks ---for juvenile arthritis Adverse ---demyelination
Abatacept
MoA ---CTLA-4 analog to antagonize CD28 receptor ---T cell inhibitor PK ---SC injection weekly ---for moderate-severe RA Adverse ---serious infection risk ---infusion reaciton --- not used in those with COPD
Rituximab
MoA ---anti-CD20 monoclonal antibody ---inhibits B cells PK ---IV two weeks apart then wait 6 months ---combination with methotrexate Adverse ---infection risk is high ---progressive multifocal leukoencephalopathy
NSAIDS for Arthritis
- Naproxen is safest
- usually not sufficient for RA
Glucocorticoids for Arthritis
- prednisone mostly
- toxicity with long term use
- used in combo for RA
- bridging agent
Triple Drug therapy
- start with methotrexate
- if no go then try hydroxychloroquine + sulfa
- if no go then try all three
- multiple drugs = synergistic effect and reduced side effects
Side Effects of Biologic Agents for RA
- Increased infection risk
- Blood dyscrasias
- Increased cancer incidence
- GI, rash, headache
Local Anesthetic Properties
- weak bases
- the charged form is the active form
- lower pKa = more uncharged species
Local Anesthetic MoA
- block open Na channels along axons
- is reversible
- blockage is from inside the cell
With progressive concentrations
—excitation threshold increases
—impulse conduction slows
—action potential ability is abolished - blocks small C and B fibers first then larger fibers
- pain blocked first then sensory then motor
- epinephrine used to limit systemic absorption
Potency of Local Anesthetics
- potentcy is directly correlated to lipid solubility
- Most to least
- –Tetracaine, Bupivacaine, Ropivacaine, Lidocaine, Cocaine, Mepivacaine, Procaine
Types of Local Blocks
- Topical
- Field - ring around wound area
- Peripheral - upstream block
- Spinal - within epidural space
Clearance of Local Anesthetics
- dependent on age, liver function and type
- esters (by cholinesteraces) are hydrolyzed faster than amino amides (by CYP 450)
Adverse Effects of Local Anesthetics
Systemic Toxicity
—allergic deramatitis
—fatal anaphylaxis
—sedation, visual and auditory toxicity
—tonic-clonic convulsions
Neural toxicity
— Transient - with lidocaine, procaine and mepivacaine
Drugs used to treat spasm
- chlorzoxazone
- cyclobenzaprine
- orphenadrine
- methocarbamol
- diazepam
Drugs used to treat spasticity
- Baclofen
- Tizanidine
- Gabapentin
- Botulinum toxin
- Dantrolene
Chlorzoxazone
- anti-spasm drug
- 60 min onset
- 1 hour duration
Methocarbamol
- anti-spasm drug
- 30 min onset and 1-2 hour duration
- similar structure to tricyclic antidepressants
Adverse
—discoloration of urine
—dizziness and loss of coordination
—CNS depression and addiction
Cyclobenzaprine
MoA ---reduces tonic somatic activity at alpha and gamma neurons ---noradrenergic and serotonergic PK ---60 min onset and 12-24 hour duration Adverse ---anticholinergic, drowsiness ---respiratory depression, hypoTN, flaccid paralysis, addiction
Orphenadrine
- anti-spasm drug
MoA
—anticholinergic - atropine like
Baclophen
Uses
—decrease spasticity with MS and spinal injury
—hiccups and neuropathic pain
MoA
—GABAb receptor agonist to decrease substance P release
PK
—given intrathecally
Tizanidine
Uses
—decrease spasticity with MS and spinal injury
MoA
—alpha 2 adrenergic agonist - inhibits release of excitatory neurotransmitters
Gabapentin
MoA ---increases GABA biosynthesis Uses ---reduce muscle spasticity ---reduce anxiety
Diazepam
MoA
—agonist of GABAa receptors - presynaptic inhibition
Uses
—to calm patients
Dantrolene
MoA ---reduces the release of Ca from SR in fast twitch muscle fibers - stopping contraction Uses ---decrease spasticity with upper motor neuron lesions, strokes, spinal injury ---treat malignant hyperthermia ---treat neuroleptic malignant syndrome Adverse ---causes excessive muscle weakness ---don't use with ALS pt
Botulinum Toxin
MoA ---inhibits acetylcholine release from pre-synaptic terminal Uses ---decrease spasticity with cerebral palsy, stroke, MS ---treat excessive sweating PK ---paralysis within 48 hours ---lasts for 12-16 weeks Adverse ---excess weakness ---toxin absorption systemically
What are the stages of ansethesia?
