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238 Cards in this Set
- Front
- Back
role of sympathetics and parasympathetics in the eye
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-Sympathetics: iris dilator muscle=alpha adrenergic; superior tarsal muscle (raise eyelid)=alpha adrenergic; relaxation of ciliary muscle for far vision=beta adrenergic
-Parasympathetic: constrictor muscle in iris=muscarinic; contraction of ciliary muscles for accomodation=muscarinic |
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Signs of Horner's syndrome
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1. Anisocoria: effected eye less dilated; accentuated by darkness; light reaction good
2. Ptosis 3. Raised eyebrow (because need to use voluntary eye muscles to keep eye open) 4. If present for a few years, lighter colored eye (because less sympathetic stimulation of melanocytes) |
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Describe the sympathetic pathway to the eye
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-First order neuron: Cell bodies originate in hypothalamus and descends to C8/T1 in spinal cord
-Second order neuron: Cell bodies in C8/T1...give off preganglionic axons that pass over the apex of the lung and under the subclavian artery...synapses on superior cervical ganglia -Third order neuron: cell bodies in superior cervical ganglia...give off postganglionic axons that course through cavernous sinus to the eye |
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What is 10% cocaine solution used for?
|
To diagnose Horner's syndrome
-Will block reuptake of NE and cause pupil dilation in normal eye -If have Horner's syndrome, then the effected eye will not dilate because no NE is being released from the third order neuron anyways -Does not discriminate whether the Horner's syndrome is from dysfunction of the first, second, or third order neuron |
|
What is 1% hydroxyamphetamine (Paredrine) used for?
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To determine whether Horners syndrome is caused by dysfunction in third order neurons or first/secodn order neurons
-Paredrine increases the release of NE from nerve terminals, causing normal pupils to dilate -If have third order nerve dysfunction (i.e. tumor in cavernous sinus), will not effectively caused NE release and will not dilate -If first or second order neuron dysfunction, hydroxyamphetamine should still be able to elicit NE release from 3rd order neuron, and pupil will dilate |
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What is Adie's (tonic) Pupil?
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-Decreased parasympathetic innervation of the eye causes effected pupil to be more dilated than the other
-The anisocoria is accentuated in response to light -Pupil is slow to constrict; also slow to dilate -Many of these patients will have decreased deep tendon reflexes -Usually caused by damage to the post-ganglionic parasympathetic fibers leaving the ciliary ganglion -usually seen in young women from teens into 30s -benign condition |
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How do you diagnose Addie's (tonic) Pupil?
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-If have Addie's pupil for a few weeks, will develop denervation hypersensitivity
-1/8% pilocarpine can cause constriction in only hypersensitive eyes; cannot constrict normal eyes -1% pilocarpine will constrict any eye, unless it is pharmacologically dilated |
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What are two commonly used drugs that can inadvertantly cause pharmacological pupil dilation?
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-Jimson Weed (bella donna alkaloids)
-Scopolamine (used as transdermal patch for travel sickness prevention) |
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Effects of cholinergic antagonist drops on the eye
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1. Inhibit pupil constriction (i.e. cause dilation)
2. Inhibit ciliary muscle contraction (i.e. inhibit accomodation and can't read) |
|
Atropine eye drops
-MOA -duration -uses |
-MOA: mAchR antag, causes dilation and cycopegia
-Very potent; lasts for up to 2 weeks -Used when long term dilation is necessary: following eye surgery, very bad iritis, or very bad uveitis |
|
0.5%-1% Tropicanimide (Mydriacyl) eye drops
-MOA -duration -uses |
-mAchR antagonist, causes cyclopegia and pupil dilation
-Has shortest duration and is fastest acting of all dilator drops; get max dilation in 30 minutes and lasts for 4-6 hours -used for eye exams and determining refraction errors in childen |
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Cyclopentolate (Cyclogyl) drops
-MOA -duration -uses |
-mAchR antagonist; causes pupil dilation and cyclopegia
-Lasts up to 24 hours -Used a few times per day for corneal abrasions to ease discomfort from ciliary muscle spasm; can be used in children for accurate refraction correction; can be used in any mild condition where you want the eye relaxed for a few days |
|
Homatropine drops
-MOA -duration -uses |
-mAchR antagonists; causes pupil dilation and cyclopegia
-Lasts 1-3 days -Prescribed 4x/day for corneal abrasions, chemical burns, or for iritis, uveitis, and post-op |
|
Scopolamine drops
-MOA -duration -adverse effects -uses |
-mAchR antagonist; causes pupil dilation and cycloplegia
-Lasts 2-4 days or about a week -More toxic reactions than other dilators: psychosis, restlessness, hallucination, confusion, vomiting, urinary incontinence -used transdermally for motion sickness; can cause unilateral pupil dilation |
|
2.5% Phenylephrine (Neosynephrine)
-MOA -duration -uses -adverse effects |
-alpha agonist: causes pupil dilation, inhibits accomodation, and causes eyes to open wider; also causes vasoconstriction
-dilates within 45 minutes, lasts 6 hours -can be used in eye exam; also added in small amounts to Visine because of its vasoconstricting properties -causes rebound hyperemia in Visine; if use 10% phenylephrine, can cause hypertensive crisis, occipital headaches, ventricular arrhythmias, and tachycardia |
|
What drugs are used for routine pupil dilation?
