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PSYCHOACTIVE, NEUROLEPTIC , ANTIDEPRESSANT DRUGS
BENZODIAZEPINES
MECHANISM OF ACTION
-benzo’s bind to specific high affinity sites on the cell membrane adjacent to receptor for
GABA  ehances affinity of GABA receptors more frequent opening of chloride channels
WITHDRAWAL SYNDROME
USES: PROFESSIONAL
USES: UNPROFESSIONAL
DURATION OF ACTION
ACUTE ADVERSE EFFECTS
LONG TERM ADVERSE EFFECTS
1. Anxiolytic (severe): selectively inhibiting neuronal circuits in limbic system of brain
2. Sedative/Hypnotic (insomnia, night terrors, sleep walking)
3. Anticonvulsive: treat or interrupt seizures (eclampsia)
4. Central Muscle Relaxant (pre medication before general anesthesia):
- relaxes spasticity of skeletal muscles;
-↑ presynaptic inhibition in spinal cord
5. Symptomatic emergency treatment of withdrawal syndromes
6. Diverse emergency indications (MI, arrhythmia)
7. Co-medication w/neuroleptics, lithium, antidepressants
NOT ANTIPSYCHOTIC, NOT ANTIDEPRESSANT
1. Use with caution:
-Psychovegetative disorders:
-irritable bowel syndrome, gastric ulcer, PMS, chronic fatigue syndrome
-Social performance anxiety
2. Absolute NO-NO’s
-analgesia
-proper medical treatment of disease
-psychosocial or psychiatric assistance
Diazepam
Long acting; long acting metabolites
Chlordiazepoxide
Intermediate-acting; long acting metabolites
Oxazepam
Temazepam
Intermediate acting (t1/2 about 10-12 hrs)
Lorazepam
Clonazepam
Triazolam
Alprazolam
Short acting
Midazolam
1. CNS depression (no problem with therapeutic doses)
-drowsiness, sedation
-ataxia
-vertigo, headache, confusion, slurred speech
-decrease under continuous administration
2. Respiratory depression/Hypotension
-seen w/high i.v. doses or in combo w/other sedatives
-normally absent in anxiolytic-sedative-hypnotic doses
-relevant in cases of predisposition
3. Amnesia: (retrograde and anterograde – more frequent w/short acting)
4. Paradoxical excitement:
-hostility, aggression, disinhibition
-seen w/predisposing factors (organic brain disease, central anticholinergic syndrome)
1. Addiction/dependency:
**Low dose dependency:
-benzo is prescribed for valid medical reasons
-low dose intensity, no increase in doses
-full patient compliance
**Conventional dependency:
-benzos may or may not be prescribed for valid medical reasons
-increasing doses required, indicating tolerance
-black market benzos may be used to cover demand
-Alcohol is often abused as amplifier
2. Sleep disturbances (same as alcohol)
-REM sleep suppressed (sleep less refreshing)
-REM – rebound (nightmares) at discontinuation
3. Amotivational syndrome:
-may be long term high dose exposure
-less pronounced than w/cannabinoids
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BENZO’S DURING PREGNANCY
BENZO’S AND SEXUAL DYSFUNCTION
DRUG INTERACTIONS
PSYCHOACTIVE, NEUROLEPTIC , ANTIDEPRESSANT DRUGS
1. Teratogenic potential
-generally recognized as safe
-weak ass. w/cleft palate
2. Perinatal period:
-floppy baby syndrome
-withdrawal syndrome (presents weeks later due to long half life of benzo’s)
3. Breast feeding:
-Oxazepam, Lorazepam, Alprazolam, Midazolam = limited distribution into breast milk
(American Academy of Peds advise against prescribing benzo’s to nursing mothers)
1. Endocrine: slight inhibition of steroid metabolism
2. Libido:
-Decreases as a usual side effect of all sedatives at normal to high doses
-Performance anxiety/Psychosocial inhibition:
-low to mod doses of benzo’s may restore or improve sexual dysfunction
**Alcohol: acute low dose is comparable
**Cocaine: CNS stimulant  directly increases drive but severely inhibits sexual function
Enhanced sedation, respiratory and/or cardiovascular depression occurs in combination
w/other CNS depressant drugs:
-alcohol
-antidepressants
-antiepileptics
-antihistamines
-general anesthetics
-neuroleptics/antipsychotics
-opioid analgesics
-other sedatives
**All except for alcohol are manageable by clinical monitoring
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PSYCHOACTIVE, NEUROLEPTIC , ANTIDEPRESSANT DRUGS
DRUG
PK
-i.v.
