Term
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Definition
Muscarinic receptor antagonist- competitive antagonist
MOA: reversible blockade of Ach receptors; inverse agonist
Effects: eye dilation (mydriasis); cycloplegia (loss of accommodation); tachydcardia; bronchodilation; dry mouth; reduced GI motility; reduced urination; reduced sweating
Use: cholinergic poisoning; eye examination
Given IV, topically (drops)-> well absorbed from conjunctival and gut membranes
Toxicity: increased intraocular pressure in closed angle glaucoma; dry mouth, flushed skin; agitation; delirium; hyperthermia-> dry as a bone, blind as a bat, red as a beet, mad as a hatter |
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Term
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Definition
Muscarinic receptor antagonist
Effects: eye dilation (mydriasis); tachydcardia; bronchodilation; dry mouth; reduced GI motility
Use: vertigo; nausea
Given IM or transdermal
Faster onset of action than Atropine but shorter duration of effect and crosses CNS more readily -> well absorbed from gut and conjunctival membranes; can also cross skin
Toxicity: tachycardia, blurred vision, delirium, xerostomia (dry mouth), drowsiness, amnesia, hallucinations, coma |
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Term
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Definition
Only NT in parasympathetic, first NT in sympathetic
Muscarninc and nictonic receptors
acetyl CoA + choline via choline acetyltransferase -> acetylcholine
Hydrophilic-> poorly absorbed, poorly distributed to CNS; rapidly hydrolyzed
Effects: DUMBELSS |
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Term
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Definition
Muscarinic cholinergic receptor agonist
Effects: miosis; vasodialation, slowing of HR (at higher levels of receptor activation); bronchial constriction, increased respiratory secretion; increased GI motility and secretion, sphincter relaxation=> DUMBELSS
High resistance to hydrolysis
Use: post-op urinary retention or paralytic ileus
Oral or parenteral; does not enter CNS
Toxicity: parasympathomimetic effects, bronchospasm in asthmatics |
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Term
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Definition
Muscarinic cholinergic receptor agonist
More resistant to hydrolysis than acetylcholine
Use: glaucoma |
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Term
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Definition
Nonselective muscarinic and nicotinic agonist
High resistance to hydrolysis
Use: topically for glaucoma |
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Term
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Definition
Muscarinic cholinergic receptor agonist
Metabotropic receptor
Effects: miosis; vasodilation, slowing of HR (at higher levels of receptor activation); bronchial constriction, increased respiratory secretion; increased GI motility and secretion, sphincter relaxation=> DUMBELSS
Occurs through actions on effector cells |
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Term
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Definition
Nicotinic cholinergic receptor agonist
Ionotropic receptor- increased Na+ influx and depolarization
Nn receptor: PNS, SNS, ganglion cells
Nm receptor: neuromuscular junction
Activate both the sympathetic and parasympathetic nervous systems, but the net effect depends on
the organ and the predominant tone
Highly lipophilic-> penetrates BBB, well absorbed across skin
Toxicity: increased GI activity; increased BP; continued agonist occupancy is associated w/ desensitization (depolarization blockade)-> flaccid paralysis/respiratory arrest
Can also be used as a pesticide |
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Term
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Definition
Muscarinic cholinergic receptor agonist (partial agonist)
Effects: miosis; vasodialation, slowing of HR (at higher levels of receptor activation); bronchial constriction, increased respiratory secretion; increased GI motility and secretion, sphincter relaxation=> DUMBELSS
Use: glaucoma, Sjogren Syndrome (impaired saliva/tear production)
Oral or topical |
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Term
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Definition
Present in high concentrations in cholinergic synapses; also in RBC
acetylcholine via acetylcholinesterase -> acetic acid + choline |
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Term
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Definition
Aka pseudocholinesterase; synthesized in the liver and circulating in the plasma
Also inhibited by AchE inhibitors, but its inhibition plays little role in the action of indirect-acting cholinomimetic drugs |
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Term
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Definition
AchE inhibitor; Organophosphate
MOA: Prevents breakdown of acetylcholine; phosphorylates the active site of AchE and forms a bond that is extremely stable; excess activation of muscarinic and nicotinic Ach receptors by excess Ach in synapse-> parasympathetic effects predominate=> DUMBELSS
Hydrolyzes at an extremely slow rate (100s of hours)
Can undergo aging where there is strengthening of the AchE-phosphorus bond
Poorly absorbed
Uses: glaucoma
Toxicity: brow ache, uveitis, blurred vision |
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Term
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Definition
AchE inhibitor; Organophosphate insecticide
MOA: Prevents breakdown of acetylcholine; phosphorylates the active site of AchE and forms a bond that is extremely stable; excess activation of muscarinic and nicotinic Ach receptors by excess Ach in synapse-> parasympathetic effects predominate=> DUMBELSS
Hydrolyzes at an extremely slow rate (100s of hours)
Can undergo aging where there is strengthening of the AchE-phosphorus bond
Very well absorbed
Prodrug that is activated in animals and plants; not detoxified in vertebrates |
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Term
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Definition
AchE inhibitor; Organophosphate insecticide
MOA: Prevents breakdown of acetylcholine; phosphorylates the active site of AchE and forms a bond that is extremely stable; excess activation of muscarinic and nicotinic Ach receptors by excess Ach in synapse-> parasympathetic effects predominate=> DUMBELSS
Hydrolyzes at an extremely slow rate (100s of hours)
Can undergo aging where there is strengthening of the AchE-phosphorus bond
Relatively safe for humans because it is metabolized into an inactive product
Very well absorbed
Prodrug that is activated in animals and plants |
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Term
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Definition
AchE inhibitor; Organophosphate nerve gas
MOA: Prevents breakdown of acetylcholine; phosphorylates the active site of AchE and forms a bond that is extremely stable; excess activation of muscarinic and nicotinic Ach receptors by excess Ach in synapse-> parasympathetic effects predominate=> DUMBELSS
Hydrolyzes at an extremely slow rate (100s of hours)