|
Either 0.5-1% Tropicanimide alone, or 1% Tropicanimide with 2.5% Neosynephrine
|
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Diagnosis of open angle glaucoma
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-Increased intraocular pressure
-Enlarged optic cup -Peripheral vision effected first |
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Signs of closed angle glaucoma
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-Severe eye pain or headache
-Redness of sclera -N/V -cloudy cornea -fixed, irregular mid-dilated pupils -can be instigated by pupil dilation |
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Pilocarpine drops
-MOA -uses |
-direct Ach agonist; causes pupillary constriction, spasm of accomodation, and reduces intraocular pressure by stretching the trabecular network as the iris in contracted and pulled in
-miotic agent (lasts 1 day) used for anisocoria testing; wide angle glaucoma; narrow-angle glaucoma with physostigmine |
|
Epinephrine drops
-MOA -adverse effects |
-direct alpha and beta agonist; causes conjunctival constriction, slight mydriasis, and reduces intraocular pressure by effecting beta receptors in the trabecular meshwork and increasing outflow
-hypertensive crisis, tachycardia, localized burning and irritation, localized allergic reacton, and accumulation of melanin granules |
|
Dipivefrin (Propine) drops
-MOA -uses |
-lipophilic prodrug of ephinephrine; does not enter tear system and cause side effects; converted to epinephrine in eye
-used to reduce intraocular pressure; more potent and safer than EPI |
|
Timolol drops
-MOA -uses -adverse effects |
-non-selective beta blocker; decreases aqueous humor production via receptors in the ciliary body
-#1 drug for glaucoma, better than pilocarpine and EPI -can cause lethargy, lightheadedness, fatigue, memory loss, bradycardia, hypotension, syncope, arrhythmias, wheezing, pulmonary edema, CHF |
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Levobunolol (Betagan) drops
|
-same as Timolol, non-selective beta blocker, but cheaper
|
|
Betaxolol drops
-MOA -Uses |
-selective beta1 blocker
-used in glaucoma patients with history of CHF or asthma, when Timolol would be contraindicate |
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3 Properties of NSAIDs
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1. Analgesic (mostly peripheral; reduces mild to moderate dull pain)
2. Anti-inflammatory (reduces vasodilation and edema) 3. Antipyretic (reduces fever) |
|
Acute uses of NSAIDs
|
For acute pain releif, acute inflammation, and fever reduction
-headache -minor injuries -dysmenorrhea -symptoms and fever of cold or flu -acute bursitis |
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Chronic uses of NSAIDs
|
used to relieve symptoms of chronic inflammatory diseases, but do not stop their progression
-Osteoarthritis -Rheumatoid arthrits -Ankylosing spondylitis |
|
Functions of COX1
|
-Constitutively active
-Produced by platelets, endothelial cells, GI, kidney, most cells -GI protection: PGs decrease acid secretion, etc. -Regulation of blood flow -Regulation of platelet function: thromboxanes recruit and aggregate platelets vs. PGs and Pcyclins -Regulating kidney function: PGs cause vasodilation, etc. |
|
Functions of COX2
|
-Inducible
-Produced by macros, synoviocytes, endothelial cells -induced by growth factors, cytokines, and hormones -mostly involved in inflammation, pain, and fever |
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Selective COX-1 Inhibitors
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-Ketorolac
|
|
Relatively COX-1 Selective
|
-Flurbiprofen
|
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Non-selective COX Inhibitors
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-Ketoprofen
-Indomethacin -Aspirin -Naproxen -Ibuprofen |
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Relatively COX-2 Selective
|
-Celecoxib
|
|
COX-2 Selective
|
Rofecoxib, Valdecoxib (both withdrawn from the market)
|
|
MOA of acetylsalicylic acid (Aspirin)
|
irreversible acetylation of COX enzymes; non-selective
|
|
Uses of aspirin
|
1. Daily baby aspirin (80 mg) reduces risk of MI and stroke via its anti-coagulant effects (inhibits platelet aggregation). May reduce incidence of colon cancer with long term use
2. To reduce low intensity pain, reduce fever, and anti-inflammatory (325 to 650 mg) 3. Rheumatoid arthritis (1-4 mg/day; more likely to have side effects) |
|
How does salicylic acid effect
1. Inflammation |
1. Inhibits PG synthesis of WBCs at inflammatory site; inhibits PG effects of vasodilation and increased PCV permeability
-so it reduces erythema and edema |
|
How does salicylic acid effect
2. Pain |
2. PGE2 sensitizes nerve endings to chemical mediators at the site of inflammation
By inhibiting PG synthesis, asprinin reduces sensation of pain -Can be used in combo with opioids -Used for low intensity pain, 325-650 mg |
|
How does salicylic acid effect
3. Fever |
-reduces production of PGE2, which induces fever in the hypothalamus; doesn't effect body temperature of normal individuals
|
|
How does salicylic acid effect
4. Platelets |
-Irreversibly inhibits the production of TXA2 from platelets (platelets cannot synthesize new COX), reducing platelet aggregation (80 mg). Its effect on TXA2 is greater than on prostacyclin, which inhibits platelet aggregation
|
|
Aspirin
-Absorption |
-Aspirin is a weak acid, and is readily absorbed in the low pH of the stomach
-But most absorption occurs through the small intestine because of the larger surface area available for absorption |
|
Aspirin
-Distribution |
-Widely distributed, includeing CSF, peritoneal cavity, synovial fluid
-Bound to plasma proteins, which can displace other drugs from these proteins and increase their toxicity -Aspirin acetylates albumin and can affect drug binding to albumin |
|
Aspirin
-Metabolism |
-Deacylated by the liver (and plasma)to salicylic acid, which is also an active NSAID
-T1/2 at low doses (325-650) 3 hours -T1/2 at high doses (1 gram)=15 hours -The liver's ability to deacetylate aspirin is limited, so higher doses have much longer half lives and action must be taken for ODs |
|
Aspirin
-Excretion |
-Excretion in urine is pH dependent
-At higher pHs, salicylic acid is ionized, and is better excreted |
|
Adverse Reactions to Asprin
|
1. GI: Bleeding, ulceration, perforation
2. Hypersensitivity: Airway hyperreactivity or rash (may also be allergic to ibuprofen, use acetominophen instead) 3. May cause Reye's Syndrome in children-Liver damage (fatty liver) and encephalopathy; children should take acetiminophen instead 4. Salicysm (OD) 5. Respiratory alkalosis (because stimulates respiratory centers; usually is compensated) 6. Anticoagulant 7. Can cause gout episodes (at low doses, decreases urate excretion; at high doses, increases urate excretion)-don't use aspirin for gout 8. Difficulty breathing and wheezing 9. Can cause acute renal failure if have renal disease, cirrhosis, heart failure, or are on diuretics |
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How does aspirin cause acute renal failure?
