-
cyclosporin A
- calcineurin inhibitor, immunosuppressant
- -binds to cyclophilins, mediators of protein folding-> bind calcineurin, block phosphatase activity on NFAT.
- -psoriasis
- -----------
- - IBD, effective but frequent relapses, so short term only
- - SE: nephrotoxicity, hairy lip (hirsuitism), neurotoxicity, hypertension, gingival hyperplasia
-
sirolimus
- rapamycin inhibitor
- - binds to tac bp (fkbp) too, blocks 2nd messenger cascade induced by IL, so blocks prolif.
- - no nephrotox, but dec. wbc, dec. platelets, hyperlipidemia
-
lidocaine
- local anesthetic, amide
- - all routes of admin
- - mod. lipid solub
- - mod. toxicity ( esp if absorbed systemically)
-
mycophenolate mofetil
- purine biosynth inhib. (antiprolif)
- - reversible, non-comp. inhib. of IMP dehydrogenase
- - build up of IMP, dec. prolif
- - blocks prolif of T cells & suppresses Ab formation by B cells
-
procaine
- local anesthetic, ester
- - by infiltration ( dental)
- - low lipid solub, low tox
-
dobutamine
- B1-selective agonist, also A1 (vascular beds -> VC)
- - inc. peripheral R, inc. cardiac output
- - for hypotensive emergency
-
phenylephrine
- selective A agonist (A1 & 2)
- - decongestant ( constrict b.v. in mucous membranes)
- - mydriasis
- - inc. bp in emergency
-
clonidine
- A2-selective agonist
- - dec. bp at CNS to dec. SNS output
- - affect B1 (dec. Chrono / ino), A1 (dec. vasc tone)
- - no effect on baroreceptors
- - but if inject directly into bv, VC.
- - antihypertensive, analgesia
- - SE dry mouth, constip.
-
solifenacin
- M3-selectiveish, antimuscarinic
- - esp. in smooth muscle (
- bladder), not salivary.
- - SE less common dry mouth.
-
phentolamine
- non-selective A-agonist (competitive)
- - also inhibs responses of serotonin
- - agonist at musc + h1 h2 receptors
- - SE reflex tachy and antag of presyn a2 receptors
- - use in reverse local VC,pheochromocytoma, male erectile dysfxn
-
tetrodotoxin
- natural toxin, Na channel blocker
- - low lethal dose, due to paralysis of diaphragm and dec. bp
- - pain and cardiac fibres very resistant.
-
thromboxane
- txa2
- - platelet aggreg, VC
- - txa2 receptor antag/ synth inhibitors
- - developed for cvs indication, but not used yet
-
saxitoxin
- natural toxin, Na channel blocker
- - from shellfish @red tide
- - lethal @ low doses
- - pain and cardiac fibre resistant
-
basiliximab
- IL-2 receptor antag
- - inhibit association of IL2 beta +gamma subunits
- - blocks IL-2 signal path
- - competitive antag of IL-2 induced T cell prolif
- - SE hypersensitivity
-
mecamylamine
- non-comp ganglion blocker
- - open channel block of nicotinic receptor ( inc. Ach cannot overcome)
- - not quaternary NH4+ cpd, can cross BBB
- - 1st orally effective antihypertensive
- (used for essential hypertens, but bad SE
-
cevimeline
- M1, M3 selective musc agonist
- (low aff for M2 cardiac)
- - Sjogren's syndrome; autoimmune: Abs against mucous membrane --> dry mouth
- - used to inc. salivation, but inc. nausea and less bradycardia
-
prostacyclin (eprostenol)
- PGI2, agonist for IP
- - vasodilator
- - inhib platelet aggreg.
- - vasc homeostasis
- - used for pulm. hypertension
-
coal tar
- antipruritic (phenolic) + antiinflamm
- - SE irritant folliculitis, phototoxicity, allergic contact dermatitis
- - for psoriasis
-
cyanopindolol
- B3-selective agonist
- - but not really selective
- - B3: inc. lipolysis, but also tachy and tremor from other B receptors being stimd
- - may work to relax overreactive detrusor muscle of bladder
-
sulprostone
- selective EP3 R agonist (some EP1)
- - not on market
- - but may be useful for GI effects
-
alitretinoin
- non-selective retinoid R agonist
- - isomer of retinoic acid
-
alprostadil
- prostaglandin EP R agonist
- - PGE1 = PGE2 analogue
- - used for VD, maintain ductus arteriosus, treat erectile dysfxn (intracavernous or urethral supp)
- - SE penile pain, PGE effects
-
atropine
- musc. receptor antag: antimusc
- - competitive antag @ all MRs
- - effects: opposite to PSNS
- - used for Acute MI (keep heart faster), preop antinauseant (anesth induced), pesticide overdose (counters inc. Ach effect)
- - ***increases distension pain thresholds in esophagus, b/c inhibit chol. mediated esophageal contraction and gastric acid secretion.
-
trimethaphan
- comp. gang blocker
- - antag of NN receptor subtype
- - prevent depol of ANS effector
- - direct peripheral VD from A-adrenergic block
- - polar: cannot cross CNS
- - used to treat hypertens emerg
-
prazosin
- A1 selective antag
- - relaxes arterial + venous smooth muscle
- - used to treat hypertension, mild benign prostatic hyperplasia
-
pralidoxime
- cholinesterase reactivator
- - reverses toxic effects of Ach-esterase inhibs tog. w/ atropine
- - cleaves dialkylphosphate group from active site. only works acutely.
-
latanoprost
- PGF2 analogue, agonist for FP
- - lowers IOP (treat glaucoma)
- - increase matrix metalloproteinase levels to remodel extracellular matrix between ciliary muscle cells (open holes between muscle bundles)
- - inc. uveoscleral outflow by 60-100%- SE: conjunctival hyperemia,
- iris darkening (stimulation of melanogenesis in iridial melanocytes),
- increased browth and darkness of eyelashes.
