Review of sedatives and antiseizure agants by a 3rd year medical student of All saints university,Dominica.

1. REVIEW OF
SEDATIVES
ANTISEIZURES
Musa Sakina K.

2. SEDATION:It is the reductionof irritability
or agitation byadministration of sedative
drugs, generally to facilitate a medical
procedureor diagnostic procedure.

3. Sedation is typically used in minorsurgical procedures
such as endoscopy, vasectomy or dentistry and for
reconstructive surgery, some cosmetic surgeries,
removal of wisdom teethor for highanxiety patients.
It is also used extensivelyinthe intensivecare unit so
thatpatientswho are being ventilatedtolerate having an
endotrachealtube in the trachea. Also can be used
during a long term brain EEG to help patientrelax.

4. ANESTHESIOLOGISTS DEFINES THE
CONTINUUM OF SEDATION AS FOLLOWS;
Minimal Sedation - Normal response
to verbal stimuli.
Moderate Sedation – Purposeful
response to verbal/tactile stimulation
(usually referred as conscious
sedation).
Deep Sedation – Purposeful response
to repeated or painful stimulation.
General Anesthesia – Unarousable
even with painful stimulus.

5. SEDATIVES.
 Barbiturates(pentobarbital)
 Benzodiazepines(diazepam)
 Non-benzodiazepine hypnotics (zolpidem)
 1st generation
Antihistamines(diphenhydramine)
 General Anesthetics(ketamine)
 Herbal sedatives(cannabis)
 Skeletal muscle relaxants(baclofen)
 Opioids(tramadol)
 Antipsychotics(olanzapine)
 Others(alcohol)

6. BARBITURATES.
Barbiturates are derivatives of
barbituric acid.
Barbituric acid is the condensed
product of malonic acid and urea.
Thiobarbiturates – Barbiturates in
which O2 is replaced by sulphur (more
lipid soluble, shortened duration of
action, increased hypnotic potency).

8. Ultra short (20 mins) – Thiopental.
Short acting (3-10 hrs) –
Pentobarbital, secobarbital,
Amobarbital.
Long acting (1-2 d) –
Phenobarbital.

9. Barbiturates increase the duration
of the GABA – mediated chloride
channel openings and prolong
GABA activity.
At high concentration, barbiturates
may also be GABAmimetic,
directly activating chloride
channels (can act at GABA
recepotors without GABA).

10. Barbiturates do not bind to the BZ
sites, but bind to another site on
the GABA-chloride channel
macromolecular complex to exert
the GABA- facilitatory action.
Also inhibit complex 1 of electron
transport chain and hence no ATP
synthesis in neurons (has CNS
depressant action).

11. Barbiturates produce dose dependent
effects;
Mild sedation – sleep - general
anesthesia - coma
Have low therapeutic index
Tolerance to the effects on sleep occur
within a few days
Has anti-convulsant
actions(phenobarbital)
Depresses respiration in higher doses
(can be exacerbated by EtOH) - CNS
Hypnotic dose – slight decrease in BP
and HR(sleep)
Toxic dose – marked fall in
BP(ganglionic blockade,vasomotor

12. Induce CYP450 enzyme system
Increase ALA synthetase – dangerous
exacerbation of porphyria.
Orally well absorbed,distributed widely
and crosses the placenta
Duration of the action is dependent on
the redistributiuon
Tolerance occurs more rapidly than
BZDs.Barbiturates and ethanol have
greater abuse liability than BZDs.

13. SIDE EFFECTS OF BARBITURATES.
 Drowsiness, distortion of mood, irritability,
confusion.
 Impairment of fine motor skills
 Hypersensitivity
 Induce metabolism of most lipid-soluble
drugs such as Ocs, Warfarin,
Carbamazepine, Phenytoin
 Life threatening respiratory depression
when taken with other CNS depressants
 Increase porphyrin synthesis
 Dependence
 More intense withdrawal symptoms(than

14. Overdose treatment is supportive;
 Maintenance of ABC
 Gastric lavage
 Forced alkaline
diuresis(Mannitol + NaHCO3)
 Hemodialysis

