Indirect inhibitor of factor Xa w/o effect on thrombin
-Prevents Acute PE
-stable and unstable angina: decreases incidence of MI-bypass: decreases thrombotic graft closure and LT graft
-inhibits fibrin binding to the GPIIb/IIa receptor-Prevents aggregation
Nonpeptide, peptidomimetic à inhibits fibrin binding to the GP IIB/IIa receptor-Prevents Aggregation
-Use: hi risk ACS, PCI
Can be used as a sole anesthetic agent
Cardiac and respiratory depression
NO muscle relaxation (exception; see 4 above)
As with other IV agents, high doses or prolonged infusions fill Vd and require metabolism for termination of effect
Also iv, but is only iv agent that increase cerebral blood flow Dissociative anesthesia (I’m in pain but I don’t know what that means)
Low doses produce analgesia, dysphoria
Preserves airway reflexes
Short acting INCREASES cerebral blood flow
Shouldn’t give to patient with brain tumor due to increasing intra cranial pressure.
Can lower adrenocorticos
First injectable anesthetic to be synthesized
Developed by Alfred Einhorn in 1904-1905
Classified as an Ester - Metabolized in the plasma by Pseudocholinesterase
Excreted by the Kidneys
serotonin NE reuptake inhibitors. D-also aproved for osteoarthritis and fibromyalgia
Venlafoxine-Inhibits serotonin transporter, and at high doses inhibits NE transporters, its active metabolite and drug have same half life 11 hours
Duloxetine -(cymbalta) Can be used in diabetic pain. Moderate CYP2D6=inhibition of TCA's bad reaction
Desipramine-Secondary amine, More NE effect than 5HT.
Amitriptyline-Tertiary amine, more 5HT than NE. Has high ACH effects, and down regulates adreno receptors.
Nortriptyline-Secondary, more NE than 5HT
Imipramine- Tertiary, more 5HT than NE. Hig
Clomipramine-tertiary, more 5HT than NE. High ACH effect and sexual side effects. Good for OCD, better 5HT reuptake inhibition.
Phenelzine- Irreversible inhibition of MAO a&b.
Isocarboxazid- Irreversible inhibition of MAOa&b
Tranylcyromine-Resembles amphetamine and can cause CNS stimulation, also irreversible inhibition of MAO a&b
Selegiline-Has amphetamine like metabolit
Stops monoamine from reaching vesicles=depression due to complete absence of monoamines.
Selective Reversible MAOa inhibitors
MeclobemideNot in the US selective for MAOa RIMAs are displaced from MAO-A in the presence of tyramine,rather than inhibiting its breakdown in the liver as general MAOIs do.MAO-B remains free and continues to metabolize tyramine,nospecial diet needs
atypical antipsycotics good for anorexics?
yeah weight gain and get rid of crazy thoughts
c is good for schizophrenia
Clozapine-Very low D2,5HT. May cause agranulocytosis (lowWbcs). Reserved for treatment resistant patients. Causes salvation, may cause seizure.
Risperidone- EPS at high dose, medium weight gain, medium EPS. increase prolactin secretion(hyperpro
Aripiprazole-Partial agonist of D2. God for both (-) and (+). Low weight gain, low EPS, no effect on prolactin
Ziprazidone-Can cause arrhythmia. Has risk of death via prolong QT interval(seen in elderly)
Potency:EPS:Nonspecific side effects(high=less side effectsMAYBE)
Haloperidol-High,High,Low-Used in tourette and PCP intoxication
Perphenazine-Med,Med,Med.Can help with nausea vomiting and migraine.
Chlorpromazine-Low,Low,High, also helps with nausea, vomiting and migraine.
Potency-EPS-nonspecific sideeffects(higher=more side effects)
Thioradizine-Low,Low,High. Can cause arrhythmia, and ocular problems. Lowers seizure threshold.