-
tyramine
- indirect sympathomimetic
- - releases stored catecholamines
- - metabolized by MAO
- - high 1st pass metab @liver
-
zileuton
- leukotriene inhibitor
- - treat asthma, 2o choice in mild-mod persistent
- - direct inhibition of enzyme 5-lipoxygenase
- - SE (broad b/c blocks all LTs), GI, headache, nausea
- - metabd by cyt p450 (warf, theophyll, prop)
- -**LTD4 is 100x more pitent than histamine at causing bronchoconstriction
-
benztropine
- antimuscarinic (non-selective)
- - CNS > periphery
- - treat tremor in pts w/ Parkinsons
- - less drooling too
-
ipratropium
- antimuscarinic
- - inhaled: low systemic SE (anticholinergic)
- - topical bronchoD and decrease mucus secretion (b/c block M3 for bronchoD, and prevent vagal stimulation)
- - SE: causes dry mouth
- - not rescue
- - useful if lots of vagally mediated bronchoC, mucous plugs
-
calcipotriene
- synth vit d3 deriv
- - for psoriasis treatment
- - inc. differentiation and dec. prolif of keratinocytes
- - VDR and RXR: DNA target gene
- - SE burning, itching, dryness, erythema, hypercalcemia
-
nicotine
- nicotinic receptor agonist
- - nonselective neuronal and skeletal m
- - activates PSNS and SNS
- - CNS effects bc cross BBB - tremors, nausea (chemoreceptors)
- - SNS heart (hypertens, tachy)
- - PSNS bronchoC, inc. resp sec, GI (N/V), inc.VP
-
acebutolol
- B1 selective antag, partial agonist
- - for hypertens, angina
- - SE fatigue, dizziness, (less brady, affect lipid)
-
carbachol
- nonselective musc & nic agonist
- - resistant to cholinesterases
- - for open angle glaucoma ( inc. trabecular outflow by tugging on trabecular meshwork)
- - SE: blurred vision(cycloplegia), dimmed vision, bad night vision, ciliary muscle spasm, cataracts.
-
pilocarpine
- musc. selective agonist
- - treat open-angle glaucoma (dec. IOP by inc. trabecular outflow, pull on trab. meshwork)
- - treat xerostomia (dry mouth) from cancer chemo or Sjogren's syndrome
- - increases salivation and sweat
- - SE: blurred vision (cycloplegia), dimmed vision, bad night vision, ciliary muscle spasm (headache), cataracts
-
scopolamine
- anti-muscarinic
- - competitive antag @ all MRs
- - crosses BBB better than atropine, so causes drowsiness/fatigue
- - SE mydriasis, cycloplegia, less effect on HR
- - treat motion sickness (but dec. saliva, acts on CNS to dec. nausea)
-
azathioprine
- purine biosynthesis inhib (antiprolif), immunosuppressant
- - pro-drug -> converted to 6-mercaptopurine -> 6-mp ribonucleotide
- - looks like IMP, competes
- - inc. [IMP] = -ve feedback, dec. prolif
- - acts early during prolif cycle of T and B cells
- ------------
- - induce and maintain remission in UC and CD
- - 3-6 mo of treatment, 50-60% pts get remiss.
- - can allow steroid reduction/elimination
- - SE: increased risk of infection, N/V, leukopenia, hepatotoxicity, pancreatitis, alopecia
-
butaprost
- selective EP2 agonist
- - cause joint inflamm
- - not on market
-
tolterodine
- anti-musc
- - may be selective for bladder > salivary
- - vs. Oxybut: less dry mouth, but less effective
- - may selectively antag M2?
- - blocks PSNS inhib. of SNS med'd relax
- - also causes tachycardia
-
acetylcholine
- non-selective cholinergic
- - but most effects from muscarinic
- - PSNS effects plus:
- - sweating (musc, even though SNS)
- - VD (MR on vascular epi) -> hypotension -> baroreceptors -> reflex tachy
- - dec. inotropy (ventricular force)
- -------------------------
- - IPAN release ACh, induce vagal excitation
- - ENS excitatory neurotransmission -> interneurons -> enteric motor neurons on smooth muscle (M3)
-
epinephrine
- direct-acting sympathomimetic
- non-selective adrenergic agonist
- - made in adrenal glands
- - not cross BBB, but indirect CNS effects: fear, tremor...
