Flashcards in Neuro Pharm Deck (147):
How do you treat essential tremor (postural tremor)?
ETOH (decreases tremor amplitude)
How do you precipitate Wernicke-Korsakoff syndrome?
Giving glucose without B1 to a B1 deficient patient
Treat subarachnoid hemorrhage?
Nimodipine (Ca channel blocker)
What is indicated in ischemic stroke?
tPA within 4.5 hours
as long as paint presents within 3 hours of onset & there is no major risk of hemorrhage
What are some ALS therapies?
Riluzole (decrease presynaptic glutamate release)
Baclofen (GABA-B agnoist to dec spasticity)
What is contraindicated in closed (narrow angle) glaucoma?
(bc causes mydriasis)
How do you treat Dry ARMD (nonexudative age-related macular degeneration)?
prevent progression-- multivitamins & antioxidants
How do you treat Wet ARMD (exudative age-related macular degeneration)?
anti-VEGF injections or laser
(stops choroidal neovascularization)
How do you treat MS?
Natalizumab (monoclonal AB against alpha-4 integrin for cell adhesion)
Glatiramer (immune modulator)
Symptomatic Tx: 1) Baclofen (GABA-B agonist-- tx spasticity), 2) Muscarinic antagonist & catheterization (neurogenic bladder), 3) Opiods (pain)
How do you treat Guillain-Barre?
Respiratory ventilator support
IV immune globulins
What is the DOC for partial (focal) seizures?
How do you treat cluster HA?
How do you treat migraine?
Prophylacitc-- propranolol, topiramate
What is the general mechanism of glaucoma drugs?
decrease amount of aqueous humor to decrease intraocular pressure
Which drug classes are used to treat glaucoma?
Which alpha-agonists are used to treat glaucoma?
Brimonidine (alpha 2)
What is the MOA of alpha-agonists in glaucoma?
decrease aqueous humor synthesis
(epi does so via vasoconstriction)
Side effects of alpha-agonists in glaucoma?
Mydriasis-- Epi is contraindicated in closed-angle glaucoma
blurry vision, ocular hyperemia, foreign body sensation, ocular allergic rxn, ocular pruritis
Which beta-blockers are used in glaucoma?
What is the MOA of beta-blockers in glaucoma treatment?
Dec aqueous humor synthesis
*no pupillary or vision change S/E
Which diuretic is used to treat glaucoma?
What is the MOA of acetazolamide?
dec aqueous humor synthesis via carbonic anhydrase inhibition
*no pupillary or vision change S/E
Which cholinomimetics are used to treat glaucoma?
Direct-- Pilocarpine, Carbachol
Indirect-- Physostigmine, Echothiphate
What is the MOA of cholinomimetics in glaucoma?
inc outflow of humor via contraction of ciliary muscle and opening of trabecular meshwork
Which cholinomimetic is very effective in emergencies?
Pilocarpine (direct cholinomimetic)
acts quickly at opening trabecular meshwork into canal of schlemm
What are the side effects of cholinomimetics in glaucoma?
Cyclospasm (contraction of ciliary muscle)
Which prostaglandin is used in glaucoma?
What is the MOA of prostaglandin used in glaucoma?
inc outflow of aqueous humor
What is the S/E of prostaglandin in glaucoma?
Darkening of the iris (browning)
What are the common opioid analgesics?
What is the MOA of opioid analgesics?
agonists at opioid receptors to modulate synaptic transmission
opens K channels & closes Ca channels to decrease synaptic transmission.
inhibits release of ACh, HE, 5-HT, glutamate, substance P
What are the opioid receptors?
Mu = morphine
delta = enkephalin
kappa = dynorphin
Clinical use of opioid analgesics?
cough suppression (dextromethorphan)
diarrhea (loperamide & diphenoxylate)
acute pulmonary edema
maintenance for addicts (methadone)
Toxicity of opioid analgesics?
miosis (pinpoint pupils)
additive CNS depression with other drugs (esp ETOH, BZD, Barbs)
NO tolerance to miosis & constipation
What is the antidote to opioid OD?
Naloxone or Naltrexone
(opioid receptor antagonists)
What is the MOA of Butorphanol?