Can undergo aging where there is strengthening of the AchE-phosphorus bond
Very well absorbed across skin and respiratory and GI tracts
Used in warfare and bioterrorism
Treatment: atropine, decontamination, maintenance of vital signs |
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Term
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Definition
AchE inhibitor; carbamate ester
MOA: forms covalent bond w/ AchE that is resistant to hydrolysis; excess activation of muscarinic and nicotinic Ach receptors by excess Ach in synapse-> parasympathetic affects predominate=> DUMBELSS
Hydrolysis can occur but at a slow rate (30min-6hr)
Well absorbed but in general carbamates are not
Use: glaucoma; antimuscarinic drug intoxication |
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Term
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Definition
AchE inhibitor; carbamate ester
MOA: forms covalent bond w/ AchE that is resistant to hydrolysis; excess activation of muscarinic and nicotinic Ach receptors by excess Ach in synapse-> parasympathetic affects predominate=> DUMBELSS
Hydrolysis can occur but at a slow rate (30min-6hr)
Does not enter CNS; poorly soluble
Use: long term treatment of myasthenia gravis, postop paralytic ileus and urinary retention
Short acting requiring frequent dosing; oral or parenteral every 4 hours |
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Term
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Definition
AchE inhibitor; carbamate ester
MOA: forms covalent bond w/ AchE that is resistant to hydrolysis; excess activation of muscarinic and nicotinic Ach receptors by excess Ach in synapse-> parasympathetic affects predominate=> DUMBELSS
Hydrolysis can occur but at a slow rate (30min-6hr); longer acting than Neostigmine
Does not enter CNS; poorly soluble
Use: long term treatment of myastenia gravis; preventive therapy for cholinesterase inhibitors by impeding binding of the organophosphates (protection limited to PNS)
Short acting requiring frequent dosing; oral or parenteral every 6 hours |
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Term
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Definition
AchE inhibitor; 4° alcohol
MOA: Forms an electrostatic/H-bond with AchE that is reversible; excess activation of muscarinic and nicotinic Ach receptors by excess Ach in synapse-> parasympathetic affects predominate=> DUMBELSS
Short-lived inhibition (~2-10 min)
Poorly absorbed in brain due to its permanent charge
Use: diagnosis and treatment of myasthenia gravis; paralytic ileus; arrhythmias
Given parenterally |
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Term
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Definition
AchE inhibitor
MOA: excess activation of muscarinic and nicotinic Ach receptors by excess Ach in synapse-> parasympathetic affects predominate=> DUMBELSS
Use: long term treatment of myasthenia gravis
Short acting requiring frequent dosing; oral every 6 hours |
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Term
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Definition
Acetylcholinesterase regenerator
Used for organophosphate intoxication
MOA: strong nucleophile-> breaks AchE phosphorous bond
Only works before aging occurs-> aging rate depends on the agent; cannot enter CNS
Given IV; regenerates AchE within 48 hours; not recommended for use against carbamate AchE inhibitor poisoning
Toxicity: muscle weakness in overdose |
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Term
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Definition
Contains muscarine
Treatment w/ atropine if ingested
Causes nausea, vomiting, diarrhea, urinary urgency, vasodilation, reflex tachycardia, sweating, salivation, bronchonsonstriction |
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Term
| Triorthocresyl phosphate (TOCP) |
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Definition
Neuropathy target esterase inhibitor; organophosphate in lubricating oils
Toxicity: delayed neuropathy associated w/ demyelination-> weakness of extremities, unsteady gait 1-2 wks after exposure |
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Term
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Definition
Carbamate pesticide
MOA: inhibit AchE by carbamoylation
Clinical effects are shorter duration than those of organophosphates
DO NOT treat w/ pralidoxime |
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Term
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Definition
Botanical pesticide- insecticidal ester
Absorbed after inhalation or ingestion, though not highly toxic to mammals
MOA: effects voltage gated Na, Ca, and Cl channels
Treatment is symptomatic
Toxicity: excitation, convulsions, tetanic paralysis, irritation of eye, skin and respiratory tree |
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Term
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Definition
Botanical pesticide
Toxicity: GI irritation; conjunctivits; dermatitis; pharyngitis; rhinitis
Treatment is symptomatic |
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Term
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Definition
Depolarizing neuromuscular blocking agent
Structure is of 2 Ach molecules linked end-to-end
MOA: nicotinic Ach receptor agonist, esp Nm; longer acting effects than Ach; poor synapse metabolism = prolonged depolarization and desensitization
Initial depolarization causes contractions, followed by flaccid paralysis
Rapid metabolism by plasma butyrylcholinesterase-> only a small % ever reaches the NM junction
Rapid onset (<90seconds) w/ very short duration of action (~5min)
Highly polar and inactive orally-> given parenterally
Use: intubation, control of muscle contractions
Toxicity: hyperkalemia, increased intraabdominal/intraocular pressure, post-op muscle pain; can cause slight histamine release-> hypotension; tachycardia; malignant hyperthermia |
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Term
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Definition
Nondepolarizing neuromuscular blocking agent- isoquinoline
MOA: competitive antagonist of nicotinic Ach receptors, esp Nm; also blocks presynaptic Na+ channels; prevents depolarization-> flaccid paralysis
Renal excretion (~40-60min)
Highly polar and inactive orally-> given parenterally
Use: surgery (rarely in use now)
Toxicity: can cause histamine release-> hypotension; weak block of cardiac muscarinic Ach receptors, apnea
Drug Interactions: inhaled anesthetics may increase effects |
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Term
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Definition
Nondepolarizing neuromuscular blocking agent- isoquinoline
MOA: antagonist of nicotinic Ach receptors, esp Nm; also blocks presynaptic Na channels; prevents depolarization-> flaccid paralysis
Hepatic and spontaneous elimination via enzymatic and nonenzymatic hydrolysis-> Hofmann elimination; intermediate acting duration (20-35min)
Highly polar and inactive orally-> given parenterally
Toxicity: breakdown product Laudanosine readily crosses BBB-> seizures, increased anesthetic requirement; can cause slight histamine release-> hypotension
Cis-isomer (cisatracurium) has less byproduct and less hepatic dependence
Drug Interactions: inhaled anesthetics may increase effects |
