Neuro Flashcards
Epinephrine (alpha1), Brimonidine (alpha 2)
[Effect in Glaucoma]
> Epinephrine: vasoconstriction – dec. aqueous humor synth; can cause mydriasis via alpha1 (not for closed-angle glaucoma).
Brimonidine: dec. aqueous humor synth
Timolol, Betaxolol, Carteolol (B-blockers)
[Effect in Glaucoma]
Dec. aqueous humor synth by the ciliary epithelium.
Acetazolamide (diuretic)
[Effect in Glaucoma]
Inhibit carbonic anhydrase – dec. aqueous humor synth.
Pilocarpine, Carbachol (direct cholinomimetics).
Physostigmine, Echothiophate (indirect).
[Effect in Glaucoma, SE]
Contracts ciliary muscle (M3) and opening of trabecular meshwork – Inc. aqueous humor outflow.
*Pilocarpine for emergencies: effective in opening canal of Schlemm.
SE: mitosis, cyclospasm.
Latanoprost (PGF2a)
[Effect in Glaucoma, SE]
Inc. outflow of aqueous humor (by inc. uveoscleral outflow).
SE: darkens iris color (browning)
Opioid analgesics Drug names (4)
Morphine, Fentanyl, Codeine
Loperamide, Methadone, Meperidine
Dextromethorphan, Diphenoxylate Pentazocine
Opioid analgesics
MOA
> Agonists at opioid receptors – open K channels, close Ca channels – dec. synaptic transmission.
Inhibits release of neurotransmitters (ACh, NE, 5HT, glutamate, substance P).
[Mu - morphine, Delta - enkephalin, Kappa - dynorphin]
Opioid analgesics
Use
Pain. Cough suppression (dextromethorphan). Diarrhea (loperamide, diphenoxylate). Acute pulmo edema. Maintenance for heroin addicts.(methadone, buprenorphine + naloxone)
Opioid analgesics
Toxicity
Addiction, Respi depression, constipation. Pinpoint pupils (miosis). Tx: Naloxone, Naltrexone (opioid receptor antagonist).
Butorphanol
[use]
Kappa receptor agonist; partial agonist to Mu-receptor.
For severe pain (migraine, labor).
*Don’t give w/ full opioid agonist – withdrawal sx due to competition for receptors; overdose not easily reversed w/ naloxone
Tramadol
[use, SE]
Weak opioid agonist; also inhibits 5HT and NE reuptake.
For chronic pain.
SE: Serotonin syndrome.
Ethosuxamide
[Seizure type, MOA, SE]
Absence seizures.
>MOA: Blocks thalamic T-type Ca channels – inhibits the transient depolarizations necessary to make spike-wave patterns seen in Absence (maintains rhythmic discharge in thalamic neurons).
>SE: Fatigue, GI distress, Headache, Itching, SJS.
Diazepam, Lorazepam
[Seizure type, MOA]
Status epilepticus; Eclampsia seizures.
MOA: Inc. GABA-A action by inc. frequency of Cl- channel opening.
Phenytoin
[Seizure types, MOA, SE]
Tonic-clonic (1st line), Status epilepticus (prophylaxis); partial seizures.
>MOA: Inc. Na channel inactivation (dec. propagation)
>SE: gingival hyperplasia, megaloblastic anemia, teratogenesis, SJS, osteopenia
Carbamazepine
[Seizure types, MOA, SE]
1st line: Partial seizures, Tonic-clonic.
1st line: trigeminal neuralgia.
>MOA: Inc. Na channel inactivation.
>SE: blood dyscrasias (agranulocytosis, aplastic anemia), teratogenesis, liver toxicity
Valproic acid
[Seizure types, MOA, SE]
Tonic-clonic (1st line), absence, Partial seizures.
>MOA: Inc. Na channel inactivation; Inhibits GABA transaminase (inc. GABA conc.).
>SE: Neural tube defects, CI in preg
Gabapentin
[Seizure types, MOA]
Partial seizures.
>MOA: inhibits voltage-activated Ca channels (GABA analog).
*Also for peripheral neuropathy, postherpetic neuralgia
Phenobarbital
[Seizure types, MOA]
Partial seizures, Tonic-clonic.
MOA: inc. GABA-A action by inc. duration of Cl- channel opening.
*1st line in neonates
Lamotrigine
[Seizure types, MOA, SE]
Partial seizures; Tonic-clonic, Absence.
MOA: Blocks voltage-gated Na channels.
SE: SJS (titrate slowly).
Topiramate
[Seizure types, MOA]
Partial seizures, Tonic-clonic.