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-Prostaglandins are vasodilators and usually counteract vasoconstrictors in the kidney (ang II, catecholamines, ADH)
-In disease states with increased vasoconstrictors and decreased renal blood flow (cirrhosis, nephrosis, heart failure, diuretic use, cardiovascular diseases), NSAIDs will inhibit PG synthesis and potentiate vasoconstriction |
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Moderate Salicylism (Aspirin toxicity)
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-Sweating, vomiting, epigastric pain, tinnitus, and vision blurring
-Early respiratory alkalosis (not seen in children) due to respiratory centor stimulation -Later metabolic acidosis, due to uncoupling of oxidative phosphorylation, increased oxygen consumption and increased CO2 output, which is compounded by decreased respiratory rate from respiratory alkalosis -Can progress to severe salicylism |
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Severe salicylism
|
-Metabolic acidosis reduces the ionized form of salicylic acid, which enhances tissue penetration
-Increased penetration in the CNS leads to agitation, tremor, coma, and respiratory dperession |
|
Management of salicylate poisoning
|
-Mild to moderate salicylate poisoning: Use oral or IV rehydration with particular attention to K supplements
-Marked signs/symptoms of salicylism: First=oral activated charcoal, second=Simple alkalinisation (e.g. 1.26% of NaHCO3 over 2 hours and repeated, keep urine greater than pH 7.5); third=hemodialysis if levels greater than 1000 mg, have persisent acidosis, or deteriorating level of consciousness |
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How does salicylic acid cause GI complications?
|
Inhibition of PG synthesis decreases gastric mucous ecretion, increases acid secretion, and has an antiplatelet effect which increases GI bleeding
|
|
What can you give to reduce the GI complications of NSAIDs?
|
-Misoprostol (synthetic PGE1): reduces risk of gastric and duodenal ulcers; but causes diarrhea and can cause abortions
-Also can use proton pump inhibitors |
|
Drug interactions of acetylsalicylic acid
|
-concommitant use of aspirin with other NSAIDs (e.g. ibuprofen) or other salicylates can decrease its anti-inflammatory and anti-platelet effect
-avoid use with alcohol (acidosis will reduce excretion) |
|
Ibuprofen (Advil, Motrin)
-MOA |
-non-selective, reversible inhibitor of COX
-at doses less than 2400 mg, works as analgesic; at greater than 2400 mg, is anti-inflammatory -also anti-pyretic |
|
Naproxen
|
-non-selective NSAID thats like Ibuprofen
|
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Ibuprofen drug interactions
|
-Can increase blood levels of Lithium
-Can reduce blood pressure lowering effects of anti-hypertensive drugs -May increase levels of aminoglycosides -Should not be taken with anticoagulants (warfarin) |
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Adverse effects of Ibuprofen
|
-Hypersensitivity (esp. if allergic to aspirin)
-GI complications -acute renal failure -dizziness and orthostatic hypotension |
|
Uses of Ibuprofen
|
-Rheumatoid arthritis
-Osteoarthritis -Patent Ductus Arteriosus (also can use Indomethican) |
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Indomethacin
-MOA |
-Very potent non-selective COX inhibitor
-Causes significant GI toxicity |
|
Indomethacin
-Uses |
-Reserved for moderate to severe arthritic pain
-gouty arthritis, ankylosing spondylitis, and osteoarthritis of the hip -Also used for patent ductus arteriosus |
|
Sulindac
|
Prodrug related to Indomethacin; GI side effects are less severe because it's activated in the liver
|
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Ketorolac
-MOA -administration |
-COX-1 selective inhibitor
-ONLY NSAID available for IM administration |
|
Ketorolac
-Uses |
-Moderate to severe pain (i.e. post operative) because has strong analgesic properties
-Not used as an anti-inflammatory -Not used before surgery because of GI upset, renal effects, and increased risk of bleeding |
|
Aceteminophen (Tylenol)
-Uses |
-Analgesic and anti-pyretic
-Not anti-inflammatory |
|
Acetaminophen toxicity
|
-Metabolized by cytP450 into benzoquinone imine...the formed benzoquinone imine normally reacts with glutathione to form non-toxic metabolite
-If have insufficient Glutathione or take too much, the benzoquinone imine can cause liver necrosis -Treatment=provide free sulfhydryl groups, e.e Mucomyst (N-acetyl cysteine) -Avoid drugs affecting liver metabolism (carbamezepine, isoniazid, rifampin), alcohol |
|
Celecoxib (Celebrex)
-MOA |
-relatively COX-II selective inhibitor
|
|
Inidications of Celecoxib
|
-relief of osteoartrhtitis and rheumatoid arthritis in adult patients; chronic inflammatory states
-acute pain management in adults -Treatment of primary dysmenorrhea -Management of familial adenomatous polyposis (FAP) to reduce the number of adenomatous colorectal polyps |
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Cardiovascular and GI Black box warnings on Celecoxib and other prescription NSAIDs
|
-Cardiovascular: May increase risk of cardiovascular thrombotic events, MI, and stroke
-GI: increase risk of bleeding, ulceration, or perforation; elderly patients at greatest risk of GI event |
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Why do COXII inhibitors cause CV events?
|
COXII inhibitors may effect PGI2 synthesis in endothelial cells more than TXA2 synthesis in platelets
|
|
What is the FDA recommended therapy for arthritis?