-hepatic elimination
-t1/2= short (<1.5 hrs)
FLUMAZENILE
PD
-blocks many actions of:
-benzo’s
-zolpidem
-zaleplon
 reversal of sedation, hypnosis,
narcosis  improvement of
respiratory depression
-ineffective w/other sedativehypnotics, opioids, general
anesthetics or alcohol
USES
1. To reverse CNS
depression after
benzo overdose
2. To hasten recovery
following use of
benzo’s for anesthetic
and diagnostic
procedures
ADVERSE EFFECTS
1. Agitation
2. Confusion
3. Dizziness
4. Nausea
5. Anxiety
BUSPIRONE
BARBITUATES
CHLORAL
HYDRATE
MEPROBAMATE
(MILTOWN)
-p.o.
-short acting
-(1-4 hrs)
-hepatic metabolism
-p.o.
-high first pass
-hepatic metabolism
-major metabolite = α2
blocker
-liver dysfunction may ↓
clearance
-i.v./p.o./i.m./rectal
-hepatic metabolism
-hep enzyme inducer
-long half lives
-watch 4 accumulation
-p.o./rectal
-t1/2= 5-10 hrs
-converted to active
compound
trichloroethanol
-p.o.
-t1/2= 6-17 hrs
2. observe possible
protective effects of benzo’s
in mixed (suicidal)
intoxications (tricyclic antidep
+ benzos)
3. CI in benzo addiction 
severe w/drawal syndrome
(including convulsions)
BENZO ANTAGONIST
ZOLPIDEM
ZALEPLON
CONTRAINDICATIONS
1. Beware of short half life, to
avoid, re-sedation, repeated
dosing is required
-drugs bind to BZ1 (benzo agonist)
-effects mostly as for benzo’s
-as for benzos at
equivalent/effective doses
-anxiolytic w/out marked sedative or
euphoric effects
-unlike benzo’s
-effects take > 7 days to establish
-no rebound anxiety
-no w/drawal syndrome
-no potentiation w/sedatives
-less psychomotor impairment
-reversible depression of activity of all
excitable tissue
-CNS most sensitive
-CV system least sensitive, but
affected in intoxication
-Compared to Benzo’s:
-low selectivity
-low therapeutic index
-same tolerance, abuse pot.
1. Tachycardia
2. Palpitations
3. Nervousness
4. GI distress
1. Respiratory ↓
2. Paradoxial excitement
3. After-effects (hangover)
4. Drug interactions
w/centrally active drugs
5. Pain (↓pain threshold)
6. Hypersensitivity
7. Tends to accumulate:
accidental o/d; intoxication
1. Bad taste
2. Hepatic damage
3. Severe withdrawal
Anti-anxiety agent
introduced in 50’s;
widely used as
nighttime sedative,
high abuse potential,
street drug
1. More generalized CNS
depression than benzo’s, but
less complete than with
barbituates
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PSYCHOACTIVE, NEUROLEPTIC , ANTIDEPRESSANT DRUGS
NEUROLEPTICS:
CONVENTIONAL ANTYPSYCHOTICS/NEUROLEPTICS
SCHIZOPHRENIA
NEUROLEPTIC DRUG INDUCED RECEPTOR BLOCKADE
ANTIPSYCHOTIC ACTIONS OF NEUROLEPTICS
MAJOR ADVERSE EFFECTS OF NEUROLEPTICS
1. Chlorpromazine
2. Fluphenazin
PHENOTHIAZINES
3. Prochlorperazine
4. Promethazine
5. Thioridazine
BUTYROPHENONES
6. Haloperidol
THIOXANTHENES
7. Thiotixene
8. Clozapine
ATYPICAL ANTIPSYCHOTICS,
9. Olanzapine
HETEROCYCLICS
10. Quetiapine
11. Risperidone
12. Lithium
Common and serious mental disorder characterized by:
-loss of contact with reality (psychosis)
-false perceptions (hallucinations)
-false beliefs (delusions)
-abnormal thinking
-restricted range of emotions (flattened effect)
-diminished motivation, disturbed work and social functioning
Subtypes:
-Paranoid
-Disorganized
-Catatonic
-Undifferentiated
Dopamine D2 block
Virtually all neuroleptics
Dopamine D4 block
Clozapine
Α-adrenergic block
All neuroleptics listed especially, Phenotiazines,
Thiothixene
5-HT block
Atypical neuroleptics, not haloperidol
Muscarinergic block
All neuroleptics, except haloperidol
Histamine H1 block
All neuroleptics except haloperidol
1. Gradual reduction of hallucinations and delusions
2. Reduction of agitation, emotional upset
3. Reduction of spontaneous physical movement
4. Patient relieved from stressful experience, inner conflict, terror, anxiety
 reconciliation w/reality  improvement of psychosis
NO:
-anxiolysis
-euphoria
-improvement of mood
Intellectual and sensory functions intact