Mu-opioid receptor partial agonist
Kappa-opioid receptor agonist
Clinical use of Butorphanol?
Analgeisa for severe pain (migraine, labor, etc)
causes less respiratory depression than full opioid agonists.
What is the toxicity of Butorphanol?
opioid withdrawal symptoms if also taking full opioid agonist (competition for opioid receptors)
OD not easily reversed with Naloxone
What is the MOA of Tramadol?
Very weak opioid agonist
inhibitis serotonin & NE reuptake
What is the clinical use of Tramadol?
What is the toxicity of Tramadol?
similar to opioids-- resp depression, miosis, constipation, etc.
decreases seizure threshold
Benzodiazepines (Diazepam or Lorazepam)
1st line for tonic-clonic?
1st line for Complex partial?
1st line for simple partial?
1st line for absence seizure?
1st line for status epilepticus?
Acute tx-- loreazepam (or diazepam)
MOA of Phenytoin?
inc Na channel inactivation (use-dependent blockade)
inhibits glutamate release from excitatory presynaptic neuron
Use of Phenytoin?
tonic-clonic (also simple partial, complex partial)
status epilepticus prophylaxis
*use Fosphenytoin if parenteral
Class 1B antiarrhythmic
MOA of Carbamazepine?
Inc Na channel inactivation
Use of Carbamazepine?
1st line for simple partial, complex partial, tonic-clonic, and trigeminal neuralgia
MOA of Lamotrigine?
blocks voltage-gated NA channels
Use of Lamotrigine?
Simple partial, complex partial, tonic-clonic
MOA of Gabapentin?
inhibits high-voltage-activated Ca channels
Use of Gabapentin?
simple partial, complex partial, tonic-clonic
peripheral neuropathy, postherpetic neuralgia, migraine prophylaxis, bipolar disorder
MOA of Topiramate?
blocks Na channels
inc GABA action
Use of Topiramate?
simple partial, complex partial, tonic- clonic
MOA of phenobarbital?
inc GABA-A Action
Use of Phenobarbital?
1st line in children w/ simple partial, complex partial, tonic-clonic
MOA of Valproic Acid?
inc Na channel inactivation
inc GABA concentration
Use of valproic acid?
1st line for tonic clonic
simple partial, complex partial, absence, and myoclonic seizures (can be used for all seizure types)
MOA of Ethosuximide?
blocks thalamic T-type Ca channels
Use of Ethosuximide?
absence seizures (1st line)
MOA of benzodiazepines in seizures?
inc GABA-A action
Use of Bezodiazepines in seizures?
1st line for acute status epilepticus
Use for eclampsia seizures (after 1st line MgSO4)
MOA of Tiagabine?
inhibits GABA reuptake
Use of Tiagabine?
simple & complex partial seizures
MOA of Vigabatrin?
irreversibly inhibits GABA transaminase to increase GABA
Use of Vigabatrin?
simple & complex partial seizures
MOA of Levetiracetam?
may modulate GABA and Glutamate release
Use of Levetiracetam?
simple & complex partial
Toxicity of benzodiazepines?
induction of cytochrome p450
Toxicity of Carbamazepine?
Blood Dyscrasias (agranulocytosis & aplastic anemia)
induction of cytochrome p450
SIADH (dec Na)
Toxicity of Ethosuximide?
GI distress, fatigue, aggression
may worsen generalized tonic-clonic seizures
Toxicity of Phenobarbital?
induction of cytochrome p450
Toxicity of Phenytoin?
Teratogenesis (fetal hydantoin syndrome & inc risk of cleft palate)
Nystagmus & Diplopia (will develop tolerance)
megaloblastic anemia (dec folate absorption)
induction of p450
Toxicity of Valproic Acid?
Hepatotoxicty (rare but fatal-- measure LFTs)
Neural tube defects (spina bifida)-- Contra in pregnancy
tremor, weight gain
Toxicity of Lamotrigine?
(increase dosage slowly)
Toxicity of Gabapentin?
Toxicity of Topiramate
Weight loss = decreases appetite
What are common barbiturates?