MOA: Blocks Na channels, Inc. GABA action.
*Also for migraine prevention
Tiagabine
[Seizure types, MOA]
Partial seizures.
MOA: Inhibits GABA reuptake.
Barbiturates
[Drug names, use]
Phenobarbital, Pentobarbital, Thiopental, Secobarbital.
Sedative for anxiety, seizures, insomnia.
Induction of anesthesia (thiopental).
Barbiturates
[MOA, toxicity]
> MOA: Inc. duration of Cl channel opening – inc. GABA-A action – dec. neuron firing.
SE: respi and cardiovascular depression; CNS depression, dependence.
Benzodiazepines
[Drug names, use]
> Diazepam, Lorazepam, Triazolam, Temazepam, Oxazepam, Midazolam, Chlordiazepoxide, Alprazolam.
For anxiety, Status epilepticus (lorazepam, diazepam), detoxification (alcohol-w/d DT), general anesthetic, night terrors, hypnotic.
Benzodiazepines
[MOA, toxicity]
> MOA: GABA-A receptor; Inc. frequency of Cl channel opening – inc. GABA-A action.
SE: dependence, additive CNS depression w/ alcohol; less risk of respi depression vs barbiturates.
*Tx overdose: flumazenil (competetive antagonist)
Non-BZ hypnotics
[Drugs, MOA, use]
Zolpidem, Zaleplon, Eszopiclone.
Acts on BZ1 subtype of GABA receptor.
For insomnia (short-term tx).
*Effects reversed by flumazenil
Inhaled anesthetics
[Drug, effects]
Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane; N2O.
>Effects: myocardial depression, respi depression, inc. cerebral blood flow (dec. cerebral metabolic demand).
Inhaled anesthetics
Toxicity
Hepatotoxic (halothane); Nephrotoxic (methoxyflurane); Proconvulsant (enflurane).
Expansion of trapped gas in body cavity (N2O).
*Malignant hyperthermia: life-threatening, hereditary; inhaled anesthetics (except N2O) and succinylcholine induce fever, muscle contractions; Tx is Dantrolene.
Why is thiopental (as an IV barbiturate) most commonly used for induction of anesthesia and short surgical procedures?
Has high potency, high lipid solubility, and rapid entry into brain.
Rapid redistribution into tissues terminates effects.
Which benzodiazepine is most commonly used for endoscopy? What are possible side effects?
Midazolam, used adjunctively w/ gas anesthetics and narcotics.
May cause severe post-op respi depression and dec. BP (tx overdose w/ flumazenil).
Possible anterograde amnesia
Ketamine
[use, MOA, SE]
PCP analog.
>Blocks NMDA receptors. Cardiovascular stimulants.
>Starting and maintaining anesthesia – induces a trance-like state; provides pain relief, sedation, memory loss; inc. cerebral blood flow.
>SE: disorientation, hallucination, bad dreams
Propofol
[use, MOA]
Used for sedation in ICU, rapid anesthesia induction, short procedures.
Less post-op nausea vs thiopental.
Potentiates GABA-A.
Local anesthetics (-caine) [Names (Esters, Amides), uses]
> Esters: Procaine, Cocaine, Tetracaine
Amides: Lidocaine, Mepivacaine, Bupivacaine.
For minor surgeries, spinal anesthesia.
Local anesthetics.
How do you enhance local action?
To enhance local action, can give w/ vasoconstrictors (Epi) – dec. bleeding; dec. systemic concentration to inc. local anesthesia.
Local anesthetics.
How do you use a local anesthetic in tissue that’s infected (acidic)?
In infected (acidic) tissues, need more anesthetic because alkaline anesthetics are charged and can’t penetrate membrane effectively.
Local anesthetics.
Order of nerve blockade (diameter, myelination)
- Small diameter > large diameter (predominates).
- Myelinated > nonmyelinated.
- Small myelinated > small unmyelinated > large myelinated > large unmyelinated
Local anesthetics.
Order of loss (sensations)
1) pain
2) temp
3) touch
4) pressure
Local anesthetics
MOA
Binds to receptors on inner portion of Na channels – blocks Na channels.
Preferential for activated Na channels – effective in rapidly firing neurons.
Local anesthetics
Toxicity
Severe cardiovascular toxicity (bupivacaine).
Arrhythmias (cocaine).
Methemoglobinemia (benzocaine)
Succinylcholine
[MOA, clinical use, SE]
Neuromuscular blocker; muscle paralysis in surgery or mech vent; selective for motor N-receptors.
>Succinylcholine: strong ACh receptor agonist – sustained depol, prevents muscle contraction.
>SE: hyperCa, hyperK, malignant hyperthermia
Reversal of blockade made by Succinylcholine
> Phase I: prolonged depol – SCh has longer duration than ACh, keeps membrane above threshold and prevents repol; no antidote; potentiated by cholinesterase inhibitors.
Phase II: repolarized but blocked – SCh persists in cleft at high conc.; ACh receptors available but desensitized – antidote is cholinesterase inhibitors.
Tubocurarine, atracurium, mivacurium, pancuronium, etc.
How to reverse blockade?
> Nondepolarizing neuromuscular blockers (vs. depolarizing Succinylcholine).
Compete w/ ACh for receptors.
Reversal of blockade: neostigmine (give w/ atropine), edrophonium, other cholinesterase inhibitors.
Dantrolene
[MOA, use]
> Prevents Ca release from SR of skeletal muscle.
>For malignant hyperthermia, neuroleptic malignant syndrome.
Baclofen
[MOA, use}
> Stimulates GABA-B receptors at spinal cord level – induces skeletal muscle relaxation.
For muscle spasms (acute low back pain).
Cyclobenzaprine
[MOA, use]
> Centrally acting muscle relaxant. >Structurally related to TCAs w/ similar anticholinergic side effects.
For muscle spasms.
Dopamine agonists
Names (ergot, non-ergot)
> Ergot: Bromocriptine.
>Non-ergot (preferred): Pramipexole, Ropinirole
Drug that inc. dopamine availability
Amantadine
>inc. dopamine release, dec. dopamine reuptake
>Toxicity: ataxia, livedo reticularis
Drugs that inc. L-DOPA availability
Prevent peripheral (pre-BBB) L-DOPA degradation -- inc. central L-DOPA for conversion to dopamine in CNS. >Levodopa (L-DOPA)/carbidopa: carbidopa blocks peripheral conversion to dopamine by inhibiting DOPA decarboxylase. >Entacapone, tolcapone: prevent peripheral degradation to 3-OMD by inhibiting COMT
Drugs that prevent dopamine breakdown
Act centrally (post-BBB) to block dopamine breakdown -- inc. available dopamine. >Selegiline: blocks conversion of dopamine into 3-MT by inhibiting MAO-B. >Tolcapone: blocks conversion into DOPAC by inhibiting central COMT
L-dopa/Carbidopa
[MOA, use]
For Parkinson dse; inc. dopamine in brain
>L-dopa can cross BBB (vs dopamine) – central DOPA decarboxylase converts L-dopa in to dopamine.
>Carbidopa is a peripheral DOPA decarboxylase inhibitor – inc. bioavailability of L-dopa in brain, limits peripheral SE.
L-dopa/Carbidopa
[Side effects, “On-off phenomenon”]
Arrhythmias from inc. peripheral catechs.
>”On-off” phenomenon: long-term use can lead to dyskinesia ff. admin, akinesia b/w doses.
Selegiline
[MOA, use]
> Inhibits MOA-B (preferentially metabolizes dopamine over NE, 5HT) – inc. dopamine bioavailability.
For Parkinson dse (adjunct to L-dopa).
Entacapone, tolcapone
Inhibits COMT – prevents PERIPHERAL L-dopa degradation to 3-OMD.
*Tolcapone also blocks CENTRAL dopamine conversion to DOPAC by inhibiting COMT.
Alzheimer dse drugs: Memantine; Donepezil, Galantamine, Rivastigmine, Tacrine
> Memantine: NMDA receptor antagonist – prevents excitotoxicty (mediated by Ca).
Donepezil, Galantamine, Rivastigmine, Tacrine: AChE inhibitors.
Tx for Huntington dse: Tetrabenazine, Reserpine; Haloperidol
> Huntington: Dec. GABA, Dec. ACh, Inc. dopamine.
Tetrabenazine, Reserpine: inhibit VMAT; limit dopamine vesicle packaging and release.
Haloperidol: D2 receptor antagonist
Sumatriptan
[MOA, SE/CI]
5HT-1B/1D agonist.
>For acute migraine, cluster headache attacks (abortive).
>Inhibits trigeminal nerve activation; Prevents vasoactive peptide release; Induces vasoconstriction.
>SE: coronary vasospasm – CI in CAD, Prinzmetal angina.
GABA-A receptor vs. GABA-B receptor
> GABA-A: chloride channel – Cl entry inhibits depolarizing/firing – inhibits neurons.
GABA-B: transmembrane protein linked to K channels via G-proteins – K channels remain open longer and hyperpolarize neuron at end of AP – block voltage-gated Na channels from opening, block depolarization.