These drugs may enhance (-) symptoms by blocking MESOlimbic pathways. Effective and long lasting D2 receptor blockade.
inability to feel pain while conscious.
unmyelinated axons which slowly conduct action potential to spinal cord giving rise to burning quality of pain. These nerve fibers have small diameter cell bodies
Projection neurons transmit info of noxious stimuli from dorsal horn of spinal cord to thalamus, reticular formation, or periaqueductal gray region of midbrain. Further pathways carry info to somatosensory cortex where pain sensations are perceived.
from brain to spinal cord. Stim of descending inhibitory pathways reduces activity of nociceptive neurons in dorsal horn of spinal cord resulting in reduced pain perception. Several NTs act @multiple sites along ascending pathways to incr or decr nociceptive signals. Descending pathways activated by pain, psychological factors, & therapeutic agents such as opioid drugs or clonidine, resulting in antinociceptive or analgesic effect. Descending fibers directly inhibit second order nociceptive neurons; activate inhibitory interneurons w/in dorsal horn. Activation of neurons releases endogenous opioids, which acts on both 1st & 2ndorder nociceptive neurons to inhibit output
Nonselective COX I and COX II inhibitors
Prototype NSAID: Aspirin (acetylsalicylic acid)
Reduces low intensity pain, reduces fever, anti-inflammatory (325 mg)Low doses decr risk of MI & strokes due in part to its anticoagulant properties (it inhibits platelet aggregation) (80 mg/day). Decrs Sx of Rheumatoid arthritis (1-4 g/day). These high doses may incr risk of MI & strokes
Nonselective COX I and COX II inhibitors
Prototype NSAID: Aspirin (acetylsalicylic acid)
Readily absorbed from stomach/small intestine & widely distributed in all tissues (e.g. CSF, peritoneal cavity, synovial fluid).
Bound to plasma proteins therefore, aspirin can displace other drugs from these proteins & incr their toxicity.
Deacylated in liver & plasma to yield salicylic acid (also NSAID). Low dose (325-650mg), T1/2= 3hrs. High dose (1g), T1/2= 15 hrs.
Urinary excretion pH dependent. Na+ bicarbonate incrs urine pH & thus promotes excretion of salicylic acid.
Nonselective COX I and COX II inhibitors
Prototype NSAID: Aspirin (acetylsalicylic acid)
Adverse Reactions to Aspirin
Gastrointestinal upset (bleeding, ulceration, perforation). Prostaglandins protect stomach/GI tract by stim-ing mucus prod & decr-ing acid prod. NSAIDs reduce PG prod, leaving stomach/GI tract w/ reduced protection.; Hypersensitivity-like reaction (aspirin allergy); Reye's syndrome (potentially fatal condition associated w/ aspirin consumption by children w/ viral illness.); Salicylism; Acid base imbalance (uncouples ox-phos); Anticoagulant; Acute renal failure in pts w/ chronic renal disease, CHF or using diuretics. In pts w/ renal disease or CHF, PG in kidney maintain blood flow. NSAIDs reduce PG leading to reduced blow flow & nrenal failure
Approximately equal to aspirin for relief of arthritic pain; lower frequency of GI irritation. Recently approved as a preparation for IV admin. Non-selective.
For moderate-severe arthritic pain. Drug is very potent COX inbitor that exhibits significant GI toxicity. Not for use in children <14 yr or during pregnancy; caution when used in elderly. Non-selective.
Naproxen (Aleve; Naprosyn)
Diclofenac (Cataflam, Voltaren)
Methods to reduce the GI side effects of NSAIDs
Use the lowest effective dose for the shortest duration.Co-administer a proton pump inhibitor (PPI) such as omeprazole (Prilosec).
includes acute renal failure in pts w/ chronic renal disease, congestive heart failure or using diuretics.
ALL NSAIDs (w/ possible exception of naproxen) incr risk of MI & stroke in patients at high risk for heart disease.
