Dr. Wang's CNS Pharmacology
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| Tetrodoxin | puffer fish toxin -- helped us understand action and resting membrane potential by blocking sodium channels
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| Strychnine | Glycine receptor antagonist
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| Frontal lobe | skeletal muscle movement, information coordination, behavioral integration
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| parietal lobe | somatic sensory
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| occipital lobe | vision
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| temporal lobe | hearing
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| Cerebral cortex | integrates sensory/motor activity, controls thought/memory/consciousness
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| limbic system | integrates emotions with motor coordination
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| Basal ganglia -- part of? function? | Part of the limbic system -- forms extrapyrimidal motor system
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| Hippocampus -- part of? function | part of limbic system -- incorporates recent memory
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| thalamus -- part of? function | part of limbic system -- contains nuclei which relay information between sensory and cortical pathways
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| Hypothalamus -- part of? function? | part of limbic system -- integrates autonomic nervous system (temp, water balance, sleep, BP regulation)
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| Two motor systems | Pyramidal and extrapyramidal
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| Pyramidal motor system | located on outer cerebral cortex in motor strip, move limbs voluntarily (conscious effort)
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| Extrapyramidal motor system | Located in deep brain structures (outside pyramidal system), controls tone-posture-other involuntary motor functions (do not require conscious effort. Functions and locations are less well-defined compared to pyramidal system.
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| Antipsychotics have what effects on the extrapyrimidal system? | Toxic - parkinsonian syndrome
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| Brain stem is composed of? | pons and medulla
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| Brain stem is the center of? | life
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| brain stem function | coordinates essential reflexes, swallowing, vomiting, cardiovascular, respiratory
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| Reticular activating system is part of and does what | part of brain stem, regulates sleep, wakefulness, arousal, and eye movement
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| chemoreceptor trigger zone is part of and does what | part of brain stem, responds to drugs via emesis
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| emesis | vomiting
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| cerebellum function | posture, visceral function, learning, memory
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| spinal cord | motorneurons, sensory relay cells, these convey signals between brain and periphery
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| Hierarchical neuronal system function | sensory perception and motor control
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| Hierarchical neuronal system composition | large, myelinated fibers capable of fast conduction
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| Hierarchical neuronal systems and lesions | incapacitates system
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| lesion | damage
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| Two types of hierarchical neurons | Relay/projection and local circuit
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| relay/projection hierarchical neurons | excitatory/glutamate
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| glutamate excitatory or inhibitory | excitatory
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| local circuit hierarchical neurons | inhibitory/GABA or glycine
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| GABA excitatory or inhibitory | inhibitory
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| Connection ratio for hierarchical systems | 1:1
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| Connection rato for diffuse/nonspecific neuronal systems | More than 1:1
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| Diffuse or nonspecific neuronal systems use what neurotransmitter types | monoamine or peptides
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| monoamines | 5-HT, catecholamines
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| Diffuse or nonspecific neuronal systems axon type | fine, unmyelinated, slow, long-lasting conduction
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| Diffuse or nonspecific neuronal systems convey what sort of information | non-topographically specific
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| Diffuse or nonspecific neuronal systems control | sleep/wake cycle, attention, appetite, emotion
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| Classify neurons by function | excitatory, inhibitory
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| classify neurons by location | cortical, subcortical, spinal
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| classify neurons by neurotransmitter | gabanergic, adrenergic, dopanergic, seritonergic
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| two types of synapse signalling | electrical and chemical
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| two types of ion channel on synapses | voltage and ligand gated
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| two types of receptors on synapses | metabotropic and ionotropic
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| action potential | brief fluctuation in membrane potential cuased by rapid opening and closing of voltage-gated ion channels
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| synapse in greek | to fasten together
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| stimulus to presynaptic neuron causes? | influx of calcium that induces NT release, NT binds postsynaptic neuron and causes EPSP or IPSP
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| EPSP | Depolarization
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| IPSP | hyperpolarization
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| 2 neuron cell types | axons and dendrites
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| Place were axons synapse | terminal or terminal bouton
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| Synthesis of NT requires what from where? | ATP from mitochondria
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| recurrent neuronal interaction | negative feedback from a neuron to itself
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| feed-forward neuronal interaction | negative feed-forward from a neuron to itself
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| Axoaxonic neuronal interaction | negative input from one neuron to another
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| dendrodendritic neuronal interaction | complicated, not just axon-axon, gives brain sophistication
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| voltage gated channels -- which ions? | Ca, Na, K
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| Ligand-gated channels (ionotropic receptors) respond to? | ligands
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| membrane-delimited/diffusible second messenger metabotropic ion channels are what? | GPCRs
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| A GABAa receptor is what kind of channel receptor? | ligand-gated channel
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| Excitatory pathways involve ionotropic receptors that allow what ions through to induce depolarization? | K+ and Na+
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| Inhibitory pathways allow what ion through to cause hyperpolarization? | Cl-
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| Criteria for a neurotransmitter | Localization, release, and synaptic mimicry
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| Neurotransmitter -- localization criterion | present in the presynaptic terminals of the synapse and in the neurons from which those presynaptic terminals arise
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| Neurotransmitter -- release criterion | released from the presynaptic nerve as a result of presynaptic nerve stimulus. neurotransmitter release is dependent on Ca2+ influx into the presynaptic terminal and corresponding voltage change
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| Neurotransmitter -- synaptic mimicry criterion | Exogenous copies of the molecule thought to be a neurotransmitter induce the same effect when introduced to the synapse
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| Amino acid neurotransmitters | y-aminobutyric acid (GABA), glycine, glutamate
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| glycine (excite or inhibit) | inhibitory
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| Amine neurotransmitters | dopamine, norepinephrine, serotonin, histamine
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| Which amine neurotransmitters have reuptake transporters? | Dopamine, norepi, and serotonin -- NOT histamine!
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| Peptides | Substance P, endogenous opioids (enkephalins, beta endorphin), cholecyctokinin (CCK), vasoactive intestinal peptide (VIP), angiotensin (AT), and neuropeptide Y (NPY)
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| NO and CO are gases but also? | neurotransmitters
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| where are amino acid neuortransmitters synthesized? | in the nerve terminals
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| GABA, BZDs, flumanzenil, and zolpidem bind to what site on the GABA receptor? | allosteric sites
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| GABAa is a channel for what ion? | Cl
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| muscimol affects what receptor as an agonist or antagonist? | GABAa agonist
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| picrotoxin -- receptor? affect? | competitive GABAa antagonist
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| bicuculline -- receptor? affect? | competitive GABAa antagonist
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| GABAb is what kind of receptor? | GPCR
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| Baclofen -- receptor? affect? | GABAb agonist
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| 2-OH-saclofen -- receptor? affect? | GABAb antagonist
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| Baclofen relieves spasticity of? | ALS (Lou Gehrig's disease)
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| Picrotoxin is an alkaloid derived from? | plants
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| glutamate receptors are both? | ionotropic and metabotropic
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| Glutaminergic ionotropic receptors are excitatory or inhibitory? | excitatory
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| three types of glutaminergic ionotropic receptors | N-methyl-D-aspartate (NMDA), kainate receptor, and AMPA
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| NMDA is an agonist of? | NMDA excitatory glutaminergic ionotropic receptors
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| dizocilpine (MK-801) is an antagonist of? | NMDA excitatory glutaminergic ionotropic receptors
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| AMPA is an agonist of? | AMPA excitatory glutaminergic ionotropic receptors
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| CNQX is an antagonist of? | AMPA excitatory glutaminergic ionotropic receptors
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| Glutaminergic metabotropic receptors -- excitatory or inhibitory? | Both
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| Glutaminergic metabotropic receptors -- ionotropic or GPCR? | GPCR
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| glutaminergic metabotropic receptors have 3 groups. Group 1 is where? Groups 2 and 3 are where? | Group 1 is post-synaptic, excitatory. Groups 2 and 3 are presynaptic and inhibitory.
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| Glycine receptors -- excitatory or inhibitory? | inhibitory
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| Taurine -- receptor and effect -- why found in Red Bull? | glycine receptor agonist -- for its calming effects
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| Beta-alanine -- receptor and effect | glycine receptor agonist
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| strychnine -- receptor and effect | glycine receptor antagonist
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| function of Ach and Ach receptor systems | arousal, sleep-wake cycle, learning, memory
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| Ach tract 1: Medial septal nuclei innervates? | hippocampus
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| Ach tract 2: basal nucleus meynert (cell body in basal forebrain) innervates? | neocortex
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| Ach tract 3: basal forebrain innervates? which then innervates? | cerebral cortex and pontomesencephalotegmental complex, which innervates the thalamus and forebrain
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| AchE inhibitors are used to treat? | Alz
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| Alz is characterized by a lack of what NT? | Ach
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| DA system is comprised of two brain regions -- they are? | substantia nigra (Parkinson's), and the ventra tegmental area (VTA) -- reward center/schizophrenia
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| NE system is where in brain? | locus coeruleus (blue spot)
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| is the NE system diffuse or specific? | diffuse -- 1 neuron can have 250,000 synapses
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| NE system functions | attention, arousal, sleep-wake cycles, learning, memory, anxiety, pain, mood, brain metabolism
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| 5-HT functions | control of sleep-wake cycles, different stages of sleep, emotional behavior
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| 5-HT system brain region | raphe nuclei in midline of brain stem, and ascending reticular activating system (responsible for arousal and awakening)
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| Raphe | Ridge or seam
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| Serotonin is derived from | tryptophan
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| 5-HT is related to emotional behavior. Drug classes include | SSRI -- for anxiety, OCD, and depression
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| Peptide neurotransmitters work alone or in concert | Work with coexisting transmitter, can have 1+ at the same time
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| peptides are not small molecules synthesized in terminal. they are | peptides synthesized from mRNA in the ER. They are synthesized as precursors, transported to the terminals from the perinuclear cytoplasm, and are NOT reuptaken into the terminal
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| 4 types of general/nonspecific CNS depressants | General anesthetics, some sedative hypnotics, alcohol, and local anesthetics if accidentally injected (applied systemically)
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| 3 types of general or nonspecific CNS stimulants and their 2 mechanisms | Work through disinhibition or direct stimulation. analeptics (strychnine, pentylenetetrazol, picrotoxin), methyxanthines (caffeine), and amphetamines/amphetamine-like drugs
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| Analeptics disinhibit | glycine or gaba receptors
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| methylxanthines like caffeine inhibit | phosphodiesterase (PDE), preventing cAMP degradation
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| amphetamines and amphetamine like drugs function | inhibit reuptake of NE or DA and increase concentration of catecholamines/MOAs in the presynaptic terminal, then induces their release
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| 4 stages of general anesthetics | 1- induction
2- excitation (don't raise dose! Body is fighting anesthesia)
3- surgical anesthesia
4- overdose
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| Steps toward excitation | Normal>alertness>hyperexcitation>convulsion>death
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| Steps toward depression | Normal>sedation/hypnosis>anesthesia>coma>death
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| Characteristics of Selective CNS Drugs | Selective distribution, differential actions on different neurons (5-HT vs. Dopaminergic), selectivity through functional neuron state, and interaction with specific sites (presynaptic vs. postsynaptic receptors and autoreceptor feedback)
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| dopamine hypothesis | many antipsychotics block D2 receptors in CNS, drugs that up DA activity aggravate schizophrenic symptoms, increased DA receptors sensitivity is found in schizophrenics, and homovanillic acid (DA breakdown product) urine levels change in treated pts
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| Apomorphine | DA agonist, induces psychosis
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| levodopa | provides DA precursor
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| amphetamine and DA | stimulates DA release
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| Problems with DA hypothesis -- current antipsychotics treat how many patients? | some not all
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| Problems with DA hypothesis -- phencyclidine is an NMDA receptor antagonist does what when given to healthy pts? | Induces much more schizophrenia like symptoms than DA agonists.
