Neurology- Pharmacology Flashcards
Epilepsy drugs
Pag. 528
Eclampsia seizures 1st line treatment
MgSO4
Seizures 1st line in neonates
Phenobarbital (phenoBABYthal)
Phenytoin, fosphenytoin
- Adverse effects
PHENYTOIN: P450 induction, Hirsutism, Enlarged gums, Nystagmus, Yellow-brown skin, Teratogenicity (fetal hydantoin syndrome), Osteopenia, Inhibited folate absorption, Neuropathy
Vigabatrin action mechanism
Irreversible GABA TRansaminase INihibitor:
viGABATRIN
Barbiturates
- Names
- Mechanism
- Clinical uses
Phenobarbital, pentobarbital, thiopental, secobarbital
Facilitate GABA-A action
Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental).
Barbiturates
- Adverse effects
Respiratory and cardiovascular depression; CNS depression (can be exacerbated by alcohol use); dependence; drug interactions (induces cytochrome P-450).
Overdose treatment is supportive (assist respiration and maintain BP). Contraindicated in porphyria
Benzodiazepines
- Mechanism
- Short acting benzoodiazepines
Facilitate GABAA action
Mosthave long half-lives and active metabolites (exceptions [ATOM]: Alprazolam, Triazolam, Oxazepam, and Midazolam are short acting)
Benzodiazepines
- Adverse effects
- Benzodiazepines with liver disease
Dependence, additive CNS depression effects with alcohol. Treat overdose with flumazenil
“OK for Terrible Livers”
Oxazepam, Temazepam, and Lorazepam: they can be used to treat alcohol withdrawal in patients with liver disease due to minimal first-pass metabolism.
Nonbenzodiazepine hypnotics
- Names
- Mechanism
- Clinical use
- Adverse effects
hypnotics Zolpidem, Zaleplon, esZopiclone
Act via the BZ1 subtype of the GABA receptor. Effects reversed by flumazenil. Sleep cycle less affected.
Insomnia
Ataxia, headaches, confusion, low dependence risk.
Suvorexant
- Mechanism
- Clinical use
- Adverse effects
Orexin (hypocretin) receptor antagonist
Insomnia
CNS depression, headache, dizziness, abnormal dreams, upper respiratory tract infection. Contraindicated with strong CYP3A4 inhibitors
Ramelteon
- Mechanism
- Clinical use
- Adverse effects
Melatonin receptor agonist, binds MT1 and MT2 in suprachiasmatic nucleus.
Insomnia
Dizziness, nausea, fatigue, headache. No dependence
Triptans (sumatriptan)
- Mechanism
- Clinical use
- Adverse effects
5-HT1B/1D agonists. Inhibit trigeminal nerve activation; prevent vasoactive peptide release; induce vasoconstriction.
Acute migraine, cluster headache attacks.
Coronary vasospasm, mild paresthesia, serotonin syndrome
Parkinson disease drugs
BALSA
Bromocriptine, Amantadine, Levodopa (with carbidopa), Selegiline (and COMT inhibitors), Antimuscarinics
Dopamine agonists
Ergot—Bromocriptine.
Non-ergot (preferred)—pramipexole, ropinirole; toxicity includes impulse control disorder, postural hypotension, hallucinations/confusion.
Drugs increasing dopamine availability
Amantadine; toxicity = ataxia, livedo reticularis
Drugs increasing l-DOPA availability (agents act peripheral)
Levodopa (l-DOPA)/carbidopa—carbidopa blocks peripheral conversion of l-DOPA to dopamine by inhibiting DOPA decarboxylase
Entacapone prevents peripheral l-DOPA degradation by inhibiting COMT. Used in conjunction with levodopa.
Drugs: Prevent dopamine breakdown (agents act centrally)
Selegiline, rasagiline—block conversion of dopamine into DOPAC by selectively inhibiting MAO-B.
Entacapone—blocks conversion of dopamine by inhibiting central COMT.
Drugs: Curb excess cholinergic activity
Benztropine, trihexyphenidyl (Antimuscarinic; improves tremor and rigidity but has little effect on bradykinesia in Parkinson disease).
Levodopa/carbidopa
- Adverse effects
Nausea, hallucinations, postural hypotension from increase peripheral formation of catecholamines.
Long-term use can lead to dyskinesia following administration (“on-off” phenomenon), akinesia between doses.
Tetrabenazine, reserpine
Inhibit vesicular monoamine transporter (VMAT) dopamine.
Huntington chorea, tardive dyskinesia
Riluzole
Decrease neuron glutamate excitotoxicity
ALS (Lou Gehrig)
Alzheimer disease drugs
Memantine: NMDA receptor antagonist; helps prevent
excitotoxicity
Donepezil, rivastigmine, galantamine: AChE inhibitors.
Anesthetics—general principles
- MAC
Minimal Alveolar Concentration (of inhaled anesthetic) required to prevent 50% of subjects from moving in response to noxious stimulus (eg, skin incision).
Anesthetics—general principles
- Low solubility in blood
- High solubility
Rapid induction and recovery times: Nitous oxide
High potency = 1/MAC: Halothane, propofol, and thiopental (high potency and slow induction)
Inhaled anesthetics
- Names
- Mechanism
- Effects
Desflurane, halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, N2O.
Mechanism unknown.
Myocardial depression, respiratory depression, nausea/emesis, increase cerebral blood flow.
