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Definition
is competitive inhibitor of the GABA transporter in neurons and glia (selective for GAT-1)
Increases both synaptic and extrasynaptic GABA concentrations, non-specific agonism both ionotropic and metabotropic GABA receptors
90% bioavailability, highly protein bound, metabolized by CYP3A4
Adverse Effects
confusion, sedation, amnesia, ataxia
Can potentiate other GABAA receptor modulators (i.e. alcohol, benzodiazepines, barbiturates) |
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Definition
γ-Vinyl GABA (vigabatrin)- is “suicide inhibitor” of GABA-transaminase (GABA-T). Blocks the conversion of GABA to succinic semialdehyde, leading to GABA concentrations synaptic release
Used in treatment of epilepsy. Being investigated for treatment of drug addiction, panic disorder, obsessive-compulsive disorder
Adverse Effects
Drowsiness, confusion, headache, bilateral visual field defects (from accumulation of drug in the retina) |
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Definition
GABA Receptor Agonist
bind directly to and activates GABAA. Muscimol was first derived from the the hallucinogenic Amanita muscaria mushroom. Full agonist at several GABAA subtypes primarily used as a research tool. |
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Definition
GABA Receptor Antagonist
is a non-competitive inhibitor of GABAA receptor that blocks the ion pore
All GABAA antagonist induce epileptic convulsions and are exclusively used for research |
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Definition
GABA Receptor competitive antagonist
All GABAA antagonist induce epileptic convulsions and are exclusively used for research |
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Definition
GABA Receptor Inverse agonist
can elicit anxiogenic effects and convulsions |
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Definition
BZPs Antagonist
Reversal of BZP activity
Adverse Effects
Seizures, cardiac arrhythmias, dizziness, blurred vision, agitation, diaphoresis (excessive sweating)
Flumazenil can cause severe withdraw symptoms in patients with BZP dependence
Contraindicated
Patients being given BZPs for intracranial hypertension or status epilepticus
Patients with serious tricyclic anti-depressant ovedose |
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Definition
is the only compound used in clinically that targets GABAB receptor
Primarily used for treatment of spasticity associated with motor neuron disease (multiple sclerosis) or spinal cord injury
Severe spasticity may be treated with intrathecal Baclofen
Baclofen stimulates downstream 2nd messenger to act on Ca2+ and K+ channels
May also modulate pain and cognition and being investigated for drug addiction.
Adverse Effect
Baclofen can cause sedation, somnolence(drowsiness), ataxia
Overdose produce blurry vision, hypotension, cardiac and respiratory depression, coma
Withdraw of Baclofen (especially intrathecal) can cause hyperspasticity, rhabdomyolsis (skeletal muscle breakdown), pruritus (itchy skin), delirium, fever, multi-organ failure, coagulation abnormalities, shock, and death |
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Definition
Ethanol acts as an anxiolytic and sedative by causing CNS depression; acts on multiple targets including GABAA and glutamate receptors.
Ethanol GABAA-mediated Cl- influx and excitatory effects of glutamate at NMDA receptors
Acts synergistically with other sedative, hypnotics, antidepressants, anxiolytics, anticonvulsants, and opioids
Ethanol tolerance is associated with changes in receptor function; chronic ethanol exposure alters GABAA receptor subunit expression; induces posttranslational modifications; and changes in 2nd messenger system (PKC)
Prolong ethanol use up-regulates NMDA receptors |
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Term
| Gamma-hydroxybutyric acid (GHB) |
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Definition
| GABA isomer used as sedative and treatment for narcolepsy |
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Definition
Fast acting BZP that can cause amnesia and prevent recall of events
These drugs have also been reported to facilitate “date rape” due to the amnesia effects |
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Definition
Tricyclic Antidepressants (TCAs)
Mechanism- inhibit reuptake of 5-Htand NE from synaptic cleft by blocking 5-Htand NE reuptake transporters, thereby enhancing postsynaptic responses
Drugs in this class
Amitriptyline, Clomipramine, Imipramine*, Desipramine, Nortriptyline
Clinical Applications
Depression, pain syndromes such as headaches, chronic fatigue syndrome, other somatic pain disorders, nocturnal enuresis (bed wetting), obsessive-compulsive disorder (OCD)
Adverse Effects
Heart block, cardiac arrhythmia, orthostatic hypotension, myocardial infarction, agranulocytosis (severe lowering of white blood cell count), jaundice, seizure, worsening of depression with suicidal thoughts
Bloating, constipation xerostomia, dizziness, blurred vision, urinary retention
Contraindicated
Concomitant use of monoamine oxidase inhibitors, cardiac conduction system defects, patients recovering from myocardial infarction |
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Definition
Selective Serotonin Reuptake inhibitors (SSRIs)
Mechanism- selectively inhibit reuptake of serotonin and thereby synaptic serotonin levels; also cause increased 5-HT receptor activation and enhanced postsynaptic responses. At high doses binds to NE transporters
Drugs in this Class
Fluoxetine (Prozac)*, Fluvoxamine, Paroxetine, Sertraline, Citalopram, Escitalopram
Clinical Applications
Depression, anxiety, obsessive compulsive disorder (OCD), post-traumatic stress disorder, pain syndromes
Adverse Effects
Serotonin syndrome from concomitant use of MAOIs (characterizes by hyperthermia, muscle rigidity, myoclonus, rapid fluctuation in mental status and vital signs)
May precipitate mania in bipolar patients
Sexual dysfunction, GI distress, vasospasm, sweating, anxiety, somnolence
Contraindicated
Concomitant use of monoamine oxidase inhibitors |
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Definition
aminoketone antidepressant that weakly inhibits neuronal uptake of 5-HT, DA, and NE. Used for treatment of smoking cessation
Clinical Applications
Depression , smoking cessation, insomnia
Adverse Effects
Tachyarrhythmia, hypertension especially combined with nicotine patch, seizure, may exacerbate depression or mania in susceptible patients, pruritus, sweating, rash, dyspepsia, constipation, dizziness, tremor, blurred vision, agitation, agranulocytosis, priapism, orthostatic hypotension, liver failure
Contraindicated
Concomitant use of monoamine oxidase inhibitors, seizures, bulimia or anorexia, electrolyte abnormalities.
Patients undergoing abrupt discontinuation of alcohol or sedatives (including BZPs) |
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Definition
Serotonin Receptor Agonist
5-HT1A selective agonist treatment of anxiety
Clinical Applications
Migraine headaches
Adverse Effects
Myocardial ischemia or infarction, stroke, dizziness, confusion, headache, excitement, blurred vision, hostile feelings and behavior, nervousness
Hypertensive crisis, chest pains, flushing, nausea
Contraindicated
Concomitant use of monoamine oxidase inhibitors, hypersensitivity to Buspirone, uncontrolled hypertension, ergot agents or 5-HT agonist within 24 hours
Ischemic cardiac, cerebrovascular or peripheral vascular syndromes |
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Definition
Serotonin Receptor Agonist
Clinical Applications
Migraine headaches
Adverse Effects
Myocardial ischemia or infarction, stroke, dizziness, confusion, headache, excitement, blurred vision, hostile feelings and behavior, nervousness
Hypertensive crisis, chest pains, flushing, nausea
Contraindicated
Concomitant use of monoamine oxidase inhibitors, hypersensitivity to Buspirone, uncontrolled hypertension, ergot agents or 5-HT agonist within 24 hours
Ischemic cardiac, cerebrovascular or peripheral vascular syndromes |
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Term
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Definition
Lamotrigine- inhibits electrical neurotransmission by use of dependent block of neuronal voltage gated sodium channels
Clinical Application: Bipolar I disorder, focal and tonic-clonic seizures, Atypical absence seizures, Trigeminal neuralgia
Adverse Effects: Aplastic anemia, agranulocytosis, thrombocytopenia, leukopenia, arrhythmia, Steven Johnson syndrome-toxic epidermal necrolysis, atrioventricular block, hyponatremia, Syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), hypocalcemia, porphyria, hepatitis, nephrotoxicity, rash, confusion, nystagmus, blurred vision, bone marrow suppression, ataxia,
Contraindicated- Concomitant use of monoamine oxidase inhibitors; history of bone marrow suppression |
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| Lithium Carbonate (Lithotab) |
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Definition
mimics other monovalent and disrupts proteins and transporters that require cation cofactors.
Lithium enters via sodium channels and inhibits inositol phosphatase which dephosphorylates IP2 to inositol phosphate (IP1) and inhibits the inositol phosphatase that dephosphorylates IP1 to free inositol, thereby blocking the phosphatidylinositol signaling in the brain. Block in the regeneration of PIP2, lithium inhibits central adrenergic, muscarinic, and serotonergic transmission.
Lithium also increase 5-HT neurotransmission, decreasing NE and DA neurotransmission, inhibiting adenylyl cyclase by decoupling G-proteins from the receptor, also altering electrochemical gradients across cell membranes by substituting for Na+ and/ or blocking K+ channels
Clinical Applications: Bipolar affective disorder
Adverse Effects: Acute lithium intoxication causes nausea vomiting, diarrhea, renal failure neuromuscular dysfunction, ataxia, tremor, confusion, delirium, and seizures, severe bradyarrhythmia, hypotension , sinus node dysfunction, hyperkalemia, pseudotumor cerebri (benign intracranial hypertension), polyuria, Nephrogenic diabetes insipidus, hypothyroidism, goiter, ECG EEG abnormalities, renal impairment, transient visual field scotoma, muscle weakness. |
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Definition
Inhibitors of Serotonin Storage
Amphetamine and related drugs interfere with ability of synaptic vesicles to store monoamines such as 5-HT
Amphetamine, methamphetamine, methylphenidate displace 5-HT, NE, and DA from storage vesicles
For atypical depression and depression in elderly these drugs are useful as second line agents because of the combine effects of 5-HT, NE, and DA
Also used for treatment in ADHA (seems counterintuitive), but NE promotes attention in the CNS and higher cognitive processes
More inhibitors of 5-HT, DA, NE storage: Modafinil, Dextroamphetamine, Lisdexamfetamine
Clinical Applications
Atypical depression, narcolepsy, obstructive sleep apnea
ADHD
Adverse Effects
Cardiac arrhythmias, hypertension, dizziness, insomnia, agitation, restlessness, rhinitis
Substance abuse, sudden death, tachyarrhythmia, hyperthermia, hypersensitivity disorder, psychotic disorders, loss of appetite, seizures
Lisdexamfetamine Gilles de la Tourette syndrome (motor, vocal tics)
Lisdexamfetamine Stevens-Johnson syndrome (Life threatening skin condition) |
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| Methylphenidate (Ritalin) |
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Definition
Inhibitors of Serotonin Storage
Amphetamine and related drugs interfere with ability of synaptic vesicles to store monoamines such as 5-HT
Amphetamine, methamphetamine, methylphenidate displace 5-HT, NE, and DA from storage vesicles
For atypical depression and depression in elderly these drugs are useful as second line agents because of the combine effects of 5-HT, NE, and DA
Also used for treatment in ADHA (seems counterintuitive), but NE promotes attention in the CNS and higher cognitive processes
More inhibitors of 5-HT, DA, NE storage: Modafinil, Dextroamphetamine, Lisdexamfetamine
Clinical Applications
Atypical depression, narcolepsy, obstructive sleep apnea
ADHD
Adverse Effects
Cardiac arrhythmias, hypertension, dizziness, insomnia, agitation, restlessness, rhinitis
Substance abuse, sudden death, tachyarrhythmia, hyperthermia, hypersensitivity disorder, psychotic disorders, loss of appetite, seizures
Lisdexamfetamine Gilles de la Tourette syndrome (motor, vocal tics)
Lisdexamfetamine Stevens-Johnson syndrome (Life threatening skin condition) |
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Term
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Definition
Mechanism and Target: acts directly on Na+ channels to slow rate of channel recovery from the inactivated state to the close state, increases threshold potential and prevents repetitive firing
This stabilizes seizure focus preventing the paroxysmal depolarizing shift (PDS) that initiates the focal seizure
Also prevents the spread of seizure activity to other neurons, thereby prevents secondarily generalized seizures
Phenytoin targets Na+ channels in use dependent manner (GABA potentiators are not use dependent)
Clinical Applications
Focal and secondary generalized (tonic-clonic)seizures, status epilepticus, non-epileptic seizures
Seizures related to eclampsia, neuralgia
Ventricular arrhythmias unresponsive to to lidocaine, arrhythmias induced by cardiac glycosides
Adverse Effects
Agranulocytosis, leukopenia, pancytopenia, thrombocytopenia, megaloblastic anemia, hepatitis, Steven Johnson syndrome (toxic epidermal necrolysis), ataxia, nystagmus, incoordination, confusion, hirsutism, facial coarsening, gingival hyperplasia
Contraindicated
Sinus bradycardia, SA node block, 2nd and 3rd degree AV block, Stokes-Adam syndrome, Hydantoin hypersensitivity
Drug interaction
Interacts with a number of drugs, induces P450 enzymes, 95% bound to plasma albumin. Metabolism shows properties of saturation kinetics.
Can induce metabolism of carbamazepine and visa versa through P450 induction |
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Definition
Mechanism and Target: acts directly on Na+ channels, use dependent block
Clinical Applications
Focal and Tonic-clonic seizures, bipolar disorder, trigeminal neuralgia (intense pain in the face)
Adverse Effects
Aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, atrioventricular block, arrhythmias, Steven Johnson syndrome (toxic epidermal necrolysis), hyponatremia, hypocalcemia, hepatitis, nephrotoxicity, nystagmus, incoordination, confusion, rash, blurred vision, syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), porphyria
Contraindicated
Concomitant use of MAO inhibitors, history of bone marrow depression, prescreen for HLA-B*1502 in patients of Asian decent to avoid risk of Steven Johnson syndrome |
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Term
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Definition
Mechanism and Target : inhibits low threshold T-type calcium channels.