|
-Naproxen with a proton pump inhibitor
|
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Tramadol (Ultram)
-MOA |
-Used as analgesic, NOT anti-inflammatory and NOT anti-pyretic
-Weak opiod agonist and inhibits NE and 5HT reuptake |
|
Adverse reactions of Celebrex other than usual NSAID side effects
|
-Increased URT infections
-Back pain -insomnia -peripheral edema |
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Drugs that can induce gout in those who are susceptible
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-diuretics
-aspirin -niacin -cyclosporine -L-DOPA |
|
Most common treatments for acute gout attacks
|
-Indomethacin or naproxen (NSAIDs)
-Prednisone (intra-articular corticosteroid) |
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Colchicine MOA
|
-Inhibits microtubule polymerization
-Inhibits leukocyte migration and phagocytosis -Inhibits LTB4 formation -Reduces the inflammation and pain associated with gouty arthritis |
|
Colchicine uses
|
-At low doses, used for prophylaxis of an attack
-Given for acute treatment of gout if not responsive to NSAIDs or corticosteroids |
|
Colchicine administration
|
-Onset of action=1 day;
-Give every hour until develop nausea, vomiting, and diarrhea, then taper off -Use daily in small doses if using for prophylaxis |
|
Adverse effects of colchicine
|
-Nausea
-Vomiting -Diarrhea |
|
What drugs are used prophylactically to prevent gout attacks?
|
-NSAIDs
-Small daily doses of cochicine |
|
MOA of Probenecid
|
-Competes with uric acid for reabsorption in the kidney via the anion transporter
-Decreases total body urate pool in gout patients |
|
Uses of Probenecid
|
-Used to prevent gout attack in patients with impaired urate excretion
-Also inhibits secretion of weak acids such as penicillin, and can be used to increase penicillin t1/2 |
|
Adverse effects of Probenecid
|
-GI irration (take with food or antacids)
-Rash -May aggravate gout at first (treat concurrently with colchicine, introduce drug slowly, keep patient well hydrated) |
|
What are the limitations of using Probenecid in patients with impaired uric acid secretion?
|
-Many patients already have reduced renal function
-Uricosuric agents may cause crystallization of uric acid in the kidney if hydration is ot maintained -Many drug interactions: alters clearance of Methotrexate, oral hypoglycemic agents, and zidovudine |
|
What are the drug interactions with Probenecid?
|
-Alters clearance of methotrexate, oral hypoglycemic agents, and zidovudine
|
|
MOA of Allopurinol
|
-Irreversibly inhibits Xanthine oxidase; reduces plasma urate levels and increases hypoxanthine and xanthine levels, which are more soluble
|
|
Allopurinol
-Metabolism -Administration |
-It is converted by the liver to a more potent metabolite, alloxanthin, which also has a longer t1/2
-Can be given 1x per day, unlike probenicid |
|
Uses of Allopurinol
|
-Reduce serum uric acid in overproducers, people with impiared urate excretion
-Can be used in patients with recurring renal urate stones and renal dysfunction (with caution) -Also used for secondary hyperuricemia associated with melignancies |
|
Adverse effects of Allopurinol
|
-Increased risk of gout early in therapy (can prevent by increasing dose slowly)
-Skin rash or allergic reactions -GI disturbances -Rarely causes hepatic toxicity and interstitial nephritis, but need to monitor liver and kidney function -rare: peripheral neuropathy and bone marrow suppression |
|
Drug interactions with allopurinol
|
-Increases levels of Azathioprine and Mercaptopurine, which are metabolized by XO
-Can be dangerous in people with reduced activity of TPMT, leaving no other method of metabolizing azothioprines except by hypozanthine phosphoribosyl transferase into a highly toxic 6 thioguanine nucleotide |
|
MOA of uricase enzymes
|
-metabolize uric acid to allantoin
|
|
MOA of Febuxostat
|
Nonpurine selctive inhibitor of XO
-Can be tolerated by patients with an allergy to allopurinol -Can be used in patients with renal insufficiency because metabolized by liver |
|
Blood vessels
-Histamine receptor type -Effect |
-H1 and H2
-Vasodilation |
|
Heart (SA Node)
-Histamine receptor type -Effect |
-H2
-Increases heart rate |
|
Myocardium
-Histamine receptor type -Effect |
-H2
-Increased contraction |
|
GI secretory tissue
-Histamine receptor type -Effect |
-H2
-Increased production of acid and pepsin secretion in stomach |
|
Capillaries
-Histamine receptor type -Effect |
-H1
-Increased permeability...edema and hives |
|
Bronchioles
-Histamine receptor type -Effect |
-H1
-Bronchoconstriction |
|
Uterus
-Histamine receptor type -Effect |
-H1
-Uterus contractions |
|
Nerves
-Histamine receptor type -Effect |
-H1
-Increases pain and pruritus |
|
Brain/thalamus
-Histamine receptor type -Effect |
-H3
-Increases pain |
|
MOA of anti-histamines
|
-Competetive antagonists of Histamine receptors (H1 and H2)
|
|
Name six First Generation H1 Blockers
|
1. Tripelenamine (PBZ)
2. Diphenhydramine (Benadryl) 3. Dimenhydrinate (Dramamine) 4. Chlorpheniramine (ChlorTrimemton) 5. Meclizine (Antivert) 6. Promethazine (Phenargan) |
|
Name four Second Generation H1 Blockers
|
1. Loratadine (Claritin)
2. Fexofenadine (Allegra) 3. Cetirizine (Zertec) 4. Terfenadine (Seldane; removed from market) |
|
Name 4 H2 Blockers
|
1. Cimetidine (Tagamet)
2. Rantidine (Zantac) 3. Famotidine (Pepcid) 4. Nizatidine (Axid) |
|
Methotrexate MOA
|
-Folic acid analogue that inhibits dihyrofolate reductase, thus decreasing dTMP and DNA synthesis
