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How do benzo's work?
- Mimics GABA receptors; benzo receptors co-located with GABA receptors (presynaptic inhibitory receptors); Benzo's bind at benzo receptor- enhancing the effects of GABA, where chloroid ion channels open-providing gateway for chloride.
- GABA NE are agonist (inhibitory) vs. excitatory
Medical illnesses causing anxiety SX:
- Hyperglycemia (or hypo?)
- Adrenal stress
Drugs causing anxiety...
Cocaine, caffeine, amphetamines, steroids, decongestants, nasal sprays (!permanently change nasal membranes!)
Anxiety as part of illnesses...
Depression, S/A, schizo., brain prob's
Using BUSPAR for anxiety...
Buspar (buspirone)- PRO: non-habit forming, doesn't interact with CNS depressants, no impaired psychomotor functions, no memory issues. CON: delayed onset (2-6 weeks); not always effect w/ people-esp who have used benzo's.
Antihistimines for anxiety...
Vistaril, Atarax, Benadryl: blocks histaine receptors in CNS causing sedation- thereby reducing anxiety. Can also cause drowsiness/imparied performance. Works in 20-30 min. lasting 4-6 hours. Disadvantage: tolerance can develope- narrow therapeutic window between reducing anxiety and producing sedation.
Beta Blockers used for anxiety...
- BB act by blocking effects of NE at the receptor. Effective at reducing peripheral manifestations of anxiety (phys. SX- tremor, sweating, heart rate); but not internal exp. Useful for public speaking.
- Propranolol (Inderal) most popular.
- Can cause dizziness, lowered bp; depression over time. Have been used as adjunctive agents in panic D/O.
Clonadine for anxiety...
Clonidine (Catapres): alpha 2 adrenergic agonist; presynmaptic inhibitor of NE release. Used to tx hypertension (like BB). Also used for opitate W/D.
Tiagabine for anxiety...
Tiagabine (Gabitril)- anticonulsant, selective GABA reuptake inhibitor
How long should benzo's be used?
- -Avoid unless anxiety severe or other things haven't worked..
- -Short-term!! Use over 6 months may lead to tolerance/dependence.
What was the first benzo?
What are benzo's used for? Mech. of action...
Anxiety- (sedative); insomnia (hypnotic); quick acting-effective
Difference between difft drugs (1/2 life, metabolism)
- Pharmacodynamics... half-life and metabolism. Longer half life tends to build up in system, even if taken 1/day. Most metabolized by liver, so not recommended with liver dysfunction.
- Least 3 dependent on liver: lorazepam (ativan); tempazepam (restoril); oxazepam (serax).
Short half-life benzo's...
- Triazolam (Halcion); Midazolam (Versed); Lorazepam (ativan-but to shorter degree); may cause anterograde amnesia: loss of memory briefly after drug wears off.
- Hypnotics: Sonata, Lunesta.
Atypical (nonbenzo's) benzo's..
Used as hypnotics- Estazolam (ProSom)- triazolobenzodiazepine with quick onset, intermediate half life, no active metabolites so doesn't buld up or make sedated during day. Quazepam (Doral) similar to flurazepam (dalmane). Zolpidem (ambien) and eszopiclonoe (Lunesta) are short acting. Sonata half life is one hour...shortest acting nonbenzo hypnotic. *Interacts with specific benzo receptor- less cognitive impairement/ reduced dependency.
Benzo's and addiction/withdrawal
- Look at prior history of abuse; good predictor- not always present. Short half-lives most abused.
- W/D: problems when reducing doses, esp if quitting cold turkey. When treated daily for more than a few weeks (esp mod-high doses) the nervous sys adapts to presence of drugs. Any rapid drop precipitates w/d sx. Mild-Mod SX: anxiety, resless, insomnia, nightmares. Severe: seizures, high fever, psychosis, death. Short half life more likely to produce w/d.Defining feature of w/d vs. illness: if persisting more than 2 weeks usually underlying cause. Restart or return to meds used then do very gradual w/d routine- 5-10% reduction
Benzo's for certain conditions/D/O...
- Stress related: benzo's for short term. Sedatives. (ativan xanax, klonopin less sedating)
- Insomnia- hynotics: ambien, halcion, sonata- NOT given if chronic.
- Panic: benzo's (klonopin, xanax- usually higher doses). Antidepressants/SSRI's may reduce # of attacks, CON: slow acting. MAOI- CON- strict diety
- Social phobia: therapy, beta blockers- slows heart rate when ligand binds with beta receptor. Don't sense immediate anxiety, mostly reducing phys. sx.
Benzo's, Atypical, Anti-panic meds...
- Benzo's: valium, librium, centrax, tranxene, klonopin, ativan, xanax, serax.
- Atypical/Other: buspar, atarax, vistaril, inderal, tenormin, catapres, tenes
- Anti-panic: HIGH potency- ativan, klonopin, xanax. SSRI's, MAOI's.
Antipsychotic Meds: Low Potency (As effective, weaker DA blockers causing less neurolocgical side effects). This group revolutionized TX of psychosis.
- Thorazine, Mellaril, Clozaril, Serentil, Seroquel, Geodon
- *higher in sedation, besides seroquel, geodon.
Antipsychotic meds: HIGH potency
*Potent DA blockers called neuroleptics because of neurological side effects. Siggnificant side effects, particularly extrapyramidal.
Abilify, moban, trilafon, loxitane, stelazine, prolixin (atypical), navane, haldol, orap, risperdal, zypres, envega
How antipsychotics work..
chemical blockade of dopamine D2 postsynapic receptors and clinical potencycoreelates to degree of DA blockade. This also led to DA hypothesis of schizophrenia
1st antipsychotic used..
Thorazine, first used as postoperative sedative.
Grouping and classification of side effects...(Extrapyramidal)
- Ranked by high or low potency; as well as tendency to produce extrapyramidal SX (EPS) vx. sedation and anticholinergic.
- EPS: bc blocks DA in mesolimbic region (good to lessen psych. sx), but also blocks DA in basal ganglia. Parkinsonian- resemble parkinsons...slow movements, tremor, dec. facial expression, shuffling gait. Dystonic: muscle spasms, usually neck/shoulder. Akathasia: intense restlessness. Can be confused with psychotic agitation leading to increase in doseage- further leading to akathasia. When severe, associated with noncompliance and higher risk of suicide.
- Due to blocking acetylcholine receptors and affecting parasympathetic nervous system.
- Dry membranes, constipation, difficulty uringating, sedation, sexual dysfunction. Mild-disabling.
Due to producing an alpha-adrenergic blockade, leading to orthostatic hypotension.
All other SE appear in first few hours, or days, or with increase in doseage. TD appears late in tx or when meds reduced.discontinued. *D/O involving involuntary muslce movements.
Atypical antipsychotics... Description/Side Effects
- strong seratonin blockers, producing varying degress of DA blockade.
- *clozapine (clozaril) is prototypical agent, effect for both pos, neg sx. 40% of those who failed to respond to haldol, thorazine respond to clozapine. Sedating, anticholinergic/antiadrenergic side effects. Lowers seizure threshold- hepatitis. Side effect