What is the MOA of barbiturates?
facilitate GABA-A action by increasing DURATION of Cl channel opening thus decreasing neuron firing)
*BARBI (barbituates) likes it longer, BEN (benzodiazepines) wants it more often
What condition are barbiturates contraindicated in?
Clinical use of barbiturates?
(anxiety, seizures, insomnia, induction of anaesthesia-- thiopental)
Toxicity of Barbiturates?
Respiratory and cardiovascular depression (may be fatal)
CNS depression (exacerbated with BZD & ETOH use)
drug interactions (induces p450)
Antidote for Barbiturate OD?
supportive-- respiratory assistance & BP maintenance
What are common Benzodiazepines?
What is the MOA of Benzodiazepines?
facilitate GABA-A action by increasing the FREQUENCY of Cl channel opening
dec REM sleep
most have long-half lives
*Barbi likes it longer, Ben wants it more frequently
Short-half life benzodiazepines?
*higher addictive potential
Clinical use of Benzodiazepines?
anxiety, spasticity, status epilepticus, detoxification (ETOH withdrawal/DT's), night terros, sleepwalking, general anethetic, hypnotic.
Toxicity of Benzodiazepines?
additive CNS depression effects w/ ETOH & Barbs
Less coma & resp depression risk than Barbs
Antidone for OD?
competitive antagonist at GABA benzodiazepine receptor
Zolpidem, Zaleplon, Eszopiclone
MOA of non-benzo hypnotics?
act via BZ-1 subtype of GABA receptor
clinical use of non-benzo hypnotics?
Toxicity of non-benzo hyponotics?
ataxia, HA, confusion
rapid metab by liver enzymes = short duration of action
few amnestic events and modest day-after psychomotor depression
lower dependence risk than BZDs
Anesthetic drugs with low solubility in blood
rapid induction and recovery times
Anesthetic drugs with high solubility in lipids
high potency = 1/ MAC
MAC = minimal alveolar concentration at which 50% of the population is anesthetized. varies with age
Effects of inhaled anesthetics?
myocardial depression, respiratory depression, nausea/ emesis, inc cerebral blood flow (dec cerebral metabolic demand)
Toxicity of inhaled anesthetics?
malignant hyperthermia (all but nitrous oxide-- rare & life-threatening, inherited susceptibility)
expansion of trapped gas in body cavity (Nitrous oxide)
Arylcyclohexylamines (ketamine-- PCP analogs)
Opioids (morphine & fentayl)
high potency-- high lipid solubility & rapid entry into brain
used for induction of anesthesia & short surgical procedures
effects terminated by rapid redistribution into tissue & fat
decreased cerebral blood flow
most common drug used in endoscopy
used adjunctively with gas anesthetics & narcotics
may cause severe post-op respiratory depression, dec BP (tx OD w/ Flumazenil) and amnesia
Ketamine/ PCP analogs
block NMDA receptors
cause disorientation, hallucination, and bad dreams
inc cerebral blood flow
Morphine & Fentanyl
used with other CNS depressants in general anesthesia
sedation in ICU
rapid induction of anesthesia
short procedure anesthesia
less post-op nausea than thiopental
1) esters--- procaine, cocaine, tetracaine
2) amides--- lidocaine, mepivacaine, bupivacaine (all have 2 I's in name)
*if ester allergy, give amide
MOA of local anesthetics
blocks Na channels by dividing into specific receptors on inner portion of channel
preferentially bind to activated Na channels-- so most effective in rapidly firing neurons
tertiary amine local anesthetics penetrate membrane in uncharged form, then bind to ion channels as charged form
Order of nerve blockade in local anesthetics?
small-diameter fibers > large-diameter fibers
myelinated fibers > nonmyelinated fibers
*size predominates over myelination status
sm myelinated > sm unmyelinated > lg myelinated > lg unmyelinated
Order of loss of sensations in local anesthetic?
What happens when you give local anesthetic at an infected tissue?
infected tissue is acidic
anesthetic is alkaline and charged (therefore cannot penetrate membrane as effectively)
*must give more anesthetic at infected tissues
What can you combine with local anesthetics to enhance local action?
decreases bleeding, increases anesthesia locally by decreasing systemic concentration
Clinical use of local anesthetics?