15. BENZODIAZEPINES.
BZDs facilitate GABA receptors
action by increasing frequency of
CL-channel opening.
GABA + GABA receptor = opening
of CL channel (hyperpolarization)
BZDs do not directly activate
GABA receptor but require the
presence of GABA to express
their effects (no GABAmimetic

16. BZDs act by binding at a site distinct
from GABA binding site on the
receptor (allosteric binding).
Binds to alpha and gamma subunits in
GABA receptor.
Binding sites; BZ1 and BZ2
 BZ1: associated with alpha 1
subunit, mediates sedation,
anterograde amnesia,
anticonvulsant action, tolerance.
 BZ2: associated with alpha 2
subunit, mediates antianxiety action,

17. CNS EFFECTS
Reduction of anxiety and aggression
Induction of sedation and sleep
Increased presynaptic inhibition in the
spinal cord causes reduction of muscle
tone and co-ordination
MUSCLE RELAXANT EFFECT IS
INDEPENDENT OF SEDATIVE
ACTION.
Anti convulsant effect(tolerance)
Anterograde amnesia
Depression of medullary respirtory
center(no effect at hypnotic dose and
less than barbiturates)

18. CVS EFFECTS
Hypnotic dose – no effect
In pre-anesthetic dose – reduce
BP and HR
At toxic dose – circulatory
collapse due to depression in
myocardial contractility (-ve
inotropic affect) and vascular tone.

19. All BZDs are lipophilic, crosses
placental barrier(floppy baby
syndrome) and secreted in the
milk.
No effect on CYP450 enzyme
system
Most of them are metabolized by
hepatic CYP450 enzyme system
to active compounds (biological

20.  LONG ACTING (1-3 D)
 Flurazepam
 Diazepam
 Chlordiazepoxide
 Chlorazepate
 INTERMEDIATE ACTING (10-20 H)
 Alprazolam
 Lorazepam
 Temazepam
 SHORT ACTING (3-8 H)
 Triazolam
 Midazolam
 Oxazepam

21. Lorazepam, Oxazepam,
Temazepam do not have active
metabolites and involves only
conjugation, preferred in elderly.

22. SIDE EFFECTS
 Impairment of mental and motor functions
 Tolerance (not to anxiolytic actions)
 Produce cross tolerance between BZDs,
barbiturates and ethanol.
 Dependence
 Abrupt withdrawal leads to withdrawal symptoms
(slower onset and less than barbiturates)
 Short acting BZDs have higher addictive potential,
severe withdrawal effects.

23. FLUMAZENIL
Competitive antagonist at BZ
binding sites.
Antidote for BZD overdose (can
not be used for barbiturates and
alcohol)
Precipitates withdrawal symptoms
in BZD dependent patients.

24. NON BZD HYPNOTICS
 Zolpidem
 Zaleplon
 Eszopiclone
 Zopiclone
 Act via the BZ1 site of the GABA
receptor.Effects reversed by flumazenil.
 Unlike older sedative-hypnotics, cause only
modest day –after psychomotor depression
and few amnestic effects.
 Decreased dependence risk than BZDs.

25. ANTISEIZURE
DRUGS.

26.  Partial (focal) seizures
 Arise in one cerebral
hemisphere
 Simple partial seizure;
 No alteration of
consciousness
 Complex partial seizure;
 Altered consciousness,
automatisms, and
behavioral changes
 Secondarily generalized
seizure;
 Focal seizure becomes
generalized and is
accompanied by loss of
consciousness
 Generalized seizures
 Arise in both cerebral
hemispheres and are
 Increased muscle tone is
followed by spasms of
muscle contraction and
relaxation
 Tonic seizure;
 Increased muscle tone
 Clonic seizure;
 Spasms of muscle
contraction and relaxation
 Myoclonic seizure;
 Rhythmic, jerking spasms
 Atonic seizure;
 Sudden loss of all muscle
tone
 Absence (petit mal)
seizure;
 Brief loss of
consciousness often with
blank stare, with minor

27. BARBITURATES
 Barbiturates interact with specific receptors
on the GABA receptor-chloride ion channel
macromolecular complex.
 USES:
 Simple partial seizure
 Complex partial seizure
 Grand mal seizure
 ADRs:
 Sedation, Tolerance, Dependence
 Induction of CYP450
 Cardiorespiratory depression