-Or may work my increasing levels of adenosine, which acts as an anti-inflammatory mediator [therapeutic effect of methotextrate is not reversed by folic acid] |
|
Methotrexate administration
|
-Give once a week
-Orally or IM or IV |
|
Methotrexate pharmacokinetics
|
-Converted to active metabolite in the liver, 7-hydroxymethotrexate
-Also poly glutamated, and the polyglutamated methotrexate has a longer half life; only needs to be given once a week |
|
Methotrexate elimination
|
-Eliminated by the kidney via the same pathway as aspirin and probenecid are eliminated in the proximal tubule
-Therefore can compete with high dose aspirin and probenecid for excretion |
|
Adverse effects of methotrexate
|
-Mucosal ulcers
-Nausea -Diarrhea -Can reverse the above effects with leucovorin, a folate acid analog -Hepatotoxicity and abnormal LFTs, esp. if alcoholic or already have reduced liver function; Need to monitor hepatic function -Bone marrow suppression at higher concentrations -Do not use in pregnant women |
|
Clinical uses of methotrexate
|
- first line for Rheumatoid arthritis; slows disease progression
-Psoriasis -Chemotherapy -Immunosuppression |
|
MOA of Hydroxychloriquine
|
-Drug is basic and accumulates in lysosomes; Eventually increases lysosomal pH and inhibits sphingomyelase; this increases ceramide levels, which then inhibits TNF transduction and the production of proinflammatory mediators
|
|
Pharmacokinetics of Hydroxychloriquine
|
-Given orally, once a day
-Half life=40 days, a steady state is not reached in months -Has long latency period (12-24 weeks) before it exerts its action |
|
Adverse effects of Hydroxychloroquine
|
-Rash
-GI upset (can be avoided by taking with food) -Leukopenia -Peripheral neuropathy -Ocular effects; should do baseline eye exam before administration |
|
Clinical uses of hydroxychloroquine
|
-Second line for Rheumatoid arthritis; used if not responding to NSAIDs; slows disease progression
-Malaria |
|
Sulfasalazine MOA
|
-Unknown; may prevent antigen absorption from the gut
|
|
Sulfasalazine Pharmacokinetics
|
-Administered orally
-For rheumatoid arthritis, sulfapyridine is the active moeity: sulfasalazine is converted to sulfapyridine by bacteria in the colon |
|
Sulfasalazine Adverse effects
|
-GI upset
-CNS complications -Skin rashes -Neutropenia: should do routine full blood counts -Heptatoxicity: should do routine liver function tests |
|
Clinical uses of Sulfasalazine
|
-Second line for Rheumatoid arthritis; slows disease progression
|
|
Pro-inflammatory effects of IL-1 and TNFa
|
-Increase COX2
-Increase PGE2 -Increase NO -Increase adhesion -Increase chemokines -Increase collagenases -Increase osteoclast activation -Increase angiogenesis |
|
What are some common properties of Biological response modifiers used in Rheumatoid arthritis? (i.e. TNF and IL-1 inhibitors)
|
-Proteins; need to be injected
-Can be used with methotrexate -Don't combine biologics with one another -Decrease ability to combat infections: Don't start if have active infection or chronic infections |
|
MOA of Etanercept (Enbrel)
|
-Mimics TNF receptor; consists of 2 soluble TNF p75 Receptors linked to the Fc portion of human IgG1; binds 2 TNF alpha (and beta) molecules
|
|
Etanercept
-Administration |
-Given via subcutaneous injection
-Given twice weekly -Improvement may occur in a week |
|
Etanercept
-Adverse effects |
-Injection site reactions common
-Increases risks of serious infections -Antibodies against Etanercept develop, but do not effect drug efficacy -Do not give to people with multiple sclerosis and demyelinating diseases |
|
Etanercept
-Clinical uses |
-Rheumatoid arthritis; can be given with methotrexate, and the combo is more potent than methotrexate alone
-Psoriatic arthritis -Ankylosing spondylitis |
|
MOA of Infliximab (Remicade)
|
-Part human, part mouse monoclonal antibody against TNF alpha
|
|
Pharmacokinetics of Infliximab
|
-Given IV only, at 0,2,6 weeks, and then every 4 to 8 weeks
-Can be used alone or in combo with methotrexate |
|
Adverse effects of Infliximab
|
-Upper respiratory infections
-Allergic reactions -Antibodies form against infliximab, but do not effect drug efficacy and are reduced by methotrexate -Can aggravate heart failure; do not use in patients with CHF -Do not use during pregnancy -Increased incidence of TB |
|
Clinical use of Infliximab
|
-Used for rheumatoid arthritis, +/- methotrexate
-Also used from Crohn's disease, ulcerating colitis, and ankylosing spondylitis |
|
MOA of Adalimumab (Humira)
|
-Fully human anti-TNFalpha antibody; blocks TNF alpha binding to p75 and p55 TNF receptors
|
|
Pharmacokinetics of Adalimumab
|
-Given subcutaneously, every other week
-Can be used alone or with methotrexate; combo more effective than methorexate alone |
|
Adverse effects of Adalimumab
|
-Ijection site reactions
-Increased incidence of TB, invasive fungal infections and other opportunistic infections |
|
Clinical uses of Adalimumab
|
-Alone or in combo with methotrexate for rheumatoid arthritis
|
|
MOA of Anakinra (kineret)
|
-Recombinant human IL-1 receptor antagonist; binds to IL-1 instead of IL-1 receptor, reducing cartilage degredation and bone resorption
|
|
Pharmacokinetics of Anakinra
|
Given as subcutaneous injection, given daily
|
|
Adverse reactions of Anakinra
|
-Injection site reactions common
-Increases risk of serious infections -May cause lymphoma |
|
Clnical use of Anakinra
|
