A: 25-28 Flashcards
Benzo’s MOA
Bind GABA-A receptor (BZ-binding site) > facilitate Cl- channel opening & increases frequency
- membrane hyperpolarization
Benzos and DOA
super MaN is super fast
DC movies are super long
A is in the middle of mAn
T1/2= 2-40 hrs
Midazolam (oral, I.V) , Nitrazepam (oral)
Alprazolam (oral)
Diazepam (oral, IV) , Clonazepam (oral)
- metabolism: hepatic conjugation
Benzo’s indication
- Status epilepticus (diazepam)
- skeletal m. relaxation ( diazepam)
- absence and myoclonic seizure, infantile spasms (clonazepam)
- bipolar disorder (clonazepam)
- acute anxiety attack
- panic attack
- generalised anxiety disorder
- Sleep problems
Not for major depression
Diazepam indicationns
- Inducation of Anesthetia (IV)
- Preoperative Sedation
- treatment muscle spasticity : centrally acting skeletal Muscle relaxant
- Anxiety, Panic and phobic disorders
- Withdrawal state (ethanol, other sedative hypnotics) - because longer acting benzo
- status epilepticus
Clonazepam indic.
- Anxiety, panic & phobic disorders
- Bipolar
- Seizures
oral!
Benzo’s drug interaction
Antihistamines gen 1
Alcohol
Barb’s
- Additive CNS dep occurs when sedative hypnotic are used with other drugs in the class
- 1st gen antihistamine
- Anti-pscychotics
- opioid analgesics
- tri-cyclic antidepressant
- Barbiturate
- alcohol
Alprazolam indications
oral
- Anxiety, panic and phobic disorders
Nitrazepam indication
Nitra = NIGHT
oral
- Sleep disorders
- insomnia
Midazolam indication
oral, I.V
- preoperative sedation
- Anasthesia (iv)
Toxicities of benzos
- Extension of CNS deppressant action
- tolerance
- dependence liability
Benzo’s antag.
Flumazenil (antagonist at BZ-specific binding site on GABA-A r)
-مازن-
also for zolpidem ocerdose
Non Benzo’s
Zaleplon, Zolpidem- (newer hypnotics) GABA-A agonist
- binds to GABA-A receptor site
- facilitates chloride chn opening and increase duration
Your BMR is up when you sleep well
Busiprone- 5HT partial agonist & possible D2-r Busi is prone to allergies
Melatonin-
Rameltone- Melatonine-r agonist.( activates MT1 & MT2 receptors in supra-chiasmatic nucleus) ram sleeps and dream on Elton
+ SSRI (selective serotonin reuptake inhibitors) : Fluoxetine , (ES) citalopram, Sertraline
flumazenil
administration, duration
toxicities
- I.V
- short T1/2
- SE
- Agitation
- confusion
- possible withdrawal syndrome
- seizures
Zaleplon,
Zolpidem
indication, administration, pharmacokinetics
- Sleep disorders esp when sleep onset is delayed
- oral
- P450 substrate
- Short T1/2
- additive CNS depression with ethanol and other CNS depressants
Zaleplon, zolpidem toxicities
- Extension of CNS depressant effects
- dependence liability ( less than that of benzos because withdrawal symtpms are minimal after sudden discontinuation
Ramelteon mechanism and indication
Activation MT1 & MT2 receptors in suprachiasmatic nucleus (melatonin-r agonsit)
- Sleep disorders esp when onset of sleep is delayed ( same as zaleplon , zolpidem)
- NOT a controlled substance
Ramelteon administration, metabolism , toxicities
- oral
- forms active metabolite via CYP1A2
- Fluvoxamine inhibits metabolism
- SE:
- dizziness
- fatigue
- endrocrine changes
which drug is used in generalized anxiety states
Buspirone ( partial 5-HT agonsit, possibly D2-r)
Buspirone mechanism , indication, administration
- ( partial 5-HT agonsit, possibly D2-r)
- treat : generalized anxiety state
- oral , forms active metabolite
- short T1/2
buspirone toxicities and interaction
- GI distress
- tachycardia
- paresthesia
- interations with CYP3A4 inducer and inhibitors
SSRI (selective serotonin reuptake inhibitors) drugs and mechanism
- Fluoxetine
- (ES) citalopram
- Sertraline
- selective inhibition of 5-HT reuptake (allosterically inhibits transporter)
- minimal inhibitory effects on NE-transporter, cholinergic, adrenergic receptors
SSRI (selective serotonin reuptake inhibitors) characteristics
- oral
- hepatic metabolism
- Long T1/2 ( 18-24 hrs) because forms active metabolite
- Inhibitor of CYp450 enzyme (fluoxetine most potent)
- treatment response may require up to 4-6 weeks
SSRI (selective serotonin reuptake inhibitors) clinical usage
- Major depressive disorders
- Anxiety disorders ( GAD)
- OCD
- PTSD
- Premenopausal dysphoric disorder (PMDD)
- panic disorder
- bulimia
potential OFF-label use of ssri : premature ejaculation
SE of SSRI
- Anxiety , agitation
- sleep disorder
- bruxism
- sexual dysfunction (mediated by 5-HT2A r) - Decreased libido, anorgasmia, erectile dys
- weight gain
- SIADH
- withdrawal syndrome : flu-like symptoms, dizziness, anxiety, tremor , palpitation
NOTE: BENZOs may be given as adjunct therapy in first few weeks of ssri treatment to reduce anxiety and agitation
Drug interactions ssri
- Inhibition of p450
- increased level of (due to decreased clearance)
- TCA ,
- BENZO
- warfarin
- increased level of (due to decreased clearance)
- Serotonin syndrome with MAO-A inhibitors , TCA, meperidine
- muscle rigidity
- myoclonus
- hyperthermia
- CV instability
- ANS instability
Citalopram is the least frequenctly ass with drug-drug interaction
1st gene antipsych. and SE
Also MOA
CHF is a chronic old Disease (CHFD)
- Phenothiazine
- Chlorpromazine- low potency! Corneal deposits (high dose)
- thio-xanthenes
- Flupentixol- wheb you have FLU you PENT IX on ALL
- Butyrophenones
- Haloperidol- Neuroleptic malignant Synd. & tardive dyskinesia
- Droperidol
Promise me there is no Chlor!