Psychochemical straightjacket
Most adverse effects occur early, antipsychotic effects take weeks  severe
impairment of quality of life
1. Extrapyramidal motor effects:
-acute dystonias (mouth, face, eye) which the patient is fully aware of and has
not control over it at all; very embarrassing to patient (responsive to
anticholinergic drugs)
-Parkinson-like bradykinesia, rigor, tremor (responsive to anti-cholinergic
drugs)
-Motor restlessness (akathisia) (responsive to anticholinergic drugs)
-Tardive dyskinesia: after long term treatment, may be slowly reversible or
irreversible (not responsive to anti-cholinergic drugs; may actually worsen
symptoms)
2. Reduction of autonomous nervous system activity
-central anticholinergic (blurred vision, dry mouth, sedation, confusion)
-anticholinergic (GI, UT)
-antiadrenergic (orthostatic hypotension, lightheadedness)
-impairment of body temperature regulation
2. Endocrine
-hyperprolactinemia
-amenorrhea, galactorrhea, infertility, impotence, loss of libido
3. Blood dyskrasias: especially Clozapine
4. Seizure threshold is lowered
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PSYCHOACTIVE, NEUROLEPTIC , ANTIDEPRESSANT DRUGS
DRUG
PK
PD
USES
1. Acute Psychosis
-low potency neuroleptic drug,
D1 and D2 antagonist
-p.o./i.m./i.v./rectal
-stimulates prolactin secretion
CHLORPROMAZINE
(CPZ)
2. Acute/Chronic
schizophrenia
3. Manic phase of manic
depression
-hepatic metabolism
-antiemetic, 5HT blocking
-weak antihistaminic
4. Control severely
disturbed, agitated/ violent
behavior
-sedative (subject to tolerance)
5. Intractable hiccup
-t1/2= 30 hrs
-plasma binding >95%
6. Adjunct tx of severe
anxiety
HALOPERIDOL
-p.o./i.m
comparable to (CPZ)
1. DOC: strong antipsychotic effect is requrd
-blocks D2, D4, 5-HT & others
-effective in therapy-resistant
cases
-anticholinergic, antiadrenergic
-sedative
CLOZAPINE
LITHIUM
-high potency neuroleptic drug
-p.o. w/in 6-8 hrs
-t1/2= 30 hrs
-renal excretion (70%
tubular reabsptn, ↑ed in
hyponatremia)
-↑ Li plasma levels w/
NSAIDs, diuretics, Na
restriction
-saline infusions facilitate
elimination
-dialysis: remove Li
Hypothetical: competition
w/sodium explains side effects
1. Mood stabilizer
-prophyl of mania
-prophyl of manic dep
-prophyl of recurrent
unipolar depression
-tx of mania w/adjunct
meds
ADVERSE EFFECTS
1. Lesser degree of central
sedation than barbiturates or
benzos
2. Tolerance = fast
3. Antimuscarinergic:
-mydriasis
-blurred vision
-dry mouth
-difficulty w/peeing
4. CV:
-tachycardia
-EKG changes
-ortho hypotension
5. CNS:
-confusion
-delirium
-insomnia
-nightmares
-depression (sign of o/d)
-catatonic-like states (stiff
inside and out; can’t
move/emotion less)
-hypothermia
6. Extrapyramidal dysfunction
a. Acute dystonia
-muscles of face/neck/trunk
-jaw clenching
-oral dystonia
-pharyngeal dystonia = fatal
-tx: antimuscarinics, benzo
Same as for CPZ
More pronounced EPM syn
1. EPM: symptoms absent
(pre-existing tardive dyskinesia
may even improve)
2. Grandulocytopenia (1%/pt yr)
3. Convulsions (3%/pt yr)
1. Initial nausea, diarrhea,
muscle wkness, dazed feeling
2. Therapeutic levels:
-fine hand tremors
-polyuria, polydipsia
-wt gain, edema, no diuretics
-skin disorders worsen
-EKG changes (T depression)
-hypothyroidism
OTHER
b. Akathisia:
-mental/motor restlessness
-tx: antimusc, propran,
benzos
c. Parkinsonism: (reversible)
-rigor/tremor/akinesis
-tx: antimuscarinics
d. Tardive dyskinesia:
-irreversible
-orofacial dyskinesias
-protrusion of tongue
-lateral chewing
-pouting of lips
-tx: none; avoid antimusc
-prvnt: clozapine/risperidone
as antispychotics
7. Convulsions
8. Neuroleptic malignant
syndrome:
-hyperthermia
-severe extrapyramidal sx’s
-impaired consciousness
-mus rigidity & sk. mus dmg
-autonomic dysfunction
-tx: discontinue NL,
symptomatic tx
CI in children due to EPM syn
-prototype butyrophenone NL
Related drug: Olanzapine: less
