Sedatives and Hypnotics Pharm Flashcards
Anxiety vs Fear
Anxiety: Response to ANTICIPATED threat
- May be vague
Fear: A response to an IMMEDIATE, clear and present danger
What are the psychological manifestations of anxiety?
- Negative emotions eg worry
- Arousal
- Lack of concentration
- Insomnia
What are the physical manifestations of anxiety?
- Tachycardia
- SOB
- N/V
- Ulcers (from gastric acid hypersecretion)
- Trembling (due to overactivation of skeletal muscles)
What is the biochemical basic of anxiety?
CNS:
- Main transmitter is noradrenaline/norepinephrine
PNS:
- Main transmitter is adrenaline/epinephrine
Fight or flight response:
- Peripheral noradrenergic/adrenergic activation
Stress response:
- Secretion of cortisol from hypothalamus-pituitary-adrenal (HPA) axis
What is GAD?
- Excessive, uncontrollable worry over everyday matters
~ Interferes with daily functioning - For >6 months
What is the therapeutic rationale of CNS depressants on anxiety?
Need to depress CNS as it is too aroused in anxiety
- Sedatives: Causes relaxation, sedation
- Hypnotics: Induces sleep/drowsiness
~ More depressant effects
~ May have amnestic effects - Anxiolytic: Reduces anxiety
^^ As these drugs are closely related, functions may differ according to dose
- (Least) Anxiolytic/sedative -> Hypnotic -> Anesthesia eg for surgery
What are the main drugs used to treat anxiety?
BZP (main)
- Anxiolytics, sedatives
~ DIAZEPAM, LORAZEPAM
- Hypnotics
~ DIAZEPAM, TRAZOLAM
- Pre-anesthetics
~ DIAZEPAM, MIDAZOLAM
- anti-convulsants
~ Diazepam
Non-BZP
- Barbiturates
~ PHENOBARBITAL
~ ZOLPIDEM
~ BUSPIRONE
~ PROPANOLOL
What is the MOA of BZP?
GABA receptor complex
- 5-peptide complex
~ 1 barbiturate site
~ 1 BZP site
~ 1 GABA site (inhibitory transmitter)
- Chloride channel in the middle
1) When the receptor is empty/ no agonists, it is inactive and the Cl- channel is closed
2) Binding of GABA causes the Cl- channel to open
- Influx on negatively-charged Cl- into the cell reduces membrane potential
~ Leads to hyperpolarisation/reduced inclination of cell depolarisation
~ Firing is slower when Cl- channel is open (depressive effect)
3) Binding of GABA is enhanced by BZP
- Greater entry of Cl- ion
IMPT:
What is the duration of action of BZP?
Short acting (3-8 hrs)
- Midazolam
- Triazolam
Intermediate-acting (10-20 hrs)
- Lorazepam
- Temazepam
- Alprazolam
Long-acting (1-3 days)
- Diazepam
- Flurazepam
- More for chronic symptoms, none used for surgery
What are the adverse effects of BZP?
1) Acute toxicity / overdose
- Can cause severe respiratory depression
- Treatment by FLUMAZENIL
2) Drowsiness, confusion, amnesia
3) Impaired muscle coordination
4) Tolerance may develop faster for epilepsy use than sleep
5) Dependence may develop
- Withdrawal effects eg insomnia, rebound anxiety, tremor, convulsions
- Has addiction potential
What are the MOA of non-BZP?
1) Barbiturates
- Potentiates GABA-mediated Cl- but at a different site from BZP
- Not used as often anymore due to tendency to develop tolerance and dependence
~ Replaced by BZP
~ Severe withdrawal symptoms
~ Flumazenil not effective in treating barbiturate overdose
- At anesthetic doses, bbt such as PHENOBARBITAL can directly open Cl- channels and block Na+ channels
2) ZOLPIDEM
- Potentiates GABA at the same site as BZP
- Good hypnotic effect
~ Treats insomnia
- Not as effective as anxiolytics
3) BUSPIRONE
- Serotonin-5HT receptor agonist
- Binds to dopamine receptors
- Indicated for GAD but anxiolytic effects take 1-2 weeks
- Lacks anticonvulsant and muscle relaxant properties
~ As there is no GABA binding
4) PROPANOLOL
- Beta-adrenergic receptor antagonist
- To treat performance anxiety and social phobias
- Reduces physical symptoms associated with adrenergic activation
- Contraindicated in px with:
~ Asthma (will cause bronchoconstriction)
~ Heart conditions (b-blockers make the heart work less optimally)
What is the duration of action of barbiturates?
Ultrashort (20 mins)
- eg Induction of anesthesia
- THIOPENTAL
Short (3-8 hrs)
- Sedative and hypnotic
- PENTOBARBITAL
- AMOBARBITAL
Long acting (1-2 days)
- Anticonvulsant
- PHENOBARBITAL
What is the dose-dependent depression of CNS?
Sedation/disinhibition/anxiolysis -> Hypnosis -> Anesthesia -> Medullary depression -> Coma
Barbiturates
- Linear
- Increases to the point of coma
BZP:
- Log graph
- Plateaus at anesthesia and medullary depression
