neuro drugs Flashcards
Glaucoma:
a-agonists:
Epi and Brimonidine (a2)
Epi: decrease Aq H synthesis via vasoconstriction
side effects: mydriasis, do not use in closed angle glaucoma
Glaucoma:
Brimonidine (a2 agonist)
decreases Aq H synthesis
side effects: blurry vision, ocular hyperemia, foreign body sensation, ocular allergic reactions and ocular pruitius
Glaucoma:
B-blockers: timolol, betexolol, carteolol
- decrease Aq H synthesis
- side effects no pupillary or vision changes
Glaucoma:
acetozolamide
decreases Aq H synthesis via inhibition of CA
-no pupillary or vision change side effects
Glaucoma:
Pilocarpine and carbachol
- direct cholinomimetics
- incease outflow of aqueous humor via contraction of ciliary muscle and opening of the trabecular meshwork
side effects: mitosis, cyclospasm (contraction of ciliary muscle)
Use pilocarpine in emergencies
Glaucome:
physostigmine and echothiphate
inderect cholinomimetics (AchEI) -incease outflow of aqueous humor via contraction of ciliary muscle and opening of the trabecular meshwork
side effects: mitosis, cyclospasm (contraction of ciliary muscle)
Glaucoma:
Latonoprost PGF2alpha
prostaglandin
-increase outflow of aqeous humor
side effects:
darked color of the iris –> browning
opiods: which one do we use for pain, cough suppression?
dextropmethorphan…. although you were prescibed codeine once
opiods: which one do we use for diarrhea?
loperamide and diphenoxylate
opiods: which one do we use for maintenance program for heroid addicts?
methadone
How do we treat toxicity of opiods?
naloxone or naltrexone (opiod receptor antagonists)
name some opiods
morphine, fentanyl, codeine, loperamide, methadone, meperidine, dextromethorphan and diphenoxylate
opiods basics
-act an opiod receipts, mu = morphine, delta (enkephalin), kappa = dynophin to modulate synaptic transmission
OPEN K+ channels CLOSE Ca2+ channels –> decrease synaptic transmission
-inhibit the release of ACh, NE, 5-Ht, glutamate, substance P
what are toxicities of opiods?
- addiction
- respirator depression
- constipation
- miosis (pinpoint pupils)
- additive CNS depression with other drugs
- tolerance does not develop to miosis and constipiation!
Butophanol
- mu-opiod receptor PARTIAL agonist and kappa-opiod recept agonist
- produces analgesis
use: severe pain migraine/labor, causes less respiratory depression
tox:
opiod withdrawal symptoms if patient is also taking full opiod agonist (competition opiod receptors). the overdose is not easily reversed with naloxone =(
Tramadol
Tram it all!
-very weak opiod agonist, also inhibits sertoning and NE reuptake.
use:
chronic pain
tox: similiar to opiods, decreases seizure threshold, SERETONIN SYNDROME
Which epilepsy drugs work by inactivation Na channels or blocking them?
Phenytoin Carbamazepine Valproic acid (has some gaba) Topiramate (block) Lamotrigine (voltage gated Na channels)
Which epilepsy drugs work via GABA
Benzodiazepines Valproic acid (some Na) Phenobarbitol Topiramate (some Na) Levetiracetam Tiagabine Vigbatrin
Steven johnson syndrome
prodrom of malaise and fever followed by rapid onset of erythematous.purpuric macules (oral, occular, genital). Skin lesions progress to epidermal necrosis and sloughing
Ethosuximide
Sux to have silent seizures
- 1st line abscence seizures
- blocks thalamic T-type Ca2+ chanels
side effects:
GI, fatigue, headache, urticaria, Steven johnson
Benzodiazepines for seizures
diazepam and lorazapam
1st line in acute status elipticus
-increased GABAa action increasing frequency of Cl channel opening
side effects: sedation, tolerance, depedance, respiratory depression
also use for eclampsia seizures (note first line is mgso4)
First line for eclampsia seizures?
MgSo4
second: benzooos
Phenytoin
work on all seizures but abscence
1st line for tonic clonic
1st line prophylaxis for status elipticus
fosphentoid for parenteral use
increases na channel inactivation, note that it has zero order kinetics~~~
Side effects: nystagmus, diplopia, ataxia, sedation, gingical hyperplasia, hirsutisim, peripheral neuropathy, megloblastic anemia, teratogenesis , SLE like syndrome, lymphadenopathy, steven Johnson syndrome and osteopenia
INDUCES P-450!!
Carbamazepine
use for all focal seizures and tonic clonic, it is 1st line for these
-increases Na channel inactivation
side effects: diplopia, ataxia, blood dyscrasias (AGRANULOCYTOSIS APLASTIC ANEMIA), liver toxicity, teratogenesis, SIADH, Steven Johnson syndrome
INDUCES c P-450!!