Acetaminophen (TYLENOL: Not an NSAID): Not anti-inflammatory. Acetaminophen (paracetamol) is a popular analgesic & antipyretic agent w/ a low incidence of adverse GI, renal & cardiovascular effects as compared w/ aspirin & other non-steroidal anti-inflammatory drugs. NOT associated with Reye's syndrome.
unknown.Does not inhibit COX I or COX II. Recent reports suggest that a metabolite of acetaminophen acts on the endogenous cannabinoid system
any compound regardless of chemical structure that binds to opioid receptors
any of the opioid alkaloids found as natural products in the opium poppy plant, as well as many semisynthetic chemical derivatives of such alkaloids.
Mu (m; MOR)
Delta (d; DOR)
Kappa (k; KOR)
Localization of opioid receptors
Opioid receptors located on sensory neurons in dorsal root ganglion & widely distributed throughout brain, including PAG, thalamus, cortex, & limbic system. Mu, kappa, & delta receps are all present in spinal cord. Located in dorsal horn on both on presyn terms of primary nociceptive neurons & on second order neurons. Endogenous opioids released from local dorsal horn interneurons act on presyn opioid receps to decr NT release, & on projecting neurons to decr excitability. Direct application of opioids into spinal cord has robust analgesic actions & minimizes central side effects. However, opioid receps widely distributed through body where they modulate many processes in addition to pain perception which accounts for side effects of opioid analgesics.
Activates mu opioid receptors at multiple points along pain pathway (including brain+spinal cord) resulting in reduction in pain perception. However, mu opioid receps widely distributed throughout body & thus morphine (&other mu opioid recep agonists) can result in side effects.
Triad of symptoms; coma, pinpoint pupils & low respiratory rate. Other symptoms include, decr BP, depressed urine formation & urinary retention. Tx includes ventilation & use of narcotic antagonists. Caution should be employed since narcotic antagonist, naloxone has a short duration of action relative to morphine.
The repeated use of opioids results in tolerance and physical dependence and may result in addiction. Addiction liability is apparently very low in chronic pain patients.
Cellular adaptation occurring in response to repeated drug administration such that discontinuance of drug results in characteristic withdrawal or abstinence syndrome. Abrupt stoppage of opioid administration results in symptoms that are opposite of initial effects of drug. These signs include sweating, nausea, diarrhea, insomnia & muscular aches/pains. Time of onset depends upon half-life of opioid. Morphine w/drawal Sx peak in 36-48 hrs, whereas methadone w/drawal Sx may take several days to peak & may persist for up to 2 wks.
potent but short-acting synthetic opioid analgesic, used for anaesthesia during surgery (administered by injection for fast onset of effects and precise control of dosage. Produces strong respiratory depression.
A centrally acting analgesic w/ a dual mode of action as agonist of μ-opioid receptor & as norepi reuptake inhibitor. Approved for use in 2009.
Analgesic effects of these opioids results from kappa agonist activity. They are mu recep antagonist or weak partial agonists @ mu recep. Thus, admin of these to morphine tolerance pt or heroin addict may cause w/drawal. Advantage of this class is that extent of respiratory depression is limited. κ-agonism can cause dysphoria @ therapeutic or supertherapeutic doses, thus kappa opioid recep agonists have lower abuse potential relative to mu opioid recep agonists.
Naloxone (short acting)NARCAN
Naltrexone (longer acting)TREXAN
Naloxone & naltrexone are pure opioid antagonists. Most potent at mu opioid receptor but they will antagonize actions of delta & kappa agonists. Used to reverse effects of opioid overdose (eg respiratory depression & coma). CAUTION: these drugs will cause abrupt w/drawal syndrome in opioid treated patient or heroin addict.
BZDs are thought to exert their anxiolytic, sedative-hypnotic, anticonvulsant, and skeletal muscle relaxant actions largely by virtue of their ability to enhance the inhibitory action of the neurotransmitter -aminobutyric acid (GABA) in the central nervous system.
non selective COX inhibitor.
Properties: analgesic (my head hurts) woosy. Anti-inflammatory. Antipyretic: reduces fever caused by high PG levels in hypothalamic thermoregulatory area.