blood dyskrasias
-narrow margin of safety
-effects delayed by 8-10 days
Toxic:
-hyperreflexia
-severe GI symptoms
-ataxia, blurred vision
-tinnitus, syncope
toxic psychosis, circulatory
failure, coma
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PSYCHOACTIVE, NEUROLEPTIC , ANTIDEPRESSANT DRUGS
ANTI-DEPRESSANT DRUGS
ANTIDEPRESSANT DRUGS:
DRUG LIST
COMMON CLINICAL FEATURES OF
ANTIDEPRESSANTS
AMINE UPTAKE BLOCKING DRUGS
Α2 RECEPTOR AGONIST MAO INHIBITORS
Tricyclics:
-Amitriptyline
Clonidine
Phenelzine
-Doxepin
Tranycypromine
-Desipramin
-Imipramin
-Protriptylin
-Nortriptylin
Heterocyclics(2nd gen)
-Amoxapine
-Bupropion
-Trazodone
-Maprotiline
Heterocyclics (3rd gen)
-Mirtazapine
-Nefazodone
-Venlafaxine
5-HT SSRI
-Fluoxetine
-Paroxetine
-Citalopram
-Sertraline
1. High rate of non-responders
2. Highly variant array of drug; receptor interactions for each drug:
-very complex, mainly hypothetical mechanisms of action
-non-responders to one drug in a class may respond to another drug in the
same class
-choice of drug requires specialist experience
-complex and variant pattern of adverse effects
3. Sequential onset of effects
-some adverse effects occur immediately
-suppressed mental and physical activity is restored soon (w/in days)
-anxiolytic & mood elevating effects (takes >2 wks to become effective)
Consequences:
Simplifying hypothesis of action are untenable ???
Initial antidepressant therapy aggravates the risk of suicide, since activity is
restored long before anxiety and negative mood are improved
6
DRUG
AMITRYPTILINE
PK
-p.o.
-low and inconsistent BA
-t1/2= 20 hrs
-metabolites = 30hrs
-hepatic cyt P450 mets
-renal elimination
2ND AND 3RD
GENERATION
ANTIDEPRESSANTS
Improved PK:
-acclerated elimination
-less interactions
FLUOXETINE
-slowly metabolized by
P450
t1/2 = up to 10 days
-active met = 3-30 days 
equilibrium of plasma
levels after many weeks 
many PK interactions
PHENELZINE
TRANYLCYPROMINE
PD
-p.o.
-rapidly excreted in urine
-biological t1/2=1-3 wks
Improved spectrum of
effects: combo of some
sedative, anxiolytic, or
neuroleptic effects
w/antidepressant qualities
PSYCHOACTIVE, NEUROLEPTIC , ANTIDEPRESSANT DRUGS
ADVERSE EFFECTS
OTHER
Precautions:
1. Sedation
2. Antimuscarinic
-cardiac disease
3. Ortho hypotension
-hepatic dysfunction
(blockade of alpha
-bipolar disease (may
receptors)
precipitate mania)
Sx’s of intoxication:
4. Cardiovascular
1. severe major
(tachycardia, AV block)
-agitation, delirium
depression
5. CNS
-tremor, convulsions
2. neuropathic pain
6. Leukopenia
-resp depression
7. Symptoms abrupt at
-cardiac conduction
w/drawal
defects and severe
CI:
arrhythmia
-therapy w/MAO inhib.
-circulatory collapse
-intox w/sedatives/OH
-coma
-glaucoma, prostatic
Triad: Cardiotoxicity,
adenoma
Convulsions, Coma
Improved toxicities:
Frequent disadvantages
-less autonomous AE
-incr blood dyskrasias
-less impairment of sexual
-seizure threshold
dysfunctions
lowered
USES
1. most frequently
prescribed antidepressant
drug
-MAO-inhibitors (almost
irreversible)
-MAO-A
-MAO-B
2. major depression
3. bulimia, anorexia, OCD
4. social anxiety d/o?
5. PMS ?
-if unresponsive or
allergic to 1st choice
-special subypes of
depression, when
stimulant effect is
particularly beneficial
-anxiety
-insomnia
-wt loss, ↓ appetite,
-anorexia
-tremors
-loss of libido/sexual dysf.
-nausea
NO anticholinergic
effects
NO ortho hypotension
NO wt gain
NO arrhythmia at O/D
1. Persist for wks after
discontinuation
2. Cheese syndrome:
Tyramine  massive
release of catecholamines
Hypertension
Arrtythmia
Nausea
Headache
Stroke
Serotonin Syndrome:
Caused by combo of
SSRI and MAO inhib
-↑5HT stores and
inhibition of reuptake 
massive increase of
serotonin at synapses
-hyperthermia
-muscle rigidity
-myoclonus, seizures
-imparied mntl status
-autonomous
decompensation
Tx: symptomatic, 5HT
blocker (cyproheptadine)
O/D: seizures, mild
w/drawal syndrome
7