Valproic acid
Treat all seizures except status ellipticus
1st line in tonic clonic (so is carbamazapine)
-can be used for myoclonic seizures (drop)
-increases Na channel inactivation, increases GABA concentraion by inhibiting GABA transaminase
side effecs: GI distrsss, rare but fatal HEPATOTOXICITY (measure lfts), neural tube defects in fetus (spin bifid a), temor, wt gain,
Gabapentin
Can use for simple, complex and tonic clonic
- inhibits high voltage activated Ca channels
- side effects: sedation, ataxia
used for: peripjeral neuropathy, posttherpetic neuralgia, migraine prophylaxis and bipolar disorder
Phenobarbital
can use for simple, complex and tonic clonic
1st line for neonates
-increases GABA action
side effects:
sedation, tolerance, dependance, cardiorespiratory depression
INDUCES P450!
which epilepsy drugs indue P450?
phenytoin, carbamazepine, phenobarbitol
Topiramate
simple, complex and tonic clonic
-used for migraine prevention
blocks the Na channels and increased GABAa action
side effects: sedation, mental dulling, Kidney stones, wt loss
Lamotrigrine
simple, complex, tonic clonic and abscence seizures
blocks volatege-gated Na channels
side effects: must be titrated slowly or…..
STEVEN JOHNSON SYNDROME
Levetiracetam
simple, complex, tonic clonic
-may modulate GABA and glutamate release
Tiagabine and vigabatine
simple and complex focal seizures
increase GABA
tiagabine - inhbits GABA reuptake
Vigabatrin - inhbits GABA transaminase
Barbituates: phenobarbitol pentobarbitol, thipental, secobarbital
- facilitate GABA action by inscreasing DURATION of Cl channel opening , thus decreasing neuron firing
- contraindicated in porphyria
clinical: sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental)
tox: resp and cardiovascular depression, CNS depression can be exacerbated with EtOH, dependence, drug interactions due to INDUCTION OF P450
overdose: supportive
Benzodiazepines:
diazepam, lorazepam, triazolam, temazepam, oxazepam, midaolam, chlorodiazepoxide, alprazolam
- facilitate GABA action by increasing FREQUENCY of Cl channel opening.
- decrease REM sleep
- most have long half lives
triazolam, oxazepam and midazolam are short acting –> higher addictive potential
clinical use: anxiety, spasticity, status elepticus (lorazepam and diazepam), detoxification (especially alcohol withdrwal and delerium tremens), night terros, sleep walking, general anesthetic (amnesia, muscl relaxation), hypnotic (insomnia)
tx: dependence, additive CNS depression effects with eton, less risk of resp depression and coma than barbs
treat overdose with flumazenil (competitive antagonist at GABA benzodiazepine receptor)
Which benzos are short acting?
triazolam, oxazepam and midazolam are short acting –> higher addictive potential
What do we use to treat oversode of benzos?
Flumazenil a competitive antagoinist at the GABA benzodiazepine receptor
Zolpidem (ambien)
Zaleplon, esZoicoline
zzzzzzzz sleepppyyy hypnotics
-act via BZ1 subtype of the GABA receptor.
reversed with flumazenil
treat: insomnia
tox: ataxia, headaches, confusion, short duration as they are rapidly metab at liver
- cause only modest day after psychomotor depression and few amnestic effects
- less dependance than benzodiazepines
anesthesia general principles
CNS drugs must be lipid soluble
increased solubility in lipids = increased potency
Drugs with decreased solubility in the blood= rapid induction and recovery times
example) halothane has high lipid solubility and blood solubility, so it will be more potent and have slow induction
example) N2O decreased blood solubility and lipid solubility so its less potent but a faster induction and recovery time
MAC minimal alveolar concentration of inhaled anesthetic
MAC required to prevent 50% of subjects from moving in respinse to noxious stimulus (like a skin incision)
potency = 1/MAC
malignant hyperthermia caused?
rare life threatning hereditary condition caused by inhaled anesthetics (not N2O) and succinylcholine
- fever
- muscle contractions
treat: dantrolene (prevents the release of Ca from the SR)
Inhaled anesthetics: halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide
mechanism: unknown ahahah
Effects:myocardial depression, resp depression, nausea/emesis, increased cerebral blood flow (decreased cerebral metabolic demand)
tox: halothane - hepatoxicity Methoxyflurane - nephrotoxicity enflurane - proconvulsant N2O - expansion of trapped gas in body cavity
can cause malignant hyperthermia (not N2O)
name some intravenous anesthetics?
barbituates (thiopental), benzodiazepines (midazolam), arylcyclohexylamines (ketamine), opiods (morphine and fentanyl), propofol
Thiopental
-barbituate
-high potency, high lipid solubility, rapid entry into brain
-used for induction of anesthesia and short surgical procedures
-effect is terminated by rapid redistribution into tissue and fat.