-In patients over 18 who have failed one or more Disease Modifying Antirhumatic Drugs (DMARDs; methotrexate, chloroquin, sulfasalazine)
-Cannot be used in combo with anti-TNF alpha drugs |
|
MOA of Leflunomide
|
-Inhibits dihydroorotate dehydrogenase, decreasing UMP (lymphocytes need much more pyrimidine synthesis form proliferation than purine synthesis)
-Arrests cells in G1 -Mostly decreases B cells, but also effects T cells |
|
Pharmacokinetics fo Leflunomide
|
-Prodrug; converted to active form my intestinal mucosa and liver
-Has plasma half life of 15 days, which is long due to plasam protein binding and enterohepatic recirculation -Cholestyramine increases rate of elimination by decreasing enterohepatic circulation |
|
Adverse effects of Leflunomide
|
-Diarrhea
-Reversible allopecia -Elecvation of liver enzymes -contraindicated in pregnancy -Inhibits a p450, causing increased levels of ibuprofen and other NSAIDs |
|
Clinical uses of Leflunomide
|
-Rheumatoid arthritis +/- methotrexate
-Wegener's Granulomatosis -SLE -Myasthenia gravis |
|
MOA of Abatacept
|
-Recombinant CTLA-4 that binds to CD80 and CD85 on APCS, preventing their bidning with CD28 on T lymphocytes and inhibiting costimulation
|
|
Pharmacokinetics of Abatacept
|
-Given IV every 2 weeks
|
|
Adverse reaction of Abatacept
|
-Increase in infections
-Headache -Nasopharyngitis -Nausea -Exacerbates COPD |
|
Clinical uses of Abatacept
|
-Used in Rheumatoid arthritis if all other drugs fail
|
|
MOA of Rituximab
|
-Monoclonal antibody that binds to CD20 on B cells, preventing their activation and causing their lysis
|
|
Pharmacokinetics of Rituximab
|
-IV injection
-Given on days 1 and day 15 -Half life is 19 days |
|
Adverse reactions of Rituximab
|
-Chills
-Fever -Headache -Nausea -Myelosuppression in long term |
|
Clinical uses of Rituximab
|
-Rheumatoid arthritis when other drugs fail
|
|
What does it mean for a drug to have anticholinergic properties?
|
Xerostomia, blurred vision from mydriasis and cyclopegia, Anhidrosis leading to cutaneous vasodilation (hot, flushed skin), constipation, difficulty urinating; tachycardia; CNS effects of confusion, sedation, and delirium
|
|
What does it mean for a drug to have alpha blockade side effects?
|
-Impotence, edema, hypotension, reflex tachycardia
|
|
What are adverse effects of first generation H1 blockers?
|
-Sedation
-anticholinergic -alpha blockade |
|
First generations H1 blockers:
-administration -duration -uses |
-Given PO
-Last 2-6 hours -Used for allergic reactions, pruritis, motion sickness (H1) |
|
Second generation H1 blockers
-adverse effects |
-No anticholinergic, no alpha blockade, no sedation effects
-Can cause headache and tremor |
|
Second generation H1 blockers
-Administration -Duration -Uses |
-Given PO
-Last 12 hours -Used for allergies |
|
Cimetidine (Tagamet)
-MOA |
-H2 blocker, ihibits gastric acid and pepsin secretion
|
|
Cimetidine
-Administration -Uses |
-Given PO and IV
-#1 for acute peptic ulcers in hospital |
|
Why is Cimetidine not used to treat peptic ulcers and heart burn chronically?
|
-Metabolized by p450, and is a universal inhibitor of the p450 system; increases the levels of many drugs if used for more than 2 weeks
-Decreases testosterone levels in males, cuasing penis shrinkage, testicle shrinkage, and gynecomastia (good for transvestites) -Can cause psychosis -Increases risk of CHF; do not give to heart failure patients |
|
Rantidine (Zantac)
-MOA |
-H2 blocker, inhibits gastric acid and pepsin secretion
|
|
Rantidine
-Administration |
-Given PO
|
|
Rantidine
-Adverse effects |
-No effects of p450, testosterone, and psychosis like cimetidine
-Can cause some sedation and tremor -Does have small increased risk of CHF |
|
Rantidine
-Uses |
-peptic ulcers
-heart burn -other secretory syndromes and GI tract problems |
|
Diphenhydramine (Benadryl)
-Class -Anticholinergic properties -Sedation properties -Uses |
-1st generation H1 blocker
-has strong anticholinergic properties -has strong sedative properties -Used for motion sickness and allergies |
|
Dimenhydrinate (Dramamine)
-Class -Anticholinergic properties -Sedation properties -Uses |
-1st generation H1 blocker
-Has strong anticholinergic properties -Has strong sedation properties -used for motion sickness |
|
Tripelenamine
-Class -Anticholinergic properties -Sedation properties -Uses |
-1st generation H1 blocker
-slight anticholinergic properties -intermediate sedative properties -used for allergies |
|
Hydroxyzine
-Class -Anticholinergic properties -Sedation properties -Uses |
-1st generation H1 blocker
-no anticholinergic properties -intermediate sedation -used for allergies and puritis in hospitals, also sedation |
|
Meclizine
-Class -Anticholinergic properties -Sedation properties -Uses |
-1st generation H1 blocker
-no anticholinergic properties -mild sedation -used for motion sickness, anti-vertigo, anti-dizziness |
|
Chlorpheniramine
-Class -Anticholinergic properties -Sedation properties -Uses |
-1st generation H1 blcoker
-mild anticholinergic properties -mild sedation -used for allergies |
|
Terfenadine
-Class -Anticholinergic properties -Sedation properties -Uses |
-2nd generation H1 blocker
-No anticholinergic properties -Mild sedation -Used for allergies |
|
Loratidine
-Class -Anticholinergic properties -Sedation properties -Uses |
-2nd generation H1 blocker
-No anticholindergic properties -No sedation -Used for allergies |
|
Who expresses 5-Lipoxygenase and makes Leukotrienes?