Stage 1
- conscious but drowsy
Stage 2
- unconscious but responds in a reflex fashion
Stage 3
- regular respiration, no spontaneous movement
Stage 4
- loss of respiration and vasomotor control = death
Current
- induction, maintenance and emergence
Anesthesia effects on organs/tissues….
Cardiovascular - systemic vasodilation - myocardial suppression Respiratory - need for assisted ventilation Hypothermia
Inhaled anesthetics MoA
- enhancement of inhibitory GABA-a
- inhibition of excitatory glutamate, nicotinic and 5-HT3
Pharmacokinetics of Inhaled Anesthetics
- effect takes place with equilibrium between alveolar gas and brain tissue
- low blood solubility (less hydrophilic) have more rapid induction rates
- the more blood soluble (more hydrophilic) the more drug that must be taken up to get to equilibrium
- bulk uptake of a drug into the blood can accelerate induction (mainly in low solubility agents) - can increase uptake of a second drug by this method
- pulmanary ventilation rate plays a major role in induction
- recovery is prolonged with more soluble drugs
Potency of Inhaled Anesthetics
- the minimum alveolar concentration (MAC) required to induce anesthesia
- the higher the MAC the lower the potency
- MAC values are additive making combination treatments capable of using less drug amounts
- Infancy, chronic alcohol, hypernatremia and sympathomimetics will decrease the potency
- age, acute alcohol intake, pregnancy, opioids and hypothermia will increase potency
Nitrous Oxide
Uses ---alone as sedative/analgesic ---in combo to reduce required doses Advantages ---rapid acting ---minimal cardio effects ---reduces side effects of combo'd drug Adverse ---not a good muscle relaxant ---cause diffusion hypoxia ---myelosuppression and teratogenic
Halothane
Uses ---induction and maintenance in children Advantages ---non-pungent and rapid ---muscle relaxant and bronchodilator Adverse ---slow elimination ---cardiac depression and increases intracranial pressure ---can cause halothane hepatitis = immune response
Isoflurane
Uses ---maintenance Advantages ---maintains cardiac function Adverse ---pungent
Desflurane
Uses ---widely for maintenance Advantages ---very rapid ---maintains cardiac function Adverse ---pungent
Sevoflurane
Uses ---induction and maintenance in children Advantages ---low pungency ---maintains cardiac function
Malignant hyperthermia Characteristics
- triggered when exposed to halogenated anesthetics or succinylcholine
Presentation - hypercapnia
- muscle rigidity
- tachycardia, hyperthermia, hyperkalemia
Genetics - mutations in ryanodine receptors = excess Ca++
Treatment - stop triggering drug
- 100% O2
- dantrolene
Methohexital
- IV anesthetic MoA --- barbituate acting on GABA-a PK ---onset 30 sec and duration 10 min
Propofol
- IV anesthetic MoA ---GABA-a agonist PK ---onset 40 second and duration about 6 min Adverse ---hypotension and respiratory depression ---pain at the injection site
Etomidate
- IV anesthetic MoA ---potentiates GABA-a currents Uses ---induction and maintenance in pt's with hypotension Adverse ---myoclonic movements ---adrenal insufficiency
Ketamine
- IV anesthetic
MoA
—NMDA receptor antagonist to block glutamate
Uses
—induciton and maintenance of children and pt’s with airway problems
Adverse
—CNS psychotomimetic - hallucinations, euphoria
—tachycardia and hypersalivation
