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230 Cards in this Set
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Glutamate
GABA |
Fast NTs acting at ligand-gated ion channels
Inotropic Receptors |
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Dopamine
Serotonin |
Slow NTs acting at GPCRs
Metabotropic receptors |
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Inhibitory NTs
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GABA
Glycine |
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GABA-A
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Metabotropic (Cl ion channel)
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GABA-B
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GPCR
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Glycine
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Inhibitory
Inotropic receptor NMDA receptor |
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Strychnine
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Inhibits glycine at NMDA receptor
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Glutamate
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Excitatory NT
Inotropic: NMDA, AMPA, Kainate receptors Metabotropic - GPCRs |
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Aspartate
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Excitatory NT
Inotropic: NMDA |
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Acetylcholine
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Excitatory and Inhibitory NT
Nucleus Basalis Ionotropic: Nicotinic receptor Metabotropic: Muscarinic, M1-M5 (GPCRs) Parkinsons and Alzheimer's relation |
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Dopamine
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Exitatory and Inhibitory NT
Monoamine NT Ventral tegmental area (VTA) to limbic Substantia nigra to striatum NO inotropic receptors Metabotropic: Dopamine, D1-D5 Schizophrenia (too much) Parkinson's (too little) |
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Norepinephrine
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Monoamine NT
Excitatory and Inhibitory Locus Ceruleus Inotropic: NONE Metabotropic: alpha/beta receptors Regulates mood, attention, arousal Depression (lack of) |
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Serotonin (5-HT)
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Monoamine neurotransmitters
Excitatory and Inhibitory Dorsal Raphe Nucleus Inotropic: 5-HT3 Metabotropic: 5-HT1,2,4 Regulates sleep, depression, appetite, aggression, sex Depression (lack of) |
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Neuropeptides
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peptides made in cell body, not nerve terminals
Slower onset of action; Neuromodulatory Ex: endogenous opioid peptides (endorphins), tachykinins (substance P) |
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Cognitive Processing
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Drugs affecting: antipsychotics, CNS stimulants, hallucinogens, sedative-hypnotics
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Prefrontal cortex
Memory and emotion Delirium and Schizophrenia |
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Memory
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Drugs affecting: anti-Alzheimer's (cholinesterase inhibitors), sedative-hypnotics
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procedureal memory - motor - cerebellum, basal ganglia, limbic
Declarative memory - thoughts - hippocampus, amygdala, thalamus |
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Emotional Processing
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Drugs affecting: anti-anxiety, antidepressants, antipsychotics, CNS stimulants, opioids, other addictive agents
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hypothalamus, amygdala, hipocampus, limbic and frontal cortex
Anxiety states, manic-depressive disorders, schizophrenia |
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Sensory Processing
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Drugs affecting: antidepressants, hallucinogens, local and general anesthetics, opioids, sedative-hypnotics
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5 senses
spinal cord, spinothalamic pain, spinobulbar Thalamus to sensory cortex Brainstem nuclei, locus ceruleus and raphe nuclei, NorEpi and 5-HT projections for consciousness, sleep, alertness Disorders: sleep, chronic pain |
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Motor Processing
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Drugs affecting: antiparkinson, antispasmodics, CNS stimulants, muscle relaxants, sedative-hypnotics
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cerebellum, basal ganglia, vestibular nuclei, motor cortices, substantia nigra
Disorders: Parkinson's, Huntington's, degenerative/demyelinating disorders |
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Autonomic processing
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Drugs affecting: antidepressants, antiparkinson agents, antipsychotics, anticholinergics, anti-Alzheimer's
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Integrates activity of peripheral ANS, sympathetic/parasympathetic tone
Situated in brainstem with modulation from the hypothalamus Key area of vasomotor center and cranial nuclei of parasympathetic system Disorders: orthostatic hypotension, postural tachycardia syndrome |
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Sedation
vs. Hypnosis |
Anxiolytic (relief of anxiety)
vx. to encourage sleep - induce drowsiness |
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First medical sedatives
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Bromide in 1850s
Barbital in 1903 Chlordiazepoxide in 1957 |
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Benzodiazepines (BDZ)
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Sedative-Hypnotic
Weakly basic. Mostly absorbed in the high pH of the duodenum. Rate of absorption correlate with lipophilicity Excreted as glucuronide metabolites Bind to allosteric sites on the GABA-A receptor-Cl- ion channel complex |
Increase GABA inhibition
Only with GABA present Adv: Anterograde Amnesia |
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Diazepam
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BDZ
Fast uptake (highly lipid soluble) |
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Triazolam
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BDZ
Fast uptake (highly lipid soluble) |
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Chlordiazepoxide
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BDZ
Slow uptake |
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Flurazepam
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BDZ
Slow uptake |
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Clorazepate
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BDZ
Prodrug |
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Oxazepam
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BDZ
No active metabolite |
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Temazepam
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BDZ
No active metabolite |
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Lorazepam
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BDZ
No active metabolite |
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Clonazepam
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BDZ
No active metabolite |
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Barbiturates (BARB)
