Pharmacology Flashcards
neostigmine
cholinergic agonist
quaternary acetylcholinesterase (does not cross BBB)
reverses anesthetic paralysis
SLUDGE
pyridostigmine
cholinergic agonist
long(est) acting acetylcholinesterase, quaternary (does not cross BBB)
preferred drug in myasthenia gravis
SLUDGE
physostigmine
cholinergic agonist
tertiary acetylcholinesterase (does cross BBB = CNS effects)
antidote for atropine
SLUDGE, convulsions, coma
pralidoxime
cholinergic ANTagonist
regenerates acetylcholinesterase
treats OD on cholinergic agonists
anti-SLUDGE
benzocaine
local anesthetic, ester
topical-only anesthetic
if internal use, serious methylglobinemia –> cyanosis
tetracaine
local anesthetic, ester
long-duration LA used for spinal anesthesia
mechanism of action of all local anesthetics
blocks Na+ channels on nociceptive receptors, especially small and unmyelinated neurons
adverse events of all local anesthetics if they are administered IV
v tach, v fib, other potential arrythmias, heart block, bradypenia, hypotension, convulsions, coma, possible death
lidocaine
local anesthetic, amide
most commonly used LA, intermediate duration, can be topical, injected subQ, spinal anesthesia
bupivicaine
local anesthetic, amide
long duration, used for epidurals
heart problems are especially severe if IV
atropine
anti-cholinergic muscarinic antagonist
blocks downstream muscarinic signalling (G-protein pathway)
has CNS effects, antidote to acetylcholinesterase inhibitors (anti-SLUDGE), treats bradycardia, bedwetting, pupil dilation
can cause tachycardia, hyperthermia, delirium, dizziness, anti-SLUDGE
scopolamine
anti-cholinergic muscarinic antagonist
blocks downstream muscarinic signalling (G-protein pathway)
long-acting and has CNS effects - prevents vomiting from motion sickness, surgery, etc.
sedation, confusion, anti-SLUDGE
glycopyrrolate
anti-cholinergic muscarinic antagonist
blocks downstream muscarinic signalling (G protein pathway)
similar to atropine, but in PNS only: anti-acetylcholinesterase, bradycardia, etc.
like atropine, tachycardia, anti-SLUDGE (no CNS side effects like delirium, dizziness, hyperthermia)
botox
anticholinergic
cleaves SNAREs that are needed for neurotransmitter vesicle fusion to pre-synaptic membrane, so ACh is not released
spasm, strabismus, dystonia, hyperhydrosis (execs sweating), tension/migraine headache, cosmetics
3-6 months duration
pilocarpine
cholinomimetic muscarinic agonist
direct muscarinic agonist = directly binds to muscarinic receptor and induces G protein signalling
ciliary contraction in glaucoma, tear and salivary gland production in Sjorjen’s syndrome
SLUDGE
tubocurarine
non-depolarizing NMJ blocker (curare)
nicotinic receptor competitive antagonist (binds active site) without depolarizing post-synaptic membrane
no longer used d/t many side effects, but is the parent compound for other curares
atracurarium
non-depolarizing NMJ blocker (curare)
as with other curares, nicotinic receptor competitive antagonist (blocks active site) without post-synaptic membrane depolarization
no CNS effects, intermediate-acting time
anesthetic paralysis and intubation
of currently used curares, most likely to cause side fx: widespread histamine, PNS neurotoxin (e.g. seizure)
rocurarium
non-depolarizing NMJ blocker (curare)
as with other curares, non-depolarizing nicotinic receptor competitive antagonist
no CNS effects, short-acting
anesthetic paralysis
similar side fx to other curares but less extreme d/t more quickly metabolized
succinylcholine
depolarizing NMJ blocker
step 1: ACh mimetic, causes widespread vasiculations
step 2: desensitization/receptor fatigue
step 3: broken down by plasma pseudocholinesterase
rapid onset (<1 min) and short duration (<10 min)
in genetically susceptible individuals (pseudocholinesterase mutations), effects can last for several hours
sugammedex
NMJ blockade reversal
releases/sequesters non-depolatorizing NMJ blocker from active site of nicotinic receptor, restoring normal signalling. sugammedex-curare complex then excreted renally.