Minor surgical procedures
Toxicity of local anesthetics?
severe cardiovascular toxicity (bupivacaine)
hypertension, hypotension & arrhythmias (cocaine)
What are neuromuscular blockade drugs used for?
muscle paralysis in surgery or mechanical ventilation
selective for motor nicotinic receptor (not autonomic)
What are the two types of neuromuscular blockade drugs?
Nondepolarizing (Tubocurarine, etc)
What is the common depolarizing NM blocking drug?
(strong Ach receptor agonist)
What is the MOA of succinylcholine?
produces sustained depolarization and prevents muscle contraction
How does blockade reversal occur in succinylcholine?
Phase I-- prolonged deloparization.
no antidone. block potentiated by cholinesterase inhibitors.
Phase II-- repolarized but blocked (ACh receptors are available but desensitized)
antidote = neostigmine (cholinesterase inhibitors)
Complication of succinylcholine?
Common Non-depolarizing NM blocking drugs?
MOA of non-depolarizing NM blocking drugs?
competitive antagonists-- compete with ACh for receptors
Reversal of blockade by non-depolarizing NM blocking drugs?
neostigmine & edrophonium
MOA of Dantrolene?
prevents Ca release from sarcoplasmic reticulum of skeletal muscle
Clinical use of Dantrolene?
Treats malignant hyperthermia
(rare, but life-threatening S/E of succinylcholine & inhalation anesthetics-- except N2O.
Neuroleptic Malignant Syndrome (toxicity of antipsychotic drugs)
General Parkinson's Disease Drug strategies:
increase dopamine release
prevent dopamine breakdown
curb excess cholinergic activity
Dopamine agonists used in Parkinsons?
(non-ergots are preferred)
Agents that Increase Dopamine release in Parkinsons?
Amantadine* (inc dopa release & also antiviral against influenza A & rubella)
L-dopa/Carbidopa* (converted to dopamine in CNS)
Agents that prevent Dopa breakdown in parkinsons?
Selegiline* (selective MAO-B inhibitor)
Entacapone, Tolcapone (COMT inhibitors-- prevent L-Dopa degradation = inc dopamine availability)
Agents that curb excess cholinergic activity in Parkinsons?
(antimuscarininc that improves tremor & rigidity but has little effect on bradykinesia)
*PARK your mercedes-BENZ here.
Typical regimen in Parkinson's Disease?
Levodopa (+ Carbidopa)
Toxicity associated with Amantadine?
MOA of Levodopa/Carbidopa?
increases level of dopamine in the brain
unlike dopa, L-dopa can cross BBB and is converted by dopa decarboxylase in CNS to dopamine.
Carbidopa = peripheral decarboxylase inhibitor
given with L-dopa to increase brain bioavailability and limit peripheral side effects
Toxicity of Levodopa/Carbidopa?
Arrhythmias-- bc inc peripheral formation of catecholamines
Long term use = dyskinesia following administration & akinesia between doses
MOA of selegiline?
Selective inhibits MAO-B (which preferentially metabolizes dopamine over NE & 5-HT) = increase availability of dopamine
Toxicity of selegiline?
may enhance adverse effects of L-dopa (arrhythmia & dyskinesia with long term use)
Donepezil, Galantamine, Rivastigmine
MOA of Memantine?
un-competitive NMDA receptor antagonist
helps prevent excitotoxicity (mediated by Ca & glutamate)
Toxicity of Memantine?
MOA of Dopepezil, Galantamine & Rivastigmine?
Acetylcholinesterase inhibitors = keep ACh levels up
Toxicity of Acetylcholinesterase inhibitors in Alzheimer's dz?
dizziness, insomnia, urinary incontinence
Tetrabenazine & Reserpine = inhibit VMAT (limit dopamine vesicle packaging & release)
Haloperidol- dopamine receptor antagonist
5-HT (1B/1D) agonist
inhibits trigeminal nerve activation
prevents vasoactive peptide release
half-life < 2 hrs
Clinical use of Sumatriptin?
Cluster HA attack
Toxicity of Sumatripin?
coronary vasospasm (CONTRA in CAD or Prinzmetal's Angina)