FA Neurology Flashcards
Glaucoma Drugs
α-agonists (epinephrine, brimonidine), β-blockers (timolol, betaxolol, certeolol), diuretics (acetazolamide), cholinomimetics (direct: pilocarpine, carbachol; indirect: physostigmine, echothiophate), Latanoprost (PGF2α)
Epinephrine Mechanism [glaucoma]
↓ aqueous humor synthesis via vasoconstriction
Epinephrine Side Effects [glaucoma]
Mydriasis; do not use in closed-angle glaucoma
Brimonidine (α2) Mechanism [glaucoma]
↓ aqueous humor synthesis
Brimonidine (α2) Side Effects [glaucoma]
Blurry vision, ocular hyperemia, foreign body sensation, ocular allergic reactions, ocular pruritus
Timolol Mechanism [glaucoma]
↓ aqueous humor synthesis
Betaxolol Mechanism [glaucoma]
↓ aqueous humor synthesis
Carteolol Mechanism [glaucoma]
↓ aqueous humor synthesis
Timolol Side Effects [glaucoma]
No pupillary or vision changes
Betaxolol Side Effects [glaucoma]
No pupillary or vision changes
Carteolol Side Effects [glaucoma]
No pupillary or vision changes
Acetazolamide Mechanism [glaucoma]
↓ aqueous humor synthesis via inhibition of carbonic anhydrase
Acetazolamide Side Effects [glaucoma]
No pupillary or vision changes
Pilocarpine Mechanism [glaucoma]
Direct cholinomimetic. ↑ outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork
Carbachol Mechanism [glaucoma]
Direct cholinomimetic. ↑ outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork
Pilocarpine Side Effects [glaucoma]
Miosis and cyclospasm (contraction of ciliary muscle)
Carbachol Side Effects [glaucoma]
Miosis and cyclospasm (contraction of ciliary muscle)
Physostigmine Mechanism [glaucoma]
Indirect cholinomimetic. ↑ outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork
Physostigmine Side effects [glaucoma]
Miosis and cyclospasm (contraction of ciliary muscle)
Echothiophate Mechanism [glaucoma]
Indirect cholinomimetic. ↑ outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork
Echothiophate Side Effects [glaucoma]
Miosis and cyclospasm (contraction of ciliary muscle)
Latanoprost (PGF2α) mechanism [glaucoma]
Prostaglandin; ↑ outflow of aqueous humor
Latanoprost (PGF2α) side effects [glaucoma]
Darkens color of iris (browning)
Opioid Analgesics
Morphine, fentanyl, codeine, loperamide, methadone, meperidine, dextromethorphan, diphenoxylate
Opiod Analgesic Mechanism
Act as agonists at opioid receptors (mu = morphine, delta = enkephalin, kappa = dynorphin) to modulate synaptic transmission – open K+ channles, close Ca2+ channels → ↓ synaptic transmission. Inhibit release of ACh, norepinephrine, 5-HT, glutamate, substance P.
Opiod Analgesic Use
Pain, cough suppression (dextromethorphan), diarrhea (loperamide and diphenoxylate), acute pulmonary edema, maintenance programs for heroin addicts (methadone)
Opioid Analgesic Toxicity
Addiction, respiratory depression, constipation, miosis (pinpoint pupils), additive CNS depression with other drugs. Tolerance does not develop to miosis and constipation. Toxicity treated with naloxone or naltrexone (opioid receptor antagonist).
Butorphanol Mechanism
Mu-opioid receptor partial agonist and kappa-opioid receptor agonist; produces analgesia.
Butorphanol Use
Severe pain (migraine, labor, etc.). Causes less respiratory depression than full opioid agonists.
Butorphanol Toxicity
Can cause opioid withdrawal symptoms if patient is also taking full opioid agonist (competition for opioid receptors). Overdose not easily reversed with naloxone.
Tramadol mechanism
Very weak opioid agonist; also inhibits serotonin and norepinephrine reuptake (works on multiple neurotransmitters – “tram it all” with tramadol).
Tramadol Use
Chronic pain.
Tramadol Toxicity
Similar to opioids. Decreases seizure threshold. Serotonin syndrome.
