Anxiolytics/Sedatives/Hypnotics - Stattery Flashcards
What is the definition of anxiolytic in pharmacology?
- Patient is relaxed
- Unconcerned with his/her surroundings
- Fully functional
What is the definition of sedative in pharmacology?
- Decreased activity
- Moderates excitement and calms patient
- Patient is awake
What is the definition of hypnotic in pharmacology?
- Produces drowsiness
- Facilitates the onset and maintenance of sleep
- Patient may be easily aroused
What is the definition of general anesthesia in pharmacology?
Loss of consciousness from which the patient cannot be aroused.
What factors determine the duration of action of barbituates?
- Absorbed rapidly into the blood PO
- Rate of uptake into brain is dependent on lipid solubility
- high lipid solubility –> 30 sec effect
- low lipid solubility –> 20 min effect
- Major metabolic pathways = oxidation by hepatic enzymes
- The overal rate of hepatic metabolism is usually slow
- elimination half-life (phenobarbitol) = 4-5 days
- Multiple dosing can lead to cumulative effects
- Barbs increase activity of hepatic drug-metabolizing enzymes (esp. phenobarbital)
- may result in an increase in drug’s own hepatic metabolism as well as that of other drugs
What are the three main clinical uses of barbiturates?
- Hypnosis
- Seizure control
- Anesthesia induction
What is the MOA of barbiturates?
- CNS depressant
- Bind to multiple isoforms of GABAA receptor in neuronal membranes in the CNS
- receptor functions as a Cl- ion channel
- activated by the inhibitory NT GABA which hyperpolarizes the neuron
- Increase the duration of the GABA-gated chloride channel openings
- Also depress the excitatory actions of glutamate by binding to the AMPA receptor
Why might changing urinary pH be useful in treating an overdose of phenobarbital?
- Significant percentage excreted unchanged for some barbs (phenobarbital)
- Phenobarbital is a weak acid (pKa 7.4)
- Weak acids are reabsorbed at low pH
- Increasing urinary pH leads to increased drug excretion
- Urinary pH elevated by administering sodium bicarbonate IV in overdose of phenobarbital
In terms of needing an increase in the dose of barbiturates to maintain symptomatic improvement or promote sleep, what is meant by the terms pharmacokinetic/metabolic tolerance and pharmacodynamic tolerance?
- Pharmacokinetic/metabolic tolerance:
- increase in the rate of drug metabolism because barbs increase activity of hepatic drug-metabolizing enzymes
- Pharmacodynamic tolerance:
- changes in responsiveness of the CNS
What is the MOA of benzodiazepines?
- Bind to multiple isoforms of the GABAA receptor
- Enhance GABA’s effects allosterically without directly activating GABAA receptors or opening the associated chloride channels
- Increase in the frequency of chloride channel-opening events
- Increase the efficiency of GABAergic synaptic inhibition
What are the most common adverse effects of barbiturates and benzodiazepines?
- May cause cardiovascular depression in patients with disease that impair CV function (heart failure)
- Toxic doses/Overdose
- myocardial contractility and vascular tone may both be depressed by central and peripheral effects, causing circulatory collapse
- reversible depression of ALL excitable tissue, although CNS is most sensitive
- Compulsive misuse/Dependence
- increased anxiety
- insomnia
- CNS excitability that may progress to convulsions
What are the clinical uses of benzodiazepines?
- Anxiety
- Insomnia
- Seizures
- Muscle relaxation
- Pre-anesthetic medication
- better quality sedation
- more amnesia
- more marked anxiolytic action
- less pain on injection that other drugs
What happens in the biotransformation and excretion of benzodiazepines?
- Hepatic metabolism accounts for the clearance of all benzodiazepines
- Many pharmacologically active metabolites
- some with long half-lives
- can lead to cumulative effects over a course of days
- For most, the water-soluble metabolites are excreted mainly via the kidney
- Unlike barbs, benzos have little impact on hepatic drug-metabolizing enzyme activity with continuous use
What are the advantages of non-benzodiazepine benzodiazepine receptor agonists?
- Rapid onset
- Short duration of action
- No residual effects upon waking up
- Slow tolerance development
- Less psychomotor impairment than benzos
- does not affect driving skills
What drug is a novel hypnotic drug specifically useful for patients who have difficulty falling asleep, works as a melatonin receptor agonist, has no direct effects on GABAergic neurotransmission in the CNS therefore having a minimal potential for abuse and no rebound insomnia or significant withdrawal symptoms, regular use does not result in dependence, and the only adverse effects include dizziness, drowsiness, fatigue, and endocrine dysfunction?
Ramelteon (Rozerem)