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Sedative-Hypnotic
Absorbed best in stomach Rapidly absorbed metabolites of all BARBs are inactive All BARBs self-induce hepatic drug-metabolizing systems Excreted as glucuronide metabolites |
Bind to allosteric sites on the GABA-A receptor-Cl ion channel complex
Increase GABA inhibition CAN WORK WITHOUT GABA PRESENT Blocks glutamate (NMDA) receptors Stage III anesthesthetic (BDZ not able to) Toxic doses decrease respiratory function Leathal in porphyria diseases as they enhance porphyrin synthesis |
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Thiopental
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BARB
Fastest onset |
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Phenobarbital
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BARB
Slowest onset Cross into breast milk and placenta Hepatic enzyme induction |
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Endozepine
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Natural GABA agonist
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BDZ/BARB
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bind to allosteric sites on GABA-A
Sedation - decrease in responsiveness to stimulation with decreased spontaneous activity and ideation Hypnosis - stage 2 non-REM increased, REM decreased, slow-wave sleep decreased |
Withdrawal often see REM rebound
Tolerance, psychological dependence, and physical dependence common physical - increased anxiety and seizures (esp. alprazolam), muscle twitches/cramps, HTN and tachycardia |
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Alprazolam
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BDZ
Panic disorders and agoraphobia Adv: seizures if not tapered |
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Antihistamines
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Sedative-Hypnotic
Antagonists at H1 receptors in brain Reduces ACh NT in reticular activating system. blocks direct histamine-mediated arousal in cortical neurons |
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Diphenhydramine
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Antihistamine
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Hydroxyzine
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Antihistamine
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Doxylamine
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Antihistamine
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Chloral hydrate
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Sedative-Hypnotic
Only used in state mental hospitals Toxic metabolite that may be carcinogenic |
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Ethchlorvynol
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Sedative-Hypnotic
Only used in state mental hospitals |
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Meprobamate
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Sedative-Hypnotic
Only used in state mental hospitals |
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Melatonin
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Sedative-Hypnotic
Natural hormaone synthesized in the pineal gland regulating sleep-wake cycle Released when photic inhibition is removed |
Non-prescription
Effective in jet-lag, insomnia in night-shift workers, insomnia in elderly |
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Zolpidem
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Sedative-Hypnotic
Ambien - Very Popular Treatment of insomnia No withdrawal |
Act more selectively on GABA-A receptors
Less hangover effect Less amnesia More rapid onset |
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Zaleplon
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Sedative-Hypnotic
Sonata - Very Popular Treatment of insomnia Ultra-short half-life (1h) No withdrawal |
Act more selectively on GABA-A receptors
Less hangover effect Less amnesia More rapid onset |
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Eszopiclone
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Sedative-Hypnotic
Insomnia Lunesta - Very Popular Active stereoisomer of zopiclone Better for sleep-onset insomnia rather than sleep-maintenance insomnia |
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Ramelteon
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Sedative-Hypnotic
Melatonin receptor agonist Sleep-onset insomnia No abuse properties Not a controlled substance |
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Buspirone
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Non-sedating anxiolytic
5-HT partial agonist Minimal abuse potential |
Only CNS depressant that can be taken with CNS depressants
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Propranolol
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Non-sedating anxiolytic
Beta-blocker Stage-fright, performance anxiety, acute situational anxiety Prevents tachycardia and other sympathomimetic effects of acute anxiety |
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Anxiety
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Enhanced vigilance, motor tension, autonomic hyperactivity
Deficiency of GABAergic neurotransmission |
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Clinical uses of Sedative-Hypnotics
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Anxiety, sleep disorder
Sedation and anmesia for medical and surgical procedures Treatment of epilepsy and seizures IV adjuvant in general anesthesia Control of ethanol/sedative-hypnotic withdrawal Muscle relaxation in neuromuscular disease |
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Toxic actions of Sedative-Hypnotics
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Direct:
drowsiness, impaired judgment, decreased motor skills Elderly caution as decreased metabolic ability Common suicide drug of choice |
Ixn:
All CNS depressants(opioids, ethanol, antipsychotics, antihistamines, anti-HTN) Buspirone is only exception and can be taken with CNS depressants |
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Flumazenil
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BDZ
Site selective antagonist |
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Drugs for partial seizures and generalized tonic-clonic seizures
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Carbamazepine (Tegretol)
Oxcarbazepine (Trileptal) Phenytoin (Dilantin) Phenobarbital (Luminal) Primidone (Mysoline) Valproic acid (Depakene) |
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Adjunct drugs for partial seizures
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Clorazepate (Tranxene)
Felbamate (Felbatol) Gabapentin (Neurontin) Lamotrigine (Lamictal) Topiramate (Topamax) |
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Drugs for generalized absence, myoclonic, or atonic seizures
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Clonazepam (Klonopin)
Ethosuximide (Zarontin) Lamotrigine (Lamictal) Valproate (Valproic acid, Depakene) |
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Drugs for status epileticus
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Diazepam (Valium)
Lorazepam (Ativan) Phenobarbital (Luminal) Fosphenytoin (Cerebyx) |
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Seizure
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Refers to a transient alteration of behavior due to the disordered, synchronous, and rhythmic firing of brain neurons.
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Caused by the synchronous discharge of a group of neurons in the cortex.