Fluoxetine-Protoypic drug, STRONG cyp450 inhibitor w/long half life. Metabolite is Norfluoxetine half life 8 days.
Fluvoxamine- Lowest risk for discontinuation syndrome.
Citalopram- Pure S-Enantiomer.
Paroxetine -potent cyp450 inhibitor.
Sulindac-Used for acute or chronic inflammatory conditions, is a prodrug body converts to the active NSAID
½ life= 7.8 hrs for Sulindac and up to 16.4 for active metabolites.
NaPROxen (ALEVE)-Treats fever, and pain, pain caused by arthritis gout menstrual cramp, tendinitis headache, backache, and toothache.
Don’t overdose or take for more than 10 days.
Ibuprofen (Motrin or Advil)- Equivalent to asprin for arthritic pain, lower GI irritation 2400mg/day, lower dose has analgesic properties. Used for rheumatoid and osteoarthritis
IV administration (Caldolor)
Flurbiprofen-COX I selectiveUsed to relieve pain, tenderness, swelling, and stiffness due to osteoarthritis and rheumatoid arthritis.
Celecoxib (CELEBREX) (increased risk of cardiovascular problems)-Relief of signs and symptoms of Osteo and Rheumatoid arthritis
Management of acute pain and primary dysmenorrhea
Reduces the number of adenomatous colorectal polyps (FAP)
Diclofenac (increases risk of heart attack)- Relief of signs and symptoms of oseto and rheumatoid arthirits.
For acute or long-term use to relieve anklyosing spondylitis.
Extended release-Voltaren-XR oral use
VOIXX and BEXTRA-Removed from the
Ketorolac (Toradol) -COX I selective, given IM, IV, and orally used for moderate to severe pain. analgesic potency equal to morphine.Can cause GI upset and renal effects. Should not be taken longer than 5 days orally, 2days IV or IM.
Acetaminophen (Tylenol) (second most common cause of liver failure needing transpant!)- Not anti-inflammatory, is analgesic and antipyretic (may like maybe interact with TRPV1 and CB1 receptors)
Does NOT inhibit COX I & II
Used to relive mild to moderate pain, headache, muscle aches, menstrual, colds, sore throats, etc. etc etcReduces fever. Available over the counter and Rx
Fentanyl- Short acting, but powerful opioid analgesic 100x that of morphine.
Used for breakthrough pain. Available as transdermal patch.
Remifentanil (Ultiva)- potent ultra short-acting synthetic opioid analgesic given during surgery to relieve pain and in adjunct to an anesthetic.
Alfentanil (alfenta)- potent but short-acting synthetic opioid analgesic
Used for anesthesia during surgery.
Strong respiratory depression.
Sufentanil (Sufenta)-powerful synthetic opioid analgesic
5 to 10 x more potent than its analog, fentanyl used during surgery.
Potent ultra short-acting synthetic opioid analgesic used during surgery in precise doses, if given to rapidly can cause respiratory arrest. Causes respiratory depression.
Codeine (3-methylmorphine)- Compound of that POPPY. Used as an antitussive and analgesic in mild pain.
Prodrug! Bc is metabolizes in vivo to morphine and codeine-6-glucuronide.
Heroin (diacetylmorphine or diamorphine)-Nonpolar, rapidly enters the brain, where it is metabolized into morphine. Prodrug Intense euphoria
Methadone (dolophine)- Orally active long acting mu opioid receptor agonist.
Cross tolerance with morphine or heroin, therefore useful as treatment for addicts
Meperidine (Demerol)- Weak mu opioid agonist used for analgesia during delivery. Does not delay birth process, does not antagonize oxytocin
CAUTION: used with MAO inhibitors causes severe reactions: respiratory depression, excitation, delirium, and convulsions.
Morphine (Opiate)-Administered: IV, orally, or rectally. Strong pass effect.
