Neurology Flashcards
Epinephrine - alpha1
Brimonidine - alpha2
alpha agonists
MOA: decrease aqueous synthesis via vasoconstriction
Use: Glaucoma
Adv. effects: Mydriasis Blurry vision Ocular hyperemia Foreign body sensation Ocular allergic reactions Ocular pruritis
Do not use in close-angle
Timolol
Betaxolol
Carteolol
Beta blockers
MOA: decrease aqeous humor synthesis
Use: Glaucoma
Adv. effects:
No pupillary or vision changes
Acetazolamide
Diuretic
MOA: decrease aqueous humor synthesis via inhibition of of carbonic anhydrase
Use: Glaucoma
Adv. effects:
No pupillary or vision changes
Pilocarpine
Carbachol
Direct cholinomimetic (M3)
MOA: increase outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork
Use: Glaucoma
Pilocarpine used in emergencies (very effective at opening meshwork into canal of Schlemm)
Adv. effects:
Miosis
Cyclospasm
Physostigmine
Echothiophate
Indirect Cholinomimetic (M3)
MOA: increase outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork
Use: Glaucoma
Adv. effects:
Miosis
Cyclospasm
Bimatoprost
Latanoprost (PGF2a)
Prostaglandins
MOA: increase outflow of aqueous humor
Use: Glaucoma
Adv. effects: darkens color of iris (browning), eyelash growth
Opioid analgesics
Morphine Fentanyl Codeine Loperamide Methadone Meperidine Dextromethorphan Diphenoxylate Pentazocine
MOA:
Agonist at opioid receptors
Open K+ channels, close Ca2+ channels –> decrease synaptic transmission
Inhibit release of ACh, norepinephrine, 5-HT, glutamate, substance P.
Use: Pain Couch suppression (Dextromethorphan) Diarrhea (Loperamide, Diphenoxylate) Acute pulmonary edema Maintenance programs for heroin addicts (methadone)
Adv. effects:
Addiction, respiratory depression, constipation, miosis (Except meperidine –> mydriasis), additive CNS depression with other drugs.
Tolerance does not develop to miosis and constipation
Treat toxicity with naloxone or naltrexone (antagonists)
Pentazocine
MOA: k-opioid receptor agonist, u-opioid receptor antagonist
Use: Analgesia for mod. to severe pain
Adv. effects:
opioid withdrawal symptoms if patient also taking full opioid antagonist (compete for opioid receptors)
Butorphanol
MOA:
k-opioid receptor agonist, u-opioid receptor partial agonist; produces analgesia
Use: Severe pain. Causes less resp. distress than full opioid agonists
Adv. effects:
opioid withdrawal symptoms if patient also taking full opioid agonist (compete for opioid receptors)
overdose not easily reversed with naloxone
Tramadol
MOA:
very weak opioid agonist
inhibits 5-HT and norepinephrine reuptake
works on many neurotransmitters (“tram it all”)
Use: Chronic pain
Adv. effects:
similar to opioids
decreases seizure threshold
serotonin syndrome
Ethosuximide
MOA: Blocks thalamic T-type Ca2+ channels
Use: first line for Absence seizures
Adv. effects:
Fatigue, GI distress, Headache, Itching (urticaria), and Stevens-Johnson syndrome
“Sucks to have Silent (absence) Seizures”
Benzodiazepines
diazepam, lorazepam, midazolam
MOA: Increase GABAa action
Use: first line for acute status epilepticus; eclampsia seizures
Adv. effects:
Sedation, tolerance, dependence, respiratory depression
Phenobarbital
MOA: Increase GABAa action
Use: Partial (focal) seizures, Tonic-Clonic seizures
First line in neonates
Adv. effects:
Sedation, tolerance, dependence, induction of cytochrome P-450, cardiorespiratory depression
Phenytoin
Fosphenytoin
MOA: Blocks Na+ channels; zero order kinetics
Use:
first line for Tonic-Clonic seizures
first line for prophylaxis of status epilepticus
partial seizures
Adv. effects:
Neuro - nystagmus, diplopia, ataxia, sedation, peripheral neuropathy
Derm - hirsutism, Stevens-Johnson syndrome, gingival hyperplasia, DRESS syndrome.
MSK - osteopenia, SLE-like syndrome
Heme - megaloblastic anemia
Reproductive - teratogenesis (fetal hydantoin syndrome)
Other - cytochrome P-450 induction
Carbamezapine
MOA: Blocks Na+ channels
Use:
first line for trigeminal neuralgia
first line for partial seizures
tonic-clonic seizures
Adv. effects:
Diplopia, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity, teratogenesis, induction of cytochrome P450, SIADH, Stevens-Johnson syndrome.
