Sedatives/Hypnotics Flashcards
MOA of Benzos and Baribiturates
Benzos–> increase the frequency of Cl- ion channels (by acting on GABAa receptors)
Barbi–> they increase the duration of Cl- ion channel opening (by acting on GABAa receptors)
*barbis block glutamic acid (excitatory transmitter) and at increasing concentrations, chloride channels
How are Benzos metabolized?
mostly in the liver–> converted to active metabolites with long half-lives–> excessive sedation
however, some benzos like Lorazepam and Oxazepam are meatbolaized outside of the liver (Extraheaptic congucation–> no active metabolite)
Adverse effects of Benzos
1) Respiratory depression
2) Cardiovascular and CNS depression
less sever side effects:
1) Nausea
2) Vomiting
3) cognitive impairement
4) Increased reaction time
5) Lightheadedness
Patients taking Benzos may develop Tolerance to the drug, what measurements are taken to reverse this effect?
withdrawal is done slowly by switching the patient to a Benzo with a long Half-life
What pharmacological Agent can be used to treat an overdose of Benzos? what is its MOA?
Flumazenil (BZP Antagonist)
MOA: reverses CNS depressant effect of benzo overdose
- it has no effect on Barbi’s
What are the withdrawal symptoms of moderate Drug use of Benzos?
1) increased sensitivity to light and sound
2) Muscle cramps
3) Dizsiness
4) Anxiety & agitation
5) Myoclonic jerking
6) Sleep disturbance
7) Paresthesias
What are the withdrawal symptoms of high-dose or long-term use of Benzos?
1) Seizures
2) Delirium
Name a few Benzo drugs
1) Lorazepam (sedation)
2) Diazapam (anesthesia)
3) Estazolam (1st choice for insomnia)
4) Midazolam (Anasthesia)
5) Triazolam (insomnia)
6) Oxazepam (sleep disorders)
7) Temazepam (sleep disorders/Anxiety)
Benzos used for Insomnia?
1) Estazolam–> primary insomnia
2) Triazolam
3) Oxazepam
4) Temazepam
- Estazolam and Triazolam cannot be given to patients with liver dysfunction
- Oxazepam and Temazepam are safe to give patients wiht liver problems as they undergo extrahepatic conjugation
New drugs used for insomnia?
Zolpidem
–> Non-BZP agonist at the GABA receptors
What are the adverse effects of Zolpidem?
1) confusion
2) Dizziness
3) Psychomotor depression with less amnestic effects
Indication of Lorazepam?
1) Anesthesia
2) Anxiety
3) Epilepticus
safe to use on patients with liver dysfunction as it undergoes Extrahepatic conjugation
Indication of Diazepam and Midazolam?
Diazepam:
1) Anesthesia
2) Epilepticus
3) muscle relaxant
4) Anxiety
Midazolam:
1) Anesthesia
2) Adjuvant (increase half-life)
*not safe for patients with liver dysfunction as they are metabolized in the liver
Barbi’s block the excitatory transmitter ——— and at increasing concentrations , ————
Glutamic acid , sodium channel
Adverse effects of Barbiturates?
1) Respiratory depression
2) Diarrhea
3) Vomiting
4) Nausea
5) Vertigo
Overdose of Barbi’s result in induction of ——— metabolic enzymes of the liver microsomal enzyme –> ———— can occure
CYP450, Drug interaction
How are Barbi’s metabolized?
Barbiturates are extensively metabolized (exception of phenobarbital)
Barbi used for Anesthesia puroses?
Thiopental
(has short-action)
Name a few Barbiturate drugs
1) Phenobarbital
2) Secobarbital
Indication of Phenobarbital
1) Tonic-clonic seizures in children
2) Epilepticus
3) Sedation
Indication of Secobarbital
1) Acute seizuers
2) Sedation
3) Insomnia
Indication of Buspirone
1) Generalized anxiety disorders
2) Panic disorders (less effective in panic disorders)
MoA of Buspiron
Selective anxiolytic, with minimal CNS
depressant effects.
PK/PD of Buspiron
–> No anti-convulsant or muscle relaxant properties.
–> Interacts with the 5-HT1A receptor as a partial agonist (unknown precise MoA as
anxiolytic).
–> Less effective in panic disorders
Adverse effects of Buspiron
- Tachycardia.
- Paresthesias.
- Pupillary constriction.
- GI distress.
Category of Busprion
Atypical Sedative-Hypnotic, Non-BZP agonist at the GABA receptor
What are the acute pharmacological effects of Ethanol?
1) CNS depression
2) Slurred speech
3) impaired motor function
4) depressed and impaired mental function
5) Respiratory depression
6) cutaneous vasodilation
7) Diuresis
8) GI side effects
9) impaired myocardial contractility
What are the chronic pharmacological effects of Ethanol?
1) Alcoholic fatty liver
2) Alcoholic hepatitis
3) Cirrhosis
4) Peripheral neuropathy
5) alcohol amnesic syndrome
6) Gastritis
7) Pancreatitis
8) cerebellar degeneration
How is alcohol metabolized?
1) Ethanol –> Acetaldehyde by alcohol dehydrogenase and at higher doses of ethanol by microsomal ethanol- oxidizing system (MEOS).
2) Acetaldehyde –> acetate by aldehyde dehydrogenase
What is the pharmacologic basis for using Benzodiazepines to manage alcohol withdrawal?
Both alcohol and Benzos enhance the effect of GABA on GABAa neuroceptors, resulting in decreased overall brain excitibility.
–> this explains why A long-acting benzo (e.g. chlordiazepoxide, diazepam) is given – reduce the dose regimen until no withdrawal symptoms are seen.
withdrawal symptoms of alcohol
1) Insomnia
2) Tremor
3) Anxiety
4) in sever cases , life-threatning seizures and delirium tremens
Drugs used in acute ethanol withdrawal and protect against Wernicke-Korsakoff Syndrome?
Diazepam with Thiamine (IV)
Thiamine–> corrects electrolyte embalance (IV)
