sedative and hypnotic

what are sedative and hypnotic drugs?

they are CNS depressants used to induce sedation, promote sleep and reduce anxiety

are they prescribed in dentistry?

yes in cases such as extreme fear and anxiety

what is the goal of sedative-hypnotics in dentistry?

to remove the anxiety and fear in patients who need it as for a lot of people dental clinics are considered to be stressful situations

how is diazepam given for patients who extreme fear and anxiety over dental appointments?

1 pill before the night of the appointment and 1 pill one hour before the appointment

what does sedation cause?

drowsiness, decreased reaction time

when dose is increase, what hypnotic effects cause?

promotes sleep and confusion and patient is unconscious, however any stimuli will wake them up. if dose is increased, anesthetic effect will be achieved. any higher, death or coma will happen

how are sedative-hypnotics classified?

• barbiturates (phenobarbital, thiopental)

• benzodiazepines (diazepam, alprazolam, midazolam, clonazepam and chlordiazepoxide)

• z-drugs, nonbenzodiazepine drugs (zolpidem, zopiclone)

what is an example of a long-acting barbiturates?

phenobarbitone

what is an example of a short-acting barbiturates?

• butobarbitone

• pentobarbitone

what is an example of a ultra short-acting barbiturates?

• thiopentone

• methohexitone

what are examples of hypnotic acting benzodiazepines?

• diazepam

• flurazepam

• nitrazepam

• alprazolam

• temazepam

• triazolam

what are examples of antianxiety acting benzodiazepines?

• diazepam

• chlordiazepoxide

• oxazepam

• lorazepam

• alprazolam

what are examples of anticonvulsant acting benzodiazepines?

• diazepam

• lorazepam

• clonazepam

• clonazepam

• clobazam

are barbiturates or benzodiazepines prescribed in dentistry?

benzodiazepines

what is thiopental used for?

general anesthesia. it is use via IV only

what is phenobarbitone used for?

used in epilepsy (grand-mal or tonic-clonic convulsions)

what is chlordiazepoxide used to treat?

IBS

what is burning mouth syndrome?

a chronic, painful condition causing a burning, scalding, or tingling sensation in the mouth which is common in postmenopausal women

what can be prescribed to treat burning mouth syndrome?

clonazepam, via 2mg tab. 1×1×30 days (2mg tablet once a day once daily for 30 days)

what is the trade name for diazepam?

valium

mechanism of action of benzodiazepines

• they bind to the benzodiazepine site on the GABA_A receptor

• does not activate GABA receptor and it requires GABA neurotransmitter to be present

• potentiates or enhances GABA’s actions by increasing the frequency of Cl^- channel opening, increasing Cl influx, trigger neuronal hyperpolarization, which decreases neuron excitability and enhances GABA mediated inhibitory neurotransmission

what are the clinical effects of benzodiazepines?

• α1 (isoform 1): has sedative, hypnotic, anticonvulsant and amnesia effects

• α2 (isoform 2): has an anxiolytic or antianxiety effect

• α3: muscle relaxation

• α4: learning and memory (amnesia / cognitive effects)

what is the mechanism of action of barbiturates?

• bind to a different site on GABA receptor

• enhance GABA by increasing the duration of Cl channel opening

• at high doses, they can directly activate GABA_A receptor even without GABA neurotransmitter present

• excessive Cl^- present → profound hyperpolarization → generalized CNS inhibition

what is the clinical significance of the MOA of barbiturates?

greater risk of respiratory depression, coma and fatal overdose compared to benzodiazepines, which is why they’re not preferred for use in dentistry

which has a higher safety margin?

benzodiazepines, as at high doses, barbiturates are extremely lethal at high doses and cause generalized CNS inhibition

absorption of benzodiazepines and barbiturates

all absorbed well from GIT

what benzodiazepine is given IV only?

remimazolam

which barbiturate is given IV only?

thiopental

distribution of benzodiazepines and barbiturates

distributed well across all tissues. crosses BBB, placenta and are secreted in milk

how does redistribution occur in benzodiazepines?

highly lipid soluble drugs, such as diazepam

how does redistribution occur in barbiturates?

highly lipid soluble drugs, as in thiopental

where does metabolism of benzodiazepines occur?

in the liver via oxidation, with active metabolites and conjugations

where does metabolism of barbiturates occur?

liver, forming inactive metabolites.

most barbiturates are what?

microsomal enzyme inducers, especially phenobarbitone

where does excretion of benzodiazepines and barbiturates occur?

via renal

when does antianxiety effect of barbiturates and benzodiazepines occur and which is preferred?

in small doses, and benzodiazepines are preferred as they are stronger and safer

when does hypnotic effect of barbiturates and benzodiazepines occur and which is preferred?

in larger doses and benzodiazepines are preferred as barbiturates are dose-dependent

what barbiturate has an anesthetic effect?

thiopental, used via IV and is an ultra short acting anesthetic

which benzodiazepine has an anesthetic effect?

midazolam via IV and is a short acting anesthetic

what effect do barbiturates and benzodiazepines have on skeletal muscles?

they relax them

what barbiturate is used for its anticonvulsant effect?

phenobarbitone which is used in grand mal epilepsy, also known as tonic-clonic convulsions. does generalized CNS inhibition

what benzodiazepine is used for its anticonvulsant effect?

clonazepam which is used in petit mal epilepsy, also known as absence seizures

what is the effect of barbiturates on body systems?

it depresses them all EXCEPT for the liver (induces it)

what type of amnesia do benzodiazepines cause?

anterograde amnesia, which blocks you from making memories during the drugs duration

what are the therapeutic uses of phenobarbital?

• treatment of grand mal epilepsy (tonic-clonic seizures)

• treatment of neonatal jaundice by activating liver enzymes (bilirubin)

what are the therapeutic uses of thiopental?

it is used as an ultra short anesthesia via IV in short procedures

what are the therapeutic uses of benzodiazepines?

1. anxiety disorders such as generalized anxiety disorder (GAD), panic attacks and social phobia. if it persists after 6 weeks of use, SSRIs are used instead

2. insomnia

3. anticonvulsants

4. short surgical procedures

which benzodiazepine is used for insomnia?

temazepam

which benzodiazepine is used as anticonvulsant?

clonazepam is used in treatment of absence seizures in children, and diazepam is used in management of febrile seizures via rectal route

which benzodiazepine is used for short surgical procedures?

midazolam

what are the general adverse effects of barbiturates and benzodiazepines?

1. tolerance and physical dependence due to decreased sensitivity of GABA receptors

2. rebound insomnia after discontinuation

3. hangover, which is a state of psychomotor depression occurring the following day, known as the residual effect

what is an adverse effect of barbiturates?

respiratory and myocardia depression

what is an adverse effect of benzodiazepines?

memory disturbance

what has been studied for the conscious sedation in a mentally retarded dental patient?

propofol and midazolam

which benzodiazepine can be given for reduction of dislocation temporomandibular joint TMJ?

midazolam paired with propofol