Valproic acid
MOA:
Increase Na+ channel inactivation
Increase GABA concentration by inhibiting GABA transaminase
Use: first line for tonic-clonic seizures absence seizures partial seizures myoclonic seizures, bipolar disorder, migraine prophylaxis
Adv. effects:
neural tube defects, hepatotoxicity (rare but fatal), GI distress, pancreatitis, tremor, weight gain
Contraindicated in pregnancy***
Vigabatrin
MOA: Increase GABA by irreversibly inhibiting GABA transaminase
Use: partial seizures
Gabapentin
MOA: Inhibits high-voltage-activated Ca2+ channels; GABA analog
Use:
peripheral neuropathy
postherpatic neuralgia
partial seizures
Adv. effects:
Sedation, ataxia
Topiramate
MOA:
Blocks Na+ channels
Increase GABA action
Use:
partial seizures
tonic-clonic seizures
migraine prevention
Adv. effects:
Sedation, mental dulling, kidney stones, weight loss
Lamotrigine
MOA: Blocks voltage-gated Na+ channels
Use:
partial seizures
tonic-clonic seizures
absence seizures
Adv. effects:
Stevens-Johnson syndrome (must be titrated slowly)
Levetiracetam
MOA: unknown; may modulate GABA and glutamate release
Use:
partial seizures
tonic-clonic seizures
Tiagabine
MOA: Increase GABA by inhibiting reuptake
Use: partial seizures
Barbiturates
phenobarbital, pentobarbital, thiopental, secobarbital
MOA: Increase DURATION of Cl- channel opening (facilitate GABAa action)
—-> decrease neuron firing
Use: sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental)
Adv. effects:
respiratory / cardio depression - can be fatal
CNS depression - can be exacerbated by alcohol
dependence
induces cytochrome P450
Contraindicated in porphyria
Overdose treatment is supportive
Benzodiazepines
diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam
MOA:
Increase FREQUENCY of Cl- channel opening (facilitate GABAa action)
Decrease REM sleep
Long half lives and active metabolites - except Alprazolam, Triazolam, Oxazepam, Midazolam (short acting —> higher addictive potential)
Use: Anxiety (sedative) Spasticity Status epilepticus (lorazepam, diazepam) Eclampsia Detoxification (esp. alcohol withdrawal - DTs) Night terrors, sleepwalking General anesthetic (amnesia, muscle relaxation) Hypnotic (insomnia)
Adv. effects: d
dependence
additive CNS depression w/ alcohol
less risk of resp. depression and coma than w/ barbiturates
Treat overdose with flumazenil (competitive antagonist)
- can precipitate seizures by causing acute benzo withdrawal
Hypnotics
Zolpidem, Zaleplon, Eszopiclone
MOA: act via BZ1 subtype of GABA receptor
Use: Insomnia
Avd. effects:
ataxia, headaches, confusion
modest day-after psychomotor depression and few amnestic effects
less dependence risk than benzodiazepines
sleep cycle less affected than with benzo
Effects reversed by flumazenil
Nitrous oxide (N2O)
inhaled anesthetic
low blood and lipid solubility —–> fast induction and low potency
Halothane
inhaled anesthetic
high lipid and blood solubility ——> high potency and slow induction
Inhaled anesthetics
Desflurane, Halothane, Enflurane, Isoflurane, Sevoflurane, Methoxyflurane, N2O
MOA: unknown
Effects: Myocardial depression Respiratory depression Nausea / Emesis Increase cerebral blood flow (decrease cerebral metabolic demand)
Adv. effects: Hepatotoxicity (Halothane) Nephrotoxicity (Methoxyflurane) Proconvulsant (Enflurane) Expansion of trapped gas in a body cavity (N2O) Malignant hyperthermia
Malignant hyperthermia
life threatening
Inhaled anesthetics or succinylcholine induce fever and severe muscle contractions
Susceptibility can be inherited as AD w/ variable penetrance.
Mutations in voltage-sensitive ryanodine receptor cause increase Ca2+ release from sarcoplasmic reticulum.
Treatment: Dantrolene (ryanodine receptor antagonist)
Barbiturates (Thiopental)
Intravenous anesthetic
High potency, high lipid solubility, rapid entry into brain
Used for induction of anesthesia and short surgical procedures
Effect terminated by rapid distribution into tissue and fat
Decrease cerebral blood flow
Benzodiazepines (Midazolam)
Intravenous anesthetic
Used for endoscopy
Used adjunctively w/ gaseous anesthetics and narcotics
May cause severe postoperative respiratory depression, decrease BP (treat overdose w/ flumazenil), anterograde amnesia
Arylcyclohexylamines (Ketamine)
Intravenous anesthetic
PCP analogs that act as dissociative anesthetics
Block NMDA receptors
Cardiovascular stimulants
Cause disorientation, hallucination, bad dreams
Increase cerebral blood flow
Propofol
Intravenous anesthetic
Used for sedation in ICU, rapid anesthesia induction, short procedures
Less postoperative nausea than thiopental
Potentiates GABAa
Opioids
Intravenous anesthetic
Morphine, fentanyl used with other CNS depressants during general anesthesia
Local anesthetics
Esters (Procaine, Cocaine, Tetracaine, Benzocaine)
Amides (Lidocaine, Mepivacaine, Bupivacaine) - 2 I’s in amides
MOA:
Block Na+ channels (bind inner portion of channel)
Most effective in rapidly firing neurons.