|
-Inflammatory cells: Polys, macrophages, and mast cells
|
|
Actions of 12-HETE (leukotriene)
|
-chemottractant for smooth muscle, causing myointimal proliferation after injury
|
|
Actions of LTC4
|
1. Decrease myocardial contractility
2. Decrease coronary blood flow 3. Bronchoconstriction 4. Increase vascular permeability and exudation 5. Increase airway mucus secretion 6. Chemoattraction and activation of eosinophils |
|
Actions of LTD4
|
1. Decrease myocardial contractility
2. Decrease coronary blood flow 3. Bronchoconstriction 4. Increase vascular permability and exudation 5. Increase airway mucus secretion 6. Chemoattraction and activation of eosinophils |
|
Actions of LTB4
|
1. Produced by colonic cells to increase neutrophil chemotaxis
2. Chemoattraction and activation of neutrophils |
|
Actions of thromboxanes
|
1. Smooth muscle mitogen
2. Vasoconstriction 3. Contraction of respiratory smooth muscle and bronchoconstriction 4. Potent platelet aggregator 5. Renal vasoconstriction, but only if renal inflammatory process occuring |
|
Action of prostacyclins
|
1. Vasodilation
2. Bronchodilation/relaxation of respiratory smooth muscle 3. Inhibits platelet aggregation 4. Increases renin release 5. Vasodilation of afferent arteriole and increases GFR 6. Increase Na and H20 excretion (diuresis) because prevents ADH from increasing intracellular AC activity 7. Induces hyperalgesic response |
|
Actions of Prostaglandins
|
1. Vasodilation
2. Stimulates mucus production, increases blood flow, and inhibits acid secretion in the GI tract 3. Contraction of ciruclar and longitudinal smooth muscle in GI tract, producing colicky cramps 4. PGE2 causes bronchodilation (PGF causes bronchoconstriction) 5. Inhibit platelet aggregation 6. Increase renin release 7. Vasodilate afferent arteriole and increase GFR 8. Increase Na and H20 excretion (diuresis) 9. PGE and PGF2a soften the cervix, induce labor, and cause uterine contractions 10. PGD2 induces natural sleep 11. PGE and PGE2 increase body temperature set point 12. Increase GH, PRL, TSH, ACTH, FSH, and LH levels 13. Increase bone turnover and increase bone formation 14. Decrease intraocular pressure and increase outflow of aqueous humor 15. Hyperanalgesic response |
|
PGE2 binds to which receptors?
|
-EP1 (G, increases Ca2+, contractile)
-EP2 (Gs, increases cAMP, relaxant) -EP3 (Gi, decrease cAMP, inhibitory) -EP4 (Gs, increase cAMP, relaxant) |
|
PGD2 binds to which receptors?
|
-DP1 (Gs, Increase cAMP, relaxant)
-DP2 |
|
PGF2 binds to which receptors?
|
-FP (Gq, increases Ca, contractile)
|
|
PGI2 binds to which receptors?
|
IP (Gs, increases cAMP, relaxant)
|
|
TXA2 binds to which receptors?
|
TP (Gq, increase Ca, contractile)
|
|
LTB4 binds to which receptors?
|
-B-LT1 (Gi, decreases cAMP, involved in chemotaxis)
-B-LT2 (Gq, increases Ca, involved in neutrophil secretion activation) |
|
LTC4 and LTD4 bind to which receptors?
|
-CysLT1
-CysLT2 |
|
Which eicosanoid receptors are relaxant receptors (Gs, increase cAMP?)
|
-IP
-DP1 -EP2, EP4 |
|
Which eicosanoid receptors are contractile receptors (Gq, increase Ca?)
|
-EP1
-FP -TP |
|
Which eicosanoid receptors are inhibitory receptors (Gi, decrease cAMP)
|
-EP3
|
|
Montelukast
-MOA -Uses |
-CysLT1 receptor antagonist (blocks LTC4 and LTD4)
-Used for asthma |
|
Montelukast
-Adverse effects |
Most frequent:
-Abnormal hepatic function tests -Headache disorder Less Frequent: -Increased respiratory, GI, and skin infections -Fever Abdominal pain -etc. |
|
Zileuton
-MOA -Uses |
-5-Lipoxygenase inhibitor (inhibits leukotriene formation)
-Used for asthma |
|
Zileuton
-Adverse effects |
Most frequent:
-Dyspepsia -Nausea Less Frequent: -Abdominal pain with cramps -Generalized weakness |
|
Zileuton
-Drug interactions |
-NEVER use with Pimozide (antipsychotic)
-Severely increases the effects of Astemizole and Terfenadine (anti-histamines) -Severly increases the effect of Tizanidine (muscle relaxant) -Moderately increase the effect of Propanolol -Moderate adverse reaction with theophylline |
|
Zafirlukast
-MOA -Uses |
-CysLT1 receptor antagonist (blocks effects of LTC4 and LTD4)
-used for asthma |
|
Adverse effects of Zafirlukast
|
-Headache disorder
-Nausea |
|
Drug interactions with Zafirlukast
|
-Zafirlukast increases the effects of selected anti-coagulants
|
|
Dinoprostone
-MOA -Uses |
-Synthetic PGE2
-Used for the induction labor and pregnancy termination |
|
Dinoprostone
-Adverse effects |
-V/D
-fever -Bronchoconstriction -Fetal cardiac rhythm abnormalities |
|
Misoprostol
-MOA -Uses |
-Synthetic PGE1
-Usesd for ulcer treatment, but not recommended in the US because of side effects |
|
Misoprostol
-adverse effects |
-Abdominal pain/cramps
-Diarrhea |
|
Latanoprost
-MOA -uses |
-PGF2a derivative
-used for glaucoma |
|
Adverse effects of Latanoprost
|
-Blurred vision
-Conjunctival hyperemia -Iris hyperpigmentation etc. |
|
Epoprostenol
-MOA -Uses |
-Prostacyclin
-Used for primary pulmonary hypertension (because dilates respiratory vessels and is naturetic) |
|
Carboprost
-MOA -Uses |
-PGF2a analogue
-Used for abortion in the second trimester -Used for post partum hemorrhage |
|
How are amide local anesthetics metabolized?