Side effect: constipation, sphincter of Oddi spasms, decreased respiration, hypotension
Oxycodone (Oxycontin)-Weak opioid agonist used with NSAIDs for analgesia
Loperamide (Imodium)-Mu opioid agonist, poorly absorbed after oral administration.
Used as antidiarrheal due to being retained in GI tract
No analgesic properties
Buprenorphine-Partial Mu Opioid receptor agonist but a Kappa opioid receptor antagonist
Combined with naloxone (SUBUTEX) and SUBOXONE, treats addiction
Lower dose used for acute pain
Unique effect of Aspirin: Irreversible inhibition of COX
Patent ductus arteriosus (PDA) is a heart problem that occurs soon after birth in some babies.vessel is supposed to close within a few days as part of the normal changes occurring in the baby's circulation. In some babies, however, the ductus arteriosus remains open (patent). This opening allows blood to flow directly from the aorta into the pulmonary artery, which can put a strain on the heart and increase the blood pressure in the lung arteries.
The tendency of an anesthetic dissolved in blood to come out of solution
The more soluble an anesthetic in blood, the more molecules are needed to achieve a given partial pressure Inhalation I is still most common way of anesthesia, allows for easier fine control.
More soluble=less reaching the brain
Anesthetic effect is a result of partial pressure NOT concentration
Highly soluble agents require more dissolved molecules (more time) to produce anesthesia
LESS SOLUBLE AGENTS PRODUCE FASTER INDUCTION AND FASTER RECOVERY
Low blood gas coefiecient=low solubility=faster acting
Naturally-Occurring Local Anesthetic
First LA: has high local neural toxicity and potential of abuse. Is still popular topical anesthetic because of its vasoconstrictive properties, which is due to its blockade of the reuptake of cathecholamines in sympathetic nerve terminals
Customary solution is 4%, will onset in 4-5 min. Max dose is 200mg
Tetracaine: Ester Local Anesthetics
Slow onset due to its high pKa
Maximun dose is 100 mg
Excellent topical anesthetic
The last of the esters introduced and one of the safest in terms of toxicity
Duration of 45-60 min Rapid termination of effect IV -- causes thrombophlebitis Benzocaine-Ester Local Anesthetics First synthetic LA Benzoic acid derivative
Effective only in high concentration Used mostly in mucous membranes Methemoglobinemia
First amide-type local anesthetic
Developed by Niles Lofgren 1943
Marketed in 1948 Metabolized in the liver Excreted by the kidneys LA to which all others are compared Amide Local Anesthetics Dibucaine
Inhibitor of plasma cholinesterase Only for topical use as a cream High potency and toxicity
Mepivacaine local amid anesthetic
Similar to Lidocaine, but less vasodilation
Slightly greater potency and duration
Useful in epidural, spinal, peripheral nerve block and local infiltration
Potential for accumulation makes it unsuitable for prolonged epidural infusion
Amide Local Anesthetics
Greater potency and duration
Several concentrations from 0.05 to 0.75%
0.75% is not recommended in obstetrics.
Good for spinal anesthesia as isobaric or hyperbaric solution.
Epinephrine adds little to the duration.
Significant frequency-dependent block
Major risk of cardiac toxicity associated with high systemic blood levels
Amide Local Anesthetics
Almost pure S isomer
Less potent and lasting than Bupivacaine
Better frequency-dependent block
Several concentrations: 0.2%,0.5%, 1%
Amide Local Anesthetics Prilocaine
Most rapidly metabolized amide LA
Has an Ortho-Toluidine ring, which produces methemoglobinemia
Adjuvants to local anesthetic
Epinephrine: 1:200,000 (5Microgr/ml), may decrease absorption and prolong duration. Also used as a monitor.
Bicarbonate: Increases pH of the solution, accelerating onset. May decrease duration. May precipitate in Ropivacaine and Bupivacaine.
Antagonizes the NMDA receptor and it may also potentiate GABAA receptor responses
Blocks AMPA receptors, a glutamate binding site. Also blocks kainate receptors and Na+ channels, and enhances GABA currents
Blocks AMPA receptors.
