csv-export (3) Flashcards
What is Levodopa administered with?
carbidopa (it is unable to cross the BBB and inhibits the enzyme that converts L?dopa to DA, so L?dopa crosses the BBB)
What are indications for carbidopa?levodopa?
parkinsons disease (GOLD STANDARD)
parkinsonian symptoms in other diseases (lewy body dementia)
restless leg syndrome
which symptoms of parkinsons does carbidopa?levodopa effective in treating?
bradykinesia, tremor, and rigidity, NOT postural instability
side effects of L?dopa
dose dependent:
nausea/vomiting?? esp with carbidopa
orthostatitc hypotension
psychosis
or dskinesia (can be choreic or dystonic)
metabolism of dopamin
L dopa converted to dopamin intracellulary, then DA is metabolized into homovanillic acid via the enzyme monoamine oxidase
older dopamine agonist
newer dopamin agonist
bromcriptine
pramipexole and ropinirole are newer
mnuemonic: bros are old news. the new thing to do is to rope people into going to the prom
what is bromocriptine used for?
suppress secretion of prolactin from anterior pituitary, used in treatement of prolactoma and endrocrine disorder
** risk of cardiac valve fibrosis
what is pramipexole and ropinirole used for?
restless leg syndrome and parkinsons
can be started in early course of PD before Ldopa is necessry, but can be used later to to reudce Ldopa induced dyskinesias and motor fluctuations
side effects of dopamine agonist
N/V, orthostatic hypotension, visual hallucinations
bromocriptine: heart valve fibrosis
pramipexole/ropinirole: sleep attacks
drug interaction for ropinirole
uses CYP1A2 in metabolism, cannot be used with ciprofloxacin (elderly patients with PDs and UTIs)
MAOb inhibitors
selegiline and rasgiline
way to remember: people had to LINE up behind dictator MAO
risk for MAO inhibitors
because it breaks down tyrosine too, you have the risk of hypertensive crisis when taken with tyramine containing food
but selegine and rasgiline are MAOb specfic so they are safer
use of MAObs
side effects
benefit in early parkinsons disease
selegine and rasagiline are associated with nausea and heachache
selegiline can cause confusion and insomnia
which drugs should you not take with MAOis
SSRIs or tricylclic antidepressants due to risk of serotonin syndrome
amantadine
NMDA glutamate antagonist, increases DA release and blocks DA reuptake
remember: glutamate is excitatory?? a man does not get excited too often
(not great)
indicaitons for amantadine
early tremor predominant parkinsons disease or late in parkinsons to treat dyskinesia and motor fluctuations
side effects of amantadine
ankle edema, confusion, insomnia
COMT inhibitors
tolcapone, entacapone
this is a stretch?? al capone has to use computers to do all his bad guy stuff
(and he needs his hit men just like COMT inhibitors need L dopa to work)
what are COMT inhibitors used with?
its inefective wihtout carbidopa/L?dopa
used to treat pt with L dopa motor fluctuations who are experiencing end of dose wearing off” periods
anticholinergics
trihexyphenidyl and benztropine
used bc dopamine depletion produces state of cholinergic sensitivity, so anticholinergic agents improve parkinsonian symptoms
most often used for treatment of drug?induced parkinsonism
side effects of anticholinergics
dont give to elderly?? memory impairment, confusion, hallucinations
also anti?muscarinic effects: dry mouth, orthostatic hypotension, blurred vision, constipation, nausea, urinary retention
depolarizing neuromuscular blockers
non?depolarizing neuromuscular blockers
depo: succinylcholine (agonist)
non?depo: cisatracurium, pancuronium, rocuronium, vecuronium (competitive antagonist)
indications of NMJ blockers?