|
-Amides are metabolized by P450 system
|
|
How are ester local anesthetics metabolized?
|
-Esters are metabolized by plasma pseudocholinesterase
|
|
What is the MOA of local anesthetics?
|
-Increases stability of inactive state of neuronal sodium channels
-Therefore decreases size of action potentials, decreases firing rate of neuron, and increases refractory period |
|
How does local pH effect the efficacy of local anesthetics?
|
-Local anesthetics are weak bases that blocks Na channels in the ionized form intracellularly
-But needs to be unionized to cross the cell membrane -Therefore, alkaline conditions are better |
|
What does it mean for a local anesthetic to be "use dependent?"
|
-If a nerve is stimulated at a high frequency (i.e. during pain), more Na channels will be in the inactivated state because they will have less time to recover before the next action potential
-Therefore, local anesthetics have a greater affinity for more actively stimulated neurons |
|
How does the size of the nerve fiber effect the efficacy of local anesthetics?
|
-The smaller the nerve fiber, the more susceptible to local anesthetics
-Smallest: Type C pain fibers, most susceptible -Medium: Type B Autonomic Fibers, some effect -Large: Type A Motor Fibers, little if any effect by only a few long-duration amides |
|
How does the position of a nerve fiber within a nerve bundle effect the action of local anesthetics?
|
-Nerves innervating proximal sites in nerve bundles are located on the outside of nerve bundles and are effected first (because the anesthetic has to diffuse through the rest of the bundle)
-Also, larger motor fibers are located to some degree on the outside of the bundle, causing a small decrement in motor control preceding the pain block |
|
How can local anesthetics be injected?
|
1. Topical/surface: skin and mucosa
2. Infiltration: direct injection (i.e. knee) 3. Peripheral nerve block: Injected close to nerve trunks (i.e. brachial) 4. Spinal: injected into subarachnoid space near spinal cord 5. Epidural: Injection just above the dura surrounding the spinal cord, near the nerve roots (less effect on spinal nerves as a spinal block, so can preserve more motor function) |
|
Adverse effects of local anesthetics:
-CNS |
1. Low dose: Tremors, oral numbness, dizziness, confusion, agitation (exception=cocaine)
2. Moderate dose: Muscle twitching, followed by convulsions (can prevent with anti-convulsant, like thiopental) -High doses: possible respiratory depression |
|
Adverse effects of local anesthetics:
-Cardiovascular |
1. Vasodilation (exception=cocaine); can give with EPI to decrease washout and penetration into systemic circulation
2. Myocardial depression, possibly reducing cardiac output 3. Ventricular arrhythmias and cardiac arrest with unintentionally high levels (but can occur with normal IV doses of Bupivacaine) |
|
Adverse effects of local anesthetics:
-Dermatologic |
-May cause local dermatitis with some topicals; rare systemic allergic response with injected esters due to PABA metabolite
|
|
Drug interactions with local anesthetics
|
-Potentiate the action of non-depolarizing NMJ blockers
|
|
Lidocaine (Xylocaine)
-Type -Kinetics |
-Amide
-Rapid onset, medium acting (1-2 hours) |
|
Lidocaine
-Uses -issues |
-Everything: topical, spinal, PNB, epidural, infiltration
-Potent and can cause Preventricular Contractions |
|
Ropivacaine
-Type -Kinetics |
-Amide
-Long lasting (3-10 hours) |
|
Ropivacaine
-Uses -Issues |
-Epidural, PNB, infiltration
-Less potent substitute for Bupivacaine |
|
Tetracaine
-Type -Kinetics |
-Ester
-Onset slow -Lasts long for an ester (3 hours): very hydrophobic, gets stuck in membranes, and is then slow released |
|
Tetracaine
-Uses -Issues |
-Spinal, topical
-Highest risk of toxicity because of its slow clearance from membranes |
|
Mepivicaine (Carbocaine)
-Type -Kinetics |
-Amide
-Medium to long lasting |
|
Mepivicaine
-Uses -Issues |
-#1 for peripheral nerve block; also infiltration
-Causes less vasodilation, but is toxic to the fetus (don't use during delivery) |
|
Etidocaine (discontinued from US)
-Type -Kinetics |
-Amide
-Long (5-10 hours) |
|
Etidocaine (discontinued from US)
-Uses -Issues |
-Iniltration, PNB, epidural
-Preferentially causes motor block |
|
Benzocaine
-Type -Kinetics |
-Ester
-Rapid onset, short duration |
|
Benzocaine
-Uses |
-Topical
-Also in spray form |
|
Prilocaine
-Type -Kinetics |
-Amide (similar to lidocaine)
-Medium duration (1-2 hours) |
|
Prilocaine
-Uses -Issues |
-Peripheral Nerve Block (dental), infiltration, topical (with Lidocaine)
-Less vasodilation -Lower CNS toxicity -Toxic to fetus, not for delivery |
|
Cocaine
-Type -Kinetics |
-Ester
-Short |
|
Cocaine
-Uses -Issues |
-Topical/nasomucosal
-Vasoconstrictor -Potential for abuse |
|
Dibucaine
-Type -Kinetics |
-Amide
-Long acting |
|
Dibucaine
-Uses -Issues |
-Topical
-Very potent; too toxic for injection |
|
Bupivacaine (Marcaine)
-Type -Kinetics |
-Amide
-Long lasting |
|
Bupivacaine
-Uses -Issues |
-Topical
-Not for injection, too toxic |
|
Procaine
-Type -Kinetics |
-Ester
-Short acting |
|
Procaine
-Uses |
-Limited because too shrot acting
|
|
2-Chloroprocaine
-Type -Kinetics |
-Ester
-Very short |
|
2-Chloroprocaine
-Uses -Issues |
-Epidural
-OB: Just before delivery to control pain |