Test #1 Flashcards
1
Q
Uricostatic agents
A
- allopurinol and febuxostat
2
Q
Uricosuric agents
A
- probenecid, salicylate, losartan
- increase the rate of excretion of uric acid
3
Q
Enzymes for gout treatment
A
pegloticase
4
Q
Anti-inflammatory agents for gout
A
colchicine and indomethacin
5
Q
Allopurinol
A
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
6
Q
Febuxostat
A
- non-competitive xanthine oxidase Uses ---hyperuricemia with gout Adverse ---bad for liver, nausea
7
Q
Probenecid
A
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
8
Q
Losartan
A
- moderate uricosuric agent
9
Q
Pegloticase
A
- pegylated recombinant porcine uricase Uses ---refractory gout ---not for chronic gout Adverse ---BBW - anaphylaxis and hymolytic anemia
10
Q
Colchicine
A
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
11
Q
Indomethacin
A
NSAID - inhibitor of COX 1/2 Adverse --- narrow therapeutic window --- 50% of SE ----severe frontal headache ---seizures, depression and psychosis
12
Q
Hydroxychloroquine
A
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
13
Q
Sulfasalazine
A
Uses ---immune suprressive for RA PK ---oral daily ---metabolized in gut and poorly absorbed Adverse ---GI and diarrhea ---skin rash ---blood dyscarsias/agranulocytosis
14
Q
Methotrexate
A
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
15
Q
Leflunomide
A
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
16
Q
Minocycline
A
MoA ---tetracycline antibiotic ---inhibits metalloproteinases to decrease collegen degradation in RA PK ---experimental ---twice daily oral Adverse --- dizziness and hyperpigmentation
17
Q
Etanercept
A
- 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
18
Q
Infliximab
A
MoA ---monoclonal antibody against TNF PK ---IV every 4-8 wks with methotrexate Adverse ---Cause hypotension
19
Q
Adalimumab
A
MoA ---Anti-TNF humanized antibiody PK ---SC injection per 2 weeks ---for juvenile arthritis Adverse ---demyelination
20
Q
Abatacept
A
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
21
Q
Rituximab
A
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
22
Q
NSAIDS for Arthritis
A
- Naproxen is safest
- usually not sufficient for RA
23
Q
Glucocorticoids for Arthritis
A
- prednisone mostly
- toxicity with long term use
- used in combo for RA
- bridging agent
24
Q
Triple Drug therapy
A
- 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
25
Side Effects of Biologic Agents for RA
- Increased infection risk
- Blood dyscrasias
- Increased cancer incidence
- GI, rash, headache
26
Local Anesthetic Properties
- weak bases
- the charged form is the active form
- lower pKa = more uncharged species
27
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
28
Potency of Local Anesthetics
- potentcy is directly correlated to lipid solubility
- Most to least
- --Tetracaine, Bupivacaine, Ropivacaine, Lidocaine, Cocaine, Mepivacaine, Procaine
29
Types of Local Blocks
- Topical
- Field - ring around wound area
- Peripheral - upstream block
- Spinal - within epidural space
30
Clearance of Local Anesthetics
- dependent on age, liver function and type
| - esters (by cholinesteraces) are hydrolyzed faster than amino amides (by CYP 450)
31
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
32
Drugs used to treat spasm
- chlorzoxazone
- cyclobenzaprine
- orphenadrine
- methocarbamol
- diazepam
33
Drugs used to treat spasticity
- Baclofen
- Tizanidine
- Gabapentin
- Botulinum toxin
- Dantrolene
34
Chlorzoxazone
- anti-spasm drug
- 60 min onset
- 1 hour duration
35
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
36
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
```
37
Orphenadrine
- anti-spasm drug
MoA
---anticholinergic - atropine like
38
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
39
Tizanidine
Uses
---decrease spasticity with MS and spinal injury
MoA
---alpha 2 adrenergic agonist - inhibits release of excitatory neurotransmitters
40
Gabapentin
```
MoA
---increases GABA biosynthesis
Uses
---reduce muscle spasticity
---reduce anxiety
```
41
Diazepam
MoA
---agonist of GABAa receptors - presynaptic inhibition
Uses
---to calm patients
42
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
```
43
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
```
44
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
45
Anesthesia effects on organs/tissues....
```
Cardiovascular
- systemic vasodilation
- myocardial suppression
Respiratory
- need for assisted ventilation
Hypothermia
```
46
Inhaled anesthetics MoA
- enhancement of inhibitory GABA-a
| - inhibition of excitatory glutamate, nicotinic and 5-HT3
47
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
48
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
49
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
```
50
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
```
51
Isoflurane
```
Uses
---maintenance
Advantages
---maintains cardiac function
Adverse
---pungent
```
52
Desflurane
```
Uses
---widely for maintenance
Advantages
---very rapid
---maintains cardiac function
Adverse
---pungent
```
53
Sevoflurane
```
Uses
---induction and maintenance in children
Advantages
---low pungency
---maintains cardiac function
```
54
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
55
Methohexital
```
- IV anesthetic
MoA
--- barbituate acting on GABA-a
PK
---onset 30 sec and duration 10 min
```
56
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
```
57
Etomidate
```
- IV anesthetic
MoA
---potentiates GABA-a currents
Uses
---induction and maintenance in pt's with hypotension
Adverse
---myoclonic movements
---adrenal insufficiency
```
58
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