Inhaled anesthetics
- Adverse efects
Hepatotoxicity (halothane),
Nephrotoxicity (methoxyflurane),
Proconvulsant (enflurane, epileptogenic),
Expansion of trapped gas in a body cavity (N2O).
Malignant hyperthermia
- Cause
- Mutation
- Treatment
inhaled anesthetics or succinylcholine induce fever and severe muscle contraction.
Mutations in voltage-sensitive ryanodine receptor (RYR1 gene) cause Ca2+ release from sarcoplasmic
reticulum. AD
Treatment: dantrolene
Intravenous anesthetics
Thiopental, Midazolam, Propofol (potentiates GABA A), Ketamine (NMDA antagonist)
Anesthesia use
- Thiopental
- Midazolam
- Propofol
- Ketamine
Induction of anesthesia, short surgical procedures
Procedural sedation (eg, endoscopy), anesthesia induction
Rapid anesthesia induction, short procedures, ICU
sedation
Dissociative anesthesia. Sympathomimetic
Anesthesia characteristics
- Thiopental
- Midazolam
- Ketamine
Decrease cerebral blood flow. High lipid solubility. Effect terminated by rapid redistribution into tissue and fat
May cause severe postoperative respiratory depression, low BP, anterograde amnesia.
Increase cerebral blood flow. Emergence reaction
possible with disorientation, hallucination, vivid dreams.
Local anesthetics
- Esters
- Amides
Esters—procaine, tetracaine, benzocaine, chloroprocaine.
Amides—lidocaIne, mepivacaIne, bupivacaIne, ropivacaIne (amIdes have 2 I’s in name).
Local anesthetics
- Mechanism
Block Na+ channels by binding to specific receptors on inner portion of channel. Most effective in rapidly firing neurons.
- Can be given with vasoconstrictors (usually epinephrine) to enhance local action
- In infected (acidic) tissue, alkaline anesthetics are charged and cannot penetrate membrane effectively
Local anesthetics
- Order of loss
(1) pain, (2) temperature, (3) touch, (4) pressure.
Local anesthetics
- Adverse effects
CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension, hypotension, arrhythmias (cocaine), methemoglobinemia (benzocaine).
Neuromuscular blocking drugs
- Mechanism
- Depolarizing drugs
Muscle paralysis in surgery or mechanical ventilation. Selective for Nm nicotinic receptors.
Succinilcoline
Nondepolarizing neuromuscular blocking drugs
Atracurium, cisatracurium, pancuronium, rocuronium, tubocurarine, vecuronium—competitive with ACh for receptors
Reversal of blockade—neostigmine (must be given with atropine or glycopyrrolate), edrophonium, and other cholinesterase inhibitors.
Dantrolene
- Mechanism
- Clinical use
binding to the ryanodine receptor.
Malignant hyperthermia and neuroleptic malignant syndrome (a toxicity of antipsychotic drugs).
Baclofen
- Mechanism
- Clinical use
Skeletal muscle relaxant. GABAB receptor agonist
Muscle spasticity, dystonia, multiple sclerosis
Cyclobenzaprine
- Mechanism
- Clinical use
- Adverse effects
Skeletal muscle relaxant. Acts within CNS.
Muscle spasms.
Anticholinergic side effects. Sedation.
Opioid analgesics
- Full agonist
- Partial agonist
- Mixed agonist/antagonist
- Antagonist
Morphine, heroin, meperidine, methadone, codeine.
buprenorphine
nalbuphine, pentazocine.
naloxone, naltrexone, methylnaltrexone
Opioid analgesics
- Mechanism
Act as agonists at opioid receptors (μ = β-endorphin, δ = enkephalin, κ = dynorphin) to modulate synaptic transmission
Opioid analgesics
- Clinical use
- Moderate to severe or refractory pain,
- Cough suppression (dextromethorphan),
- Diarrhea (loperamide, diphenoxylate),
- Acute pulmonary edema,
- Maintenance programs for heroin addicts (methadone, buprenorphine + naloxone).
Opioid analgesics
- Adverse effects
Nausea, vomiting, pruritus, addiction, respiratory depression, constipation, sphincter of Oddi spasm, miosis (except meperidine mydriasis), additive CNS depression with other drugs
Pentazocine
- Mechanism
- Clinical use
- Adverse effects
κ-opioid receptor agonist and μ-opioid receptor weak antagonist or partial agonist.
Analgesia for moderate to severe pain.
Can cause opioid withdrawal symptoms
Butorphanol
- Mechanism
- Clinical use
- Adverse effects
κ-opioid receptor agonist and μ-opioid receptor partial agonist.
Severe pain (eg, migraine, labor). Causes less respiratory depression than full opioid agonists.
can precipitate withdrawal. Not easily reversed with naloxone
Tramadol
- Mechanism
- Clinical use
- Adverse effects
Very weak opioid agonist; also inhibits 5-HT receptors.
Chronic pain
Similar to opioids. Decreases seizure threshold. Serotonin syndrome.
Glaucoma drugs
- β-blockers
- α-agonists
- Diuretics
Timolol, betaxolol, carteolol
Epinephrine (α1), apraclonidine, brimonidine (α2)
Acetazolamide
Glaucoma drugs
- Prostaglandins
- Cholinomimetics (M3)
Bimatoprost, latanoprost (PGF2α)
Direct: pilocarpine, carbachol
Indirect: physostigmine, echothiophate