Ethosuxamide Use [Seizures]
1st line absence seizures
Benzodiazepine (diazepam, lorazepam) Use [Seizures]
1st line for acute status epilepticus. Also for eclampsia seizures (1st line is MgSO4)
Phenytoin Use [Seizures]
Simple and complex partial (focal) seizures. 1st line tonic-clonic seizures. 1st line prophylaxis status epilepticus. Fosphenytoin for parenteral use.
Carbamazepine Use [Seizures]
1st line simple and complex partial (focal) seizures. 1st line tonic-clonic seizures. 1st line for trigeminal neuralgia.
Valproic Acid Use [Seizures]
Simple and complex partial (focal) seizures, absence seizures. 1st line tonic-clonic seizures. Also used for myoclonic seizures, bipolar disorder.
Gabapentin Use [Seizures]
Simple and complex partial (focal) seizures, tonic-clonic seizures. Also used for peripheral neuropathy, postherpetic neuralgia, migraine prophylaxis, bipolar disorder.
Phenobarbital Use [Seizures]
Simple and complex partial (focal) seizures, tonic-clonic seizures. 1st line in neonates.
Topiramate Use [Seizures]
Simple and complex partial (focal) seizures, tonic-clonic seizures. Also used for migraine prevention.
Lamotrigine Use [Seizures]
Simple and complex partial (focal), tonic-clonic, and absence seizures.
Levetiracetam Use [Seizures]
Simple and complex partial (focal) seizures, tonic-clonic seizures.
Tiagabine Use [Seizures]
Simple and complex partial (focal) seizures.
Vigabatrin Use [Seizures]
Simple and complex partial (focal) seizures.
Ethosuxamide Mechanism [Seizures]
Blocks thalamic T-type Ca2+ channels
Benzodiazepine (diazepam, lorazepam) Mechanism [Seizures]
↑ GABAₐ action
Phenytoin Mechanism [Seizures]
↑ Na+ channel inactivation; zero-order kinetics
Carbamazepine Mechanism [Seizures]
↑ Na+ channel inactivation
Valproic Acid Mechanism [Seizures]
↑ Na+ channel inactivation, ↑ GABA concentration by inhibiting GABA transaminase
Gabapentin Mechanism [Seizures]
Primarily inhibits high-voltage-activated Ca2+ channels; designed as GABA analog
Phenobarbital Mechanism [Seizures]
↑ GABAₐ action
Topiramine Mechanism [Seizures]
Blocks Na+ channels, ↑ GABA action
Lamotrigine Mechanism [Seizures]
Blocks voltage-gated Na+ channels
Levetiracetam Mechanism [Seizures]
Unknown; may modulate GABA and glutamate release
Tiagabine Mechanism [Seizures]
↑ GABA by inhibiting re-uptake
Vigabatrin Mechanism [Seizures]
↑ GABA by irreversibly inhibiting GABA transaminase
Ethosuxamide Side Effects [Seizures]
GI, fatigue, headache, urticaria, Stevens-Johnson syndrome. EFGHIJ - Ethosuxamide causes Fatigue, GI distress, Headache, Itching, and Stevens-Johnson syndrome
Benzodiazepine (diazepam, lorazepam) Side Effects [Seizures]
Sedation, tolerance, dependence, respiratory depression
Phenytoin Side Effects [Seizures]
Nystagmus, diplopia, ataxia, sedation, gingival hyperplasia, hirsutism, peripheral neuropathy, megaloblastic anemia, teratogenesis (fetal hydantoin syndrome), SLE-like syndrome, induction of cytochrome P-450, lymphadenopathy, Stevens-Johnson syndrome, osteopenia
Carbamazepine Side Effects [Seizures]
Diplopia, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity, teratogenesis, induction of cytochrome P-450, SIADH, Stevens-Johnson syndrome
Valproic Acid Side Effects [Seizures]
GI, distress, rare but fatal hepatotoxicity (measure LFTs), neural tube defects in fetus (spina bifida), tremor, weight gain, contraindicated in pregnancy
Gabapentin Side Effects [Seizures]
Sedation, ataxia
Phenobarbital Side Effects [Seizures]
Sedation, tolerance, dependence, induction of cytochrome P-450, cardiorespiratory depression
Topiramate Side Effects [Seizures]
Sedation, mental dulling, kidney stones, weight loss
Lamotrigine Side Effects [Seizures]
Stevens-Johnson syndrome (must be titrated slowly)
Barbiturates
Phenobarbital, pentobarbital, thiopental, secobarbital
Barbiturate Mechanism
Facilitate GABAₐ action by ↑ duration of Cl- channel opening, thus ↓ neuron firing. Contraindicated in porphyria.
