Sedativehypnotics & alcohol Flashcards
what is anxiety
feelings of apprehension, tension, uncertainty, dissatisfaction and fear
what is the best way to treat anxiety
- if secondary to other disorders, best to control primary illness
- other treatments = medication, psychotherapy, cognitive behavioural therapy
what drugs can be used to treat anxiety
- sedative hypnotics: benzodiazapines and barbiturates
- Ethanol (alcohol)
- Canabinoids
what are anxiolitic sedatives
drugs that produce calming effects - releif of anxiety with little or no effect on motor or mental function
dosages of differnt anxiety drugs
barbiturates: dose response more steep - low dose
benzodiazepines: dose response less steed - high dose resposne (more common to treat anxiety)
ethanol: dose response mroe steep - high dose
what is a hypnotic
drug that induces drowsiness and induces sleep
Benzodiazapines - Diazepam (Valium) Pharmacokinetics
- Phase I metabolism - oxidation
- Phase II metabolism - conj. with glucuronide
- first pass metabolism into active metabolite
Benzodiazapines - Diazepam (Valium) action
- enhances GABA neurotransmission
- binds GABAA at site disctinct from GABA
- binding increases frequency of GABA mediated opening of Cl- channel
- requires GABA for effect - does not activate GABA receptor alone
Barbituates - Phenobarbital pharmacokinetics
- Phase I - oxidation
- Phase II - conj. with glucuronide
- increase the expression of some CP450 enzymes
Barbituates - Phenobarbital action
- enhance GABA neurotransmission
- bind to all GABAa receptors at site distinct from GABA and benzo sites
- binding increased duration of opening of CL- channel
- at low doses: enhance effects of GABA
- at high doses: directly activate GABAa and inhibit glutamate receptors
what happens when sedative hypnotics bind to enhance Cl- conduction
increases inhibition of many neurons in the brain (widespread action)
clinical uses for sedative hypnotics
anxiety
insomnia
sedation and amnesia
anesthesia
psychosis (initial management)
muscle relaxation
epilepsy
management of alcohol withdrawal
adverse effects of sedative hypnotics
- dose dependent CNS depression (can lead to death)
- additive CNS depression with other drugs
- symptoms of withdwals when medication stopped after longterm use
- impaired liver function = enhanced toxicity
- extra effect of Barb - alter metabolism of self and other drugs via CP450
how does the endocannabinoid system regulate anxiety
dampens excitatory signals that involve glutamate
characteristics of endocannabinoids
- lipid neuromodulators
- produced on-demand post-synaptically
- acts on CB1 receptor causing inhibition of transmitter release
- rapidly metabolized by FAAH
CB1 receptor
- receptor for cannabinoid found on presynaptic cell
- reduces positive charge in neuron - inhibits Ca2+ coming in and enhances removal of K+
- compounds in marijuana activcate CB1
acute effects of ethanol
- dose-dependent CNS depression
- diuresis
- initial increased then decreased myocardial contraction
- decreased anxiety, slurred speech, impaired judgement
- toxic doses = CNS and respiratory depression
chronic effects
- liver failure
- pancreatitis and gastritis
- malnutrition
pharmacokinetics of ethanol
- 90% metabolized by liver (oxidation)
- major pathway = alcohol dehydrogenase
- minor pathway = MEOS
- clearance rate is constant therefore consumprion of higher quantities cause blood levels ro rise
methanol vs ethanol in the CNS
- same CNS depression mechanisms
- methanol metabolized to formic acid which accumulates in retina and leads to blindness
- treatment for methanol poisoning = ethanol
why is ethanol the treatment for methanol poisoning
- ethanol has a higher affinity for alcohol dehydrogenase so it slows methanol metabolism into formic acid