paralytic agents: facilitates tracheal intubaiton, prevents movements during surgery
side effects of succinylcholine
stimulates nicotinic receptors at PNS, SymNS, muscarinic receptors at SA node:
CV effects: arrhythmias, bradycardia, tachycardia, hypotension
not metabolized by acetylcholinesterase: prolonged muscle contraction, skeletal muscle depo cause hyperkalemia and myalgias (also trigger for malignant hyperthermia)
non depolarizing agents side effects
cistacurium, pancuronium, rocuronium, vecuronium
histamine release (cistracurium)
tachycardia
hypo/hypertension
vecuronium has minimal CV side effects and histamine release, so its popular in children
drug interactions for NMJ blockers
dont use with antibiotics, anticonvulsants, antiarrhythmias, cholinesterase inhibitors, Mg, Li, inhalation anesthesias
conditions: burn, muscular dystrophy, myasthenia graivs, nerve injury
cholinesterase inhibitors
pyridostigmine and neostigmine
indications for pyridostigmine
increase muscle strength in myasthenia gravis, help to combat orthostatic hypotension
indications for neostigmine
to reverse effects of non?depo muscle relaxants at end of surgery
side effects of pyridostigmine and neostigmine
muscarinic: GI: diarrhea, N/V, abd cramp increase bronchial and oral secretions miosis diaphoresis
nictoinic: muscle cramps, fasciculations, muscle weakness if dose too high
DONT use neostigmine and pyridostigmine with…
they prevent breakdown of Ach, so they potentiate drugs with cholinergic properties
centrally acting acetylcholinesterase inhibitors
eye drops to treat glaucoma (act via Psymp)
NMJ blocking agents
indications for NSAIDS
antipyretic, analgesic, anti?inflammatory (except acetaminophen)
what is indomethacin used for?
to close patent ductus arteriosus
its one of the most potent inhibitors of COX and has adverse effects
what do NSAIDs do biochemically?
inhibitors of cyclooxygenase (COX)?? enzyme that catalyses synthesis of prostaglandin from arachidonic acid
so it decreases production of prostaglandins (which play a role in pain, inflammation, fever)
how do prostaglandins work?
sensitize sensory nerve endings to nocioceptive stimuli
promote tissue inflammation
induce increase in setting of body’s thermostat
but they also play important role in cytoprotection of GI tract, homeostasis, and renal homeostasis
what is special about aspirin?
it irreversibly inhibits COX
3 forms of COX:
Cox 1: contitutive enzyme found in constant levels in tissues?? important role in GI tract, homeostasis, renal homeostasis
COX 2: inducible enzyme?? can be upregulated during inflammation by cytokines
COX3: inhibited by acetaminophen and other analegeis/anytipyretic drugs
where do NSAIDS work?
nonselective inhibitors of COX 1 and COX 2 except celecoxib?? selectively inhibits COX?2 and acetaminophen selectively inhibits COX 3
side effects of NSAIDS:
GI irritation, pepticu ulcers, incresed bleeding and bruising hepatic toxicity (ESPECIALLY acetaminophen) renal toxicity (EXCEPT acetaminophen) dont use during second half of pregnancy EXCEPT acetaminophen
drug interactions with which 4 drugs?
oral anticoagulants? inc risk of bleeding
lithium?? inc risk of lithium toxicity
antihypertensive agents? antagonism of antihypertensive effects
corticosteroids? inc risk of GI complications
acetaminophen: how is it different in action and use?
can be used concurrently with NSAIDS (which should not be taken together)
?lacks significant antiplatelet and anti?inflammatory activity
Reye syndrome
virus?infected children who are treated with aspirin
unique features of aspirin
?irreversibly acetylates platelet COX?? has anti?platelet effects for 14 days
? excessive doses stimulate respiratory center in medulla, cause hyperventialion, respiratory alkalosis with an anion?gap metabolic acidosis
treatment of salicylate poisoning
?induce vomiting to remove unabsorbed durg
?IV admin of sodium bicarb to counteract metabolic acidosis and enhance rate of exretion of salicylate
?admin fluids, electrolytes, supportive care
why is acetaminophne hepatotoxic?
bc a small amount is converted by cytochrome p450 into a potentially hepatotoxic quinone intermediate (is ok if therapeutic dose taken)
what is acetaminophen overdose treatment?
acetylcysteine
ketolorolac
first NSAID available for parenteral use (IV or IM)? dental surgery
celecoxib
selective COX2 can cause antiinflammaotry without GI tox, bu tit was withdrawn from the market due to increased risk of CV events
derived from poppy; frequently abused IV for its strong euphoric effect
heroin
administered by various routes for control of severe pain
morphine
approximatley 100x more potent than morphine, frequently used in anesthetic practice bc it has short time to peak analgesic effect, rapid termination of effect after small bolus doses and relative CV stability
administered IV
fentanyl
administered orally
?used for relief of chronic pain, treatment of opioid abstinence syndromes, treatment of heroin addiction
?racemic mix: one stereoisomer acts as NMDA receptor antagonist, one is mu agonist
methadone
rapid synthetic opioid is no longer used for pain control bc metabolite toxicity resulting in seizures
** does not constrict the sphincter of oddi?? drug of choice for gall bladder pain
meperidine
codeine
what is it used for?