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| Problems with DA hypothesis -- atypical antipsychotics are effective in treating schizophrenia. But they are less potent in what? | blocking D2 receptors
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| Problems with DA hypothesis -- DA blockade occurs in hours with antipsychotics. How long before therapeutic effects seen? | weeks
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| Serotonin hypothesis for schizophrenia -- hallucinogens like LSD and mescaline are? | 5-HT agonists
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| Serotonin hypothesis for schizophrenia -- clozapine and quetiapine are inverse agonists of? | 5-HT2A receptors
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| Serotonin hypothesis for schizophrenia -- 5-HT2A/C receptors regulate? | DA and NMDA neurotransmission
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| Which class of antipsychotics are the oldest first generation? | Phenothiazines
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| Chlorpromazine (Thorazine) -- class? | aliphatic phenothiazine first generation antipsychotic
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| Triflupromazine (Vesprin)-- class? | aliphatic phenothiazine first generation antipsychotic
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| Piperidine antipsychotic potency vs. aliphatic potency and extrapyrimidal/weight gain symptoms | Aliphatic antipsychotics are more potent and also have more extrapyrimidal side effects/promote more weight gain
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| Thioridazine (Mellaril) -- class | Piperidine phenothiazine first gen typical antipsychotic
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| Mesoridazine (Serentil) -- class | Piperidine phenothiazine first gen typical antipsychotic
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| Piperazine phenothiazines -- potency? selectivity and corresponding cytotoxicity? extrapyramidal side effects? | when compared to aliphatic phenothiazines: Potent (effective in low dose), selective (not sedative or hypnotic), but have severe extrapyramidal side effects
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| Fluphenazine (prolixin) -- class | piperazine phenothiazine first gen typical antipsychotic
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| Trifluoperazine (Stelazine) | piperazine phenothiazine first gen typical antipsychotic
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| Perphenazine | piperazine phenothiazine first gen typical antipsychotic
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| Two classes of thioxanthene antipsychotics | aliphatic and piperazine
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| chloprothizene (Taractan) -- class? | aliphatic thioxanthene
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| thiothixene (Navane) -- class? | piperazine thioxanthene
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| Which is more potent -- thioxanthenes or phenothiazines? | phenothiazenes are slightly more potent
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| Butyrophenones -- most famous and only member we discussed | Haloperidol
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| Haloperidol -- class, how often used, relative potency to other first gens, relative autonomic side effects, relative extrapyramidal side effects | butyrophenone, most widely used typical, unique structure, more potent, fewer autonomic but more severe extrapyramidal side effects
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| Action and mechanism of antipsychotics -- antipsychotic effects | suppression of conditioned responses, diminution of spontaneous motor activity
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| Which antipsychotics are most effective for reducing spontaneous motor activity? | haloperidol and piperazines
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| What is thought to cause psychotic events? | increased DA activity in mesolimbic/mesocortical areas -- which is also related to psychosis-related abnormal behaviors
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| Action and mechanism of antipsychotics -- mechanism | block DA receptors and thus suppress antipsychotic behaviors
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| Mesolimbic-mesocortical pathway -- DA system component responsible for? | behavioral control, also the major site of anti-psychotic effects
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| nigrostriatal pathway -- DA system component responsible for? | voluntary and involuntary movement coordination
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| tuberoinfundibular pathway -- DA system component responsible for? | neuroendrocrine regulation (mental state goes through here to change endocrine function
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| medullary-periventricular pathway -- DA system component responsible for? | eating behavior
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| incertohypothalamic pathway -- DA system component responsible for? | behavioral regulation (not control -- that's the mesolimbic-mesocortical)
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| D1 receptor family -- intracellular effects and receptor subtypes | Increases cAMP, increases PIP2 hydrolysis, mobilizes Ca2+, activates PKC -- D1 and D5
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| D2 receptor family -- intracellular effects and receptor subtypes | Decreases cAMP, increases K currents, decreases voltage-gated Ca2+ currents -- D2, D3, D4
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| All DA receptors are what type? | GPCR
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| CNS side effects/toxicity -- extension of main effect (especially caused by aliphatics | Depression, sedation, pseudodepression (at high doses)
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| CNS side effects/toxicity -- decrease of which thresh hold (especially aliphatics)? | seizure
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| CNS side effects/toxicity -- selectively depress what (thioridazine is especially good for this as a clinical effect)? | Chemoreceptor trigger zone for emesis -- anti-nausea
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| CNS side effects/toxicity -- extrapyramidal or neuroleptic symptoms occur especially with and cause them by doing? | Occur with butyrophenones and potent piperazines -- blockade of DA receptors in the basal ganglia
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| CNS side effects/toxicity -- Tardive diskinesia | Late-appearing neurological syndrome -- caused by DA receptor supersensitivity in the basal ganglia (from up-regulation of the receptor caused by years of blockade by antipsychotics)
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| Extrapyramidal symptoms and treatment -- Parkinson's Syndrome | Akinesia, resting tremor, rigidity.
Antiparkinsonism drugs of the muscarinic type or amantadine.
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| Extrapyramidal symptoms and treatment -- Akathiisia | feelings of distress/discomfort compelling one to constant movement -- may be mistaken for agitation in psychosis but will be made worse by dose increase --treated by dose reduction, antiparkinsonism drugs, or anticholindergic sedatives (diphenhydramine)
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| Extrapyramidal symptoms and treatment -- Acute dystonia | State of abnormal muscle tone, also called torticollis, treated with anticholinergic antiparkinsonian drugs
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| Extrapyramidal symptoms and treatment -- Catatonia, hyperthermia | rare. occurs only in high doses or most potent antipsychotics. seizures in chlorpromazine or clozapine.
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| Extrapyramidal symptoms and treatment -- neuroleptic malignant syndrome | emergency state, rare, occurs with high doze of antipsychotics, 10-20% of pts. die, STOP antipsychotics, give antiparkinsonism drugs, bromocriptine, and muscle relaxants like diazepam or dantrolene
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| DA neurons do what to GABA neurons? | Disinhibit their inhibition
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| ACH neurons do what to GABA neurons? | stimulate their inhibition
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| Tardive Dyskinesia -- associated with supersensitivity to what that causes a relative low concentration of what | Dopamine supersensitivity occurs as a result of upregulation, causing a relatively lower concentration of Ach
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| Tardive dyskinesia -- more pronounced in? caused by? stereotypical symptoms? treatable? | More pronounced in elderly patients. Caused by the immediate withdrawal of antipsychotic agents, characterized by sucking, smacking lips, lateral jaw movement, fly-catching darting of tongue, and coreiform movements of the extremities. Untreatable.
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| treating tardive dyskinesia | withdraw or lower dose of causative agent, switch to newer atypical agent, and eliminate all drugs with known anticholinergic effects (antiparkinsonism drugs, TCAs), add muscle relaxer like diazepam
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| DA activity in pituitary does what to prolactin release? | inhibits it
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| Lack of DA activity in pituitary does what to prolactin release? | stimulates it
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| Peripheral side effects of antipsychotics -- hyperprolactinemia and amenorrhea | Blocks DA, causes prolactin release. causes increased conversion of androgens to estrogen, leading to false-positive pregnancy tests. Infertility. Impotence. Treat with dose reduction or aripiprazole (decreases DA receptor sensitivity).
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| Peripheral side effects of antipsychotics-- poikilothermia | condition of not reacting to temperature change in environment -- cold-bloodedness
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| Peripheral side effects of antipsychotics -- Alpha-adrenergic blockade (especially aliphatic phenothiazines) | orthostatic hypotension, faintness, palpitations, nasal stuffiness, impaired ejaculation, longer QT interval
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| Peripheral side effects of antipsychotics -- Anticholinergic action | Reverse SLUDGE
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| Peripheral side effects of antipsychotics -- hypersensitivity (allergic) reaction | skin rashes, obstructive jaundice, blood dyscrasias (blood count off), photosensitivity
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| Peripheral side effects of antipsychotics -- weight gain | Especially piperazine drugs (clozapine, thioridazine, olanzapine)
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| Pharmacokinetics of antipsychotics -- absorption | most are highly lipophilic, protein bound, long duration of action
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| Pharmacokinetics of antipsychotics -- liver metabolism | significant first pass metabolism, oxidation by P450 enzymes and conjugation
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| Pharmacokinetics of antipsychotics -- elimination | metabolites excreted in urine and bile
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| Mesoridazine | metabolite of thioridazine, even more potent
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| Antipsychotic drug interactions -- combined with CNS depressants | anticholinergic effects, potentiate sedatives and analgesics, alcohol, hypnotics, and antihistamines. Overall additive/synergistic effect.
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| Antipsychotic drug interactions -- dopamine agonists or levodopa | antipsychotics inhibit the effects of these drugs, which are used to treat Parkinsonian symptoms
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| Antipsychotic drug interactions -- with antihypertensive Guanethidine | Block effects
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| Antipsychotic drug interactions -- with digitalis | quinidine like cardiac effects of thioridazine and ziprasidone nullify the inotropic effects of digitalis
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| fluphenazine decanoate | antipsychotic used for delusional paranoid state
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| All older antipsychotics can be used as antinauseas except | thioridazine -- it blocks DA receptors centrally AND peripherally
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| prochlorperazine | antiemetic
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| benzquinamide | antiemetic
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| trimeprazine (Temaril) | used for intractable hiccough
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| antipsychotics can be used to treat pruritus | severe itch or rash on skin
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| haloperidol can be used to treat what disease (proper name)? | Huntingdon's
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| butyrophenone droperidol is used in combination with fentanyl to induce? | neuroleptanesthesia -- anesthesia
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| Clozapine -- typical or atypical? | atypical
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| Clozapine -- most potent for? | D4 receptor
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| Clozapine -- potent anti? | anticholinergic
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| Clozapine -- Blocks what receptors? | 5-HT2a and limited blocking of D2 receptor
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| Clozapine -- Major side effect? | Fatal agranulocytosis. 1-2% of pts. have to do regular blood counts.
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| Clozapine -- seizure in how many pts? | 2-5%
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| Clozapine -- should you use it in old patients with dementia? | No. It has potent anticholinergic effects -- alzheimer's is due to an already existent lack of Ach
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| Clozapine -- does it cause weight gain? | yes
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| Olanzapine (Xyprexa) -- blocks what receptor? | 5-HT2a
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| Olanzapine is the most tolerated what? | atypical antipsychotic
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| Olanzapine -- older pts. with dementia? | Do not use. Increases death by stroke rate.
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| Olanzapine causes? | weight gain
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| Loxapine (Loxitane) is a? | Modern antipsychotic (second gen atypical)
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| Risperidone (Risperdal) is similar to Clozapine, but has more? | Clozapine DA antagonism
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| Risperidone (Risperdal) is similar to Clozapine, but has fewer? | Side effects from seritonergic and anticholinergic activity
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| Paliperidone | Metabolite of risperidone -- also active
🗑
|
||||
| Quetipine (Seroquel)-- similar to Risperidone how? | No anticholinergic effects
🗑
|
||||
| Which antipsychotic is the most prescribed as of 2007? | Quetipine (Seroquel)
🗑
|
||||
| Aripiprazole (Abilify)-- reduces what serious atypical side effect and has a long what | reduces weight gain, has a long half-life
🗑
|
||||
| Aripiprazole (Abilify) is used for? | depression, mania, schizophrenia, bipolar disorder, and the aggression/temper tantrums associated with autism
🗑
|
||||
| Antipsychotics have hypotensive effects. What receptor mediates these? | Alpha-adrenergic receptors
🗑
|
||||
| which 3 antipsychotics are never recommended for fat people? | Thioridazine, clozapine, olanzapine
🗑
|
||||
| Which antipsychotic is recommended for people with extrapyramidal problems? | Risperidone
🗑
|
||||
| Which antipsychotics are best for patients with alzheimer's? | Quetiapine and Risperidone
🗑
|
||||
| Neuropathology of Parkinson's | Loss of dopanergic neurons in substantia nigra, intracellular inclusions (Lewy bodies), symptomatic PD
🗑
|
||||
| Drug-induced parkinsonism (pseudoparkinsonism) is caused by what drugs? | DA receptor antagonists (antipsychotics like haloperidol/thorazine and anti-emetics like metoclopramide and prochlorperazine)
🗑
|
||||
| Pseudoparkinsonism is also caused by what toxic agent? | MPP+ derived from MPTP by MAO-B
🗑
|
||||
| Pathophysiology of parkinsons | Loss of neurons in substantia nigra
🗑
|
||||
| MTPP looks like what molecule and is converted into what, which kills neurons in the substantia nigra by doing what? | Dopamine, MPP+, being taken in by the reuptake transporter and used as if it were dopamine -- this kills the cell
🗑
|
||||
| Triad symptoms of Parkinson's Disease | Bradykinesia or akinesia (difficulty in initiating movement), resting tremor, skeletal muscular rigidity or hypertonicity
🗑
|
||||
| The substantia nigra uses dopaminergic neurons to communicate with? | The corpus striatum
🗑
|
||||
| What are the ways you can shut down DA neuronal communication in Parkinson's or pseudoparkinson's? | You can block DA receptors, destroy dopaminergic neurons, or hurt the quantity of useful dopamine in the brain (release or production)
🗑
|
||||
| How does one treat Parkinson's? | replace dopamine, decrease cholinergic neurotransmission by withdrawing cholinergic drugs and anticholinesterase drugs
🗑
|
||||
| Parkinsons and alzheimers both deal with a delicate balance between dopamine and acetylcholine. Which one is high and low in which condition? | Parkinson's: High DA. Low ACH.
Alzheimer's: Low DA. High Ach.
🗑
|
||||
| We can deal with parkinson's by upping dopamine or decreasing what? | Ach
🗑
|
||||
| Trihexyphenidyl (Artane) | Anticholinergic used to treat parkinson's
🗑
|
||||
| Benztropine (Cogentin) | Anticholinergic used to treat parkinson's
🗑
|
||||
| What characteristic must a drug have if it is to treat Parkinson's or any disease of the CNS? | The ability to penetrate the blood-brain barrier
🗑
|
||||
| Ach antagonists are used by themselves to treat Parkinson's when it is mild or severe? | Mild
🗑
|
||||
| If severe parkinson's is present, what drug(s) do we select for treatment? | Ach antagonists AND L-Dopa
🗑
|
||||
| Side effects of anti-parkinson's Ach antagonists | drowsiness, mental slowness, GI side effects, tachycardia, dry mouth, constipation (Anti SLUDGE)
🗑
|
||||
| When should you NOT give anti-parkinson's Ach atnagonists? | prostate hyperplasia (urinary retention is exacerbated), obstructive GI disease, or close-angle glaucoma (causes retention of aqueous humor) -- open angle glaucoma is OKAY
🗑
|
||||
| Too high a dose of levodopa causes | dyskinesia
🗑
|
||||
| Too low a dose of levodopa causes | akinesia
🗑
|
||||
| why not give DA -- why do we need a precursor? | DA cannot penetrate BBB
🗑
|
||||
| Tyrosine-->?-->Dopamine | Tyrosine is converted by tyrosine hydroxylase to DOPA which is converted by decarboxylase to dopamine
🗑
|
||||
| How well does L-DOPA work for Parkinson's? How long does it work? Do we use it right away? | It works very, very well -- but only for 3-4 years. Then its effects are diminished. We do NOT use it for mild idiopathic parkinson's. We save it for later, when the patient really needs help.
🗑
|
||||
| Does levodopa stop the progression of parkinson's? | No
🗑
|
||||
| What is the wearing-off affect of levodopa? | At the end of their dose, the therapeutic level may drop so far in a patient that they experience dyskinesia
🗑
|
||||
| On-off levodopa effect | akinesia and then wham, dyskinesia
🗑
|
||||
| Side effects of dopaminergic antiparkinson drugs--GI | Disturbances. drugs enhance emetic response -- you get sick to the stomach -- treat with antiemetics but be careful as these can induce parkinsonian attack
🗑
|
||||
| Side effects of dopaminergic antiparkinson drugs--Cardiovascular | tachycardia. orthostatic hypotension.
🗑
|
||||
| Side effects of dopaminergic antiparkinson drugs--dyskinesia | 80% of pts -- due to DA overload
🗑
|
||||
| Side effects of dopaminergic antiparkinson drugs--Choreoathetosis | involuntary irregular, repetitive, twisting or writhing movements alleviated by dose reduction
🗑
|
||||
| Side effects of dopaminergic antiparkinson drugs--behavioral | agitation, delirium, hallucination, psychosis. Use ATYPICAL antipsychotics like clozapine! DO NOT USE TYPICALS! These are DA antagonists!
🗑
|
||||
| Side effects of dopaminergic antiparkinson drugs--Hormonal | tonic inhibition of HPA axis and prolactin by DA. DA blocks prolactin release and DA antagonists induce its release. Massive decrease in milk production.
🗑
|
||||
| Drug interactions of dopaminergic antiparkinson drugs -- pyridoxine (vitamin B6) | This causes a big increase in dopamine levels and is an amino acid decarboxylase cofactor (boosts last step in dopamine production pathway -- DOPA-->Dopamine)
🗑
|
||||
| Drug interactions of dopaminergic antiparkinson drugs -- MAO inhibitor antidepressants | MAO-A1 is blocked and this blocks the breakdown of dopamine. It can cause hypertensive crises.
🗑
|
||||
| Drug interactions of dopaminergic antiparkinson drugs -- antipsychotics | Levodopa is simply prohibited in psychotic patients. No way, no how.
🗑
|
||||
| Drug interactions of dopaminergic antiparkinson drugs -- Physostigmine | Cholinesterase inhibitor used for glaucoma
🗑
|
||||
| AD | aldehyde dehydrogenase, converts dopamine into inactive forms
🗑
|
||||
| COMT | catechol-O-methyltransferase, converts dopamine and L-DOPA to inactive forms
🗑
|
||||
| D-beta-H | dopamine beta hydroxylase, converts dopamine to norepinephrine
🗑
|
||||
| AAD | aromatic L-amino acid decarboxylase, converts levodopa to dopamine and uses vitamin B6 as a cofactor
🗑
|
||||
| MAO | monoamine oxidase, converts dopamine to inactive metabolite
🗑
|
||||
| Sinemet | L-DOPA+carbidopa
🗑
|
||||
| carbidopa | peripheral aromatic L-amino acid decarboxylase inhibitor (blocks conversion of L-dopa into dopamine in the periphery and decreases side effects thereby -- also boosts amount that makes it to be effective in CNS) -- reduces necessary levodopa dose by 75%
🗑
|
||||
| Bromocriptine (parlodel) | D2 agonist
🗑
|
||||
| Perglide (permax) | D1 and D2 agonist, used to treat fibrosis of valves in the heart
🗑
|
||||
| Ropinirole (requip)/Ropinirole XL | selective D2 agonist, used for restless leg syndrome
🗑
|
||||
| Pramipexole (mirapex) | preferred affinity for D2 receptors
🗑
|
||||
| Rotigotine | Skin patch for early Parkinson's disease
🗑
|
||||
| DA receptor agonist other than L-DOPA are better for what phenomenon? | on/off phenomenon
🗑
|
||||
| DA receptor agonists other than L-DOPA are useful for those who cannot? | Tolerate L-Dopa's side effects
🗑
|
||||
| DA receptor agonists other than L-DOPA are useful for those who are already experiencing? | Toxicities similar to L-Dopa's side effects (GI and cardiovascular)
🗑
|
||||
| DA receptor agonists other than L-DOPA are contraindicated in which patients? | pts. with history of psychotic illness, recent myocardial infarction, GI ulceration -- this is especially true of the ergot-derived DA agonists
🗑
|
||||
| Amantadine (symmetrel) | antiviral that potentiates DA activity -- do not use in pts. with renal failure, congestive heart failure, and seizures
🗑
|
||||
| Selegiline (eldepryl) | irreversible MAO-B inhibitor that decreases L-DOPA's wearing off effect and dyskinesia. It also delays the initiation of L-DOPA therapy for PD treatment -- it buys the patient more time before they have the L-DOPA wearing off effect.
🗑
|
||||
| Entacapone (Comtan) | short duration COMT inhibitor, blocks DA degradation
🗑
|
||||
| Stalveo | Has L-DOPA, carbidopa, and entacapone. Entacapone blocks DA degradation, carbidopa blocks peripheral conversion of L-DOPA to dopamine (decreases L-DOPA dose needed), and L-DOPA is a dopamine precursor
🗑
|
||||
| Tolcapone (Tasmar) | long duration COMT inhibitor, acts at CNS and PNS, 2% hepatotoxicity, which is very high
🗑
|
||||
| Surgical antiparkinson procedures | Deep brain stimulation, injection of fetal brain tissue
🗑
|
||||
| COMT | Degrades catacholamines like DA
🗑
|
||||
| Neurodegenerative disorders | any disorder with progressive and irreversible loss of neurons from specific regions in the brain
🗑
|
||||
| Major difference between Parkinson's Disease and Huntingdon's Disease | Parkinson's is very sporadic. Huntingdon's is very genetic.
🗑
|
||||
| Major similarity between Parkinson's and Huntingdon's | Loss of neurons in basal ganglia and corresponding loss in movement control
🗑
|
||||
| Alzheimer's Disease | Loss of hippocampal and cortical neurons -- impairment of memory and cognitive capacity
🗑
|
||||
| ALS (amyotrophic lateral sclerosis) | degeneration of spinal, bulbar, and cortical motor neurons. Muscular weakness in the muscles requires to speak, swallow, and make facial expressions
🗑
|
||||
| Which nerves are hurt in Parkinsons? | Dopaminergic
🗑
|
||||
| Which nerves are hurt in Huntingdon's? | Gabanergic
🗑
|
||||
| Genetic factors associated with Huntingdon's | CAG repeats, autosomal dominant
🗑
|
||||
| Genetic factors associated with Parkinson's Disease | alpha synuclein (synaptic protein), LRRK2 (leucine-rich repeat kinase 2), Parkin (ubiquitine hydroxylase), UCHL1 (ubiquitin carboxy-terminal hydroxylase 1)
🗑
|
||||
| Genetic factors associated with Alzheimer's Disease | amyloid precursor protein (APP), presnilins (for APP processing), apolipoprotein E (cholesterol and lipid transport)
🗑
|
||||
| Genetic factors associated with ALS (amyotrophic lateral sclerosis) | mutation of SOD1 -- an enzyme that decreases the number of ROS in a cell. Loss of this enzyme through mutation increases the ROS in a cell.
🗑
|
||||
| Environmental factors that can contribute to neurological disorders | Infection agents (viral), Toxins (MPTP -- insecticides), injuries (stroke)
🗑
|
||||
| Excitotoxicity and neurological disorders | glutamate, NMDA receptors, and Ca2+ input can exceed the voltage capacity of a neuron and literally fry it. (can be due to AD or stroke)
🗑
|
||||
| Oxidative stress and neurological disorders | free radicals can be scavenged by glutathione, SOD, or vitamin E. If something happens to remove these, it is possible that ROS might cause issues
🗑
|
||||
| what is augmented in the treatment of alzheimer's | cholinergic function in the brain
🗑
|
||||
| Tacrine (Cognex) | Cholinesterase inhibitor used in the treatment of alzheimer's -- LOTS of side effects and very dose limited
🗑
|
||||
| Donepezil (Aricept) | AchE inhibitor used in the treatment of alzheimer's
🗑
|
||||
| Rivastigmine (Excelon) | AchE inhibitor used in the treatment of alzheimer's
🗑
|
||||
| Galantamine (Reminyl) | AchE inhibitor used in the treatment of alzheimer's
🗑
|
||||
| Memantine (Namenda) | NMDA antagonise used in the treatment of alzheimer's
🗑
|
||||
| Riluzole (Rilutek) | Delays ALS -- first ever approved by FDA for this. Inhibits glutamate release, blocks glutamate receptors, relieves spasticity (it's a spasmolytic)
🗑
|
||||
| Baclofen (Lioresal) | Relieves spasticity in ALS by agonizing the GABAb receptor (operates in CNS)
🗑
|
||||
| tizanidie (Zanflex) | alpha-2 adrenergic agonist (presynaptic autofeedback) (increases negative feedback mechanism in nerves)-- LOTS of cytotoxicity
🗑
|
||||
| Blocker of physiological tremors | Beta2 blocker (nonspecific beta blockers like propranolol)
🗑
|
||||
| Blocker of essential tremors | Beta1 blocker (metoprolol, atenolol, esmolol)
🗑
|
||||
| Tics | Chronic multiple tics -- Gilles de la Tourette's Syndrome
🗑
|
||||
| Tardive dyskinesia drug induced by? | DA receptor blocker
🗑
|
||||
| Tardive dystonia drug induced by? | DA receptor blocker and also anticholinergic drugs
🗑
|
||||
| tardive akathisia drug induced by? | anticholinergic antiparkinsonian drugs
🗑
|
||||
| Restless leg syndrome treated by? | pramipexole, ropinirole
🗑
|
||||
| Wilson's Disease caused by? | Recessively inherited disorder in the metabolism of copper
🗑
|
||||
| Wilson's Disease treated by? | penicillamine -- chelating agent for copper
🗑
|
||||
| Major Depressive Disorders (MDD) | Mental state of excessive sadness characterized by persistent low mood or extensive loss of pleasure or interest
🗑
|
||||
| Tricyclic antidepressants (TCA) structure | three-ring molecular core. similar to phenothiazines. most NE-reuptake inhibitors.
🗑
|
||||
| Class 1 of TCAs | Tertiary amines -- inhibit NE AND 5-HT reuptake
🗑
|
||||
| Class 2 of TCAs | Secondary amines -- selective NE reuptake inhibitors
🗑
|
||||
| Imipramine (tofranil) | Class 1 TCA, inhibits NE and 5-HT reuptake, also has anticholinergic antimuscarinic side effects
🗑
|
||||
| Amitriptyline (elavil) | class 1 TCA, blocks NE and 5-HT reuptake
🗑
|
||||
| Trimipramine (Surmontil) | Class 1 TCA, unknown mechanism, does NOT block reuptake!
🗑
|
||||
| Clomipramine (anafranil) | Class 1 TCA, the most potent of them all, also approved to treat OCD -- Doxepin/Sinequan
🗑
|
||||
| Desipramine (norpramin) | Class 2 TCA, NE reuptake only (not 5-HT), is a metabolite of imipramine and has less anticholinergic effect
🗑
|
||||
| Nortriptyline (aventyl) | Class 2 TCA, NE reuptake blocker but less selective so it still may hit 5-HT reuptake and block it too
🗑
|
||||
| protriptyline (vivactil) | Class 2 TCA, NE reuptake only, not 5-HT
🗑
|
||||
| Do TCAs have any effects in a normal person? | No. They do not elevate the mood of normal persons.
🗑
|
||||
| What do TCAs do in depressed patients? | they elevate mood and decrease time in REM sleep
🗑
|
||||
| Which have more anticholinergic action? tertiary or secondary amines? | tertiary
🗑
|
||||
| TCAs have alpha-adrenergic blockade. Which receptor do they block more? | Alpha 2 WAY over alpha 1. They have NO affinity for beta receptors.
🗑
|
||||
| Mechanism of action TCAs | Inhibit the neuronal uptake of biogenic amines in the CNS (NE, 5-HT), however exceptions of this hypothesis do exist (trimipramine)
🗑
|
||||
| Pharmacokinetic properties of TCAs | High protein binding, high lipophilic, anticholinergic effects, drug absorption (slows GI motility, delays absorption), Fairly well absorbed after oral administration, and significant first pass metabolism in the liver
🗑
|
||||
| Side effects of TCAs (anti-Ach M and alpha-adrenergic) | GI side effects and posterual hypotension (anti-alpha1-adrenergic)
🗑
|
||||
| CNS side effects of TCAs | take someone right out of depression into hypomania or mania, restlessness, insomnia, tremors, or potentiation of seizures (antihistaminic effects)
🗑
|
||||
| Cardiac toxicity caused by TCAs | palpitation, tachycardia, orthostatic hypotension (alpha-1 adrenergic effect)
🗑
|
||||
| Weight/sweating side effects of TCAs | weight gain, excessive sweating
🗑
|
||||
| TCA drug interactions -- plasma proteins and liver metabolism | compete with antiepileptics (piperazine phenothiazines in particular), antipsychotics, smoking, and barbiturates
🗑
|
||||
| TCA drug interactions -- with antipsychotic drugs | Protein binding and additive anticholinergic action (muscarinic)
🗑
|
||||
| TCA drug interactions -- with guanethidine | inhibits NE release from presynaptic nerver terminal by BEING UPTAKEN with the reuptake transporter! This is the precise mechanism BLOCKED by TCAs!
🗑
|
||||
| TCA drug interactions -- with MAO inhibitors | Serotonin syndrome when co-treated with SSRIs. causes akathisia-like restlessness
🗑
|
||||
| Serotonin Syndrome -- caused by | SSRIs given with MAOIs. SSRIs in this situation include TCAs with 5-HT reuptake inhibition.
🗑
|
||||
| Serotonin Syndrome -- severity | Can be lethal
🗑
|
||||
| Serotonin Syndrome -- cause(s) | occurs when 2+drugs that affect serotonin levels are taken simultaneously. (MAOIs, SSRIs, meperidine, dextromethorphan)
🗑
|
||||
| Serotonin Syndrome -- signs and symptoms | agitation, diarrhea, heavy sweating, fever, mental status change, muscle spasm, overactive reflexes, shivering, tremor, ataxia
🗑
|
||||
| Serotonin Syndrome -- Treatment | BZDs (diazepam, lorazepam), cyproheptadine (inhibits serotonin), withdrawal of MAOIs or SSRIs causing the syndrome, fluids/breathing machine to maintain patient until danger passes
🗑
|
||||
| Therapeutic uses for TCAs | Less popular due to side effects, but the tertiary amines are still prescribed for endogenous depression
🗑
|
||||
| TCAs are used together with lithium to treat what? | Bipolar disorder
🗑
|
||||
| TCAs can be used for what condition in children or geriatrics? | Enuresis -- provides rapid, temporary suppression
🗑
|
||||
| NE-selective TCAs can be used to treat what condition? | ADHD
🗑
|
||||
| TCAs can be used to treat what syndrome? | Tourette's
🗑
|
||||
| TCAs can be used to treat which severe anxiety disorders? | panic-agoraphobia, social phobia, obsessive-compulsive disorder
🗑
|
||||
| TCAs can be used to treat what kind of pain? | chronic
🗑
|
||||
| fluoxetine (prozac)class and serious side effect | original SSRI. Can induce suicidal ideation in juveniles/adolescents, norfluoxetine is active metabolite with 240 hour halflife
🗑
|
||||
| paroxetine (paxil) class and unique feature (has to do with how many neurotransmitters it blocks) | SERT and NET -- serotonin reuptake and also norepi reuptake inhibitor -- research shows it affects BOTH even though it's an SSRI
🗑
|
||||
| sertraline (zoloft)class | SSRI
🗑
|
||||
| SSRI | selective serotonin reuptake inhibitor
🗑
|
||||
| citalopram (celexa) class | SSRI
🗑
|
||||
| fluvoxamine (luvox) class | SSRI
🗑
|
||||
| SSRI pharmacodynamic properties | 80% inhibition of 5-HT reuptake transporter -- does NOT affect histamine, acetylcholin, or alpha-adrenergic receptors -- this decreases side effects tremendously
🗑
|
||||
| SSRI pharmacokinetics | lipophilic, EXTREMELY long half life (10 days for fluoxetine's active metabolite, norfluoxetine), and fluoxetine/paroxetine are potent inhibitors of CYP2D6 and TCA
🗑
|
||||
| Side effects of SSRIs | GI upset, weight gain, sexual function
🗑
|
||||
| SSRI drug interactions -- do NOT use with? | MAOIs
🗑
|
||||
| Therapeutic uses for SSRIs | major depressive disorder, general anxiety disorder, post-traumatic stress disorder, obsessive compulsive disorder, panic disorder, pre-menstrual depressive disorder, and bulimia
🗑
|
||||
| SNRI | serotonin/norepi reuptake inhibitor
🗑
|
||||
| Venlafaxine (Effexor) class | SNRI
🗑
|
||||
| Duloxetine (Cymbalta) class | SNRI
🗑
|
||||
| Drug interactions SNRIs | MAOI -- causes serotonin syndrome
🗑
|
||||
| Therapeutic uses SNRIs | panic disorder, social anxiety disorder, pain disorder (duloxetine is really good for diabetic neuropathic pain and fibromyalgic pain), and urinary incontinence (esp. when due to stress)
🗑
|
||||
| Trazodone (desyrel) | SNRI 5-HT2 antagonist, also a hypnotic
🗑
|
||||
| Nefazodone (Serzone) | SNRI 5-HT2 antagonist, hepatotoxicity is an issue
🗑
|
||||
| Buproprion (wellbutrin) | SNRI unicyclic, blocks dopamine/NE reuptake -- unique to this drug only, increases the availability of both neurotransmitters, and is used for smoking cessation
🗑
|
||||
| Mirtazapine (remeron) | SNRI tetracyclic, presynaptic alpha2 receptor antagonist (DISinhibitor, blocks inhibition effects of the alpha-2 receptor), blocks 5-HT2 and 3 receptors, H1 antagonist
🗑
|
||||
| MAOI | monoamine oxidase inhibitors
🗑
|
||||
| MAOI drug interactions | A LOT. In fact, this is the main reason we study them. Normally they aren't even prescribed -- but when they are, they are a BIG deal.
🗑
|
||||
| phenelzine (nardil) class | non-selective, irreversible MAOI
🗑
|
||||
| tranylcypromine (parnate) class | non-selective, irreversible MAOI
🗑
|
||||
| selegiline (eldepryl) class | selective MAO-B inhibitor
🗑
|
||||
| selegiline use | parkinson's
🗑
|
||||
| clorgyline class | MAO-A selective inhibitor
🗑
|
||||
| Pharmacological actions of MAOIs | mood elevation of depressed patients, increased motor activity, increased appetite, excitement, euphoria, suppression of REM sleep
🗑
|
||||
| mechanism of action MAOIs | inhibit oxidative deamination (degradation) of monoamines (NE, 5-HT)
🗑
|
||||
| Tranylcypromine has what type of effects? | Amphetamine-like
🗑
|
||||
| Pharmacokinetics MAOIs | aborbed readily orally, not given parenterally
🗑
|
||||
| Pharmacokinetics phenelzine | MAOI, cleaved to hydrazine and then acetylated
🗑
|
||||
| MAOI CNS side effects | excessive CNS stimulation
🗑
|
||||
| MAOI cardiovascular side effects | orthostatic hypotension (VERY prominent)
🗑
|
||||
| MAOI weight side effects | weight gain
🗑
|
||||
| MAOI sexual side effects | anorgasmia -- inability to orgasm
🗑
|
||||
| MAOI liver side effects | serious hepatotoxicity, especially with hydrazides
🗑
|
||||
| Drug interactions MAOIs | Enhance CNS depressants by interfering with their metabolism (esp. BZDs), potentiate the effects of indirect sympathomimetics (causes hypertensive crisis)
🗑
|
||||
| Food interactions MAOIs | Tyramine rich foods augment MAO inhibitors and lead to hypertensive crisis
🗑
|
||||
| Tyramine and MAOIs | Tyramine is a false neurotransmitter present in many, many foods. It is normally metabolized by MAO. But if MAOIs are blocking MAO, then it floods the nervous system and causes issues.
🗑
|
||||
| Therapeutic use of MAOIs | secondary use for depression, phobic-anxiety when TCAs and ECT (shock therapy) are inadequate
🗑
|
||||
| Uses of Lithium | bipolar disorder, esp. manic phase (slow onset), prevention of mania or depression in bipolar disorder, recurrent endogenous depression that is drug resistant, schizoeffective disorder, schizophrenia, antipsychotic/antidepressant resistant patients
🗑
|
||||
| Lithium Mechanisms | Blocks Na+ channels. Blocks IP3 and DAG production in neurons. Inhibits GSK-3 and NE-sensitive adenylyl cyclase. Decreases NE and DA turnover and increases 5-HT activity and Ach synthesis. Blocks DA receptor supersensitivity.
🗑
|
||||
| Pharmacokinetics lithium | readily and completely absorbed. eliminated via urine. Na loading enhances Li excretion. Low therapeutic index, requires blood monitoring.
🗑
|
||||
| Lithium toxicity -- acute | acute -- nausea, vomiting, diarrhea, ataxia, convulsion, confusion, coma, hyper-reflexia, cardiac arrhythmias, hypotension, tremor (manage with propranolol or atenolol)
🗑
|
||||
| Lithium toxicity -- prolonged | Ligand-GPCR uncoupling (receptor activates but nothing happens), hypothyroidism (thyroid enlargement and increased TSH production), polydipsia, polyuria, nephrogenic diabetes insipidus, and edema (Na retention and water follows Na)
🗑
|
||||
| Why does TSH cause goiters? | Because it stimulates cells OTHER than endocrine thyroid cells to perform. Low thyroid hormone = large levels of TSH = lots of stimulation to thyroid cells = large thyroid = goiter.
🗑
|
||||
| Lithium drug interactions | diuretics (esp. thiazides) -- increase reabsorption of lithium, and include aspirin and acetaminophen. Lithium antagonizes NE's effect on blood pressure. Old neuroleptics when given with Li have a much higher propensity toward extrapyramidal syndrome.
🗑
|
||||
| Carbamazepine (tegretol) use | antiepileptic/antiseizure
🗑
|
||||
| Valproate (depakene) use | first choice for antidepressant
🗑
|
||||
| Olanzapine (zyprexa) use | Good choice for antidepressant
🗑
|
||||
| Lamotrigine (Lamictal) or topiramate (Topamax) use | VG-Na channel blocker
🗑
|
||||
| Why are BZD's such better choices than older hypnotics? | the dose curve drops off below the level that induces anasthesia -- older hypnotics keep on a goin' and hit coma level effects
🗑
|
||||
| Alprazolam (xanax) class/use | BZD -- depression
🗑
|
||||
| Chlordiazepoxide (librium) class/use | BZD alcohol withdrawal syndrome
🗑
|
||||
| clonazepam (klonopin) class/use | BZD convulsion, panic disorder, muscle relaxation
🗑
|
||||
| clorazepate (tranxene) class/use | BZD convulsion
🗑
|
||||
| lorazepam (ativan) class | BZD
🗑
|
||||
| flurazepam (dalmane) class | BZD
🗑
|
||||
| oxazepam (serax) class | BZD
🗑
|
||||
| triazolam (halcion) class/use | BZD, rapid onset of action and shorter duration, early morning-insomnia
🗑
|
||||
| pharmacological properties BZDs | all have same pharmacological profiles, differe in pharmacoKINETICS -- do not EVER cause true anesthesia, rarely ever fatal unless taken with other CNS depressants--HUGE NO NO
🗑
|
||||
| Overall pharmacological profile of BZDs | sedation. hypnosis. sleep. decreases sleep latency period. increase non-REM sleep. decrease NREM or Stage 4 (deepest) sleep, decrease the duration of REM sleep.
🗑
|
||||
| When do BZDs cause muscle relaxation and how do they do it? | neuromuscular blockade at extremely high doses
🗑
|
||||
| Anterograde amnesia | inability to form or recall memories from the duration of a drug's effects -- great for preanaesthesia so the patient can't remember what happened during an unpleasant procedure
🗑
|
||||
| Can BZDs be used as anticonvulsants? | You bet. Especially clonazepam, lorazepam, and diazepam.
🗑
|
||||
| Peripheral effects of BZDs | coronary vasodilation (therapeutic doses given via IV)
🗑
|
||||
| Which receptors do BZDs bind? | GABAa
🗑
|
||||
| BZDs bind the allosteric site of the GABAa receptor, and do what? | first, they do NOT actually open the Cl channel. Instead, they potentiate GABA binding to the channel and increase the FREQUENCY of binding+opening events
🗑
|
||||
| Side effects of BZDs -- other CNS depressants | NO. Absolutely NO. BZDs potentiate other CNS depressants, including alcohol.
🗑
|
||||
| side effects BZDs -- motor function | lightheadedness, lassitude, incoordination, ataxia, and mental slowing
🗑
|
||||
| side effects BZDs -- abuse/dependence | less problematic than barbiturates or alcohol -- but still present an issue with dependence
🗑
|
||||
| side effects BZDs -- chronic use and abrupt withdrawal | rebound anxiety. insomnia. agitation. panic. paranoia. myalgia. muscle twitches. convulsions.
🗑
|
||||
| drug interactions BZDs | ethanol increases absorption rate and associated CNS depression, combined therapy of BZDs and valproate can lead to psychosis
🗑
|
||||
| Ultra-short acting BZDs | half-life less than 30 minutes. no current agents.
🗑
|
||||
| short-acting BZDs | half-life less than 6 hours
🗑
|
||||
| intermediate acting BZDs | half life from 6-24 hours
🗑
|
||||
| long acting BZDs | half life greater than 24 hours
🗑
|
||||
| Clorazepate unique characteristic | prodrug, converted to nordiazepam in stomach
🗑
|
||||
| Lunesta (eszopiclone), Ambien (zolpidem), and zaleplon all have what in common? | short half-lives (no more than 6 hours) and are used to help with insomnia
🗑
|
||||
| Oxazepam and lorazepam are similar in what way? | neither of them have active metabolites, contributing to their shorter half lives
🗑
|
||||
| Buspirone (Buspar) class | non BZD selective anxiolytic
🗑
|
||||
| Buspirone (Buspar) mechanism | agonist 5-HT1a and D2 receptors
🗑
|
||||
| Buspirone (Buspar) onset and rebound anxiety/toxic facts | Slow onset. no rebound anxiety. minimal abuse issue, less psychomotor impairment
🗑
|
||||
| Zolpidem (ambien)/zalpelon (sonata)/eszopiclone (Lunesta)--selectively binds what receptor? | BZ1 alpha 1 subtype of GABAa
🗑
|
||||
| Zolpidem (ambien)/zalpelon (sonata)/eszopiclone (Lunesta)--antagonized by what? | Flumazenil
🗑
|
||||
| Flumazenil | antagonist of GABAa allosteric binding site for BZDs (antagonizes BZD activity)
🗑
|
||||
| Zolpidem (ambien)/zalpelon (sonata)/eszopiclone (Lunesta)-- muscle relaxing/anticonvulsive activity | Very low as both a relaxant and anticonvulsive
🗑
|
||||
| Zolpidem (ambien)/zalpelon (sonata)/eszopiclone (Lunesta)--speed of onset? | Very rapid, low rebound insomnia on sudden discontinuation
🗑
|
||||
| Zaleplon (sonata) is especially good for patients who? | awake early as it has active metabolites (longer half life/duration of effect)
🗑
|
||||
| Zolpidem (ambien)/zalpelon (sonata)/eszopiclone (Lunesta)--tolerance/dependence levels | less development for both tolerance and dependence
🗑
|
||||
| Zolpidem (ambien)/zalpelon (sonata)/eszopiclone (Lunesta)--which patients need lower dose | those with hepatic dysfunction, elderly, patients taking cimetidine (blocks CYP3A4)
🗑
|
||||
| Zolpidem (ambien)/zalpelon (sonata)/eszopiclone (Lunesta)--patients which need higher dose | patients taking rifampin (increases expression CYP3A4)
🗑
|
||||
| Flumazenil (romazicon) purpose | competitive BZD receptor antagonist
🗑
|
||||
| Flumazenil (romazicon) use | reverse CNS depressant effects of BZD overdose
🗑
|
||||
| Flumazenil (romazicon) pharmacokinetics | rapid action, short half life. repeat administration.
🗑
|
||||
| Flumazenil (romazicon) dose form | IV only. Less than 25% of drug reaches general circulation if given orally.
🗑
|
||||
| Long term use of BZDs is dangerous, especially to the elderly. Why? | Because if they are taken off rapidly, they can have problems crop up.
🗑
|
||||
| Barbiturates -- general info | non-selective, dose dependent CNS depressants, go all the way to the top to coma on the dose chart, narrow margin of safety, high incidence of toxicity, greater problems of abuse/tolerance/physical dependence, limited use for sedative/hypnotic/anxiolytic
🗑
|
||||
| What is special about acidic barbiturates? | they do not affect the CNS as much
🗑
|
||||
| What is special about the alkyl group at C5 in barbiturates? | it enhances hypnotic action
🗑
|
||||
| What is special about the phenol group at C5 in barbiturates? | it is essential for anticonvulsant action
🗑
|
||||
| If there is a thio group (S) at C2, what is increased in barbiturates? | lipid solubility
🗑
|
||||
| What four variables affect the onset and duration of barbiturates | lipid solubility (greater = faster onset), tissue redistribution/affinity for plasma proteins, liver degradation level (if degraded here, short half life), or renal excretion (if dumped here, longer half life)
🗑
|
||||
| Explain how renal or hepatic degradation/excretion affects the duration of barbiturates | Renal excretion = long half life and long duration
Hepatic degradation = short half life, short duration
🗑
|
||||
| Phenobarbital relative onset, peak affect, duration of action, and half life | onset is slow (60 min), peak effect seen in 10-12 hours, duration of action is long, half life is 80 hrs
🗑
|
||||
| Amobarbital relative onset, peak affect, duration of action, and half life | moderate onset (6-8 hrs), intermediate duration of action, and half life of 25 hours
🗑
|
||||
| Pentobarbital relative onset, peak effect, duration of action, and half life | onset is rapid (10-15 min), peak effect in 3-4 hours, short duration of action, and half life of 20-50 hours
🗑
|
||||
| Secobarbital relative onset, peak effect, duration of action, and half life | rapid onset (10-15 min), peak effect in 3-4 hours, short duration of action, half life 25 hours
🗑
|
||||
| Thiopental (IV only) relative onset, peak effect, duration of action, half life | relative onset is incredibly fast (<1 min), peak effect in 0.25 hours, duration of action is ultra-short, and average half life is 3-8 hrs.
🗑
|
||||
| Oxybarbiturates | ALL except thiopental
🗑
|
||||
| Uses of the barbiturates -- sleep | sleep (oxybarbiturates only) -- induces sleep, decreases REM time, prolonged use causes rebound insomnia (REM rebound), restlessness, anxiety, and increased nightmare incidence
🗑
|
||||
| uses of the barbiturates -- hyperalgesia | stops reaction to painful stimuli
🗑
|
||||
| uses of the barbiturates -- anesthesia | thiobarbiturates and short acting oxybarbiturates can be used to induce anesthesia
🗑
|
||||
| uses of the barbiturates -- anticonvulsants | phenobarbital has a selective anticonvulsant action unrelated to its sedative action -- good for tonic-clonic seizures
🗑
|
||||
| effects of the barbiturates -- respiratory | depresses respiration (dose-related) -- depresses medullary respiratory center
🗑
|
||||
| effects of the barbiturates -- cardiovascular | dose-dependent -- only has effects at anesthetic doses, not sedative/hypnotic doses -- decreases cardiac output, renal plasma flow, and increases total peripheral resistance
🗑
|
||||
| Pharmacological properties of the barbiturates -- GI tract | decreases GI muscle tone
🗑
|
||||
| Pharmacological properties of the barbiturates -- uterus | decrease force/frequency of uterine contraction, depresses fetal respiratory rate
🗑
|
||||
| Pharmacological properties of the barbiturates -- liver | in acute doses, it competes with other drugs for P450 enzymes and other liver enzymes. In long-term use, it wildly increases their expression.
🗑
|
||||
| Pharmacological properties of the barbiturates -- tolerance | Induces metabolic and pharmacodynamic tolerance
🗑
|
||||
| Pharmacological properties of the barbiturates -- dependence | induces psychological and physical dependence
🗑
|
||||
| Mechanism of action of the barbiturates | Increases the DURATION (not frequency!) of channel opening events on the GABA-gated chloride channels. In high concentrations, it is a GABA mimetic and opens the channel itself. It also inhibits excitatory AMPA receptors.
🗑
|
||||
| Adverse effects of the barbiturates | CNS depression -- after effects, drowsiness, vertigo, nausea, vomiting, diarrhea, mood distortion, impairment of judgment and fine motor skills -- if used repeatedly, overexcitement, can induce allergic reactions and erthyematous dermatitis
🗑
|
||||
| Drug interactions of the barbiturates | CNS depressants like alcohol and antihistamines, they inhibit the metabolism of other drugs in the acute phase -- in the long term, they induce liver enzyme production and literally cause other drugs to vanish (vitamins D and K, endogenous steroids)
🗑
|
||||
| Drug interactions of the barbiturates -- plasma protein binding | Bind EXTREMELY well to plasma proteins, competing with other drugs for the spot.
🗑
|
||||
| Contraindications of the barbiturates -- acute intermittent porphyria | barbituates induce porphyrin biosynthesis
🗑
|
||||
| Contraindications of the barbiturates -- pulmonary insufficiency | This may occur in patients that already have respiratory insufficiency
🗑
|
||||
| Contraindications of the barbiturates -- cardiovascular diseases | can cause fetal cardiovascular collapse by rapid IV injection
🗑
|
||||
| Barbiturate poisoning -- signs/treatment | Can be deliberate OR accidental -- occurs if taken with other CNS depressants. Signs: difficult to diagnose, especially if subject is comatose. Treatment: general support and gastric lavage if in first 24 hours of taking
🗑
|
||||
| Uses of Barbiturates -- sedative hypnotics | available, but declined use. Replaced with safer BZDs
🗑
|
||||
| Uses of Barbiturates -- anesthetics | short acting or ultra short acting barbiturates only -- GREAT for preanesthetic use over volatile anesthetics because volatiles increase cranial pressure. In pts. with already increased cranial pressure this can be harmful.
🗑
|
||||
| Uses of Barbiturates -- anticonvulsants | popular for children
🗑
|
||||
| Uses of Barbiturates -- hypbilirrubinemia and kernicterus | hepatic glucuronyl transferase and bilirubin-binding protein (helps prevent resulting brain damage
🗑
|
||||
| Other hypnotic sedatives -- chloral hydrate (noctec) -- effects on sleep, hangover as compared to BZDs or barbiturates | short acting sedative hypnotic, no affect on REM sleep, less hangover than BZDs or barbiturates
🗑
|
||||
| other hypnotic sedatives -- chloral hydrate (noctec) -- metabolism, toxicity, tolerance/dependence, withdrawal | rapidly reduced to trichlorethanol (active metabolite) in liver, low toxicity unless given with other CNS depressants, acute intoxication resembles that of barbiturates, habitual use leads to dependence/tolerance/addiction, withdrawal=delerium/seizure
🗑
|
||||
| Other hypnotic sedatives -- chloral hydrate (noctec) -- contraindications | hepatic, renal, and cardiac disease, gastritis
🗑
|
||||
| Other hypnotic agents -- include EToH and what other anti-allergy class? | Histamines (diphenhydramine, hydroxyzine)
🗑
|
||||
| Other hypnotic agents not really mentioned in class except for by name | Glutethimide (doriden), methyprylon (noludar), meprobamate (miltown)
🗑
|
||||
| Characteristics of epilepsy | periodic and abnormal discharge of brain tissue, second most common neural disorder after stroke, 40 forms, etiology is unclear but may include infection, tumor, head injury, therapy is symptomatic to stop seizure, but no cure exists
🗑
|
||||
| Partial seizure | Only neurons in the cerebral cortex fire.
🗑
|
||||
| Generalized seizure | Neurons in both the cerebral cortex and thalamus fire (the thalamus is a subcortical region)
🗑
|
||||
| Glioma | tumor of the glial cells in the brain -- known to cause epilepsy
🗑
|
||||
| Seizure | transient alteration of behavior due to disordered synchronous and rhythmic firing of a specific population of brain neurons
🗑
|
||||
| Epilepsy | disorder of brain function characterized by periodic and unpredictable occurrence of seizures
🗑
|
||||
| Nonepileptic seizure | has a known trigger (electrical current, chemical convulsants)
🗑
|
||||
| epileptic seizure | no trigger, no electrical or chemical convulsant stimulus
🗑
|
||||
| tonic | Muscle tone is tight
🗑
|
||||
| atonic | muscle tone is slack
🗑
|
||||
| Secondarily generalized partial seizures | starts as partial seizure, goes to general after some time
🗑
|
||||
| tonic-clonic | grand-mal seizure
🗑
|
||||
| absence seizure | petit-mal seizure
🗑
|
||||
| Status epilepticus | repeated epileptic seizures that last for so long and/or occur so close together that there is no break between them and no recovery time
🗑
|
||||
| Mechanisms of antiepileptics -- blocking neuronal firing | Block NA channels (phenytoin, carbamazepine, valproate) -- block calcium channels (blocks low-threshhold t-type current) (ethosuximide, valproate, diazepam, barbiturates)
🗑
|
||||
| Mechanisms of antiepileptics -- enhancing neuron inhibition | Activating GABAa receptor (increases Cl influx to the cell -- BZDs and barbiturates), inhibition of GABA transaminase (blocks the breakdown of GABA), and inhibition of GABA transporter GAT-1 to reduce uptake of GABA
🗑
|
||||
| Mechanisms of antiepileptics -- blocking excitatory pathways | Block the NMDA receptor (valproate)
🗑
|
||||
| Phenytoin (dilantin) -- pharmacology | inhibits generation of repeat action potentials. lowers Na, K, and Ca conductance. Decreases glutamate release. Boosts GABA release.
🗑
|
||||
| Phenytoin (dilantin) -- clinical value | antiepileptic without general CNS depression -- reduces seizure but does NOT lower seizure threshhold
🗑
|
||||
| Phenytoin (dilantin) -- class | antiepileptic
🗑
|
||||
| Phenytoin (dilantin) -- metabolism | weak organic acid with good GI absorption, WAY bound to plasma proteins after oral/IV administration, metabolized by CYP450
🗑
|
||||
| Phenytoin (dilantin) -- dose-dependent metabolism | Eventually all degradative enzymes get full up -- at this point, degradation of the drug stops and an increased dose will REALLY boost you into cytotoxicity
🗑
|
||||
| Phenytoin (dilantin) -- CNS side effects at low dose | ataxia. vertigo. diplopia. nystagmus.
🗑
|
||||
| Phenytoin (dilantin) -- CNS side effects at high dose | excitation followed by dysarthria (speech disorder, weakness of speech muscles), lethargy, and finally coma
🗑
|
||||
| Phenytoin (dilantin) -- side effects -- Gingival hyperplasia | overgrowth of the gingival tissues
🗑
|
||||
| Phenytoin (dilantin) -- side effects -- GI disturbances, cardiac arrhythmias | what it says, bro
🗑
|
||||
| Phenytoin (dilantin) -- side effects -- hirsutism | occurs with chronic use. lots of hair growth in odd places.
🗑
|
||||
| Phenytoin (dilantin) -- side effects -- osteomalacia | abnormal vitamin D and calcium metabolism (softening of bone with pain/weakness)
🗑
|
||||
| Phenytoin (dilantin) -- side effects -- hypersensitivity | skin rash, fever, and lymphoadenopathy (enlargement of lymph nodes)
🗑
|
||||
| Phenytoin (dilantin) -- drug interactions | protein binding drug (90%) and metabolism. Isonaizid and cimetidine inhibit phenytoin metabolism, and phenobarbiturate induces the CYP450 that increases phenytoin metabolism.
🗑
|
||||
| Phenytoin (dilantin) -- use as an anticonvulsant | effective against partial and generalized grand mal seizures -- alternative choice for status epilepticus but not first pick
🗑
|
||||
| Phenobarbital -- oldest of what class? | anti-epileptic
🗑
|
||||
| Phenobarbital -- side effects -- sedation | calming effects, induction of sleep, highly lipid soluble
🗑
|
||||
| Phenobarbital -- side effects -- neurological and behavioral effects | development of tolerance and psychological+physical dependence
🗑
|
||||
| Phenobarbital -- side effects -- hepatic effects | toxicity
🗑
|
||||
| Phenobarbital -- side effects -- hypersensitivity/hematological | allergic reactions
🗑
|
||||
| Phenobarbital -- side effects -- bones | osteomalacia
🗑
|
||||
| Phenobarbital -- anticonvulsant use | generalized tonic-clonic (grand mal), myoclonic, but NOT petit mal (there is one agent in particular we use for this problem)
🗑
|
||||
| Phenobarbital -- first choice for what patients? | neonates, infants, and children for febrile seizures
🗑
|
||||
| Phenobarbital -- not recommended in? | pregnant women -- depresses respiration
🗑
|
||||
| Phenobarbital -- used in what condition as an alternative treatment? | status epilepticus
🗑
|
||||
| Primidone -- chemistry | deoxybarbituate analog, metabolized to phenobarbital and phenylethylmalonamine (PEMA)
🗑
|
||||
| Primidone -- mechanism of action | similar to phenytoin, independent of conversion of phenobarbital and PEMA
🗑
|
||||
| Primidone -- toxicity | systemic/CNS toxicity limit its use, side effects include sedation, vertigo, nausea, vomiting, ataxia, diplopia, nystagmus, hepatic and hematological toxicity
🗑
|
||||
| Primidone -- dose form | Oral only. Does not bind to plasma protein more than 30%. Short half life. Increase dose gradually.
🗑
|
||||
| Primidone -- interaction with other antiepileptics | phenobarbital and lamotrigine
🗑
|
||||
| Primidone -- grand mal | Used as primary therapy for grand mal if they do not respond to phenytoin or phenobarbital
🗑
|
||||
| Carbamazepine (tegretol) -- structure | tricyclic, so it is both antidepressive and anticholinergic (anti SLUDGE)) -- tertiary structure is similar to phenytoin
🗑
|
||||
| Carbamazepine (tegretol) -- mechanism | similar to phenytoin, decreases synaptic transmission presynaptically
🗑
|
||||
| Carbamazepine (tegretol) -- pharmacokinetics | complex. bioavailability after oral administration is not predictable. binds to plasma protein. almost completely metabolized. induces cyp450 (microsomal enzymes)
🗑
|
||||
| Carbamazepine (tegretol) -- side effects -- lower dose | diplopia, ataxia, GI upsets
🗑
|
||||
| Carbamazepine (tegretol) -- side effects -- higher dose | drowsiness, dizziness, blood dyscrasia (aplastic anemia, granulocytosis -- allergic reaction), erythematous skin rash (allergic), stevens johnson syndrome
🗑
|
||||
| stevens johnson syndrome | Massive allergic reaction, lethal without treatment, caused by carbamazepine, characterized by blotches all over skin
🗑
|
||||
| Carbamazepine (tegretol) -- clinical use | monotherapy for grand mal and partial seizures, primary drug for trigeminal neuralgia, and bipolar depression after lithium therapy fails
🗑
|
||||
| Ethosuximide (zarontin) -- mechanism | decreases Ca currents
🗑
|
||||
| Ethosuximide (zarontin) -- increases? | seizure threshold
🗑
|
||||
| Ethosuximide (zarontin) -- metabolism | liver metabolized, renally excreted, eliminated more rapidly in children than adults, no protein binding, valproate inhibits metabolism
🗑
|
||||
| Ethosuximide (zarontin) -- toxicity -- dose related | GI disturbance. drowsiness. headache. hiccough.
🗑
|
||||
| Ethosuximide (zarontin) -- toxicity -- not dose relates | hematological effects, allergic effects (Stevens-Johnson Syndrome)
🗑
|
||||
| Ethosuximide (zarontin) -- anticonvulsant use | monotherapy drug of choice for absence seizures (petit mal) -- VERY effective, VERY safe -- also used with carbamazepine or phenytoin for mixed seizures
🗑
|
||||
| Valproic Acid (Depakene) or VALPROATE -- mechanism | blocks high-frequency repetitive firing of neurons, including decreasing Ca current, blocking NMDA receptor excitation, GABAnergic GAT-1 inhibition and GAD facilitation, inhibits GABA transaminase at high concentrations
🗑
|
||||
| GAD | converts glutamate to GABA
🗑
|
||||
| GAT-1 | degrades GABA
🗑
|
||||
| Valproic Acid (Depakene) or VALPROATE -- distribution | Extensively bound to plasma protein. eliminated by hepatic metabolism
🗑
|
||||
| Valproic Acid (Depakene) or VALPROATE -- drug interactions | displaces phenytoin, inhibits metabolism of phenytoin/carbamazapin/phenobarbital, decreases lamotrigine clearance
🗑
|
||||
| Valproic Acid (Depakene) or VALPROATE -- dose related side effects | nausea, vomiting, GI distress, weigh gain, alopecia, hyperammonemia, tremor -- but do not often see dose related problems as only tiny doses of drug are needed for therapeutic effect
🗑
|
||||
| Valproic Acid (Depakene) or VALPROATE -- idiosyncratic side effects | hepatotoxicity, thrombocytopenia, spina bifida (Developmental disorder in fetus)
🗑
|
||||
| Valproic Acid (Depakene) or VALPROATE -- anticonvulsant uses | very effective for absence seizures, generalized absence, tonic-clonic (grand mal), myoclonic, monotherapy for mixed seizure, used for bipolar depression after Lithium fails, and for migraine prophylaxis
🗑
|
||||
| Benzodiazepenes and seizures -- side effects | sedative effect. tolerance.
🗑
|
||||
| Benzodiazepenes and seizures -- clonazepam (klonopin) -- uses | petit mal, myclonic in children. one of most potent anti-seizure medications known. long-acting.
🗑
|
||||
| Benzodiazepenes and seizures -- clonazepam (klonopin) -- side effects | sedation. dependence.
🗑
|
||||
| Benzodiazepenes and seizures -- diazepam (valium) -- uses | status epilepticus. short duration only. also good for serial seizures and prophylaxis of febrile seizures. prolonged oral use of drug is not recommended
🗑
|
||||
| Benzodiazepenes and seizures -- lorazepam (ativan) -- uses | status epilepticus. more effective and longer duration than diazepam.
🗑
|
||||
| Benzodiazepenes and seizures -- clorazepate (tranxene) -- uses | acute alcohol withdrawal syndrome, adjunctive therapy for complex partial seizures -- prodrug, has to be hydrolyzed in stomach to nordiazepam before it can be used
🗑
|
||||
| Other antiepileptics -- acetazolamine -- class? uses? | diuretic and carbonic anhydrase inhibitor. all types of seizures. limited monotherapy use (rapid tolerance), but good adjunct therapy use
🗑
|
||||
| Other antiepileptics -- gabapentin (neurontin) -- analog of? mechanism? | analog of gaba but does not stimulate GABA receptors. promotes release, reuptake, and metabbolism of endogenous GABA
🗑
|
||||
| Other antiepileptics -- gabapenting (neurontin) -- use? metabolism? | used as adjunct therapy for polytherapy of partial seizures and generalized tonic-clonic (grand mal) seizures. No hepatic enzyme metabolism, excreted unchanged into urine.
🗑
|
||||
| Other antiepileptics -- lamotrigine (lamictal) -- mechanism? use? | blocks votalge dependent Na channels and decreases glutamate release. used as adjunct therapy for polytherapy of partial seizures in people over 2 years old and for bipolar disorder, as well as life-threatening dermatitis (Stevens-Johnson syndrome)
🗑
|
||||
| Other antiepileptics -- vigabatrin (gamma-vinyl-GABA) -- mechanism? uses? side effects? | irreversible GABA aminotransferase (GABA-T) inhibitor. used for partial seizures and infantile spasms. common side effects: drowsiness, dizziness, weight gain. less common: agitation, confusion, psychosis, irreversible visual field defect.
🗑
|
||||
| Other antiepileptics -- tiagabine (gabitril) -- mechanism? use? pharmacokinetics? | inhibits GABA transporter (GABA reuptake) in both neurons and glia. used as adjunct therapy for polytherapy of partial seizures in ADULTS. rapidly absorbed after oral administration, extensively bound to proteins, metabolized by CYP450 in liver.
🗑
|
||||
| Other antiepileptics -- topiramate (topamax) -- mechanism? pharmacokinetics? | blocks voltage dependent Na channels, potentiates inhibitory effect of GABA, inhibits excitatory effects of kainate on AMPA receptors. minimal plasma protein binding.
🗑
|
||||
| Other antiepileptics -- topiramate (topamax) -- use? | used as adjunct for polytherapy of partial/primary generalized tonic clonic (grand mal) seizures, migraine treatment -- TERATOGENIC in animals
🗑
|
||||
| Other antiepileptics -- zonisamide (zonegran) -- mechanism? use? | sufonamine derivative, inhibits voltage gated Na channels and T-type CA currents, similar to phenytoin/carbamazepine.
🗑
|
||||
| Other antiepileptics -- zonisamide (zonegran) -- metabolism? | Used as adjunct polytherapy of partial seizures in adults. well absorbed orally, long half-life, bound to plasma protein, metabolized by CYP3A4 and metabolites excreted in urine
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| What drugs do we use to treat simple partial seizures? | carbamazepine, phenytoin, valproate
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| What drugs do we use to treat complex partial seizures? | carbamazepine, phenytoin, valproate
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| What drugs do we use to treat partial seizures with secondarily generalized seizures? | carbamazepine, phenobarbital, phenytoin, primidone, valproate
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| What drugs used to treat generalized absence seizures? (petit mal) | ethosuximide. valproate. clonazepam.
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| What drugs used to treat myoclonic seizures? | valproate. clonazepam.
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| What drugs used to treat tonic-clonic seizures? (grand mal) | carbamazepine, phenobarbital, phenytoin, primidone, valproate
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| Managing epilepsy: mono or polytherapy? | monotherapy is best bet if possible. reduced risk toxicity. select agent based on type of seizure.
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| Managing epilepsy: understand what about drug? | pharmacokinetics
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| Managing epilepsy: do we need to monitor plasma levels of drugs? | yes. therapeutic window is low and toxicity is common. monitoring plasma levels is extremely useful.
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| Concerns with anti-seizure drugs: teratogenicity | not confirmed, but we see fetal hydantoin syndrome (mental defect with facial structure change) with phenytoin and spina bifida by valproate in 1-2% of babies
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| Concerns with anti-seizure drugs: withdrawal | long term meds. condition of withdrawal -- 3-4 years without even 1 seizure, gradual discontinuance -- issues with BZDs and barbituates in terms of dependence
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| Concerns with anti-seizure drugs: overdose | respiratory depression. Give supportive treatment, but do NOT GIVE STIMULANTS. this may induce a massive onslaught of seizures.
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