decreased cerebral blood flow
Midazolam
-benzo
-most common drug used for endoscopy
-used adjectively with gases anesthetics and narcotics
0may cause severe postoperative resp depression
-decreased BP
-antergrade amnesia
treat overdose as per usual with friendly flumazenil
Arylcyclohexylamines (ketamine)
PCP analogue that acts as dissociative anesthetic
- block NMDA receptors
- cadiovascular stimulant
- cause disorientation, hallucination and bad dreams
- increases cerebral blood flow
morphine and fentanyl
are used with other CNS depressants during general anesthesia
propofol
used for sedation in ICU
rapid anethesia induction, short procedures
less postoperative nausea than thiopental
potentiates GABA
Name some local anesthetics
Esters: procaine, cocaine, tetracaine
amides: lidocaine, mepivacaine, bupivacaine (note the two I’s)
Local anesthetics:Esters: procaine, cocaine, tetracaine
amides: lidocaine, mepivacaine, bupivacaine (note the two I’s)
- block Na channels by binding to specific receptors on inner potion of channel. preferentially bind to ACTIVATED na channels, so most effective in RAPIDLY firing neurons.
- tertiary amine anesthetics penetrate membrane in UNCHARGED form then bind to ion channels in CHARGED form.
- can be given with epi to enhance local acton via vasoconstriction (decrease bleeding and increased anesthesia by decreasing systemic concentration
- in infected tissues (acidid) the alkaline anesthetics are charged and cannot penetrate membrane effectively –> need more anesthetic (Nh3 to NH4+)
treat: minor surgical procedures, spinal anesthesia, if allergic to esters give the amides
tox: CNS excitation, severe cardiovascular tox (bupivacaine_, HTN, hypotension and arryhthmias (cocaine)
what is the order of nerve block by local anesthetics?
small diameter fibers > large diameter
myelinated fibers> unmyelinated fibers
but size factor predominates
so small myelinated fibers> small unmyelinated fibers> large myelinated fibers? large unmyelinated fibers
What is the order of sensation loss by local anesthetics?
- pain
2, temp - touch
- pressure
Neuromuscular blocking drugs:
Depolarizing Succinylcholine
-strong Ach receptor agonist such that it produces sustained depolarization and prevents muscle contraction so it cause the depolarization as it is an agonist but is so strong it gets stuck
Phase 1: prolongue depolarization, the block potentiated by cholinesterase inhibitors no antidote
phase 2: eventually some receptors become desensitized, some Ach receptors become available. So repolarized but still blocked. Antidote - cholinesterase inhibitors –> increase Ach
Complications:
- hypercalcemia
- hyperkalemia (recall not only Na is release on binding to nicotinic receptor but also K)
- malignant hyperthermia (fever and severe muscle contractions)
Neuromuscular blocking drugs:
Nondepolarizing:
Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rocuronium
-competitive antagonists of Ach receptors, prevent depolarization but prevents Ach from binding
reverse the blockade:
ACEI neostygmine but give atropine too to prevent muscarinic effects such as bradycardia you could also use edrophonium
atropine
competitive antagonist of muscarinc Ach receptors
Dantrolene
treat malignant hyperthermia and neuroleptic malignant syndrome (toxicity of antipsychotic drugs)
- prevents Ca release from the SR in skeletal muscle
Parkinson disease drugs
BALSA
BALSA Bromocriptine Amantadine Levodopa with cabidopa Selegiline with compt inhibitors Antimuscarinics
For essential of familiar tremors use:
b-blocker propranolol
Bromocriptine
DA agonist
Amantidine
may increase DA release
-also used as an antiviral against Influenza A and rubella; toxicity = ataxia
Levodopa and carbidopa
converted to DA in CNS by dopa decarboxylase
cabidopa is a peripheral decarboxylase inhibitor, so that increased bioavailbiltiy of L-dopa to the brain and limit the peripheral effects
tox: arrhythmias from peripheral formation of catecholamines. Long term use can lead to dyskinesia following administration “on off phenomena”, akinesia between doses.
Selegiline
selective MAO type B inhibitor (MAO B is DA over 5HT and NE) thus increases its availability
may enhance adverse effects of Ldopa
entacapone, tolcapone
COMT inhibitors, they prevent L-dopa degradation
Benzotropine
antimuscarinic, improves the tremor and rigidity in Parkinson disease but has little effect on bradykinesia
Memantine
Alzheimers drugs
NMDA receptor antagonist, helps prevent excitotxicity (mediated by Ca)
dizzy, confusion side effects
AChE inhibitors: donepezilm galantamine and rivastigmine
alzheimers
side effects nausea dizzyness insomnia
Huntington drugs:
Recall in huntington decreased GABA, ACh but increased dopamine
treat:
tetrabenazine and reserpine - inhibit vesicular monoamine transporter (VMAT); limit dopamine vesicle packaging and release.
Haloperidol: DA receptor antagonist
Sumitriptan
5-HT1b/1d agonist
-inhibits trigeminal nerve activation, prevents vasoactive peptide release VIP, induces vasoconstriction, half life is < 2hours
clinical: acute migraine, cluster headache attacks
tox: coronary vasospasm contraindicated in patients with CAD anor prinzmetal angian, mild tingling