Barbiturate Use
Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental).
Barbiturate Toxicity
Respiratory and cardiovascular depression (can be fatal); CNS depression (can be exacerbated by EtOH use); dependence; drug interactions (induces cytochrome P-450). Overdose treatment is supportive (assist respiration and maintain BP).
Benzodiazepines
Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam
Benzodiazepine Mechanism
Facilitate GABAₐ action by ↑ frequency of Cl- channel opening. ↓ REM sleep. Most have long half-lives and active metabolites (exceptions: triazolam, oxazepam, and midazolam are short acting → higher addictive potential).
Benzodiazepine Use
Anxiety, spasticity, status epilepticus (lorazepam and diazepam), detoxification (especially alcohol withdrawal–DTs), night terrors, sleepwalking, general anesthetic (amnesia, muscle relaxant), hypnotic (insomnia).
Benzodiazepine Toxicity
Dependence, additive CNS depression effects with alcohol. Less risk of respiratory depression and coma than with barbiturates. Treat overdose with flumazenil (competitive antagonist at GABA benzodiazepine receptor).
Nonbenzodiazepine Hypnotics
Zolpidem (Ambien), Zaleplon, Eszopiclone
Nonbenzodiazepine Hypnotic Mechanism
Act via the BZ1 subtype of the GABA receptor. Effects reversed by flumazenil.
Nonbenzodiazepine Hypnotic Use
Insomnia
Nonbenzodiazepine Hypnotic Toxicity
Ataxia, headaches, confusion. Short duration because of rapid metabolism by liver enzymes. Unlike older sedative-hypnotics, cause only modest day-after psychomotor depression and few amnestic effects. ↓ dependence risk than benzodiazepines.
Inhaled Anesthetics
Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide.
Inhaled Anesthetic Mechanism
Mechanism unknown.
Inhaled Anesthetic Effects
Myocardial depression, respiratory depression, nausea/emesis, ↑ cerebral blood flow (↓ cerebral metabolic demand).
Inhaled Anesthetic Toxicity
Hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane), expansion of trapped gas in a body cavity (nitrous oxide). Can cause malignant hyperthermia – rare, life-threatening hereditary condition in which inhaled anesthetics (except nitrous oxide) and succinylcholine induce fever and severe muscle contractions. Treatment: dantrolene.
IV Anesthetics
Barbiturates (thiopental), Benzodiazepines (midazolam), Arylcyclohexylamines (ketamine), Opioids (morphine, fentanyl), Propofol
Thiopental [IV Anesthetic]
High potency, high lipid solubility, rapid entry into brain. Used for induction of anesthesia and short surgical procedures. Effect terminated by rapid redistribution into tissue (i.e. skeletal muscle) and fat. ↓ cerebral blood flow.
Midazolam [IV Anesthetic]
Most common drug used for endoscopy; used adjunctively with gaseous anesthetics and narcotics. May cause severe postoperative respiratory depression, ↓ BP (treat overdose with flumazenil), and anterograde amnesia.
Arylcyclohexylamines (ketamine) [IV Anesthetic]
PCP analogs that act as dissociative anesthetics. Block NMDA receptors. Cardiovascular stimulants. Cause disorientation, hallucination, and bad dreams. ↑ cerebral blood flow.
Opioids [IV Anesthetic]
Morphine, fentanyl used with other CNS depressants during general anesthesia.
Propofol [IV Anesthetic]
Used for sedation in ICU, rapid anesthesia induction, and short procedures. Less postoperative nausea than thiopental. Potentiates GABAₐ.
Local Anesthetics
Esters - procaine, cocaine, tetracaine.
Amides - lidocaine, mepivacaine, bupivacaine.
Local Anesthetic Mechanism
Block Na+ channels by binding to specific receptors on inner portion of channel. Preferentially bind to activated Na+ channels, so most effective in rapidly firing neurons. 3° amine local anesthetics penetrate membrane in uncharged form, then bind to ion channels as charged form.
Local Anesthetic Principle
Can be given with vasoconstrictors (usually epi) to enhance local action – ↓ bleeding, ↑ anesthesia by ↓ systemic concentration. In infected (acidic) tissue, alkaline anesthetics are charged and cannot penetrate membrane effective → need more anesthetic.
Order of nerve blockade: small-diameter fibers > large diameter. Myelinated fibers > unmyelinated fibers. Overall, size factor predominates over myelination such that small myelinated > small unmyelinated > large myelinated > large unmyelinated fibers. Order of loss: (1) pain, (2) temperature, (3) touch, (4) pressure.
Local Anesthetic Use
Minor surgical procedures, spinal anesthesia. If allergic to esters, give amides.
Local Anesthetic Toxicity
CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension, hypotension, and arrhythmias (cocaine).
Neuromuscular Blocking Drugs
Depolarizing - Succinylcholine
Nondepolarizing - Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rocuronium
Neuromuscular Blocking Drug Use
Used for muscle paralysis in surgery or mechanical ventilation. Selective for motor (vs. autonomic) nicotinic receptor.
Depolarizing Neuromuscular Blocking Drug Mechanism
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 available but desensitized) - antidote consists of cholinesterase inhibitors.
Depolarizing Neuromuscular Blocking Drug Toxicity
Hypercalcemia, hyperkalemia, malignant hyperthermia.
Nondepolarizing Neuromuscular Blocking Drug Mechanism
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 Mechanism
Prevents the release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle.
Clinical Use
Used to treat malignant hyperthermia and neuroleptic malignant syndrome (a toxicity of antipsychotic drugs).
Parkinson Disease Drugs
Dopamine agonists (bromocriptine, pramipexole, ropinirole), ↑ dopamine (amantadine, L-dopa/carbidopa), prevent dopamine breakdown (selegiline, entecapone, tolcapone), curb cholinergic activity (benztropine)
Dopamine agonists
Bromocriptine (ergot), pramipexole, ropinirole (non-ergot); non-ergots are preferred
Amantadine Use
Parkinsonism - may ↑ dopamine release; also used as an antiviral against influenza A and rubella
Amantadine Toxicity
Ataxia
L-dopa/Carbidopa Mechanism
↑ level of dopamine in brain. Unlike dopamine, L-dopa can cross blood-brain barrier and is converted by dopa decarboxylase in the CNS to dopamine. Carbidopa, a peripheral decarboxylase inhibitor, is given with L-dopa to ↑ the bioavailability of L-dopa in the brain and to limit peripheral side effects.
L-dopa/Carbidopa Use
Parkinson disease
Selegiline Mechanism
Selectively inhibits MAO-B, which preferentially metabolizes dopamine over norepinephrine and 5-HT, thereby ↑ the availability of dopamine
Selegiline Use
Adjunctive agent to L-dopa in treatment of Parkinson disease
Entecapone, Tolcapone Mechanism
COMT inhibitors - prevent L-dopa degradation → ↑ dopamine availability
Benztropine Use
Antimuscarinic used to improve tremor and rigidity in Parkinson disease. Has little effect on bradykinesia.
L-dopa/Carbidopa Toxicity
Arrhythmias from ↑ peripheral formation of catecholamines. Long-term use can lead to dyskinesia following administration (“on-off” phenomenon), akinesia between doses.
Selegiline Toxicity
May enhance adverse effects of L-dopa
Alzheimer Drugs
Memantine, donepezil, galantamine, rivastigmine
Memantine Mechanism
NMDA receptor antagonist; helps prevent excitotoxicity (mediated by Ca2+)
Memantine Toxicity
Dizziness, confusion, hallucinations
Donepezil, Galantamine, Rivastigmine Mechanism
AChE inhibitor
Donepezil, Galantamine, Rivastigmine Toxicity
Nausea, dizziness, insomnia
Huntington Drugs
Tetrabenazine, reserpine, haloperidol
Tetrabenazine, Reserpine Mechanism [Huntington Disease]
Inhibit vesicular monoamine transporter (VMAT); limit dopamine vesicle packaging and release.
Haloperidol Mechanism [Huntington Disease]
Dopamine receptor agonist
Sumatriptan Mechanism
5-HT1B/1D agonist. Inhibits trigeminal nerve activation; prevents vasoactive peptide release; induces vasoconstriction. Half-life < 2 hours.
Sumatriptan Use
Acute migraines, cluster headache attacks
Sumatriptan Toxicity
Coronary vasospasm (contraindicated in patients with CAD or Prinzmetal angina), mild tingling.