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Partial seizure
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Origin localized to a cortical focal point, no diencephalic involvement
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60% of all epilepsy, mostly non-genetic; tumor, damage, malformation
Simple partial: no impairment of consciousness during the seiure, diverse effects depending on region of activity, 20-60 sec Complex partial: imairment of consciousness, 0.5-2 min, also purposeless movements Partial with secondary generalization: simple or complex partial evolves into tonic-clonic with loss of consciousness. |
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Generalized seizure
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Origin involves both hemispheres, and reciprocal firing of thalamus and cortex
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Tonic-clonic: ("grand mal") as above for partial with secondary generalized but not starting at a focal point, 1-2 min
Absence: ("petit mal") abrupt onset of impaired consciousness associated with staring and cessation of ongoing activity, lasts about 30 sec. Myoclonic: shock-like contraction of muscles restricted to one part of extermity or generalized; about 1 sec, juvenile form most common (10% of all epilepsy) |
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Simple seizure
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No impairment of consciousness
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Complex seizure
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Impairment of consciousness
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Drugs for partial seizures and generalized tonic-clonic seizures
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Carbamazepine (Tegretol)
Oxcarbazepine (Trileptal) Phenytoin (Dilantin) Phenobarbital (Luminal) Primidone (Mysoline) Valproic acid (Depakene) |
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Adjunct drugs for partial seizures
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Clorazepate (Tranxene)
Felbamate (Felbatol) Gabapentin (Neurontin) Lamotrigine (Lamictal) Topiramate (Topamax) |
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Drugs for generalized absence, myoclonic, or atonic seizures
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Clonazepam (Klonopin)
Ethosuximide (Zarontin) Lamotrigine (Lamictal) Valproate (Valproic acid, Depakene) |
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Drugs for status epileticus
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Diazepam (Valium)
Lorazepam (Ativan) Phenobarbital (Luminal) Fosphenytoin (Cerebyx) |
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Seizure
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Refers to a transient alteration of behavior due to the disordered, synchronous, and rhythmic firing of brain neurons.
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Partial seizure
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Origin localized to a cortical focal point, no diencephalic involvement
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Generalized seizure
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Origin involves both hemispheres, and reciprocal firing of thalamus and cortex
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Simple seizure
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No impairment of consciousness
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Complex seizure
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Impairment of consciousness
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Antisezure drugs mechanisms of action
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inhibiting function of ion channels that promote firing (Na+ and Ca+ channels)
Partial seizures - prolong the voltage-regulated Na+ channel inactivation phase thus increasing the refractory period Carbamazepine, phenytoin, valproate, lamotrignine, topiramate, zonisamide Generalized-onset absence seizures - inhibit voltage-regulated Ca++ channels, specifically the low threshold "T" current Ethosuximide, valproate, zonisamide |
Enhancing neuronal inhibition via GABA synapses
enhance GABA-A receptor agonist action; (benzodiazepines: clonazepam, clorazepate, diazepam, lorazepam) Inhibition of GAT-1, the GABA re-uptake transporter, tiagabine Increased GABAergic activity (also block Ca++ channels) gabapentin, pregabalin |
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Carbamazepine (Tegretol)
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Anti-epileptic
Partial seizures, generalized tonic-clonic seizures Adv: drowsiness, vertigo, ataxia, gastric irritiation, hepatic toxicity, fatal aplastic anemia (rare) |
Related to the tricyclic antidepressants, used earlier for trigeminal neuralgia, also effective in manic/depressives
prolong the voltage-regulated Na+ channel inactivation phase thus increasing the refractory period Erratic absorption and self-induces own metabolic enzymes Active metabolite as potent as parent compound |
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Phenytoin (Dilantin)
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Anti-epileptic
Partial seizures, generalized tonic-clonic seizures Adv: cerebellar and vestibular depression, ataxia and nystagmus, gingival hyperplasia, hirsutism in females (connective tissue change), Folic acid and Vit D antagonism (anemia and osteomalacia) |
prolong the voltage-regulated Na+ channel inactivation phase thus increasing the refractory period
Significant differences in absorption of oral preparations metabolized in liver to inactive metabolite |
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Valproate (Depakene, Depakote)
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Anti-epileptic
Partial seizures, generalized tonic-clonic seizures, generalized absence, myoclonic, or atonic seizures Adv: GI (anorexia, Nausea/Vomiting), CNS (sedation, atatxia, tremor), Hepatic (rare fulminant fatal hepatitis, occurs more in children w/ combination) |
Simple branched chain carboxylic acid, approved in USA for use in 1987 after use in Europe for a decade
prolong the voltage-regulated Na+ channel inactivation phase thus increasing the refractory period Inhibits Ca++ current ('T' current) in thalamic pacemaker neurons Rapidly and completely absorbed No drug excreted unchanged Active metabolites, but most are short-lived |
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Lamotrignine (Lamictal)
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Anti-epileptic
Add-on drug for partial seizures in adults, absence and myoclonic seizures in children Adv: CNS (dizziness, ataxia, burred or double vision, nausea/vomiting when added to another antiseizure drug regimen) |
Phenyltriazine class
prolong the voltage-regulated Na+ channel inactivation phase thus increasing the refractory period |
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Topiramate (Topomax)
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Anti-epileptic
Adjunct drug for partial seizures Adv: very few; some somnolence, fatigue, weight loss, nervousness |
prolong the voltage-regulated Na+ channel inactivation phase thus increasing the refractory period
Enhances GABA inhibition Decreases glutamate excitation |
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Zonisamide (Zonegran)
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Anti-epileptic
Adjunct drug for partial seizures Adv: very few; some somnolence, fatigue, weight loss, nervousness |
prolong the voltage-regulated Na+ channel inactivation phase thus increasing the refractory period
Blocks Ca++ channel (T-type) activity |
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Ethosuximide (Zarontin)
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Anti-eptileptic
Generalized-onset absence seizures Adv: GI (Nausea/Vomiting, anorexia), CNS (drowsiness, euphoria, dizziness, headache, hiccough) |
Succimide class
inhibit voltage-regulated Ca++ channels, specifically the low threshold "T" current well absorbed after oral administration 25% excreted unchanged, metabolites inactive |
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Valprolate
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Anti-eptileptic:
Generalized-onset absence, partial, generalized tonic-clonic seizures inhibit voltage-regulated Ca++ channels, specifically the low threshold "T" current |
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Zonisamide
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Anti-eptileptic: Generalized-onset absence seizures
inhibit voltage-regulated Ca++ channels, specifically the low threshold "T" current |
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Clonazepam
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Anti-Epileptic, Sedative-Hypnotic (BDZ)
Generalized absence seizures, myoclonic seizures Enhances GABA-A receptor agonist action |
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Clorazepate
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Anti-Epileptic, Sedative-Hypnotic (BDZ)
Adjunctive drug for partial seizures Enhances GABA-A receptor agonist action |
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Diazepam
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Anti-Epileptic, Sedative-Hypnotic (BDZ)
Status epilepticus Enhances GABA-A receptor agonist action |
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Lorazepam
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Anti-Epileptic, Sedative-Hypnotic (BDZ)
Status epilepticus Enhances GABA-A receptor agonist action |
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Phenobarbital (Luminal)
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Anti-Epileptic, Sedative-Hypnotic (BARB)
Partial seizures, generalized tonic-clonic seizures Adv: sedation (tolerance develops), nystagmus, ataxia, irritability and hyperactivity in children w/ retard in cognitive performance, confusion and agitation in elderly |
Enhances GABA-A receptor agonist action, reduces glutamate-induced excitation
Complete but slow absorption Induces hepatic enzymes Inactive metabolites |
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Primidone (Mysoline)
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Anti-Epileptic
Partial seizures, generalized tonic-clonic seizures, myoclonic seizures in children Adv: sedation, vertigo, dizziness, ataxia, nausea/vomiting, diplopia, nystagmus, intoxication Can be combined wtih carbamazepine and phenytoin |
Congener of phenobarbiltal
Enhances GABA-A receptor agonist action Rapidly and completely absorbed Converted to 2 active metabolites: phenobarbital and phenylethylmalonamide (PEMA) Therapeutic effects from combination of all three compounds but not clear relationship which compound is most effective |
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Oxcarbazepine (Trileptal)
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Anti-epileptic
Partial, generalized tonic-clonic seizures |
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Felbamate (Felbatol)
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Anti-epileptic
Refractory partial seizures in adults, Lennox-Gastaut syndrome in children Adv: rare fatal aplastic anemia |
Dual action of inhibiting NMDA (glutamate) excitation and increasing GABA responses
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Gapapentin (Neurontin)
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Anti-epileptic
add-on drug for refractory Partial seizures, for neuropatic pain (diabetic neuropath, postherpatic neuralgia) Adv: CNS (somnolence, dizziness, ataxia, fatigue) |
Gaba analog - GABA with a cyclohexane ring attached
Designed to be a CNS active GABA agonist Increases GABAergic activity, blocks Ca++ channels; pregabalin more potent Well-absorbed and not metabolized in humans |
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Fosphenytoin (Cerebyx)
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Anti-epileptic
Status epilepticus Prodrug (IV) of phenytoin activated by phosphatases |
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Levetiracetam (Keppra)
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Anti-epileptic
Adjunct drug for partial seizures Adv: well-tolerated; minor somnolence and dizziness |
Unknown mechanism of action
Binds to a synaptic vesicle protein with unknown function |
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Tigabine (Gabitril)
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Anti-epileptic
Adjunct drug for partial seizures Adv: minor; dizziness, somnolence, tremor which lessens after continued use |
Inhibits re-uptake of synaptic GABA by flocking the GAT-1 molecule (GABA transporter)
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General methods for epilepsy pharmacotherapy
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Start with a single drug at reduced dosage
Incerase along with plasma montoring Stress patient compliance Monitor effectiveness and Adv effects IF: not effective or adv effects intolerable, switch to another agent with same start LAST RESORT to do combinations |
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Duration of therapy:
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36% of children relapsed after medication withdrawal, these children had been seizure-free during 3 years of medication
33% of children and adults with partial and generalized seizures relapsed after 2 years of seizure-free treatment |
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Status epilepticus
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35% mortality
Risk of permanent brain damage Diazepam or lorazepam given IV or rectal only IM - variable absorption Diazepam redistributes quickly back out of brain; lorazepam longer duration of action Fosphenytoin and phenobarbital also used |
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Local Anaesthetics
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two classes: esters and amides
prepared as chloride salts with low pH to keet them as cations Vasoconstrictors used to slow systemic absorption Amides break down faster than esters |
esters hydrolyzed by plasma cholinesterase to PABA
amides N-dealkylated and hydrolyzed in liver Uncharged base form penetrates lipid membranes and has general anesthetic-like effect (membrane effects) Base form passes into neuroplasm (soluble, ionic medium) and cation form dominates Cation form binds to inside of Na+ channel and blocks Na+ flow (primary mech. of action) Small nerves blocked first |
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Procaine (Novocain)
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Local Anaesthetic - ester
Produces toxic metabolite (o-toluidine) that can cause methemoglobinemia |
First synthetic LA, Ester type
Low potency, slow onset, short duration of action Metabolized to PABA - high incidence of hypersensitivity. Blocks action of sulfonamide drugs |
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Local Anaesthetics (cont)
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Some used as antiarrythmic agents (lidocaine)
CNS toxicity - drowsiness, seizures, fatal respiratory depression, neurotoxicity Cardiovascular - Deperss exciatability, conduction rate, and force of contraction. Blood - prilocaine metabolite converts Hb to methemoglobin Allergic dermatitis or asthmatic attack in sensitive individuals in ester-type LA via PABA metabolite |
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Cocaine
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Local Anaesthetic
Tupical mucus membrane use, upper respiratory indications |
Previous opthalmic use but causes sloughing of corneal epithelium
Innate sympathomimetic action of vasoconstriction due to norepinephrine reuptake blockade |
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Tetracaine (Pontocaine)
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Local Anaesthetic
slow onset and long-acting ester-type More potent and toxic than procaine Used in spinal anesthesia for its long duration |
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Proparacaine (Ophthaine)
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Local Anaesthetic - ester
A distinct form of ester, thus lack of cross-sensitivity with other esters little or no corneal irritation so widely used for ophthalmology |
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Dibucaine (Nupercainal)
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Local Anaesthetic
Toxic as an injectable agent For mucous membrane (e.g. anal itch) |
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Benzocaine (Americaine)
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Local Anaesthetic
poorly soluble in water; systemic toxicity is low Remain localized in skin; good topical anesthetic |
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Lidocaine (Xylocaine)
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Anti-arrhythmic, Local Anaesthetic - amide
Most widely used Used for individuals sensitive to ester-types More intense, quicker, and longer-lasting action than procaine More CV effects than procaine Used for indications of intermediate duration of action is desired |
Prototypical amide-type
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Mepivacaine (Carbocaine)
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Local Anaesthetic - amide
intermediate-acting amide Cxn: More toxic to neonate thus cxn in obstetrical anesthesia |
derivative of lidocaine
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Bupivacaine (Marcaine, Sensorcaine)
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Local Anaesthetic - amide
Widely used amide type with long duration of action More sensory than motor block One of the more potent LAs; causes more cardiac toxicity than lidocaine |
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Etidocaine (Duranest)
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Local Anaesthetic - amide
Onset of action faster than bupivacaine, duration of action same as bupivacaine Useful for surgery requiring intense skeletal muscle relaxation |
Derivative of lidocaine
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Prilocaine (Citanest)
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Local anaesthetic - amide
Longer onset of action and longer-lasting tahn lidocaine Unique toxic metabolite (O-toluidine: leads to methemoglobinemia) so dental use only! |
derivative of lidocaine
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Ropivacaine (Naropin)
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Local anaesthetic
Newest LA amide Slightly less potent than bupivacaine less cardiac toxicity than buvipacaine Is used for obstetric anesthesia and regional anesthesia for surgery, as well as for the management of post-operative pain Patient reactions similar to those of other local anesthetics; generally milder |
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Local Anesthetics - Clinical uses
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Topical
Infiltration Field Block Nerve Block Spinal Epidural |
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Topical Anesthesia
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Cocaine, tetracaine, and lidocaine usd in sprays for mouth, nose, throat
Cocaine used because innate vasoconstrictor ax provides less bleeding in surgical field LA do get absorbed through; systemic toxicity which has been seen with diaper rash treatment in severe cases EMLA cream (for venipuncture, skin grafts) mix of lidocaine and prilocaine; melting pt of less than either alone; works 5mm deep |
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Infiltration Anesthesia
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Administration of LA just under the skin, often with epinephrine added
Should not be used in "end artery" structures, e.g. fingers, toes, ears, nose, penis, can get vasoconstriction or gangrene Advantage is good anesthesia without disruption of normal bodily function Disadvantage is that relatively large amonts must be used for a relatively small area Used for minor surgery only |
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Field Block Anesthesia
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LA administered s.c proximal to nerve passage site to block downstream innervation
Need lower doses than infiltration anesthesia and excellent knowledge of neuroanatomy |
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Nerve Block Anesthesia
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Injection of LA intonear peripheral nervs or nerve plexus mixed nerves blocked; sensory and motor
Eamples are blocks of brachial plexus, intercostal nerve blocks, cervical plexus |
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Spinal Anesthesia
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Injection of LA into the subarachnoid space below the level of cord termination
Spread of agent along neuroaxis controlled by specific gravity of solution and position of patient Hyperbaric solutions made for this purpose 15 min later, solution becomes isobaric; "fixed" Goal is to block somatic sensory and motor fibers; also get sympathetic block due to preganglionic cell bodies in cord Respiratory depression can occur if LA goes up neuroaxis; lumbar puncture headaches |
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Epidural anesthesia
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Administration of LA into the spinal epidural space
Get higher blood concentration through as LA is absorbed and cleared from epidural space Used greatly in OB but LA can cross placenta and enter neonatal CNS if too high dose |
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General Epidural/Intrathecal Opiod Analgesia
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Specual use of opiods in anesthesiology; often LA used with opioids for epidural and direct spinal (intrathecal) anesthesia or analgesia
For example, bupivacaine and fentanyl often used together for epidural in OB |
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Nitrous oxide
|
General anaesthetic - inhalational
blocks glutamate Rs Intermittent dental anesthetic and as adjuvant Rapid induction and little toxicity (thus high margin of safety) Adv: can't use as sole agent unless hyperbaric conditions (MAC at 105%). Hypoxia if used alone. No muscle relaxant properties Can get the bends - expansion of air pockets in closed spaces of head, abdoment and chest Diffusional hypoxia can occur when stop |
No odor or taste
Valuable as an adjunct gas and reduces amount of halogenated agents needed and less hypotension produced |
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Halogenated
|
General anaesthetic - inhalational
Multiple sites including enhance GABA Potentiate glycine action Block neuronal nicotinic receptors |
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Thiopental
|
BARB, General anaesthetic - IV
GABA enhancement Ultra-short acting barbituate High lipid solubility to fast in and fast out - redistribution is reason so short acting |
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Midazolam
|
BDZ, General anaesthetic - IV
GABA enhancement Fastest onset of action |
Also used as premedication as good for producing amnesia
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Fentanyl
|
Opioid, General anaesthetic - IV
Opiod receptor agonist Used in cardiac surgery with little cardiovascular effects Used with droperidol (a dopamine antagonist) for neurolepanesthesia or "twilight sleep" |
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Droperidol
|
General anaesthetic - IV
D2 receptor antagonist |
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Ketamine
|
General anaesthetic - IV
Blocks glutamate receptors Dissociative anesthetic - get catatonia, analgesia, and amnesia due to blockade of NMDA receptor cardiostimulatory and psychotic emergence phenomena |
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Propofol
|
General anaesthetic - IV
Enhances GABA Used mostly for day surgery as faster recovery than BARB or BDZ |
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Etidomate
|
General anaesthetic - IV
Enhances GABA Sedative-hypnotic used for induction, but get pain at injection site and vomiting |
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General Anaesthetics
|
Cardio - decrease in BP
Respiratory - Ventilation rate depressed Brain - Main site of action, bizarre dreams, Reticular acivating system (RAS) in brainstem is decreased as occurs in sleep, CBF and intracrainial pressure increases Liver - BF is reduced, no ischemia |
Malignant Hyperthermia
Rare but fatal Inhalational Uncontrolled hypermetabolic reaction happens in skeletal mucle. Genetic defect in the Ca++ uptake in the sarcoplasmic reticulum Dantroline is used for treatment. Blocks release of Ca++ from SR, decreases intracellular Ca++ |
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Halothane
|
General Anaesthetic - inhalational
Adv: hypotension, insufficient analgesia, resp depression, cardiac arrhythmias Halothane hepatitis (fatal) - 2-5 days after surgery - fever, anorexia, N/V, rash, eosinophilia, enzymes indicatie of hepatitis. 50% fatal |
rapid induction, no bronchospasm, hypotension sometimes a plus if want to reduce blood loss under controlled conditions, uterine relaxation can be a plus if version or extraction of fetus desired
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Methoxyflurane
|
General Anesthetic -
Nephrotoxicity - metabolites toxic |
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Enflurane
|
General Anaesthetic - inhalational
Adv: seizure activity may ccur with high concentrations, greater uterine relaxation, so avoid in OB |
less cardiac effects than halothane, less cerebral effects, more muscle relaxant effects, more rapid and less adverse effects upon recovery
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Isoflurane
|
General Anaesthetic - inhalational
Minimal metabolism. No cases of renal or hepatic toxicity Adv: more pungent odor (need supplemental IV agents for induction), more respiratory depression (careful with opiods) |
Isomer of enflurane, less negative inotropic effects, cardiac output well-maintained.
Depth of anesthesia more easily controlled. Epinephrine can be used for hemostasis due to less potential to cause arrythmias Less increase in intracrainial pressure so is the preferred agent for neurosurgery |
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Methoxyflurane
|
General Anaesthetic - Inhalational
Most potent Adv: extreme solubility in rubber, F metabolites can cause fatal nephrotoxic products Use for short periods only Cxn: renal disease with agents inducing hepatic microsomal enzymes |
Very rapid induction, most potent of the inhalational agents
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Haloperidol (HALDOL)
|
Typical Antipsychotic, anti-emetic
Hyperactivity, agitation, mania High occurrence of EPS weak alpha-adrenergic antagonist hypothermic and anorexiant effects |
Butyrophenone class
|
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Chlorpromazine (Thorazine)
|
Typical anti-psychotic
antacids decrease absorption Avoid anti-cholinergics Additive effects with CNS depressants Cardiovascular effects: blocks peripheral alpha-adrenergic receptors (hypotension) Negative ionotropic agent |
Phenothiazine class
|
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Clozapine (Clozaril)
|
Atypical anti-psychotic
Intensification of dream activity REM sleep (85% of sleep) agranulocytosis, only used in patents unresponsive to at least 2 other drugs |
Dibenzodiazepine class
Atypical mechanism: high affinity for D1, D4, and 5-HT receptors |
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Risperidone (Risperdal)
|
Atypical Anti-psychotic
Improves both positive and negative symptoms Possible interaction with beta-blockers (substrate competition on P450 sites) Minimal sedation and low incidence of EPS |
Benzisoxazole class
5-HT2, D2, alpha-1 receptor antagonist Little affinity for alpha-2, D1, muscarinic, H1 receptors |
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Olanzapine (Zyprexa)
|
Atypical antipsychotic
improves positive and negative symptoms clearance 40% higher in smokers and 30% lower in women metabolized by many CYP enzymes. Minimal Ixns Sedation, orthostatic hypotension |
Thienobenzodiazepine class
affinities: 5-HT>DA>Muscarinic>alpha-1 little affinity at GABA-A, BZD and beta-adrenergic receptors |
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Lithium salts
|
Antimanic agent
No effects in normal individuals CNS toxicity: N/V, ataxia, convulsions, coma CV toxicity: cardiac arrhythmias, hypotension, albumenuria Polydipsia, polyuria, benign tumor enlargement, benign EEG changes |
Replace Na in nerve potentials
inhibits G-coupled inositol phosphate (IP) pathway |
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Carbamazepine
|
antimanic agent, anticonvulsant
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Valproate
|
antimanic agent, anticonvulsant
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Clonazepam
|
antimanic agent, anticonvulsant
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lorazepam
|
antimanic agent, sedative bzd
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Imipramine (tofranil)
|
Antidepressant
TCA |
non-selective for NOR and 5-HT
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Amitriptyline (Evalil)
|
Antidepressant
TCA |
non-selective for NOR and 5-HT
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Doxepine (Sinequan)
|
Antidepressant
TCA |
non-selective for NOR and 5-HT
|
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Clomipramine (Anafranil)
|
Antidepressant
TCA |
non-selective for NOR and 5-HT
|
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Trimipramine (Surmontil)
|
Antidepressant
TCA |
non-selective for NOR and 5-HT
|
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Desipramine (Norpramin)
|
Antidepressant
TCA |
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Nortriptyline (Pamelor)
|
Antidepressant
TCA |
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Amoxapine (asendin)
|
Antidepressant
TCA |
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Maprotiline (ludiomil)
|
Antidepressant
TCA |
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Protriptyline (Vivactil)
|
Antidepressant
TCA |
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Trazodone (Desyrel)
|
Antidepressant
Atypical Adv: sedation, priapism, permanent impotency |
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Bupropion (Wellbutrin, Zyban)
|
Antidepressant
Atypical Adv: Seizures |
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Nefazodone (Serzone)
|
Antidepressant
Atypical Adv: sedation, impotency |
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Fluoxetine (Prozac)
|
Antidepressant
SSRI less orthostatic hypotension, weight gain |
|
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Fluvoxamine (Luvox)
|
Antidepressant
SSRI |
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Paroxetine (Paxil)
|
Antidepressant
SSRI |
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Sertraline (Zoloft)
|
Antidepressant
SSRI |
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Citalopram (Celexa)
|
Antidepressant
SSRI |
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Escitalopram (Lexapro)
|
Antidepressant
SSRI |
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Venlafaxine (effexor)
|
Antidepressant
SNRI |
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Duloxetine (Cymbalta)
|
Antidepressant
SNRI |
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Desvenlafaxine
|
Antidepressant
SNRI |
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Phenelzine (Nardil)
|
Antidepressant
non-selective MAO inhibitor |
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Isocarboxazid (Marplan)
|
Antidepressant
non-selective MAO inhibitor |
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Tranylcypromine (Parnate)
|
Antidepressant
non-selective MAO inhibitor |
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Selegiline (Eldepryl)
|
Antidepressant
MAO-B selective |
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Corgyline
|
Antidepressant
MAO-A selective |
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Amphetamine
Dextroamphetamine Methamphetamine Lisdexamfetamine |
CNS Stimulant
ADHD, Narcolepsy, Obesity Indirect-acting adrenergic agonist |
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Methylphenidate
|
CNS Stimulant
ADHD, Narcolepsy, Obesity Sympathomimetic agent. Also inhibit dopamine re-uptake |
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Modafinil
|
CNS Stimulant
ADHD, Narcolepsy, Obesity Sympathomimetic agent. Also inhibit dopamine re-uptake |
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Armodafinil
|
CNS Stimulant
ADHD, Narcolepsy, Obesity Sympathomimetic agent. Also inhibit dopamine re-uptake |
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Atomoxetine
|
CNS Stimulant
ADHD, Narcolepsy, Obesity Nonamphetamine drug with NOR re-uptake inhibition |
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Phenteramine
|
CNS Stimulant
Obesity |
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Sibutramine
|
CNS Stimulant
Obesity |
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Morphine
|
Opioid Analgesic
Dypsnea of acute LHF and pulmonary edema |
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|
Meperidine (Demerol)
|
Opioid Analgesic
Pain of biliary colic Drug of Choice for OB: less fetal respiratory depression than morphine CNS excitation, convulsions, tremors due to build-up of toxic metabolite, normeperidine |
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Methadone (Dolophine)
|
Opioid Analgesic
Used in treatment of heroin addiction and opioid withdrawal |
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Fentanyl (Sublimaze)
|
Opioid Analgesic
Anesthesia with droperidol 80x more potent than morphine Muscular rigidity with high potency opioids Transdermal for chronic pain |
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Codeine
|
Opioid Analgesic
Post-Operative Pain Metabolism to morphine Antitussive Less abuse potential than morphine |
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Oxycodone (Percodan, Roxicodone)
|
Opioid Analgesic
Combined with NSAIDs Higher oral bioavailability than morphine |
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Propoxyphene (Darvon)
|
Opioid Analgesic
Withdrawn from market for cardiac toxicity Toxic metabolite build up with repeated dose less abuse potential; produces irritiation with IV/SC use |
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Pentazocine (Talkwin
|
Mixed opioid agonist/antagonist
|
|
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|
Nalbuphine (Nubain)
|
Mixed opioid agonist/antagonist
No significant cardiac effects Less likely to produce dysphoria |
|
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Buprenorphine (Buprenex)
|
Mixed opioid agonist/antagonist
Sublingual form |
Partial mu agonist
|
|
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Naloxone (Narcan)
|
Opioid Antagonist
Treatment of opioid overdose Neonatal respiratory depression after opioids given to mother during labor |
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|
Naltrexone (Trexan, Revia)
|
Opioid Antagonist
Greater duration of action thgan naloxone Oral maintenance of opioid addicts Transdermal for addiction therapy Recently approved for treatment of alcoholism |
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Codeine and DXM
|
Antitussive opioid
Acts on receptors in medulla cough center |
|
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Diphenoxylate (Lomotil)
|
Antidiarrheal Opioid
|
|
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Loperamide (Imodium)
|
Antidiarrheal Opioid
|
|
|
|
Parkinson's Disease
|
Loss of dopamine neurons from the sub nigra pars compacta
Increase dopaminergic output to the striatum OR deccrease muscarinic cholinergic action |
|
|
|
Levodopa (L-Dopa, Larodopa, Dopar)
|
Parkinsonism
"Precursor loading" Relieves all symptoms except dementia Adv: anorexia, N/V, orthostatic hypotension, cardiac dysrhythmias, dyskinesias, behavioral disturbances, mydriasis, acute glaucoma, blod dyscrasias, aggravation of gout, abnormal smell/taste Ixn: pyridoxine (decreased CNS L-dopa), MAOIs (except Seligiline) Cxn: schizophrenia, cardiac dysrhytyhmias, coronary insufficiency |
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|
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Carbidopa
|
Parkinsons
Analog of dopamine No N/V, diminished CV side-effects No antagonism with pyridoxine |
|
|
|
Bromocriptine (Parlodel)
|
Parkinsons
Not a first-line drug Adv: like levodopa, plus first-dose phenomena (hypotension), more hallucinations and digital vasospasm Ixn: anti-HTNs |
Ergot alkaloid (like LSD)
Dopamine agonist at D2, antagonist at D1 |
|
|
Ropinirole (Requip)
|
Parkinsons
|
|
|
|
Pramipexole (Mirapex)
|
Parkinsons
Antidepressant effects |
|
|
|
Rotigotine (Neupro)
|
Parkinsons
Transdermal patch non-ergot dopamine agonist |
|
|
|
Apomorphine (Apokyn)
|
Parkinsons
Used to treat freezing episodes |
|
|
|
Amantadine (Symmetrel)
|
Parkinsons
Adv: restlessness, depression, insomnia, agitation, hallucinations, confusion, livedo reticularis in the legs (spider veins) Cxn: Seizures, CHF |
Release of dopamine from the terminals of neurons and facilitates release of dopamine by neural impulses
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|
|
Selegiline (Deprenyl, Eldepryl)
|
Parkinsons
Inhibitor of Dopamine breakdown selective MAO-B inhibitor prevents the neurotoxic MPTP+ from forming (case of the rigid addict) |
|
|
|
rasagiline (Azilect)
|
Parkinsons
Inhibitor of dopamine breakdown newer MAO-B selective inhibitor |
|
|
|
Tolcapone (Tasmar)
|
Parkinsons
Reversible inhibitor of COMT Useful in patients with "wearing off" of L-Dopa |
|
|
|
Entacapone (Comtan)
|
Parkinsons
Reversible inhibitor of COMT Useful in patients with "wearing off" of L-Dopa Longer duration than Tocapone |
|
|
|
Benztropine (Cogentin)
|
Parkinsons
Anticholinergic agent CNS: drowsiness, confusion, agitation, mood changes eripheral: dry mouth, blurred vision, tachycardia, mydriasis, urinary retention, constipation Cxn: prostatic hypertrophy, obstructive GI disease, angle-closure glaucoma |
|
|
|
Trihexyphenidyl (Artane)
|
Parkinsons
Anticholinergic agent CNS: drowsiness, confusion, agitation, mood changes eripheral: dry mouth, blurred vision, tachycardia, mydriasis, urinary retention, constipation Cxn: prostatic hypertrophy, obstructive GI disease, angle-closure glaucoma |
|
|
|
Selegiline (Deprenyl)
|
Parkinsons
Neuroprotective agent Inhibits MAO-B (breaks down dopamine/catecholamines) |
|
|
|
Fluoxetine (Prozac)
|
Huntingtons
Treat depression and irritability |
|
|
|
Clozapine (Clozaril)
|
Huntingtons
Treat psychosis, paranoia, delusions |
|
|
|
Reserpine
|
Huntingtons
Treat large amplitude chorea |
|
|
|
Benzodiazepines
|
Huntingtons
Calm pateint |
|
|
|
Tetrabenazine (Xenazine)
|
Huntingtons
Treat Chorea |
|
|
|
Tacrine (Cognex)
|
Alzheimer's
Acetylcholinesterase inhibitors Ixn: Anticholinergic drugs, Bethanecol, cimetadine, succinylcholine, theophylline Adv: Hepatotoxicity, Cholinomimetic effects |
|
|
|
Donepezil (Aricept)
|
Alzheimer's
Acetylcholinesterase inhibitors Ixn: Anticholinergic drugs, bethanecol, cholinomimetics, succinylcholine Adv: N/V, diarrhea, muscle cramps and fatigue |
|
|
|
Rivastigmine (Exelon)
|
Alzheimer's
AChE inhibitor No liver metabolism |
|
|
|
Galantamine (Reminyl)
|
Alzheimer's
AChE inhibitor and nicotinic agonist |
|
|
|
Memantine (Namenda)
|
Alzheimer's
NMDA (glutamate) antagonist Prevents excitotoxicity due to excess glutamate |
|
|
|
Interferon beta-1b
|
Multiple Sclerosis
Increases cytotoxicity of NK cells Increases phagocytic activity of macrophages Reduces IFN-gamma |
|
|
|
Natalizumab
|
Multiple Sclerosis
Inhibits lymphocyte entry into CNS |
|
|
|
Glatiramer acetate
|
Multiple Sclerosis
Mimics myelin basic protein |
|
|
|
Mitoxantrone
|
Multiple Sclerosis
Suppresses activity of T cells, B cells, and macrophages that attach the myelin sheath |
|
|
|
Adrenal corticosterids (prednisone)
|
Multiple Sclerosis
Anti-inflammatory |
|
|
|
Antispastic drugs (baclofen, tizanidine)
|
Multiple Sclerosis
Baclofen acts on GABAB receptors to inhibit spinal reflexes |
|
|
|
Riluzol (Rilutek)
|
ALS
Inhibits glutamate release, bocks glutamate receptors Inhibits Na+ channels Adv: elevation of hepatic enzymes, N/V |
|
|
|
Baclofen (Lioresal)
|
ALS
Spasticity GABA-B agonist |
|
|
|
Gabapentin (Neurontin)
|
ALS
Spasticity |
|