Tertiary amine local anesthetics penetrate membrane in uncharged form, then bind to ion channels as charged form.
Can be given with vasoconstrictors (like epinephrine) to enhance local action - decrease bleeding, increase anesthesia by decreasing systemic concentration.
In infected tissue - alkaline anesthetics are charged and cannot penetrate membrane effectively –> need more anesthetic
Order of nerve blockade:
small-diameter fibers > large diameter fibers
Myelinated fibers > unmyelinated fibers
small myelinated fibers > small unmyelinated fibers > large myelinated fibers > large unmyelinated fibers
Order of loss: pain, temperature, touch, pressure
Use:
Minor surgical procedures, spinal anesthesia
If allergic to esters, give amides
Adv. effects: CNS excitation Severe cardiovascular toxicity (bupivacaine) Hypertension Hypotension Arrythmias (cocaine) Methemoglobinemia (benzocaine)
Depolarizing neuromuscular blocking drugs
Succinylcholine
Strong ACh receptor agonist
Produces sustained depolarization and prevents muscle contraction
Reversal of blockade: Phase I (prolonged depolarization) - no antidote. Block potentiated by cholinesterase inhibitors Phase II (repolarized but blocked; ACh receptors are available, but desensitized) - may be reversed with cholinesterase inhibitors
Use:
Muscle paralysis in surgery or mechanical ventilation. Selective for motor (vs. autonomic) nicotinic receptor.
Complications include hypercalcemia, hyperkalemia, malignant hyperthermia
Nondepolarizing neuromuscular blocking drugs
Tubocurarine, Atracurium, Mivacurium, Pancuronium, Vecuronium, Rocuronium - Competitive antagonists - compete with ACh for receptors
Reversal of blockade - neostigmine (must be given with atropine to prevent muscarinic effects such as bradycardia), edrophonium, and other cholinesterase inhibitors
Dantrolene
MOA:
prevents release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle by binding to the ryanodine receptor
Use:
Malignant hyperthermia
Neuroleptic malignant syndrome (toxicity of antipsychotic drugs)
Baclofen
MOA:
Activates GABAb receptors at spinal cord level, including skeletal muscle relaxation
Use: Muscle spasms (ex. acute low back pain)
Cyclobenzapine
MOA:
Centrally acting skeletal muscle relaxant
Structurally related to TCA, similar anticholinergic side effects
Use: Muscle spasms
Bromocriptine
Ergot
Dopamine agonist
Parkinson drug
Pramipexole, Ropinirole
Non ergot
Dopamine agonist
Parkinson drug
Amantadine
Increase dopamine release
Decrease dopamine reuptake
Toxicity = ataxia, livedo reticularis
Use: Parkinson
L-dopa (levodopa)/carbidopa
MOA: Increase level of dopamine in brain Prevent peripheral (pre-BBB) L-dopa degradation --> Increased L-DOPA entering CNS --> Increased L-DOPA available for conversion to dopamine Carbidopa blocks peripheral conversion of L-DOPA to dopamine by inhibiting DOPA decarboxylase; also reduces side effects of peripheral L-dopa conversion into dopamine (nausea, vomiting)
Use: Parkinson
Entacapone. Tolcapone
Act centrally (post-BBB) to inhibit breakdown of dopamine
MOA:
Prevent peripheral L-dopa degradation to 3-O-methyldopa (3-OMD) by inhibiting COMT
Tolcapone works centrally to block conversion of dopamine to 3-OMD by inhibiting central COMT
Use: Parkinson
Selegiline, Rasagiline
Act centrally (post-BBB) to inhibit breakdown of dopamine
MOA: Blocks conversion of dopamine into DOPAC by selectively inhibiting MAO-B.
Use: Parkinson
Memantine
MOA:
NMDA receptor antagonist; helps prevent excitotoxicity (mediated by Ca2+)
Adv. effects:
Dizziness, Confusion, Hallucinations
Use: Alzheimer’s
Donepezil, Galantamine, Rivastigmine, Tacrine
MOA: AChE inhibitors
Adv. effects:
Nausea, dizziness, insomnia
Use: Alzheimer’s
Tetrabenazine, Respirine
MOA:
Inhibit vesicular monoamine transport (VMAT) –> decrease dopamine vesicle packaging and release
Use: Huntington’s
Haloperidol
D2 receptor agonist
Use: Huntington’s
Riluzole
Treatment for ALS that modestly increase survival by decreasing glutamate excitotoxicity via an unclear mech.
“For Lou Gehrig disease, give riLOUzole”
Triptans
MOA: 5HT 1B/1D agonists Inhibit trigeminal nerve activation Prevent vasoactive peptide release Induce vasoconstriction
Use:
Acute migraine
Cluster headache attacks
Adv. effects:
Coronary vasospasm
Mild paresthesia
Contraindicated in patients with CAD or Prinzmetal angina