Halo! Drop to the Floor
- All block D2-R >> 5-HT2 r
1st gene antipsych. SE
Tardive dyskinesia
Hyperprolactinemia
Weight gain (H1 r block)
Autonomic
Thermo
Primary indication for antipsych.
Schizofrenia
1st gene antipsych. are for positive or negative symp?
Positive
Positive symptoms and which pathway causes it
- increased activity in mesolimbic pathway
- Thought disorder
- Delusions
- hallucination
- Paranoia/catatonia
- disorganized speech
- (New features , no normal/physiologic counter part)
negative symptoms of psychosis
- decreased activity of mesocortical pathway
- Amotivation
- social withdrawal
- reduced emotions
- inability to feel pleasure
- reduction/removal of normal process
- Typical agents have NO effect of negative symptoms
Effect of 1st gen anti-psychotic based on which tract is inhibited
-
blocking Dopamine-receptor in
- meso-limbic > decreased positive symptoms (delusion, hallucination)
-
meso-cortical > worsening of negative symptoms
- diminished energy
- lack of emotion
- social withdrawal
-
nigrostriatal pathways: extra-pyramidal dysfunction
- tardive dyskinesia
- parkinsons like symtpoms
- muscle rigidity
- difficulty starting/stoping movement
- tremors
-
tubulo-infundibal level: increases prolactin
- galactorrhea
- gynecomastia
- sexual dysfunction
chlorpromazine effects
- Block D2r>> 5-HT2 r
- Block alpha, muscurinic, H1-r
- sedation
- decreased seizure threshold
chlorpromazine indications, administration
- schizophrenia
- bipolar disorder (manic phase)
- anti-emesis
- pre-operative sedation
oral, IV
hepatic metabolism
long T1/2
chlorpromazine SE
- extension of alpha & muscurinic receptor blocking actions
- Extrapyramidal dysfunction
- Tardive dyskinesia
- Hyperprolactinemia
Phenothiazine group
Flupentixole mechanism, indication, SE
Blocks D2r >> 5-HT 2 r
used in schizophrenia
less risk of tardive dyskinesia
Thioxanthene group
Haloperidol
doriperidol
mechanism
Administraion
- Block D2r >> 5HT-2 r
- some alpha block
- less Muscurinic block
- less sedation than phenothiazines (chlorpromazine)
- oral/ I.V
- hepatic metabolism
Haloperidol
doriperidol indication and SE
- schizophrenia
- bipolar disorder (manic phase)
- Huntington chorea
- Tourette syndrome
- SE: extrapyramidal dysfunction (major)
Neuroleptic malignant syndrome (NMS) (high fever and muscle stiffnes, altered mental status)
and tardive dyskinesia (TD)
2nd gene antipsych.
Quiet pls! Only Whispering is Appropriate
- *Quetiapine** and Clozapine. CLOZAP! Quit tipping
- *Olanzapine**- CLOZ the door with your OLNA
- *Risperidone**- RiIS got married to mathew PERI and now they are DONE
- *Aripiprazole**- ARI PIPed to RAZ
**Cariprazine
**Tiapride
2nd gene antipsych. dominant MOA
5-HT blockade >> D2 r
- some alpha block ( clozapine, risperidone)
- M-block ( clozapine, olanzipine)
- Variable H1-block
Antagonism for Benzo’s
Flumazenil
مازن is ill with flu
Depot injection
Injection formulation of a medication which releases slowly over time
Antipsychotics antag D2-R MOA
D2-R are Gi coupled
-
found in
- caudate
- putamen
- nucleus accumbens
- cerebral cortex
- hypothalamus
So if we inhibit –> Increased cAMP (Bcs usually if Gi is active the cAMP will decrease)
Increased cAMP causes NF on the Dopamine release
D2-R are where?
Mesolimbic system
Striatal Frontal System
- caudate
- putamen
- nucleus accumbens
- cerebral cortex
- hypothalamus
- basal ganglia : if d2-r is blocked there > extrapyramidal effects:
- tremor
- slurred speech
- akathisia
- dystonia
2nd gen antipscyotic clinical application and administration
- Schizophrenia (positive & negative symptoms)
- Bipolar disorder (
- Olanzipine
- risperidone
- quetiapine
- cariprazine
- Major depression
- aripiprazole
- Agitation in alzheimers and parkinsons disease
- oral, I.V
- hepatic metabolism
2nd gen antipscychotic SE
- Agranulocytosis (clozapine)
- diabetes & weight gain
- clozapine
- olanzapine
- cariprazine ( D2/D3 antagonist, hungarian development)
- hyperprolactinemia
- Risperidone
- paliperidone
- QT-prolongation
- ziprasidone
- paliperidone
Tiapride mechanism and indication
- D2/D3 antagonsit
- management of alcohol psychosis