: Lorazepam, Diazepam, Midazolam, or Clonazepam, Clobazam
Through GABAA activation increase the frequency of channel openings
Phenobarbital / Primidone
Prolong the time of each channel opening
Tiagabine-Inhibitor of GABA reuptake
Vigabatrin-is an irreversible inhibitor of GABA aminotransferase (GABA-T), the enzyme responsible for the degradation of GABA. It may also inhibit the vesicular GABA transporter.
Phenytoin - Prolongs inactivation of Na+ channels
Oxcarbazepine Prolongs inactivation of Na+ channels, actions on K+ channels.
Zonisamide Prolongs inactivation Na+ channels, T-type Ca++ channels
Lamotrigine Prolongs inactivation Na+ channels Ca channels, inhibits glutamate release
Lacosamide Enhances slow inactivation Na+ channels, binds to CRMP-2
Valproate Multiple actions
3. Na+ Channels
Na+ channels mediate neuronal APs.
Use-dependent (or time-dependent) Na+ channel blockers act by prolonging time channel spends in inactive state. Mod sustained high-frequency firing.
Enhances KCNQ K+ Channels to stabilize resting membrane potential and reduce brain excitability
4. K+ Channels
Enhances K+ ion channels, particularly KCNQ family of ion channels, thus stabilize resting pot membrane & reduce brain excitability.
May also augment GABA.
Reduces currents on the T-type Ca2+ channels
Gabapentin and Pregabalin
Do not act directly on GABA receptors. May modify the release of GABA
Bind to a subunit of voltage-gated Ca2+ channels, decreasing Ca2+ entry, decreases the release of glutamate
5. Ca2+ Channels
Ca2+ channel blockers have not proven to be effective AEDs. However, a specific type of Ca2+ channel, called T-type channels, are critical in genrating rhythms that underlie absence seizures.
Modifies the synaptic release of glutamate and GABA through an action on SV2A.
They are not used for anxiety
Thiopental-is used for induction of anesthesia because it is ultra-short acting (redistribution)
Phenobarbital -is used an anticonvulsant
Benzodiazepines vs. Barbiturates
Benzodiazepines increase the frequency of channel openings produced by GABA. Benzodiazepines do not, by themselves, open the channel.
• Barbiturates bind to yet another site on the GABAA receptor prolong the actions of GABA and therefore increase the duration of channel opening.
• Barbiturates, in higher concentration, also open the channels by themselves.Thus, they are more dangerous drugs than benzodiazepines (which are very safe).
BzDs anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, and amnestic properties.C-first discovered
Diazepam treats Anxiety, insomnia, pre-op, muscle relax has active metabolites elimination half life 27-37
Chlordiazepoxide-used for alcohol detox and alcohol related seizure has active metabolite
Flurazepam- used for insomnia, has active metabolit
BZD on GABAa
Alprazolam(xanex),used for panic, anxiety. Temazepam- used for insomnia, also has active metabolites
Lorazepam- often used for sedation. antianxiety, and alcohol related seizure, has inactive me
Non Benzodiazepines Anti-Anxiety
• Buspirone modulates serotonergic function in the brain.
Apparent advantages of buspirone are its: (1) relatively nonsedating profile, and (2) failure to potentiate the depressant effects of ethanol.
Buspirone differs from the BZDs in that the former require days or weeks of administration to establish an anxiolytic effect.
Non Benzodiazepines Anti-Anxiety
Non Benzodiazepines Anti-Anxiety Agents
• Buspirone and related drugs are partial agonists at 5-HT1A receptors (pre and post). Buspirone also blocks DA2 receptors.
• Patients who have been maintained on benzodiazepines for anxiolytic therapy frequently report dissatisfaction with buspirone and discontinue its use. One possibility is that anxious patients who are experienced with benzodiazepines miss some of the overt drug cues associated with BZDs but not with buspirone.
Non Benzodiazepines Anti-Anxiety Agents
• Buspirone is sometimes used to augment the effect of SSRI’s in unresponsive patients.