Clinical Applications
Absence seizures
Adverse Effects
Steven-Johnson syndrome, bone marrow suppression, systemic lupus erythematosus, seizures, GI irritation, ataxia, somnolence |
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Term
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Definition
Mechanism and Target : inhibits low threshold T-type calcium channels
Clinical Applications
Absence seizures, Tonic-clonic seizures, atypical absence seizures, focal seizures
Adverse Effects
Hepatotoxicity, pancreatitis, thrombocytopenia, hyperammonemia, GI irritation, weight gain, ataxia, sedation, tremor
Contraindications
Liver disease, urea cycle disorders |
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Term
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Definition
Mechanism and Target : inhibits high voltage T-type calcium channels
Clinical Applications
Focal seizures, diabetic neuropathy, prophylaxis for migraine
Adverse Effects
Steven-Johnson syndrome, sedation, dizziness, fatigue, GI irritation, ataxia, |
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Term
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Definition
Mechanism and Target: inhibits glycine binding site of NMDA receptor-ionphore complex causing suppression of seizure activity
Clinical Applications
Refractory epilepsy, focal and Tonic-clonic seizures,
Adverse Effects
Aplastic anemia, bone marrow suppression, Steven Johnson syndrome photosensitivity, GI irritation, abnormal gait, dizziness
Contraindications
Blood dyscrasia, Liver disease |
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Term
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Definition
Enflurane
Mechanism- Modulation of ligand gated ion channels (most likely)
Clinical Applications
General anesthesia, supplement to other anesthetics agents during obstetric anesthesia
Adverse Effects
Cardiovascular and respiratory depression, arrhythmias, malignant hyperthermia, seizures with enflurane
Contraindications
Susceptibility to malignant hyperthermia, seizure and epilepsy with enflurane only |
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Term
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Definition
Mechanism- Modulation of ligand gated ion channels (most likely)
Clinical Applications
General anesthesia
Adverse Effects
Same as isoflurane*
Additionally can cause hepatitis and fatal hepatic necrosis
Contraindications
Susceptibility to malignant hyperthermia, obstetrical anesthesia, history of hepatic damage from previous halothane |
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Term
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Definition
Mechanism- Modulation of ligand gated ion channels (most likely)
Clinical Applications
General anesthesia, usually in combination with other agents
Adverse Effects
Can cause expansion of air cavities such as pneumothorax, obstructed middle ear, obstructed loop of bowel, intracranial air
Contraindications
Preexisting air cavities, should be administered without oxygen, should not be administered continuously for more than 24 hours |
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Term
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Definition
Mechanism- Modulation of ligand gated ion channels (most likely)
Clinical Applications
Induction and maintenance of anesthesia, sedation of mechanically ventilated patients
Adverse Effects
Cardiovascular and respiratory depression, injection site reaction
Contraindications
Hypersensitivity to propofol |
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Term
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Definition
Mechanism- Modulation of ligand gated ion channels (most likely)
Clinical Applications
Induction of anesthesia, Narcoanalysis, elevated intracranial pressure, seizure
Adverse Effects
Same as propofol, additionally can cause laryngeal spasm, hemolytic anemia, radial neuropathy, no injection site reaction
Contraindications
Acute intermittent porphyria or variegate porphyria |
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Term
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Definition
Mechanism- Modulation of ligand gated ion channels (most likely)
Clinical Applications
Dissociative anesthesia/ analgesia, sole agent for procedures that do not require skeletal muscle relaxation
Adverse Effects
Hypertension, tachyarrhythmia, myoclonus, respiratory depression, increased intracranial pressure
Hallucinations, vivid dreams psychiatric symptoms
Contraindications
Hypersensitivity to ketamine, severe hypertension |
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Definition
is a direct dopamine agonist (L-DOPA is indirect;
requires conversion to dopamine). It is an ergot derivative and
affects multiple pathways. |
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Term
| Pramipexole and ropinirole |
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Definition
are selective agonists for specific
dopamine receptors. They can be used alone, or with L-DOPA
to reduce the L-DOPA dose and smooth out fluctuations. Short
half lives mean multiple daily doses. May lead to compulsive
gambling/thrill seeking |
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Term
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Definition
e approved for PD, but
rarely used due to poor efficacy. |
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Term
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Definition
A low affinity
NMDA glutamate
receptor antagonist
Results in improved
activities of daily
living in advanced
patients
Effects are additive
with cholinesterase
inhibitors |
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