- - mydriasis, VC (skin), VD (skeletal muscle)
- - inc. HR (inc. SBP), VD skm (dec. DBP), bronchoD, dec. GI motility, dec. VP, sweating, palor
-
norepinephrine
- non-selective adrenergic agonist
- - + inotrope (force), + chronotrope (HR)
- - VC - more potent than epinephrine
- - less VD of skeletal muscle and bronchoD
- - decrease both DBP & SBP
-
tubocurarine
- non-selective ganglion blocker (comp)
- non-depol NM receptor blocker - postsynaptic (muscle relax)
- - can be diag. agent for MG
- - SE histamine release, increased saliva
-
black widow spider toxin
- presyn mech @ NMJ
- - cause massive release of ACh
- - empties vesicles, prevents refill -> paralysis of muscles -> death
-
hemicholinium
- non-comp ganglion blocker
- - open channel block of NR
- - depletes choline @ presyn. bouton, blocks reuptake
- - dec. efficacy of synaptic transmission
-
selegiline
- MAO inhibitor
- - blocks breakdown of NE + other catecholamines
- - 2 types of MAO:
- - A -> liver
- - B -> more CNS, so if inhibit B, can still allow A to fxn in liver and breakdown stuff
-
metoprolol
- B1 selective antag, not partial agonist
- - use in hypertension, angina, post MI, pref. for diabetes
- - B2 not blocked, so no bronchoC
- - SE fatigue, dizzy, bradycardia
-
phenoxybenzamine
- A1 selective antag (irreversible)
- - inhib. reuptake of NE, blocks histamine, Ach, serotonin
- - SE postural hypotension + tachy
-
NSAID
- COX inhibitor
- - analgesia - blocks formation of all PGs (PGE2)
- - dysmenorrhea (from inc. PGE2 and PGF2)
- - treat patent ductus arteriosus (PGE2 keeps it open after birth)
-
ephedrine
- direct mixed agonist (A and B)
- - enhances NE release
- - mild stimulant
-
pancuronium
- non-depol. NMJ blocker
- - SE no histmaine release/ganglion blockade
- - only affects NMJ - selective
-
benzocaine
- local anesthetic - ester
- - topical (skin, mucous memb)
- - moderate lipid solub
- - toxicity = methemiglobinemia
-
daclizumab
- IL-2 receptor antag (human/rodent combo Ab)
- - inhibits association of IL2 beta and gamma subunits, so blocks IL2 signalling path
- - and competitive antag of IL2 induced T cell prolif
- - SE rare hypersensitivity
-
isoproterenol
- B-selective agonist (B1 and B2)
- - B1 effects (+ chrono/ino)
- - B2 effects (vasodilator)
- - inc. cardiac output (w/ little change bp)
- - decrease DBP, increase SBP
-
mifepristone
- glucocorticoid R antagonist
- - act by preventing dissociation of glucocorticoid receptor from heat shock protein
- - also strong antiprogestin -> abortion
-
reserpine
- blocks NE uptake + storage
- - leads to catecholamine depletion
- - antihypertensive and serious depression
- - must be used with diuretic b/c alone causes sodium retention
-
pimecrolimus
- calcineurin inhibitor (immunosuppressant)
- - bind tacrolimus binding protein (fkbp)
- - bind calcineurin-->inhibit T cell prolif
-
labetalol
- mixed= A1-selective blocker, non-selective B-blocker, B2 agonist activity
- - causes hypotension w/ less tachy than A-blockers b/c B blockade prevents reflex tachy via baroreceptor reflex.
-
Parathion, Diazinon, Malathion (organophosphorus insecticides)
- acetylcholinesterase inhibitor
- - cause ACh toxicity: DUMMBELSSS
-
4-aminopyridine
- presynaptic NMJ mech
- K+ channel blocker
- - prevents repolarization, prolonged action potentional allows conduction thru damaged nerves
- - used for MS, MG, spinal cord injury
-
dantrolene
- @ muscle cells, decrease release of Ca2+ from sarcoplasmic reticulum
- - muscle relax b/c of dec. Ca2+
- - crosses BBB -> drowsy
- - treat malignant hyperthermia, spasticity
-
succinylcholine
- depolarizing NMJ blocker (non-comp)
- - maintain depol --> desensitize NR
- - broken down by pseudocholinesterases in blood
- - non-selective
- - SE arrhythmias, vomit, musclar pain, inc. IOP
-
alpha-bungarotoxin
- non-depolarizing NMJ blocker
- - from snake (cobra) bite
- - rapid paralysis of skeletal muscles and diaphragm
- - death from resp. failure
-
adapalene
- selective agonist for RAR-gamma
- - derivative of naphthoic acid
- - SE burning, stinging, peeling, erythema, inc. photosensitivity
-
tazarotene
- selective RAR-beta/gamma agonist
- - prodrug --> tazarotenic acid
- - anti-inflamm, antiprolif
- - absorbed percutaneously --> teratogen
- - therefore, female must be on contraception
-
isotretinoin
- non-selective agonist of retinoid receptors
- oral retinoid, synthetic Vit. A derivative
- - not made or converted in body
- - toxicity: like Vit A induced
- - inc. cholesterol + TG
- - headache, corneal opacities, inc. IOP, teratogenicity
-
benzoyl peroxide
- antibiotic for acne
- - penetrates stratum corneum, metabolized to benzoic acid @ epidermis/dermis
- - antimicrobial, peeling, comedolytic
- - irritation concentration dependent, contact sensitizer
- - oxidant --> bleaching
-
bexarotene
- selective RXR agonist
- - useful for cancers, i.e. cutaneous T-Cell lymphoma
- - SE inc. TG, inc. cholsterol, hypothyroidism, leukopenia
-
corticosteroids & NSAIDs
- prostaglandin synthesis inhibitors
- - corts: block all PG + LT
- - NSAID: block COX, promote LT synth (because inc. arachadonic acid)
-
prostaglandins
- products of cyclooxygenase pathway
- - COX1 -> housekeeping
- - COX2 -> expression depends on stimuli
-
isoprostanes
- prostaglandin isomers
- - COX not needed to make isoprostanes
- - potent VC, may dec. inflamm?