Pharmacological agents used to treat insomnia – non benzodiazepines
Zolpidem (Ambien) • Zaleplon (sonata) • Eszopiclone (Lunesta).
All non-benzodiazepine drugs carry labels warning that that these drugs can cause sleep-related behavior, including sleep-driving, making phone calls, and preparing and eating food while asleep.
• Blocks histamine -1 receptors and cholinergic muscarinic receptors in the CNS.
• Drugs in this class are used in several over-the-counter sleep medications.
Melatonin is synthesized in the pineal gland
It is released just before sleep and can induce sleep.
It is used to treat jet lag and insomnia in shift-change workers.
This drug is relatively safe but can cause fatigue and lethargy.
It is available over-the-counter.
• Ramelteon is a relatively new drug available by prescription that activates melatonin 1 and 2 receptors.
• This is not a controlled substance.
· 1st line in Status Epilepticus. Can be used as adjunctive therapy prn in refractory patients.
IV Lorazepam 4 mg, may repeat in 5 minutes if no response
IV Diazepam 5 – 10 mg
a group of cortical neurons that discharge abnormally
a medical disorder characterized by at least 2 unprovoked seizures separated by 24 hours
Potential reasons for 1 seizure
Anything that disrupts normal homeostasis of neurons & their stability can trigger hyperexcitability & seizures.
o Traumatic brain injury
o Mental Retardation
o Genetic mutations
o Cerebral palsy
o Neurodegenerative disorders
o Many others
o Hormonal changes (menses, puberty, pregnancy)
o Sleep deprivation
o Medications (see partial list below)
o Street drugs
o Sensory stimuli (visual, auditory)
o Emotional stress
There are multiple mechanisms that might contribute to hyperexcitability
Mechanism of Action:
Ø Enhancement of (usually gamma-aminobutyric-acid = GABA) inhibitory transmission
Ø Diminution of excitatory (usually glutamate) transmission
Ø Modification of ion channels (Na+,K+, or Ca++)
Glutamate receptors: AMPA, NMDA (N-methyl D-aspartate) & kainite. These mediate fast excitatory neurotransmission.
Antagonizes NMDA receptorMay also potentiates GABAA receptor responses (broad-spectrum AED = multiple MO
Acts on AMPA receptors, blocking the glutamate binding site. Also blocks kainite receptors
and Na+ channels, and enhances GABA currents (broad-spectrum AED)
There are also 2 major classes of GABA receps: GABAA& GABAB. GABAA is Cl- channel & mediates fast inhibitory transmission. GABAB is GPCR that mediates slow synaptic transmission by activating K+ channels; it can also be located presynaptically where it reduces NT release.
Benzodiazepines: Lorazepam, Diazepam, Midazolam, Clonazapam, or Clobazam
Prolong the time of channel opening
Prolongs inactivation of Na+ channels
Broad-spectrum AED- sometimes categorized under Na+ channel blockers. Blocks Na+ channels
May block NMDA recep-mediated excitation.Several studies have shown incred levels of GABA in brain after admin of valproate, although mech for this incr remains unclear.
Gabapentin & pregabalin do not act directly on GABA receps. They may modify release of GABA.Gabapentin & pregabalin bind mostly to subunit of voltage-gated Ca2+ channels, decring Ca2+entry. This decrs the release of glutamate.
Binds to synaptic vesicle protein SV2A. Func of this protein not understood but it's likely that levetiracetam modifies synaptic release of glutamate & GABA through an action on vesicular function.
Seizure Classifications -The International Classification of Seizures
Ø Clinical description
Ø EEG readings
Ø Classifications are Partial (Focal) or Generalized
Ø Uses age of onset, intellectual development, neurological exam, and neuroimaging
The International Classification of Seizures Partial Seizures (Focal or Local)
Asymmetric motor manifestations
Involvement of both hemispheres
Motor manifestations are bilateralLoss of consciousness
The steps in the GABA shunt are: