Pharmacology I Third Exam

Chlordiazepoxide (Librium) - relieves anxiety without sedation

- Positive allosteric modulators of the GABAa receptor Cl- ionophore complex
- potentiate the action of the inhibitory transmitter GABA at GABAa receptor
- bind to their own recognition site on GABA a receptor
- increase frequency of Cl- channel opening causing an increase in Cl- and hyperpolarization

tension, fear, apprehension, worry, diffculty thinking

trembling, tremors, muscle tension, restlessness, fatigure, hyperactive respiratory, cardiovascular, urinary and GI systems

diazepam

anxiety, alcohol withdrawl, status epilepticus, skeletal muscle relaxant, anticonvulsant, seizures, insomnia, preanaesthetic medication, jet lag, anxiety associate with depression, panic disorder,

Flumazenil (romazicon) - binds with high affinity to BZD site on the GABAa receptor but lacks activity, therefore it is a competitive anatagonist of BZDs
- used to tread overdose and reverse sedative effects
- precipitates withdrawl syndrome in long term users of BZD
- needs to be given frequently in repeated doses due to short half life

- nonBZD anxiolytic/hypnotic
- serotonin 5HT-1A agonist (part of new class of anxiolytics)
- NO CNS depressant effects
- NOT an anticonvulsant or muscle relaxant
- DO NOT REACT with withrdawl or alcohol

epoxide
azepam
ezepam
azolam

a non BZD hypnotic used for insomina
- decreases sleep latency and increases duration without altering time spent in stages 3 and 4 sleep

a non BZD hypnotic used for short term treatment of insomnia
- decreases sleep latency without increasing sleep time
- can be taken in middle of night without drowsiness upon waking
- NOT A BZD but acts on GABA-BZD receptor to poetntiate GABA transmission

(Lunesta)
- NON BZD hypnotic that acts at GABA BZD receptor
- used to treate insomnia
- side effects similar to BZDs

- Prolong open time of Cl- channel to increases hyperpolarization and inhibitory effect of GABA at GABAa receptor
- has diff binding site than BZD
- may also release or block GABA uptake

sedation > hypnosis > anaesthesia > death

- antianxiety, potentiate inhibitory effect of GABA
- inhibition of seizure activity, safe effect on sleep, minimal cardiovascular effects

Barbituates cause depression of respiratory drive center in brainstem and depress reflex response to increased carbon dioxide > respiratory depression is cause of death
- Also Barbiturates induction of liver microsomal enzymes leading to increased rate of barbiturate metabolism and metabolism of other drugs

Live enzyme induction

a mitochondrial enzyme involved in porphyrin synthesis
- its induction leads to increased porphyrinces >>> exacerbation of acute intermittent porphyria in genetically susceptible individuals

REM rebound, insomnia, excitation, agitation, termulousness, weakness, delirium, SEIZURES, death

drowsiness, hangover, potentiation of alcohol and antihistimines, tolerance

thiopental and methohexital
(both are short acting (less than an hour))

ital

Phenobarbital

not many because of abuse/tolerance/respiratory effects
- sedative/hypnotics
- anticonvulsants
- emergency treatment of status epilepticus
- preanesthetic medication
- treatment of hyperbilirubinemia and kernicterus in neonate (excess bilirubion) >>> indcution of liver enzymes to break down bilirubin

Liver enzymes break down bilirubin (pigment in blood)

Epilepsy - idiopathic

seizure

convlusion

- Focus = cortical
- no impairment of consciousness, can be confines to single limb, can spread to become generalized

secondary

FOCUS = temporal lobe
- consciousness impaired
- also called psychomotor seizures
- can generalize
- automatisms occur

automatic motor behaviors that patient performs that are not controlled
- can last 30 s to minutes
- not controlled, but patient is not unconscious

No single focus (40% of all seizures)
-consciousness impaired
- bilateral, symmetrical

(petit mal) - "little seizures"
- < 30 seconds, abrupt loss of consciousness
- common in children
- may be some symmetic moto activity
- characterized by 3 Hz spike and wave discharges on EEG

(grand mal)
- major convulsion with contraction of muscles (tonic phase) and clonic convulsive movements for a period of 1-2 min
- may have prodrominal sign or aura
- loss of consciousness
- fall to ground
- grogginess, headache, urination, defecation after

- can result from withdrawl of Barbituates/BZD
- grand mal sizures which follow one another with no intervening period of consciousness
- treated with diazepam/lorazepam

- brief contraction of one body part
- genetically determined in teens

- loss of inhibitory GABA innervation or abnormal sensitivity to stimuli

- may cause spread of seizure from focus in epilepsy
- rapid series of impulses in presynaptic neuron increased excitability of post synaptic

1. presynaptic terminal : increase in Calcium uptake >>> increase in transmitter release >>>post synaptic neurons recieve greater input
2. Na+ accumulates in neurons >>> partial depolaricastion of membrane >>>> increased excitability

- specific drugs for specific types of seizures
- patient compliance is critical for control (drug dose/frequency)
- if stop drug, phase out gradually or seizures will worsen
- combo therapy includes low does of two drugs to prevent toxicities or multiple drugs for multiple seizure patterns

- Hydantoins (phenytoin, mephenytoin, ethotoin)
- barbiturates with anticonvulsant properties (phenobarbital, mephobarbital)
- deoxybarbiturates (primidone)
- Carbamazepine
- Oxcarbazepine
- Gabapentin
- Lamotrigine
- Felbamate
- Topiramate
- Tiagabine
- Zonisamide

- most widely used antiepileptic drug
- hydantoin
- used to control all types of epilepsy EXCEPT ABSENCE SEIZURES
- no sedative effect
- stabilizes neuronal memberane (decreasing neural activity) by decreasing repetitive firing of AP via slows reactivation of NA+ channels

Phenytoin

multiple formulations by various companies

Mephenytoin

ethotoin

Phenobarbital

- Used to treat simple partial seizures and generalized tonic clonic
- potentiates GABA transmission like other barbiturates by prlonging open state of Cl- channels
- may also block excitatory response to glutamate at AMPA receptors
- elevates seizure threshold to prevent seizure spread

Mephenytoin and barbitals

mephobarbital

optimal anticonvulsant effect when no hypnotic effect is present

- deoxybarbituate used for tonic clonic and all partial seizures
- effective in combo with phenytoin, carbmazepine, and other agents

Carbamazepine

carbamazepine

oxycarbazepine

Gabapentin, Lamotrigine valproic acid, (possibly tiagabine and topiramate)

- broad spectrum antiepileptic that acts as a GABA agonist but appears to act by releasing GABA (unknown mechanism)
-

Lamotrigine

blocks NA+ channels

Felbamate - reserved for drug resistant cases

topiramate
- block sodium channels, enhances gaba transmission, blocks glutamate excitatory transmission

Topiramate

- anticonvulsant/epileptic that is broad specturm
- Mechanism:
GABA reuptake blocker (Increases GABA in synapse)
- well tolerated, minor side effects

Zonisamide

ethosuximide, valproic acid, vinyl GABA, Clonazepam

ethosuximide (block calcium channels)

toxicities and tolerance develop
(toxicities: sedation, drowsiness, lethargy, fatigure, ataxia, behaviorial distubrances)

Diazepam