28. BENZODIAZEPINES
Benzodiazepines interact with specific
receptors on the GABA receptors-
chloride ion channel macromolecular
complex.
USES:
 Status epilepticus (diazepam,
Lorazepam)- 1st line for acute
treatment.
 Eclampsia seizures
ADRs:
 Sedation, Tolerance, Dependence

29. VIGABATRIN
The enzyme GABA transaminase
is irreversibly inactivated by this
agent – enhances the effects of
GABA at synaptic sites.
USES:
 Simple partial seizure
 Complex partial seizure

30. TIAGABINE
Inhibits GABA transporters in
neurons and glia – enhances the
effects of GABA at synaptic sites.
USES:
 Simple partial seizure
 Complex partial seizure

31. VALPROIC ACID
 Blocks axonal Na+ channels in inactive state.
 Inhibits GABA transaminase.
 Blocks T-type Ca channels in thalamic neurons.
 USES:
 Simple partial seizures
 Complex partial seizures
 Grand mal seizures
 Absence seizure
 Myoclonic seizure
 Bipolar disorder(mania)
 Prophylaxis of migraine

32.  ADRs:
 Pancreatitis
 Rare but fatal hepatotoxicity
 Neural tube defects, tremor, weight gain

33. ETHOSUXIMIDE
Blocks T-type calcium channels in
thalamic neurons.
USES:
Absence seizure-1st line
ADRs:
 Fatigue,Headache,Urticaria
 Stevens-Johnson syndrome

34. PHENYTOIN
 Blocks axonal Na+ channels in inactive state.
 USES:
 Simple partial seizure
 Complex partial seizure
 Grand mal seizure-1st line
 Status epilepticus-1st line for prophylaxis
 ADRs:
 Gingival hyperplasia
 Hirsutism, Peripheral neuropathy,Nystagmus
 Diplopia,Ataxia, Sedation,Teratogenesis
 Megaloblastic anemia

36.  ADRs:
 SLE-like syndrome
 Induction of CYP450
 Lymphadenopthy
 Stevens-Johnson syndrome
 Osteopenia
FOS PHENYTOIN is a water soluble
prodrug form of phenytoin that is used
parenterally

37. CARBAMAZEPINE
 Blocks axonal Na+ channels in inactive state.
 USES:
 Simple partial seizure
 Complex partial seizure
 Grand mal seizure
 ALL ARE 1ST LINE
 ADRs:
 Hyponatremia
 Stevens –Jophnson syndrome
 Liver toxicity, teratogenesis, ataxia
 Induction of CYP450
 Blood dyscrasias

38. LAMOTRIGINE
Blocks voltage-gated Na+ channels.
USES:
 Simple partial seizure
 Complex partial seizure
 Grand mal seizure
 Absence seizure
ADRs:
 Steven-Johnson syndrome

39. GABAPENTIN
 Primarily inhibits high-voltage activated
Ca2+ channels; designed as GABA
analog.
 USES:
Simple partial seizure
Complex partial seizure
Peripheral neuropathy
Post herpetic neuralgia

40. TOPIRAMATE
Blocks Na+ channels.
USES:
 Simple partial seizure
 Complex partial seizure
 Grand mal seizure
 Migraine prevention

41. LEVETIRACETAM
Modifies the synaptic release of
glutamate and GABA through an
action on vesicular function.
USES:
 Simple partial seizure
 Complex partial seizure
 Grand mal seizure

42. FEBRILE CONVULSIONS
Because of high fever, some children
may develop convulsions. This
should not be called epilepsy.
Kids less than 5 years old, especially
less than a year old (temp. 38.9C)
Treatment includes:
 Control of fever by using
acetaminophen, if necessary,
control seizure by using diazepam
per rectum.

43. QUESTIONS.
Overdose treatment of barbiturate
is supportive, mention ways.
What is Steven-Johnson
syndrome?
Drugs that can cause Steven-
Johnson syndrome.
Which BZDs do not have active
metabolites and involves only
conjugation, preferred in elderly?