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Term
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Definition
Nondepolarizing neuromuscular blocking agent- isoquinoline
MOA: antagonist of nicotinic Ach receptors, esp Nm; also blocks presynaptic Na channels; prevents depolarization-> flaccid paralysis
Metabolized by plasma butyrylcholinesterase; rapid onset w/ short duration (10-20min)
Use: surgery (rarely in use now)
Highly polar and inactive orally-> given parenterally
Toxicity: can cause histamine release-> hypotension; flushing, bronchospasm
Drug Interactions: inhaled anesthetics may increase effects |
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Term
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Definition
Nondepolarizing neuromuscular blocking agent- steroid
MOA: antagonist of nicotinic Ach receptors, esp Nm; also blocks presynaptic Na channels; metabolized to more potent 3 or 17 or 3,17-hydroxy metabolite; prevents depolarization-> flaccid paralysis
Metabolized by kidney, w/ long acting duration (>35min)
Highly polar and inactive orally-> given parenterally
Toxicity: 3-hydroxy metabolite can accumulate-> prolonged paralysis; moderate block of cardiac muscarinic receptors-> increased heart rate and cardiac output
Drug Interactions: inhaled anesthetics may increase effects |
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Term
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Definition
Nondepolarizing neuromuscular blocking agent- steroid
MOA: antagonist of nicotinic Ach receptors, esp Nm; also blocks presynaptic Na channels; metabolized to more potent 3 or 17 or 3,17-hydroxy metabolite; prevents depolarization-> flaccid paralysis
Metabolized mainly by liver and some in the kidney, w/ intermediate duration (20-35min)
Highly polar and inactive orally-> given parenterally
Toxicity: 3-hydroxy metabolite can accumulate-> prolonged paralysis
Drug Interactions: inhaled anesthetics may increase effects |
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Term
| Diazepam (Benzodiazepines) |
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Definition
Spasmolytic
MOA: inhibition by binding GABA-A receptors and increasing Cl- permeability, leading to hyperpolarization of alpha motor neurons; only works in the presence of GABA
Metabolized by liver (12-24hrs)
Short term use for patients w/ muscle spasm of almost any origin, including trauma
Also used for IV anesthesia; anticonvulsant
SIde effects: sedation; dizziness; blurred vision; muscle weakness; ataxia |
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Term
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Definition
Spasmolytic
MOA: GABA-B receptor agonist which inhibits presynaptic release of excitatory NTs (glutamate) by lower motor neurons and also directly inhibits alpha motor neurons; inhibition is a result of increasing K+ channel conductance which causes hyperpolarization and reduces Ca2+ influx-> no vesicle exocytosis
Preferred for long term spasticity use-> ALS, spinal cord trauma, MS, cerebral palsy; also used for muscle pain
Oral or intrathecal; rapid and complete oral absorption
Side effects: increased seizure activity; sedation and dizziness; blurred vision; muscle weakness; ataxia-> effects are less severe compared to Diazepam |
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Term
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Definition
Direct acting muscle relaxant
MOA: blocks RyR1 Ca2+ release channels on SR of skeletal muscle, thereby reducing actin-myosin interactions
Use: control of spasms due to cerebral palsy, trauma, MS (oral); treatment of malignant hyperthermia (IV)
Duration 4-6hr
Toxicity: muscle weakness-> reserved use for nonambulatory patients; hepatotoxicity |
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Term
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Definition
Relief of acute muscle spasm caused by local trauma/strains
Acts at the level of the brainstem; given orally
Hepatic metabolism; 4-6hr duration
Toxicity: antimuscarinic side effects, sedation, hallucinations |
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Term
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Definition
Botulinum toxin A
MOA: blocks Ach release by cleaving SNAP25 or synaptobrevin, produces flaccid paralysis of skeletal muscle-> last weeks to months and restoration requires nerve sprouting
Use: treatment of strabismus/blepharospasm, hemifacial spasms, spasms and dystonias, hyperhidrosis of palms and axillae, removal of facial wrinkles
Toxicity: immunoresistance may develop |
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Term
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Definition
Eicosanoid made by COX-I and II from arachidonic acid
Act locally and induce local pain (i.e. sprained ankle); vasodilation; increased capillary permeability; increased local blood flow; edema; increased bone resorption, activation of osteoclasts,
allows penetration of synovium into bone; increased leukocyte and T-cell activation |
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Term
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Definition
| Eicosanoid made by lipoxygenases 15, 12, and 5 from arachidonic acid |
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Term
| Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) |
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Definition
Primarily cyclooxygenase (COX-1 and –2) inhibitors
General use: anti-inflammatory; musculoskeletal disease; analgesia; anti-pyretic
Most common side effects: GI discomfort; GI ulceration; decreased renal function in patients with compromised renal function
Less common side effects: dizziness, anxiety, drowsiness; skin rash |
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Term
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Definition
NSAID- salicylic acid derivative
MOA: irreversibly acetylates and inactives COX-1 and COX-2 (creating inactivated COX and salicylic acid), reducing TXA2 synthesis-> prevent clotting b/c platelets cannot make new COX
Use: anti-inflammatory, anti-pyretic, analgesic; prevention of cardiovascular disease; benefit in colon cancer
Toxicity: tinnitus; uncouples oxidative phosphorylation (overdose); low dose blocks actions of probenecid, high dose uricosuric-> exacerbates gout |
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Term
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Definition
| NSAID- salicylic acid derivative |
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Term
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Definition
NSAID- salicylic acid derivative
Azo link of mesalamine with sulfapyridine-> allows it to not be broken down until it reaches intestinal flora, and can exert effects in large intestine
MOA: COX inhibitor; DHFR inhibitor; scavenging free radicals
Use: IBS; mainly rheumatoid arthritis |
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Term
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Definition
NSAID- salicylic acid derivative
No oral bioavailability; given as suppository
Use: IBS; rheumatoid arthritis |
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Term
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Definition
NSAID- salicylic acid derivative
Azo link of two mesalamine molecules-> allows it to not be broken down until it reaches intestinal flora, and can exert effects in large intestine
Use: IBS; rheumatoid arthritis |
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Term
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Definition
NSAID- salicylic acid derivative
Potent anti-inflammatory
Poor CNS penetration so poor anti-pyretic |
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Term
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Definition
NSAID- salicylic acid derivative
aka salicylsalicylic acid
MOA: hydrolyzed to salicylic acid during and after absorption |
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Term
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Definition
NSAID- aka Tylenol
Poor inhibitor of COX outside of CNS and in presence of radical oxygen species (inflammation)
Use: analgesic, anti-pyretic, but NOT anti-inflammatory
Conjugated for excretion; unconjugated drug is deactivated by GSH in liver, but children lack GSH-> reacts w/ protein sulfhydryl groups in liver = toxicity
Toxicity: therapeutic index = 4 (i.e. 4X the normal limit induces toxicity); hepatic toxicity (fatal if untreated)
Treat toxicity w/ N-acetylcysteine |
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Term
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Definition
NSAID- indole and indene acetic acid
Very potent COX inhibitor
Use: acute treatment of gout; suppress uterine contractions; induce closure of ductus arteriosus
High degree of side effects w/ chronic use |
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Term
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Definition
NSAID- indole and indene acetic acid
Pro-drug that is activated in the liver
Fewer GI side effects
Also used to treat acute gout |
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Term
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Definition
NSAID- indole and indene acetic acid
Fewer GI side effects b/c large difference b/w dosing amount that is anti-inflammatory and that causes decreased GI PG synthesis |
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Term
| Mefenamic Acid; Meclofenamate |
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Definition
NSAID- fenemate
Use: analgesic; treatment of arthritis (but not initial treatment)
May decrease PG effects |
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Term
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Definition
NSAID- heteroaryl acetic acid
Well tolerated; often used for children |
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Term
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Definition
NSAID- heteroaryl acetic acid
Potent analgesic but poor anti-inflammatory
Use: post-op pain
Can be given IM |
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Term
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Definition
NSAID- heteroaryl acetic acid
Very potent COX inhibitor
May interfere w/ arachidonic acid
GI toxicity caused by PGE2 release, but lessened when given w/ misoprostol |
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Term
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Definition
NSAID- arylpropionic acid
Low incidence of GI side effects
Also used to treat acute gout |
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Term
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Definition
NSAID- arylpropionic acid
20X more potent than Aspirin but w/out an increase in GI side effects
Also used to treat acute gout |
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Term
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Definition
NSAID- arylpropionic acid
MOA: COX inhibition and also stabilizes lysosome membranes, thereby antagonizing bradykinin actions (i.e. decreased BP) |
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Term
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Definition
NSAID- arylpropionic acid
Long half-life: 40-60 hrs
Uricosuric- increases secretion of uric acid in the urine-> treatment of gout |
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Term
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Definition
NSAID- arylpropionic acid
Similar to ibuprofen-> low incidence of GI side effects |
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Term
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Definition
NSAID- enolic acid
MOA: COX inhibition and also inhibits neutrophil activation in the presences of PGs; may also inhibit collagenase and proteoglycanase
Long half-life: 50hrs |
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Term
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Definition
NSAID- enolic acid
Somewhat selective for COX-2 |
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Term
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Definition
NSAID- alkanone
Somewhat selective for COX-2
Prodrug |
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Term
| Celecoxib; Valdecoxib; Rofecoxib |
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Definition
Selective COX-2 Inhibitor-> high anti-inflammatory w/ low GI side effects
Problems: very expensive; constitutive expression of COX-2 in kidneys-> decreased synthesis of renal PGs (toxicity); increased risk/worsening HTN; lack of anti-platelet effects-> inhibition of COX-2 in vascular endothelial cells results in unfavorable TxA2 (pro-clot) vs. PGI2 (cardio protective) ratio-> increased risk of atherosclerotic/cardiovascular disease
Only used in patients w/o CV disease, renal disease, and atherosclerosis who are experiencing high GI symptoms w/ other drugs
Rofecoxib and valdecoxib have been pulled |
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Term
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Definition
Adrenocorticosteroid
Anti-inflammatory and immunosuppressive
MOA: ↓ arachidonic acid metabolism (both PGs and LTs)-> ↓ COX-2 mRNA and protein and ↓ PLA2 activity; ↓ cytokine expression (esp ILs); ↓ cell-adhesion molecule expression (traps neutrophils in vascular compartment); ↓ fibroblast DNA synthesis/proliferation
Adverse effects: adrenal suppression, fluid and electrolyte abnormalities, metabolic changes, edema, hypertension, osteoporosis, growth suppression in children, cataracts, behavioral changes
Always try NSAIDs/others before steroids
Must taper off; do not abruptly stop-> adrenal glands begin to shut down so you have to allow them to start back up |
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Term
| Hydrocortisone (cortisol) |
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Definition
Glucocorticoid
Produced in the adrenal glands
MOA: anti-inflammatory by binding to GR and causes Na+ retention in the kidneys by binding MR
Short duration of action; deactivated in the kidney to cortisone |
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Term
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Definition
Glucocorticoid
Inactivated version of cortisol; ketone on C 11 instead of hydroxyl group-> unable to bind to MR or GR
Must be activated in the liver |
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Term
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Definition
Glucocorticoid
Prodrug that must be activated in the liver to prednisolone
4X stronger anti-inflammatory than cortisol and causes less Na+ retention in the kidneys
Intermediate duration of action
SE: glucose intolerance, immunosuppresion, osteoporosis, psychosis |
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Term
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Definition
Glucocorticoid
Activated version of prednisone
4X stronger anti-inflammatory than cortisol and causes less Na+ retention in the kidneys
Intermediate duration of action |
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Term
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Definition
Glucocorticoid
Treatment of acute attacks of MS to improve function and quality of life
Given IV in pulsatile fashion
Targets inflammation without targeting autoimmunity |
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Term
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Definition
Glucocorticoid
5X stronger anti-inflammatory than cortisol w/o causing Na+ retention in the kidneys
Intermediate duration of action |
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Term
| Betamethasone; Dexamethasone |
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Definition
Glucocorticoid
25X stronger anti-inflammatory than cortisol w/o causing Na+ retention in the kidneys
Long duration of action |
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Term
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Definition
Glucocorticoid
10X stronger anti-inflammatory than cortisol but causes 125X more Na+ retention in the kidneys
Short duration of action
Used in patients who are unable to produce aldosterone |
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Term
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Definition
Treatment of acute gout
MOA: binds tubulin and prevents polymerization of microtubules-> interferes with mitotic spindle function, inhibits migration and phagocytic actions of granulocytes, inhibits neutrophil secretion of chemotactic factors
Side effects: nausea, vomiting, diarrhea, abdominal pain-> affects rapidly proliferating epithelial cells in GI tract |
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Term
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Definition
Treatment of chronic gout
MOA: allopurinol and its metabolite allxanthine inhibit xanthine oxidase-> decreased uric acid production
Can be used in patients w/ renal disease
Drug interactions: inhibits metabolism of azathioprine and 6-mercaptupurine |
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Term
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Definition
Treatment of chronic gout
MOA: nonpurine xanthine oxidase inhibitor
Side effects: diarrhea, nausea, liver function abnormalities |
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Term
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Definition
Treatment of chronic gout
MOA: uricosuric agent-> inhibits uric acid renal tubular reabsorption
Drug interactions: prevents renal secretion of penicillin and other drugs |
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Term
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Definition
Treatment of chronic gout
MOA: uricosuric
Lacks both anti-inflammatory and analgesic effects |
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Term
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Definition
Most commonly used treatment of rheumatoid arthritis
MOA: inhibition of aminoimidazolecarboxamide ribonucleotide transformylase and thymidylate synthase; decreases leukocyte adhesion to endothelial cells and alters neutrophil and lymphocyte function by inhibiting transmethylation reactions-> anti-inflammatory
Also inhibits DHFR
Side effects: nausea, mucosal ulcers; hepatotoxicity, cirrhosis (must biopsy liver after 5 yrs of use)
Reduced toxicity w/ leucovorin resuce |
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Term
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Definition
Treatment of rheumatoid arthritis
MOA: alkylating agent-> inhibits B/Tcell proliferation
SE: acrolein made as a breakdown product, toxic to bladder-> neutralize w/ MESNA; immunosuppression; infertility; increased risk of infection and neoplasia |
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Term
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Definition
Treatment of rheumatoid arthritis
MOA: converted to 6-mercaptopurine-> inhibits purine synthesis, esp in B/T cells
Toxicity: inhibits proliferation of any rapidly dividing cell populations (i.e. epithelial) |
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Term
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Definition
Treatment of rheumatoid arthritis
MOA: inhibition of inosine monophosphate dehydrogenase-> decreased purine synthesis , esp in B/T cells (lack salvage pathway); anti-inflammatory via decrease leukocyte adhesion to endothelial cells by decreased E and P selectin synthesis |
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Term
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Definition
Treatment of rheumatoid arthritis
MOA: pro-drug, when activated, inhibits ribonucleotide synthesis and triggers p53 translocation to nucleus-> cell cycle arrest
Side effects: diarrhea; liver toxicity |
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Term
|
Definition
Treatment of rheumatoid arthritis
MOA: inhibits calcineurin phosphatase, which is needed to dephosphorylate and activate transcription factors; decreases cytokine transcription-> somewhat selective for T cells
Toxicity: renal |
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Term
| Chloroquine; Hydroxychloroquine |
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Definition
Treatment of rheumatoid arthritis, SLE, and antimalarial
Very long 1/2 life
MOA: unclear; may decrease T-cell response to mitogens, decrease leukocyte chemotaxis, stabilize lysosomal membranes, trap free radicals, general decrease in DNA and RNA synthesis
Well tolerated
Toxicity: drug induced myopathy |
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Term
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Definition
Treatment of rheumatoid arthritis
MOA: anti-TNF alpha
Recombinant fusion protein consisting of two soluble TNF receptor regions linked to Fc portion of human IgG
Must given by injection; antibodies develop against this drug but don’t appear to alter efficacy
Side effects: increased risk of macrophage dependent infections-> screen for latent or active tuberculosis |
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Term
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Definition
Treatment of rheumatoid arthritis
MOA: anti-TNF alpha
Chimeric monoclonal antibody with a variable murine region linked to constant human region
Must given by injection; antibodies develop against this drug but don’t appear to alter efficacy
Side effects: increased risk of macrophage dependent infections-> screen for latent or active tuberculosis |
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Term
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Definition
Treatment of rheumatoid arthritis
MOA: anti-TNF alpha
Recombinant human anti-TNF alpha monoclonal antibody
Must given by injection; antibodies develop against this drug but don’t appear to alter efficacy
Side effects: increased risk of macrophage dependent infections-> screen for latent or active tuberculosis |
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Term
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Definition
Treatment of rheumatoid arthritis
MOA: inhibits T cell activation by binding to CD80 and 86 on APCs and preventing interaction with CD28 on T cells
Given IV
Side effects: increased risk of infection especially in combination with anti-TNF agents |
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Term
|
Definition
Treatment of rheumatoid arthritis
MOA: naked monoclonal chimeric Ab against CD20 (B cells)-> decreases antigen presentation and therefore activation of T cells
Given IV, often combined w/ methotrexate
Used for rheumatoid arthritis that is refractory to anti-TNF alpha drugs
SE: infusion reaction-> rash |
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Term
|
Definition
Gold compound
Second line defense-> rarely used anymore but can be beneficial in juvenile arthritis
MOA: unclear; inhibit macrophage and T cell function and may inhibit release of histamine, PGs, and LTs
Given orally-> lipid soluble
Toxicity: skin/mucus membrane lesions, GI, renal toxicity, hematologic abnormalities |
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Term
| Aurothiomalate; Aurothioglucose |
|
Definition
Gold compound
Second line defense-> rarely used anymore but can be beneficial in juvenile arthritis
MOA: unclear; inhibit macrophage and T cell function and may inhibit release of histamine, PGs, and LTs
Given IM-> water soluble
Toxicity: skin/mucus membrane lesions, GI, renal toxicity, hematologic abnormalities |
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Definition
| Treatment of hypercalcemia |
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Definition
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Definition
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Definition
Vitamin D analog of 25-hydroxycholecalciferol
Treatment of osteoporosis, hypocalcemia, hypoparathyroidism, nutritional deficiency
Used in patients w/ hepatic disease |
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Definition
Vitamin D analog of 1,25-dihydroxycholecalciferol
Treatment of osteoporosis, hypocalcemia, hypoparathyroidism, nutritional deficiency
Used in patients w/ renal disease |
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Definition
Vitamin D analog
Treatment of osteoporosis, hypocalcemia, hypoparathyroidism, nutritional deficiency
Does not require 1-OH for activation but does require 25-OH in liver
Able to use in patients w/ renal disease |
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Term
| 1-alpha-hydroxycholecalciferol |
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Definition
Vitamin D analog
Treatment of osteoporosis, hypocalcemia, hypoparathyroidism, nutritional deficiency
Already contains the 1-OH but requires 25-OH in liver
Able to use in patients w/ renal disease |
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Term
| Doxercalciferol (1-hydroxyvitamin D2) |
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Definition
Vitamin D analog
Treatment of osteoporosis, hypocalcemia, hypoparathyroidism, nutritional deficiency
Already contains the 1-OH but requires 25-OH in liver
Able to use in patients w/ renal disease |
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Definition
Calcitriol analog
MOA: suppressor of PTH gene expression
Limited action on intestine and bone; used in chronic renal failure w/secondary hyperparathyroidism or in primary hyperparathyroidism
Low affinity for serum binding protein leads to longer half-life than calcitriol |
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Definition
Treatment of osteoporosis, Paget's disease (in combo w/ a bisphosphonate), hypercalcemia
MOA: prevents Ca2+ absorption in the intestines and reabsorption in bone
Given parenterally |
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Term
| Synthetic human calcitonin |
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Definition
| MOA: direct effect on osteoclast to decrease bone resorption and works to decrease calcium and phosphate reabsorption in kidney |
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Definition
Salmon form is more potent
MOA: direct effect on osteoclast to decrease bone resorption and works to decrease calcium and phosphate reabsorption in kidney |
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Definition
Treatment of osteoporosis
MOA: acts on osteoblasts to decrease osteoclast recruitment and activation-> decreases IL-6, IL-1, and TNF-alpha (decreases RANKL expression) and increases IGF-1, BMP-6, TGF-beta (increases osteoprotegrin expression)
Toxicity: may cause cancer-> breast, endometriosis |
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Definition
Selective estrogen receptor modulators
Goal of these drugs is to produce beneficial estrogenic actions in certain tissues (e.g., bone, brain, and liver) during postmenopausal hormone therapy, but antagonist activity in tissues such as breast and endometrium
Use: treatment and prevention of osteoporosis
MOA: partial estrogen agonist that has antiresporptive effects in bone
Given orally
Side effects: hot flashes, deep vein thrombosis, leg cramps |
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Term
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Definition
MOA: testosterone is converted to estrogen in bone and estrogen acts on osteoblasts to decrease osteoclast recruitment and activation
Toxicity: verility |
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Definition
PTH analog
Treatment of osteoporosis
MOA: activates osteoblasts and osteoclasts
Follow w/ a bisphosphanate to deactivate osteoclasts |
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Term
| Glucocorticoid induced osteoporosis |
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Definition
May be used to treat hypercalcemia
MOA: antagonizes Vitamin D stimulated intestinal Ca absorption; stimulates renal Ca excretion; blocks bone collagen synthesis; increase PTH stimulated bone resorption |
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Definition
Bisphosphonate
Treatment of osteoporosis, Paget's disease (in combo w/ calcitonin), hypercalcemia
MOA: very similar in structure to pyrophosphate, but contains P-C bonds, which osteoclasts cannot break down; when taken up by osteoclasts, slows formation of hydroxyapatite crystals and decreases osteoclasts function; also metabolized into an ATP analog that accumulates in osteoclast and induces apoptosis
Side effect: osteomalacia |
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Term
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Definition
Bisphosphonate
Treatment of osteoporosis, Paget's disease (in combo w/ calcitonin), hypercalcemia
MOA: very similar in structure to pyrophosphate, but contains P-C bonds, which osteoclasts cannot break down; when taken up by osteoclasts, slows formation of hydroxyapatite crystals and decreases osteoclasts function
Side effect: osteomalacia; GI irritation |
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Term
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Definition
Bisphosphonate
Treatment of osteoporosis, Paget's disease (in combo w/ calcitonin), hypercalcemia
MOA: very similar in structure to pyrophosphate, but contains P-C bonds, which osteoclasts cannot break down; when taken up by osteoclasts, slows formation of hydroxyapatite crystals and decreases osteoclasts function; also inhibits protein prenylation in osteoclasts-> decreased function
Less of a side effect of decreased bone mineralization compared to the other bisphosphonates
Side effect: GI irritation |
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Term
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Definition
Bisphosphonate
Treatment of osteoporosis, Paget's disease (in combo w/ calcitonin), hypercalcemia
MOA: very similar in structure to pyrophosphate, but contains P-C bonds, which osteoclasts cannot break down; when taken up by osteoclasts, slows formation of hydroxyapatite crystals and decreases osteoclasts function
Side effect: GI irritation |
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Term
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Definition
Bisphosphonate
Treatment of osteoporosis, Paget's disease (in combo w/ calcitonin), hypercalcemia
MOA: very similar in structure to pyrophosphate, but contains P-C bonds, which osteoclasts cannot break down; when taken up by osteoclasts, slows formation of hydroxyapatite crystals and decreases osteoclasts function; also metabolized into an ATP analog that accumulates in osteoclast and induces apoptosis
Side effect: GI irritation |
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Term
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Definition
Bisphosphonate
Treatment of osteoporosis, Paget's disease (in combo w/ calcitonin), hypercalcemia
MOA: very similar in structure to pyrophosphate, but contains P-C bonds, which osteoclasts cannot break down; when taken up by osteoclasts, slows formation of hydroxyapatite crystals and decreases osteoclasts function
Side effect: GI irritation, renal toxicity |
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Term
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Definition
Treatment of hypercalcemia; Paget's disease
MOA: cytotoxic antibiotic that also decreases plasma Ca concentrations by inhibiting bone resorption
Toxicity: thrombocytopenia |
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Definition
Treatment of hypercalcemia
MOA: inhibits bone resorption
Renal toxicity |
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Definition
MOA: binds free ionized Ca
High risk procedure |
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Definition
Calcium chelator
Very high risk procedure |
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Definition
IV- Ca chloride, Ca gluconate, Ca gluceptate
Oral- Ca carbonate, Ca citrate, Ca lactate
Treatment of osteoporosis, hypocalcemia |
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Definition
Calcimimetic
MOA: inhibits PTH secretion by lowering the concentration of Ca2+ at which PTH secretion is suppressed
Use: treatment of primary and secondary hyperparathyroidism and hypercalcemia associated with parathyroid carcinoma |
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Definition
Reduces renal Ca excretion
Use: inhibits renal Ca stone formation; treatment of osteoporosis |
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Definition
Accumulates in bone and teeth
MOA: may stabilize hydroxyapatite-> increases bone volume; may increase osteoblast activity
Both acute and chronic toxicities limit use |
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Definition
Treatment: soft tissue and bone sarcomas
MOA: inhibits topoisomerase II to prevent DNA repair; forms superoxide radicals w/ cyt P450 reductase; intercalates w/ DNA to prevent replication
Toxicity: myelosuppression; cardiac toxicity
Cardiac toxicity can be counteracted w/ an iron chelator |
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Definition
Used in combo treatment w/ Doxorubicin to treat osteosarcoma
MOA: displacement of Cl in cisplatin by water activates; crosslinks DNA to prevent replication
Toxicity: nephrotoxicity, ototoxicity, marked nausea/vomiting (given w/ anti-emetic) |
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Term
| Cyclophosphamide; Ifosfamide |
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Definition
Treatment of soft tissue and osteosarcoma
MOA: alkylating agent; activated by hepatic cyt P450s; after alkylation, apoptosis induced (requires active p53)
SE: acrolein made as a breakdown product, toxic to bladder-> neutralize w/ MESNA and hydration; immunosuppression; infertility; increased risk of infection and neoplasia |
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Term
| Dactinomycin (aka actinomycin-D) |
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Definition
Treat soft tissue and osteosarcomas
MOA: intercalates DNA-> blocks transcription of DNA
Toxicity: hematopoietic suppression, nausea/vomiting |
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Definition
w/ Doxorubicin-> prolongs remission, survival, and response rate of soft tissue and osteosarcomas
MOA: alkylating agent activated by hepatic cytP450 to form MTIC; spontaneous cleavage yields active alkylator-> methyl diazonium ion
Toxicity: moderate myelosuppression, nausea/vomiting |
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Definition
In combo w/ ifofsamide-> treatment of osteosarcoma
MOA: forms complex w/ topoisomerase II and DNA that cannot dissociate and blocks replication
Cell cycle specific-> S or G2
Toxicity: myelosuppression, nausea/vomiting |
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Term
| Methotrexate (for osteosarcoma) |
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Definition
Treatment of osteosarcoma (w/ luecovorin rescue)
MOA: inhibits DHFR which indirectly inhibits thymidylate synthase (TS)-> inhibits DNA synthesis; leucovorin is converted to N5,N10-methylenetetrahydrofolate-> provides C donor for methylation of dUMP to TMP by TS
Side effects: myelosupppression, nausea/vomiting, mucosal ulcers; hepatotoxicity |
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Definition
aka granulocyte colony-stimulating factor (G-CSF)
Increases absolute neutrophil count during high dose chemotherapy |
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Term
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Definition
MOA: intercalates DNA and reacts w/ oxygen and iron to form free radicals-> fragmentation of deoxyribose
Inactivated by hydrolase-> low concentration in lungs
Side effects: pulmonary toxicity
Causes little bone marrow suppression-> often used in combo w/ dactinomycin and cyclophosphamide |
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Definition
MOA: binds beta-tubulin to prevent cell division
MOR: efflux pump
SE: neurological (peripheral neuropathy), alopecia
Causes little bone marrow suppression-> often used in combo w/ dactinomycin and cyclophosphamide |
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Definition
Antimicrobial
Good for gram (-) organisms
Treatment of choice for osteomyelitis due to Staph aureus and Strep pneumoniae, treatment of Lyme disease in children, treatment of C. botulinum from the GI tract
MOA: prevents cell wall synthesis
MOR: penicillinase
High dose given IV |
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Definition
Antimicrobial
Treatment of penicillin resistant Staph aureus osteomyelitis -> beta-lactamase resistant
Not used much anymore
MOR: altered penicillin binding protein |
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Definition
Antimicrobial
Treatment of penicillin resistant Staph aureus osteomyelitis -> beta-lactamase resistant |
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Term
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Definition
Antimicrobial
Treatment of penicillin resistant Staph aureus osteomyelitis -> beta-lactamase resistant |
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Term
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Definition
Antimicrobial
Treatment of penicillin resistant Staph aureus osteomyelitis-> beta-lactamase resistant |
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Term
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Definition
Antimicrobial
Treatment of penicillin resistant Staph aureus osteomyelitis -> beta-lactamase resistant; Treatment of osteomyelitis due to Seratia spp. and Pseudomonas aeruginosa |
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Term
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Definition
Antimicrobial
Treatment of penicillin resistant Staph aureus osteomyelitis -> beta-lactamase resistant; Alternative treatment of mixed infection osteomyelitis |
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Definition
Antimicrobial
First line treatment for osteomyelitis caused by anaerobes; alternative treatment for Staph and Strep osteomyelitis
MOA: binds 50S peptidyltransferase to block translocation;
SE: diarrhea, pseudomembranous colitis (kills GI bacteria except C. dificile)-> can be fatal |
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Definition
Antimicrobial
Treatment of methicillin resistant Staph aureus osteomyelitis
Given IV
Toxicity: ototoxicity, nephrotocicity |
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Term
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Definition
Antimicrobial
Alternative treatment for methicillin resistant osteomyelitis |
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Term
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Definition
Antimicrobial
Treatment of osteomyelitis due to enteric gram - rods and first choice for Gonococcal urethritis
MOA: inhibits DNA gyrase and topoisomerase IV |
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Term
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Definition
Antimicrobial
Treatment of ostemyelitis due to Seratia spp. and Pseudomonas aeruginosa |
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Term
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Definition
Antimicrobial-> 1st generation cephalsporin
Treatment of bone and joint infections
Given by injection every 6 hours |
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Definition
Antimicrobial-> 2nd generation cephalosporin
Treatment of bone and joint infections and 2nd choice treatment of Lyme disease (oral BID)
Given parenterally every 8 hours or orally in the acetil form every 12 hours |
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Definition
Antimicrobial-> 3rd generation cephalosporin
Treatment of bone and joint infections (first choice for Gonococcal urethritis) and treatment of Lyme disease in children
MOA: interferes w/ cell wall synthesis
MOR: beta-lactamase
Given IV every 12-24 hours; half-life = 8hrs |
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Definition
Antimicrobial
Treatment of osteomyelitis when a foreign body is involved (i.e. pin, prosthesis)
MOA: inhibits microbial RNA synthesis by inhibiting DNA-dependent RNA polymerase
MOR: target mutations |
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Definition
Antimicrobial treatment of osteomyelitis
Active against vancomycin, penicillin, and methicillin resistant organisms
MOA: prevents 70S formation by binding to 23S subunit of 50S; blocks initiation of protein synthesis in gram + bacteria like Staph aureus
MOR: mutations in 2 or more copies of the 23S rRNA-> very low
Toxicity: 2.4% incidence of thrombocytopenia in extended use (low occurrence) |
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Term
| Quinupristin-dalfopristin |
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Definition
Antimicrobial drug combo
MOA: synergistic binding and changing the conformation of 50S ribosomal subunit in gram + bacteria-> prevent polypeptide chain formation
Effective against vancomycin resistant Enterococcus faecium-> UTIs, soft tissue and blood infections; also used for skin infections of Staph aureus
Drug interactions: inhibits the cyt P450 enzyme CYP3A4 |
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Term
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Definition
Antimicrobial-> cyclic lipopeptide
Effective against methicillin, vancomycin, and linezolid resistant gram + bacteria
Given IV
MOA: binds bacterial membrane and causes rapid depolarization-> inhibition of protein, DNA, RNA synthesis
Toxicity: peripheral neuropathy w/ axonal degradation
Drug of last resort |
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Definition
Antimicrobial
First choice treatment for Lyme disease in adults
MOA: prevent tRNA binding to 30S
MOR: influx/efflux, binding site mutation, inactivation
SE: GI, photosensitivity, brown teeth for fetus/young children
Given orally BID |
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Term
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Definition
Antimicrobial
MOA: inhibition of cell wall synthesis
MOR: beta-lactamase |
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Term
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Definition
Antimicrobial
Treatment of C. tetani from wounds and C. botulinum from the GI tract
Given IV 7-10 days
MOA: prodrug that is activated to a hydroxylamine which degrades DNA in anaerobic organisms
MOR: Resistance in nonsporulating gram (+) bacilli, aerobic and facultatively anaerobic bacteria |
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Term
| Diethylcarbamazine citrate (DEC) |
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Definition
Antihelminthic
Treatment of W. bancrofti, B. malayi, and L. loa
Rapid eliminates organisms from the blood
MOA: on W. bancrofti causes organelle damage and apoptosis
Toxicity: anorexia, nausea, headache, vomiting |
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Term
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Definition
Antihelminthic
Treatment of Filariasis in combo w/ albendazole
Treatment of Onchocerciasis
MOA: in parasite, causes tonic paralysis of the musculature by activating glutamate gated Cl channels
Well tolerated |
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Term
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Definition
Antihelminthic
Treatment of Filariasis in combo w/ ivermectin
Treatment of Trichinosis
MOA: inhibit microtubule polymerization by binding to parasitic B-tubulin
Not toxic |
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Term
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Definition
Antihelminthic
Treatment of Trichinosis
MOA: inhibit microtubule polymerization by binding to parasitic B-tubulin
Not toxic |
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