-
dinoprostone
- PGE1 = PGE2 analogue
- - promotes uterine contractions (induce birth)
- - @ end of term-> delivery, otherwise abortion
- - SE abdominal discomfort, diarrhea
-
oxybutnin
- selective anti-muscarinic
- (M1 + M3 >>> M2) = less CVS SE
- - dec. frequency of detrusor muscle contraction
- - delay desire to void
- - treat urinary incontinence
- - SE dry mouth, drowsiness, constipation, blurred vision
-
acitretin
- synthetic non-sel. Vit A derivative
- - oral, for pustular forms of psoriasis
- - avoid ethanol, promotes drug
- - retinoic acid + tazarotene for less severe psoriasis
-
amphetamine, methamphetamine
- indirect sympathomimetic
- - reuptake inhibitors
- - inc. activity of CNS
-
misoprostol
- PGE1 = PGE2 analogue, acts at EP1 and EP3
- - cytoprotective @ low dose
- - inhibit gastric acid secretion @ high dose
- - prevent NSAID ulcers, abortion
- - SE abdominal discomfort, diarrhea
-
propranolol
- non-selective B-blocker
- - treats hypertens, angina, migraine, tremor, dec. sudden death post MI, hyperthyroidism
- - SE get into CNS (fatigue, dizzy), brady, inc. TG levels significantly
-
xylometazoline/oxymetazoline
- selective A-agonist
- - topical decongestant
- - oxy may cause hypotens b/c sig. affinity for A2 receptors, and therefore inc. nasal congestion b/c better perfusion in nasal mucous membrane
-
azelaic acid
- topical antibiotic
- - straight chain sat'd dicarboxylic acid
- - antimicrobial, testosterone -/-> dihydrotestosterone
- - decreases inflammation + erythema
- - treats acne vulgaris, rosacea
- - SE redness, dryness
-
salbutamol
- B2 selective agonist (short-acting)
- - for asthma
- - bronchodilation effect lasts 3-6 hours
- - for intermittent asthma, or rescue medication for acute asthma attacks in persistent asthma
- - not for frequent use, this indicates worsening control
-
montelukast
- leukotriene receptor antagonist
- competitive antag @ CystLT1 (end target of C4 D4 E4)
- - treat asthma, allergic rhinitis
- - more selective, so less SE than Zileuton
- - very expensive
-
tacrolimus
- calcineurin inhibitor (immunosuppressant)
- - binds tacrolimus binding protein (fkbp)
- - binds calcineurin and inhibits T cell prolif
- - less hypercholesteremia
-
pyridostigmine
- cholinesterase inhibitor
- - drug of choice for MG
-
neostigmine
- cholinesterase inhibitor (indirect)
- - treat post-op ileus (bowels stop)
- - treat post-op urinary retention
- - can be used for MG
-
guanethidine + bretylium
- indirect sympathomimetic
- - prevent release of NE, used as antihypertensive
- (bretylium = antiarrythmic)
-
dopamine
- 1. selective adrenergic agonist
- - D1: vascular sm relax
- - D2: suppress NE release, inc. VD renal bf
- - B1: heart
- --@ low doses: dec. peripheral R
- --@ high doses: mimic epinephrine? inc. work of heart, better perfusion
- --------------------
- 2. inhibitory neurotransmitter of ENS
- - inhibit GI motility via presynaptic D2 receptors
- - dec. ACh release by myenteric neurons
-
lubiprostone
- prostaglandin E analogue
- but not act on EP receptors when orally
- - GI: activate voltage dep. Cl- channels
- --inc. Cl- in intestinal tract, inc. fluid secretion, inc. GI transit
- - used for constipation
- - SE N/V, cramps
-
atacurium
- non-depolarizing NMJ blocker
- - slight histamine release
- - short acting
- - can be given to kidney/liver dysfxn pts
-
botulinum toxin
A (botox)
B (myobloc)
- blocks vesicle release (ACh) @ NMJ by cleaving docking proteins
- - A - cleave SNAP 25 (longer lasting)
- - B - cleave VAMP/synaptobrevin --> flaccid paralysis of skeletal muscle
-
betamethasone/dexamethasone
- potent anti-inflamm
- - no mineral cort. action b/c selective for GC receptor
-
prednisone
- corticosteroid
- - used to treat Myasthenia Gravis
- - weak anti-inflamm, but 5x more potent than HC
-
edrophonium
- acetylchilnesterase inhibitor
- - reverses paralysis from non-depol. NM blockers
- - MG diagnostic agent (will cause inc. muscle strength if MG)
- - no CNS effects
- - *** increases pain sensitivity for GERD b/c in inc. cholinergic mediated esophageal/GI smooth muscle contractions and increases gastric acid secretion.
-
muromonab-CD3 (anti-CD3 ab)
- lymphocyte-depleting agent
- - binds CD3 on T cell surface, prevents Ag binding to recognize complex, so cell-mediated cytotoxicity blocked
- - may cause cytokine release syndrome, human Ab against mouse to decrease efficacy
-
bethanechol
- musc-selective agonist
- - mostly act on GI & urinary tract
- - treat urinary retention and GERD in kids
-
pirenzapine
- M1-selective antagonist
- - lower incidence of dry mouth
- - decreases GI acid secretion, so once used to treat PUD
-
antithymocyte globulin
- lymphocyte-depleting agent (immunosuppressant)
- - rapid dec. in T and B lymphoid cells
- - knock out cell-mediated immunity, therefore inc. risk of malignancy + opportunistic infection
- - cort + calcineurin inhib. sparing
-
epibatidine
- - high affinity for neuronal + muscle (more potent than nicotine)
- - muscarinic antagonist too
- - potent analgesic (200x > morphine)
- - too toxic b/c activates all NRs
- - from poison dart frog
-
tamsulosin
- selective antag for alpha1A + D
- - greater effect on prostate sm than vascular sm
- - treat mild benign prostatic hyperplasia
- - but cause lots of dizziness
-
alefacept
- anti-CD2 Ab
- - blocks CD4 T Cell activation
- - slows down cell-mediated immunity
- - dec. T cell count, inc. risk of cancer
- - treat mod/severe plaque psoriasis
-
vesamicol
- non-selective, presynaptic cholinergic mech
- - blocks ACh uptake into vesicles
- - @ all cholinergic terminals (including NMJ)
-
retinoic acid (tretinoin)
- non-selective agonist of retinoid R
- - acid form of Vit A
- - stabilize lysosomes, inc. RNA pol activity
- - dec. cohesion btwn epidermal cells
- - inc. expulsion of comedones, white --> black
-
leflunomide
- purine biosynth inhib (antiprolif)
- - inhib. dihydroorotate dehydrogenase
- - depletes UMP, so dec. prolif b/c block de novo DNA synth
- - treat rheumatoid arthritis
- - SE no leukopenia or thrombocytopenia
-
bupivacaine
- local anesthetic, amide
- - all routes of admin
- - high lipid solub
- - high toxicity (cardiotoxic)
-
timolol
- non-selective B-blockers
- - dec. aq humor production & inc. trabecular outflow by B2 mechanism
- - SE: well tolerated, major problem: dry eyes, systemic effects (bronchoconstriction...)
-
levobunolol
- non-selective B-blockers
- - dec. aq humor production & inc. trabecular outflow by B2 mechanism
- - SE: well tolerated, major problem: dry eyes, systemic effects (bronchoconstriction...)
-
betaxolol
- B1-selective-blocker
- - dec. aq humor production & inc. trabecular outflow by B2 mechanism
- - SE: well tolerated, major problem: dry eyes, systemic effects
- - B1 selectiveness not relevant as eye drop: [drug] inc. lots, so it can block B2 too.
- - advantage: if systemic absorption, will not affect lungs b/c not B2 blocker, so less SE.
-
apraclonidine
- A2-agonist
- - dec. aqueous humor production
- - inc. uveoscleral outflow
- - SE: less effective than B-blocker, allergic conjunctivitis
- - if get into CNS: sedation & hypotension (act like clonidine and decrease SNS output.)
-
brimonidine
- A2-agonist
- - dec. aqueous humor production
- - inc. uveoscleral outflow
- - SE: less effective than B-blocker, allergic conjunctivitis
- - if get into CNS: sedation & hypotension (act like clonidine and decrease SNS output.)
-
physostigmine
- cholinesterase inhibitor
- - for open angle glaucoma ( inc. trabecular outflow by tugging on trabecular meshwork)
- - SE: blurred vision(cycloplegia), dimmed vision, bad night vision, ciliary muscle spasm, cataracts.
-
travoprost
- PGF2 analogue, agonist for FP- lowers IOP (treat glaucoma)
- - increase matrix metalloproteinase levels to remodel extracellular
- matrix between ciliary muscle cells (open holes between muscle bundles)
- - inc. uveoscleral outflow by 60-100%
- - SE: conjunctival hyperemia, iris darkening (stimulation of melanogenesis in iridial melanocytes), increased browth and darkness of eyelashes.
-
bimatoprost
- PGF2 analogue, agonist for FP- lowers IOP (treat glaucoma)
- - increase matrix metalloproteinase levels to remodel extracellular
- matrix between ciliary muscle cells (open holes between muscle bundles)
- - inc. uveoscleral outflow by 60-100%- SE: conjunctival hyperemia,
- iris darkening (stimulation of melanogenesis in iridial melanocytes),
- increased browth and darkness of eyelashes.
-
dorzolamide
- topical carbonic anhydrase inhibitor
- - decreases rate of aqueous humor formation by blocking bicarbonate formation (bicarb is produced by ciliary muscle carbonic anhydrase)
- - topical less effective than oral
- - CI: avoid if sulfa allergy
- - SE: fatigue, depression, paresthesias (burning/prickling sensations)
-
brizolamide
- topical carbonic anhydrase inhibitor
- - decreases rate of aqueous humor formation by blocking bicarbonate
- formation (bicarb is produced by ciliary muscle carbonic anhydrase)
- - topical less effective than oral
- - CI: avoid if sulfa allergy
- - SE: fatigue, depression, paresthesias (burning/prickling sensations)
-
acetazolamide
- oral carbonic anhydrase inhibitor
- - decreases rate of aqueous humor formation by blocking bicarbonate
- formation (bicarb is produced by ciliary muscle carbonic anhydrase)
- - topical less effective than oral
- - CI: avoid if sulfa allergy
- - SE: fatigue, depression, paresthesias (burning/prickling sensations)
-
budesonide
- inhaled corticosteroid
- - for maintenance/prophylaxis of asthma, most effective controller
- - reduce symptoms, inc. QOL and lung function, dec. airway hyperresponsiveness and bronchoC
- - reduce freq and severity of asthma exacerbations and decrease asthma morbidity and mortality
- - rare to have HPA-axis suppression at low dose
- - rinse mouth after: risk oral candidiasis
- - SE: cough and oral thrush
- - SE of systemic: weight gain, osteoporosis, thin skin, PUD, decreased muscle mass...
-
beclomethasone
- inhaled corticosteroid
- - for maintenance/prophylaxis of asthma, most effective controller
- - reduce symptoms, inc. QOL and lung function, dec. airway hyperresponsiveness and bronchoC
- - reduce freq and severity of asthma exacerbations and decrease asthma morbidity and mortality
- - rare to have HPA-axis suppression at low dose
- - rinse mouth after: risk oral candidiasis
- - SE: cough and oral thrush
- - SE of systemic: weight gain, osteoporosis, thin skin, PUD, decreased muscle mass...
-
fluticasone
- inhaled corticosteroid
- - for maintenance/prophylaxis of asthma, most effective controller
- - reduce symptoms, inc. QOL and lung function, dec. airway hyperresponsiveness and bronchoC
- - reduce freq and severity of asthma exacerbations and decrease asthma morbidity and mortality
- - rare to have HPA-axis suppression at low dose
- - rinse mouth after: risk oral candidiasis
- - SE: cough and oral thrush
- - SE of systemic: weight gain, osteoporosis, thin skin, PUD, decreased muscle mass...
- - fluticasone (newer) have less systemic activity than older compounds (triamcinolone)
-
albuterol
- B2 selective agonist (short-acting)- for asthma- bronchodilation effect lasts 3-6 hours
- - for intermittent asthma, or rescue medication for acute asthma attacks in persistent asthma
- - not for frequent use, this indicates worsening control
-
salmeterol
- B2 agonist (long-acting)
- - for asthma
- - BD effect lasts 12 hours
- - 3rd line, add only after used ICS and SABA and still inadequate effect.
- - should never be used for asthma without antiinflammatory medication (i.e. cort)
- - SE: skeletal muscle tremor, tachy, tolerance
- - overuse - decreased B receptor responsiveness, increased cardiovascular events (death in black males)
-
formoterol
- B2 agonist (long-acting)
- - for asthma
- - BD effect lasts 12 hours
- - 3rd line, add only after used ICS and SABA and still inadequate effect.
- - should never be used for asthma without antiinflammatory medication (i.e. cort)
- - SE: skeletal muscle tremor, tachy, tolerance
- - overuse - decreased B receptor responsiveness, increased cardiovascular events (death in black males)
-
theophylline (aminophylline)
- methylxanthine, adenosine receptor antagonist
- - bronchodilation, inc. mucociliary clearance, affects eosinophils/t-cells
- - inhibit cyclic nucleotide phosphodiesterase to inhibit degrad. of cAMP & cGMP
- - at high doses, stimulant -> inhibit sleep.
- - used orally for severe asthma.
- - SE: tachy, increased cardiac output, potential to induce tachyarrthymias (sudden death), gastric upset, weak diuresis
- - caffein: moderate bronchoD, mimics effect of theophylline
-
cromolyn sodium, nedocromil
- mast cell stabilizer
- - blocks bronchoconstriction for exercise-induced/allergic asthma, mild persistent
- - inhibit release of inflammatory mediators (histamine from mast cells)
- - altered PSNS response, leukocyte fxn
- - SE: cough, dryness, unpleasant taste. rare dermatitis/myositis
- - nedocromil more effective than cromolyn, may reduce ICS usage.
-
montelukast
- leukotriene inhibitor
- - recomb. monoclonal antibody against IgE
- - competitive antag @ CystLT1 receptor, so it affects smooth muscle constriction, immune cell infiltration, and vascular changes (edema)
- - sig. less effective (and $$$$) than ICS
- - add-on therapy, preventative, less SE than oral corts
- - SE: minor GI, headache, nausea
- - **LTD4 is 100x more potent than histamine at causing bronchoC
-
omalizumab
- leukotriene inhibitor
- - bind FC receptor on IgE, so prevents IgE from binding to mast cells --> prevent mast cell degranulation.
- - affects new IgE only, not those already bound; but blocks degranulation even if IgE already present on mast cell.
- - target strong allergic associated asthma
- - iv, can cause anaphylaxis (because mouse Ab)
- - for pts not optimally controlled on standard therapies or have sig. SE from ICS
- - **LTD4 is 100x more potent than histamine at causing bronchoC
-
adenosine triphosphate ATP
- non-cholinergic excitatory neurotransmitter for ENS, between myenteric interneurons and from interneurons-> inhibitory motor neurons.
- - acts on P2X and P2Y receptors
- - P2X: ligand-gated cation channels (like nicotinic), fast excitatory responses
- - P2Y: G-protein coupled receptor, slow excitatory effects
- - regulated release of ATP can activate sensory nerve terminals to transduce distension. Overdistension also triggers pain.
- - injury inc. ATP, so more peristaltic activity (cramping in gut injury)
-
serotonin (aka 5-hydroxy-tryptamine)
- non-chol. excitatory neurotransmitter for ENS
- - activates on 5-HT3 and 5-HT4 receptors
- - 5-HT3(cation), 5-HT4(G-protein)
- - 60-90% of total 5-HT is in enterochromaffin cells of GI mucosa
- - released by: ingestion of food, dec. pH, presence of a.a. or f.a., mucosal distortion, obstruction of gut motility.
- - modulates smooth muscle fxn (contract/relax), intestinal secretion, responses to visceral pain
- - eliminated by MAO
- ----------------
- peripheral serotonin modulates:
- - CVD fxns: platelet aggregation, smooth muscle contraction
- - GI tract motility (found in enterochromaffin cells and neurons of ENS)
- - musculoskeletal pain (receptors on nerve fibres that convey noxious input to brain)
- central roles:
- - serotonergic neurons found in raphe nuclei (brain stem, involved in mood, sleep, vomiting, pain...)
- -----------------
- Serotonin actions upon injection:
- 1) immediate chemoreceptor reflex: dec. HR/CO/BP
- 2) reciprocal inc. BP b/c of vasoconstriction (in all b.v. except skeletal muscles)
- 3) slow onset dec. in BP b/c of vasodilation in skeletal muscle b.v.
-
substance P
- non-chol. excitatory neurotransmitter for ENS
- - activates tachykinin NK-1 receptor (also by neurokinin A & B) in GI and CNS (central emetic pathways)
- - NK-1 is G-protein, so slow.
- - increased motility, perceived as discomfort (pain too, but not in humans)
- - in chemically-induced nausea/emesis, maybe IBD
- - * chemo-induced nausea: acute from 5-HT, delayed from substance P?
-
aprepitant
- NK-1 antagonist for chemo-induced emesis (esp cisplatin)
- - was initially made as analgesic, but didnt work on humans
- - poor solubility so cannot give IV/SC, must be PO. But when pt. nauseated, don't want PO...so not used often.
- - interacts with cyt P 450 --> DIs
- - very $$$$$$$$$$$
-
adenosine
- - inhibitory neurotrans of ENS
- - acts on A1, A2a, A2b, A3 receptors
- - modulates peristaltic activity and mucosal secretions
- - relaxation of intestines (slow down peristalsis) by A1 and A2b
- - antagonists at A1 receptors can enhance release of ACh or tachykinins from myenteric ganglia to speed up peristalsis (e.g. caffeine)
-
metoclopramide
- non-selective dopamine receptor antagonist
- - prokinetic drug
- - non-selective, but acts especially on D2 in gut
- - by enhancing ACh release, increase GI motility, esophageal peristaltic amplitude and sphincter pressure, gastrick emptying
- - no effect on small intestion or colonic motility
- - crosses BBB to CNS, so brain effects too: may block D2 receptors in chemoreceptor trigger zone (antinausea and antiemetic).
- - SE: CNS restlesness, drowsiness, agitation...
-
domperidone
- non-selective dopamine receptor antagonist
- - prokinetic drug
- - non-selective, but acts especially on D2 in gut
- - increases GI motility by enhancing ACh release
- - domperidone does NOT cross BBB.
- - SE: well tolerated, but elevate prolactin levels (breast enlargement, tenderness...)
-
B-endorphin, methionine-enkephalin
- endogenous pain suppressors, mu, delta, kappa receptor agonists; opioid peptide
- - primarily mu receptor agonist
- - decrease release of ACh to delay GI transit --> constipation
- - inhibit intestinal ion and fluid secretion, increase intestinal fluid, may block propulsive motility by evoking tonic spasms.
-
loperamide
- peripheral mu-opioid receptor agonist
- - does not penetrate CNS, so no effects on cognition or arousal
- - slows GI transit, inc. intestinal water absorption, increase resting sphincter tone...never lose effect.
- - used to treat diarrhea, IBS, pain(?...may have analgesic effects if work peripherally on mu-receptors in sensory fibres)
- - SE: constipation, cramping, dry mouth, nausea
-
entero-endocrine cells and hormones
- released when sense luminal contents, activate afferent nerve endings.
- D-cells: release somatostatin to inhibit afferent fibres
- Enterochromaffin cells: release serotonin to activate secretory, peristaltic, sensory reflexes
- G-cells: gastrin to increase acid
- Response to food -> G-cells in antrum release gastrin into blood -> gastrin activates CCK2 receptors on ECL-cells -> ECL release histamine -> histamine act on parietal cells to pump acid out at H+/K+ ATPase -> acid release suppresses gastrin release.
-
sumatriptan
- 5-HT1B/D agonist
- - causes vasoconstriction of cerebral arteries to terminate migraine
- - but not very selecive for cerebral arteries, so can cause coronary vasospasm --> worse for elderly males
- - used to treat acute migraine headache
- - SE: chest discomfort from coronary vasospasm
-
ketanserin
- 5-HT2 receptor antagonist
- - blocks vascular A1 adrenoreceptors, and has hypotensive action b/c of A1 blockade.
- - blocks 5-HT2A effects (platelet aggreg, vascular smooth muscle contraction), 5-HT2B effects (skeletal muscle/heart vasodilation)
- - originally marketed for antihypertensive, but withdrawn b/c of arrhythmic effects
- - SE: proarrhythmic
-
ondansetron
- prototypical 5-HT3 antagonist, non-competitive channel blocker (get stuck in channel)
- - can block nauseating effect of serotonin
- - used in prevention of N/V associated with surgery or chemo (when enterochromaffin cells damaged)
- - SE: constipation, diarrhea, headache
-
cisapride
- 5-HT4 agonist
- - was used to treat GERD/motility disorders b/c speed clearance of food from stomach to intestines.
- - but proarrhythmic (blocks K channels) so removed
- (small bowel: mediate relaxation of smooth muscle cells)
-
tegaserod
- 5-HT4 partial agonist
- - activate, but not as strong as serotonin; may also be a serotonin reuptake inhibitor? but not supported.
- - stimulates peristaltic reflex (release CGRP to stim. contraction of intestine)
- - claimed to dec. visceral afferent signaling (GI pain)
- - SE: diarrhea, heart attack, stroke, worsening heart pain
- - used to treat IBS w/ constipation, but withdrawn from market because of SE.
-
alosetron
- 5-HT3 receptor antagonist
- - reduce visceral sensitivity and colonic transit, ab pain, diarrhea
- - SE: severe constipation/ischemic colitis
- - used to treat IBS with diarrhea (but can make u become constipated!)
-
histamine
- injection (don't do it!)
- 1) dec. SBP and DBP b/c of direct vasodilation
- 2) tachy (histamine stim. heart and reflex tachy)
- 3) flushing, warmth, headache
- 4) edema (protein extravasation)
- 5) mild wheezing--> bronchoC
- ---------
- peripheral actions:
- - gastric acid release (found in ECL cells)
- - inflammation (injury-related release to cause VD, leakage of inflammatory mediators complement, CRP, antibody invasion)...
- - pain: stimulate sensory nerve endings mediating pain and itching
- -------------
- central roles of histamine:
- - histaminergic neurons in tuberomamillary body (hypothalamus) --> neuroendocrine control, CVD reg, thermal/body weight reg, arousal.
-
diphenhydramine, chlorpheniramine, dimenhydrinate
- H1 receptor antagonist (neg. effect on H2 and H3)
- - "first generation"
- - penetrate CNS, strong sedative effects, anticholinergic, alpha-adrenergic antagonist.
- - uses:
- - allergic rxns (prevent/treat symptoms, acute urticaria)
- - antinausea/antiemetic actions: prevent motion sickness, treat N/V, suppress effects on extrapyramidal symptoms associated with antipsychs
- (e.g. Diclectin: doxylamine + dimenhydrinate for pregs)
- - sedation: antimusc, effective for mild insomnia, temorary relief, cause daytime drowsiness, tolerance. (but kids may get excitation instead of sedation)
- - local anesthesia (topically): diphenhydramine blocks sodium channels like lidocaine, more potent than procaine. used when patient is allergic to conventional l.a. drugs
- - SE: unwanted sedation (50%), dry mouth, urinary retention, blurred vision (anticholinergic), orthostatic hypotension (alpha-adrenergic receptor antagonist effect)
-
loratadine, cetirizine
- second-generation H1 receptor antagonist
- - poor CNS pen, so little/no sedation
- - used in allergic conditions (hay fever, rhinitis, chronic urticaria)
- - SE: unwanted sedation (7%), tolerance.
-
ranitidine
- H2 Receptor Antagonist (highly selective)
- - competitive inhibition at parietal cell H2 receptors, so reduces histamine release from ECL cells and blocks direct stimulation of parietal cell by histamine.
- - suppresses basal and meal-stim'd acid secretion, each dose 50% reduction for 10 hours
- - 2nd line for ulcers
- - GERD, dyspepsia, stress-related ulcers (dec. incidence of bleeding)
- - SE: diarrhea, headache, fatigue, myalgias, constip...confusion, hallucinations, agitation in ICU/elderly.
- - may cause brady b/c of blocking H2, but rare.
- - crosses placenta, breast-milk.
-
famotidine
- H2 Receptor Antagonist (highly selective)
- - competitive inhibition at parietal cell H2 receptors, so reduces
- histamine release from ECL cells and blocks direct stimulation of
- parietal cell by histamine.
- - suppresses basal and meal-stim'd acid secretion, each dose 50% reduction for 10 hours
- - 2nd line for ulcers
- - GERD, dyspepsia, stress-related ulcers (dec. incidence of bleeding)
- - SE: diarrhea, headache, fatigue, myalgias, constip...confusion, hallucinations, agitation in ICU/elderly.
- - may cause brady b/c of blocking H2, but rare.
- - crosses placenta, breast-milk.
-
omeprazole
- proton pump inhibitor
- - inactive, acid-labile pro-drug, lipophilic weak base, enteric coated for delayed release in duodenum
- - upon absorption, diffuses accross lipid membranes into acidified compartments
- - become protonated, concentrated, converted to reactive thiophilic sulfonamide cation --> non-competitive, suicide inhibitor
- - sulfonamide forms covalent disulfide linkage with H+/K+ ATP-ase, only on active PPs.
- - max activity of PP during meals, so give 1 hour before a meal.
- - SE: diarrhea, headache, abdominal pain...increase risk of infection?
-
soraprazan, revaprazan
- potassium-competitive acid blockers (P-CABs)
- - compete with K+ for binding site on proton pump (prevent acid from getting pumped out)
- - fast onset, full effect with 1st dose, greater acid suppression than PPI, but still in development.
- - for PUD
-
sucralfate
- mucosal protective agent
- - sucrose X sulfated aluminum hydroxide
- - breaks down into sucrose sulfate (-), binds to (+) proteins in base of ulcers to form physical barrier
- - admin as slurry thru nasogastric tube to reduce stress ulcers in pts at risk from infection (spare antacids, H2As, PPIs)
- - no systemic absorption. rare constipation
-
erythromycin
- macrolide antibiotic, prokinetic
- - directly stimulates motilin receptors on GI smooth muscle, accelerates gastric emptying
- - used for gastroparesis (slowed stomach emptying), but tolerance develops rapidly.
-
sulfasalazine
- azo compound, progenitor compound, for IBD
- - 5-ASA bound to sulfapyridine, not absorbed in stomach or intestines
- - azoreductase (bacterial enzyme) in colon converts to 5-ASA and sulfapyridine
- - SE (caused by sulfapyridine): nausea, GI upset, headache, arthralgias, myalgias, bone marrow suppression, malaise, oligospermia
- - slow acetylators of sulfapyridine at greater risks of ADR
- - allergic reaction to sulfa.
-
5-aminosalicylic acid (5-ASA)
- aka mesalamine, azo compound, for IBD
- - absorbed from small intestine, but low absorption from colon.
- - topical antiinflam. MOA not identified, but NOT blockade of COX (NSAIDs may exacerbate.)
- - use: 1st line to treat mild-mod UC, 1st line to treat mild-mod CD in higher doses but less effective.
- - SE: well tolerated, less side effects than sulfasalazine; high serum 5-ASA --> interstitial nephritis
- - different formulations cause different release:
- --mesalamine DR: release sooner, all GI tract
- --mesalamine pH sensitive: ileum and colon
- --Olsalazine (two 5-ASA linked by azo bond, converted into single molecules by azoreductase): colon
- --sulfasalazine: colon
-
glucocorticoids (prednisone, prednisoline, hydrocortisone, budesonide)
- - used to treat IBD
- - MOA: activate GC receptors to act on promoters of target genes and regulate their transcription
- - antiinflammatory and immunosuppressive
- - used for attacks of mod-severe IBD or non-responders to 5-ASA.
- - rectal administration is prefered if disease in rectum/colon b/c of lower systemic absorption
- - not useful to maintain remission, most patients lose response over time.
-
infliximab
- biological response modifier, anti-TNF-alpha therapy
- - chimeric mouse-human monoclonal Ab to TNFa (increased levels of TNFa are associated with CD)
- - bind to TNFa to make it impossible for binding to receptor
- - IV infusion stays in plasma 8-12 weeks
- -***etanercept is not effective in CD, but ok in rheumatoid arthritis
- - used in mod-sev CD and UC, 2/3 respond, 1/3 remiss. response takes 2 weeks. 1/3 of responders lose response (ab to infliximab?) responders can be treated with repeat IV infusions q8weeks
- - SE: infection (TB b/c supressed TH1 inflammatory response), ab against mouse portion, fever, headache, dizziness, urticaria, cardiopulmonary (chest pain, dyspnea), hypotension, SOB, muscle spasms, chest discomfort, serum sickness-like infusion rxn, mylagia, arthralgia, jaw tightness, rash, edema...
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