reverses effects of non-depolarizing NMJ blockers
reasonably safe, fast-acting
aspirin
non-selective COX inhibitor, primarily COX1
IRREVERSABLE acetylation by acting as a steric block on COX.
anti platelet in addition to normal NSAID antiinflammatory antipyretic analgesic fx
Aspirin itself is rapidly excreted (within an hour) but effects last as long as it takes to make new COX/platelets
possible Reye’s syndrome in kids but this is being questioned now
Most GI effects of the NSAIDs because it is most partial to COX1; also, renal compromise and salycism
ibuprofen
non-selective COX inhibitor, about 50:50 COX1:COX2
anti-inflammatory, anti pyretic, analgesic
t1/2 = 2-2.5 hour, reversible
competitive inhibition of arachidonic acid binding, which prevents arachadonic acid –> prostaglandin rxn. prostaglandins cause vasodilation, capillary permeability, platelet aggregation
AEs: GI bleeding, kidney compromise
naproxen
non-selective COX inhibitor, about 60:40 COX1:COX2
similar to ibuprofen, but slightly less selective and much longer t1/2 (12-16 h)
indomethacin
non-selective COX inhibitor, slightly less COX2 than naproxen
similar to ibuprofen, but less selective and intermediate t1/2 (4-6 h)
better for gout than other NSAIDs
celecoxib
COX2 inhibitor
too bulky to fit in COX1 binding site = fewer side fx, stronger
moderate-to-severe inflammatory pain e.g.. OA, RA, ankylosing spondylitis
fewer GI fx, no platelet fx
acetaminophen
non-opioid analgesic; it’s own class
for mild pain and fever. no anti-inflammatory fx.
Inhibits COX by different mechanism than NSAIDs but it’s not completely known how
liver toxicity at >3000 mg/day, no platelet fx, not contraindicated in asthma
diazepam
benzodiazepine (Valium), antispasmodic at CNS level
GABA-A receptor allosteric agonist
potentiates GABA effects: facilitates GABA binding to receptor (Cl- channel) –> hyerpolarization and post-synaptic neuron inhibition
memory problems, agitation, hallucinations, mood changes, clumsiness, slurred speech …
baclofen
antispasmodic/muscle relaxant at CNS level
GABA-B receptor agonist
directly activates GABA receptors leading to more K+ efflux, hyper polarization, and post-synaptic neuron inhibition
dizziness, weakness, confusion, headache, drowsiness…
gabapentin
AED/anti-spasmodic/neuropathic pain/adjuvant at CNS level
similar effects to GABA but doesn’t actually have any effect on GABA receptors
prevents neurotransmitter release by blocking pre-synaptic Ca++ channels
no significant drug interactions, no liver metabolism (excreted directly into urine)
drowsiness, dizziness, headache, uncontrollable shaking (seizure-like event), anxiety, loss of balance…
tizanidine
antispasmodic/muscle relaxant
presynaptic alpha-2 adrenergic receptor agonist
treats spasms, cramping, muscle tightness associated with MS, back pain, or spinal injuries
dizziness, drowsiness, weakness, paresthesias…
dantrolene
anti-spasmodic/muscle relaxant, not strictly speaking an NMJ drug
binds ryanidine receptor to prevent release of calcium from the sarcoplasmic reticulum
list opioid agonists from most potent to least
fentanyl (>80x morphine) hydromorphone heroin morphine ~ oxycodone (fewest off-target side fx) ~ methadone tramadol (1/10 morphine) tapentadol codeine
opioid agonists: PD, sfx
act on endogenous pre- and post-synaptic opioid receptors (mu, kappa, delta = MOP, KOP, DOP) to INHIBIT neuron transmission
3 possible mechanisms:
- adenylate cyclase inhibition (cAMP)
- reduced Ca++ influx at pre-synaptic (inhibits nt release)
- increase K+ efflux post-synaptic (hyperpolarized)
associated with range of opioid effects analgesia, euphoria (sometimes dysphoria), miosis (eye), respiratory depression, constipation, nausea, vomiting, cough suppression, hypogonadism long term d/t endocrine (GnRH, LH, FSH) inhibition, urinary retention, gallbladder spasm, histamine release, truncal rigidity, addiction, tolerance
buprenorphine
opioid partial mu receptor agonist (kappa receptor antagonist)
ceiling effect to many pharmacologic effects including analgesia and euphoria
high binding affinity to receptors, naloxone minimally effective
less misuse potential, used in opioid use disorder
naloxone
competitive opioid receptor antagonist
t1/2 = 1-2 hours (multiple injections or continuous infusions needed)
poor oral bioavailability
naltrexone
competitive opioid receptor antagonist
longer acting than naloxone
t1/2 4 hours, also produces active metabolite with t1/2 = 12-16 hours
good p.o. bioavailability
can be used for OD or withdrawal maintenance in opioid use disorder
loperamide
opioid agonist
used to treat diarrhea
does not cross BBB, does cross gut but rapidly metabolized so very little in systemic circulation
diphenoxylate
opioid agonist
used to treat diarrhea - does not cross gut or BBB
dextromethorphan
opioid agonist and glutamate NMDA receptor antagonist
used to treat cough several potential mechanisms - recent double blind studies show little to no effect
a codeine analog
no analgesic, gi, sedative fx
OTC
codeine
opioid agonist
used to treat cough via CNS effects - weak opioid with less addictive potential
recent double-blind studies show little to no efficacy, older double-blind studies show good efficacy, reasons for discrepancy not know
AEDs for pain
topiramate, lamotrigine, carbamate
all block Na+ channels
topiramate also block Ca++ channels and inhibits glutamate release
lamotrigine also blocks Ca++ channels and potentiates GABA effects
(gabapentin also technically AED, Ca++ channel blocker)
amitriptyline
tricyclic antidepressant, adjuvant analgesic for neuropathic pain
inhibits norepinephrine and serotonin reuptake (by NET and SERT)
Na+ channel blocking
inhibit ascending nociceptive activity
“tricyclic” = 3 cyclic rings
duloxetine
SNRI, adjuvant analgesic for neuropathic pain (Cymbalta)
inhibits norepinephrine and serotonin reuptake (by NET and SERT)
Na+ channel blocking
inhibit ascending nociceptive activity
ketamine
non-competitive NMDA receptor antagonist
may potentiate GABA activation
induces dopamine
weak mu opioid receptor agonist
persistent NMDA activation by glutamate –> hyperexitability is one mechanism of central pain @spinal cord
capsaicin
destroys nerve endings, differential effect on small and unmyelinated neurons such as nociceptive
hydrocortisone/cortisol
glucocorticoid
prednisone/prednisolone
glucocorticoid 4x cortisol short half life, low cost fewer mineralocorticoid (Na+/K+) effects
prednisone = prodrug to prednisolone
prednisolone commonly prescribed in liver failure when prednisone can’t be broken down
methylprednisolone
glucocorticoid 5x cortisol
commonly used for allergy and most autoimmune diseases
dexamethasone
glucocorticoid 25x cortisol
t1/2 = 1-2 days
drug of choice for most long-acting purposes, e.g. allergy and autoimmune diseases
morphine PK
no ceiling for analgesia (more drug = less pain), dose limited by side fx
peak 30 min to 1 h after administration, t1/2 = 2-3.5h
active metabolite as well as direct morphine effects
limited oral bioavailability
methadone PK
t1/2 = 1-1.5 days, analgesic effect only 4-6 hours
milder withdrawal symptoms hence utility in opioid use disorder
excellent oral bioavailability
7-8x morphine
also an NMDA antagonist so useful in neuropathic pain
NMDA is a receptor for…
glutamate. excitatory. ionotropic.
mechanism of action glucocorticoids
phospholipase A2 inhibitor. shuts down entire prostaglandin/COX/thromboxane/leukotriene pathway
overall activates anti-inflammatory pathways and inhibits inflammatory pathways
