Anxiety+Medications

=Reading= Craig & Stitzel, chapter 32 =Goals=

5. Other drugs used to treat anxiety and their actionsn, sucha s buspirone
//**Drugs to know: Diazepam, lorazepam, zolpidem**//

AKA, sedatives & Narcotics Focus: Benzodiazapines Puspirone Antidepressant Medications SSRIs, TCAs, MAOIs

Benzodiazepines Relief of anxiety Drowsiness and sedation Skeletal muscle relaxation Anticonvulsive activity Anterograde amnesia

for colonoscopies ALl actions in CNS at GABAa receptors

CABA gamma-aminobutyric acid

receptor.... GABA-A receptor...chlride channel inhibitory.... increase negative charge....inhibitory post synaptic potential primary inhibitory transmitter in brain GABA and glutamate

Way Fun 5 sub units to channel several classes of drugs have receptor sites... benzodiazapines agonists GABA agonists: Mscimol GABA Antagonists: Bicuculine

Barbituates, Neuroactive Steroids, ALchohols, anesthetics

Convulsivants.... Picrotoxin, TBPS Take-home messages: all depressant activitiees potentiate GABA ability

antagonists are convulsants picrotoxin, bicuculin competitive antagonsits

shift to left in dose-response curve

before that...potassium bromide then barbituates barbituates can kill you, can also induce euphoria not widely prescribed

why do benzodiazepines and barbituines respond differently? affect channel differently Benzodiazapine makes shudder... phenobarbital keeps open a long time

Relative rates of absorption, metabolism, excretion differ markedly Drugs prescribed for ther pharmacokinetics Greater lipid solubility leads to greater absorption and more rapid onset elimiination half-life determined by metabolism some metabolism to active metabolites, with long half-life

Diazepam AKA, Valium First Benzodiazapine...moneymaker still a moneymaker

Gets in, gets out of brain relatively quickly....redistributes to fat length of time in which it is ative is limited by redistribution doesn't totally elave bdoy...can go live in fat metabolized to a compound hat is active, with a long elimination 1/2 life

can build up to greater than therapeutic levels

Structures Observe.... Diazepam very liipophilic

Lorazepam (ativan) used a lot in hospitals if pt hs to undergo some anxiety provoking procedure

Big business for a long time... no activity at all...can market....


 * Agonist||Trade Name||TIme to peak plasma||ELim half life|| Comments||
 * Diazepam||Valium||0.5-2.0||30-60||Very lipid soluble; anxiety status epliletpicus, preanesthetic, muscle relaxant||
 * Lorazepam||Ativan||1-6||10-18||More water soluble; anxiety||
 * Temzepa||Restoril||2-3||8-15||Slower oral absorption, insomnia||
 * Triazolam||Halcion||1-2||1.5-4||Rapidly inacivated insonia, disturbances||
 * Midazolam||Versed||IV, IM||2-5||Rapidly inactivated, pre-anaesthetic, amnesia||

//in battle creek... getting rancorous divorce took 2 halcyon went to wife's apartment beat up wife came back home went to bed went to prison 'Halcion Defense'//

Drug interactions..>CNS depressants not going to OD and die but taking with other CNS depressants: Antipsychotics, opiooids, alchohol, antihistamines, AMOIs, TCAs, anticonvulsants Inhibitors of CYP3A4: grapefruit, erythromycin, ritonavir Activator: Carbamazepine, phenobarbital

Side effects: lightheadedness increased reaction time

Hangovers: Drowsiness, confusion

rebound effcts: rebound anxiety, wakefullness, expecially with drugs wths hort t1/2 or abrupt discontinuation of the drug Ataxia and nystagmus Anerograde amnesia Paradoxical excitement: Uninhibited behavior, hostiltiy, rage, hypomania

TOlerance, Abuse, dependence Some risk for dependence and abuse but much less than barbiuates Abuse may be mor prevalent in people that abuse other substance May be no abstiancne syndrome following gradual withdrawal of drug May eb phsical dependnce after long-term use

antagonist available in hospitals can tease apart by subunit an important goal would be to hav antianxiety wthout sedation so far, just sedation w/o antianxiety different alpha sub units


 * ||alpha1||alpha2||alpha3,4,5||
 * Sedation||+||-||-||
 * Anesia||+||-||-||
 * Seizure Protection||+||-||+||
 * Anxiolysis||-||+||-||

Ambien: alpha1-selective hypnotic Ambien, lunesta, sonata alpha-1 act at same site sight

not benzodiazapines by structure, but act like benzodiazepines tend to have hal-lives can be subject to abuse

Buspirone

Chloral hydrate to dentists Rapidly converted to trichloroethanol in liver irritating to GI tract useful for sedation children or elderly undergoig uncomfortable procedures schissandra