analgesic, antitussive, antidiarrheal
less potent than morphine
hydrocodone
most frequently used opiate in teh US; usually combined with weaker analgesic such as acetaminophen, ibuprofen, aspirin
oxycodone
stucturally similar to codeine and hydrocodone, usually used for moderate to severe pain
tramadol
synthetic codeine analog, well absorbed orally
2 adverse reactions: seizures and serotonin syndrome
partial agonist
how does it work?
buprenorphine
high affinity but low efficacy at the mu receptor
also acts as a kappa antagoinst, making it useful in opioid deterrance, detox, maintenance
mixed agonist?antagonist
nalbuphine
competitive mu receptor antagonist but exerts analgesic effects by acting as kappa receptor agonist
indications for nalbuphine
for opioid induced pruritis
opioid antagonists
naloxone, naltrexone
indications for naloxone
treatment for opioid intoxication/overdose?? half life is an hour?? may need to be redosed
naltrexone
longer half life?? 24 hours after moderate oral doses, used for treatment of alcoholism
which drugs are used for an acute attack?
triptans, dihyroergotamine, analgesics (aspirin, NSAIDs, opioids), anteemetics (promethazine)
which drugs are used for migraine prophylaxis?
beta blockers (propanolol) tricyclic antidepressants (amitriptyline) anticonvulsants (valproate and topiramate)
sumatriptan
selective agonist for serotonin 5?HT1B and 5?HT1D receptors in cranial arteries?? cause vasoconstriction and reduces neurogenic inflammation associated with activation of trigeminovascular system neuronal transmission
side effects of sumatriptan
self limited: transient dizziness, tingling, chest discomfort
serious: temporary elevation of BP (vasoconstriction)
myocardial ischemia (vasoconstriction)
stroke (vasoconsriction)
?? avoided with CAD pts
drug interactions iwth sumatriptan
dont co?administer sumatriptan with ergotamines or MAO inhibitors
ergotamine derivatives
mechanism of action
dihydroergotamines
dual: alpha adrenergic blocker that simulates vascular smooth msucle to vaso constrict and an agonist of serotonin receptors
use for dihydroergotamine
treatment for acute migraine in patients who fail triptans (nasal spray as outpatient, IV or IM in hospital)
side effects of dihyrdoergotamine
self limited: rhinitis, taste disorders, nausea (need coadmin with anti?emetics)
and signifacant vasoconstriction?? myocardial and cerebrovascular ischemia
drug interactions for dihydroergotamine
SO MANY== dangerous! used with great caution
side effects of opioids:
nausea and vomiting?? can give mixed agonist/antagonist (nalbuphine)
constipation
pruritis?? antihistamines
when should high dose chronic acetaminophen be avoided?
liver disease
when should chronic systemic NSAIDS be avoided?
PUD and chronic kidney diease
also NSAIDS are are assoc with increased risk of myocardial infarction
what are the mainstay of therapy for neuropathic pain?
tricyclic antidepressants, anticonvulsants, topical local anesthetics
side effects of local anesthetics
hypersensitivity reaction: more common with esteres secondary to one of their metabolic products (para?aminobenzoic acid, PABA)
perioral numbness
seizures
amides
lidocaine
buprivicaine
ropivacaine
esters
benzocaine
procaine
tetracaine
cocaine
what determines how rapidly the drug’s onset of action is?
- the more closely the pKa approximates the physiologic pH of tissues (7.35?7.45), faster the onset of action
- drugs potency (lipid solubility)
- tissue pH?? if pH is decreased, the drug is shifted to its ionized form and the onset of action is delayed (why local anesthetics are slower acting in inflammation due to acidic environment)
which drugs will have longer duration of action?
those that are lipid soluble and heavily protein bound
how do you treat neuropathic pain?
tricylclic antidepressants, anticonvulsants, topical local anesthetics
