Depressants Flashcards
Inhibitory amino acids
GABA and glycine
Excitatory amino acids
glutamate and aspartate
Benzodiazepine drugs naming:
end in -pam or -lam except clorazepate
selective depressants are
sedative hypnotics aka: benzodiazepines barbiturates ethanol
non-selective/general depressants:
antihistamines
opioid analgesics
sedative anxilytics - what effect?
- exert a calming effect or sedation with concomitant relief of anxiety at relatively low doses
- depressant effects on psychomotor and cognitive functions
hypnotics - what effects?
- agents that produce drowsiness and encourage the onset and maintenance of sleep
- hypnotic effects: more rapid onset of sleep; increased duration of stage 2NREM; dec duration of REM and stage 4 NREM
anxiety brain regions affected;
- limbic
- amygdala - fear
- hipocampus mood emotion memory
- prefrontal cortex - cognitive function
Anxiolytic agent groups:
- benzodiazepine sedative hypnotics
- benzodiazepine anxiolytic
- benzodiazepine like (Z-drugs)
- serotonin agonists (5HT1A)
- beta blockers
Benzodiazepine sedative hypnotic drugs:
- flurazepam
- temazepam
- triazolam
- midazolam
benzodiazepine anxiolytic
anxiolytic at low dose - at high dose same sedative hypnotic
- alprazolam
- clorazepate
- diazepam
- lorazepam
- oxazepam
benzodiazepine like (Z-drugs)
- *-zolpidem
- *-eszopiclone
-zaleplon
anxiolytic serotonin agonist?
buspirone
anxiolytic beta blocker?
propanolol
Depressant agent groups:
barbiturates
antihistamines
melatonin agonists
alcohols
barbiturate drugs?
phenobarbital - LONG ACTING
pentobarbital
thiopental - SHORT ACTING
antihistamine drugs?
hydroxyzine
diphenhydramine
melatonin agonist drugs?
ramelteon
alcohol drugs?
durrrp - ethanol
dosing of sedative - hypnotics?
graded dose dependent depression of CNS:
- sedation or sleep
- anesthesia or coma
- respiratory depression and death
barbiturates and alcohol dose effects:
LINEAR relationship bw inc dose and more intense effect - less drug needed to get more intense effect (coma and death)
benzodiazepines and newer hypnotics dose effects:
NON LINEAR SLOPE- relationship bw dose and effect tapers off about anesthesia level so need WAY higher dose to get super intense effect = SAFER TO USE
**sedative-hypnotics - uses?
- *1) relief of anxiety
a) primary:GAD,panic, OCD, PTSD
b) seconday:acute MI, GI ulcers - *2) relief of insomnia
3) sedation and amnesia
4) tx of epilepsy and seizures
5) control of ethanol of other sedative hypnotic withdrawl states
6) muscle relaxation
most commonly used sedative-hypnotics?
benzodiazepines
What is required for benzodiazepine sedative-hypnotic activity?
need electronegative substituent in the 7th position (halogen or a nitro group)
*benzodiazepines - pharmacokinetics:
1) absorption: ORAL;
2) metabolism: LIVERCYP3A4+glucuronidation
a) inactive water soluble (3-OH benzos) glucuronides - rapid metabolism and no activity (lorazepam and oxazepam)
b) weakly active, short lived active metabolites - short duration and metabolites have little clinical significance (alprazolam and triazolam)
c) long lived and active metabolite - 2-keto benzos - ALL EXCEPT: lorazepam, oxazepam, alprazolam, and triazolam - ACTIVE and last a while
Inactive water soluble glucuronide drugs? means what?
- lorazepam and oxazepam
- rapid metabolism
These two have dosing that is NOT dependent on age 3-OH type
weakly active, short lived active metabolite drugs? means what?
- alprazolam and triazolam
- short duration, metabolites dont do much
long lived and active metabolite drugs and means what?
- ALL EXCEPT: lorazepam, oxazepam, alprazolam, and triazolam
- long duration?
short acting benzodiazepines: LESS THAN 5 HRS
midazolam
triazolam
intermediate acting benzodiazepines:
5-24HRS
- alprazolam
- lorazepam
- oxazepam
- temazepam
estazolam
clonazepam
long lasting benzodiazepines:
LONGER THAN 24HRS
- clorazepate
- diazepam
- flurazepam
chlordiazepoxide
prazepam
quazepam
metabolism age and benzodiazepines:
- older people have altered metabolism
- inc in age related to: dec lean body mass; inc Vd for many lipid soluble drugs; decreased rate of elimination
Which drug(s) have dosing that is NOT dependent on age?
3-OH type - oxazepam and lorazepam
Ke independent
Which drug(s) have dosing that IS influenced by age?
2-keto type - diazepam
Ke dependent
**benzodiazepines MOA?
- potentiate effects of GABA at the GABA_A receptors (CL ion channels)
- *** inc frequency of opening and conductance of the Cl channels - bind to BZ sites bw alpha1 and gamma2 subunits to open cahnnels –>influx of Cl –> inc membrane hyperpolarization and overall neuronal inhibition ==potentiate GABAergic inhibition at all levels of the neuraxis
alpha1 GABA_A receptor subtype is responsible for what effects?
- sedation
- anticonvulsant action
- anterograde amnesia
alpha 2 GABA_A receptor subtype is responsible for what effects?
-anxiolysis
*Benzodiazpines - side effects and toxicity:
1) drowsiness and sedation-impaired judgement and confusion
2) ataxia - poor motor coordination
* *3) respiratory depression - dose related - can be lethal if combined with other depressants ex alcohol!**
4) anterograde amnesia - date rape drugs - flunitrazepam
* **5) tolerance (sedative effects) takes 12-14 days to get tolerance
* **6) dependence-physical and physiological - withdrawl
7) dizziness, headache, nausea
date rape drug and drug type?
flunitrazepam - benzodiazepene
Lots of dependence/withdrawl with use of this drug type?
benzodiapenes
benzodiazepines - contraindications:
- pregnancy
- elderly (altered metabolism = increased sensitivity)
- substance abuse concern
- sleep disorders
- when alertness is requried
Benzodiazepines - drug interactions:
- ***1) additive CNS depression: ethanol, opioids, anticonvulsants, phenothiazine, antihistamines, TCA
2) cimetidine, erythromycin - carbamazepine, rifampin, phenytoin
3) estrogens
4) antacids
5) flumazenil
benzodiazepines - therapeutic uses:
- **1) anxiolytic- relieve anxiety
- **2) sedative-hypnotic - relief of insomnia
3) conscious sedation - medical procedures
4) antispasmodic - muscle relaxant
5) Acute alcohol withdrawl
6) agitated patients
7) panic attacks
8) depression
9) bipolar
10) seizures
benzodiazepine antagonist
- drug?
- MOA?
- metabolism?
- effects?
- uses?
- flumazenil
- competitive inh binds to BZ receptor - REVERSE EFFECTS OF BENZODIAZEPINES
- rapidly abs via IV - short duration (~2hrs)- metabolism by liver
- generalized CNS arousal and anxiogenic
- -uses: Terminate benzodiazepine induced sedation; diagnosisa nd Tx of benzodiazepine tox
reverse effects of benzodiazepines or benzodiazpine related newer hypnotics with what drug?
flumazenil
Benzodiazpeine related newer hypnotics (Z-DRUGS)
- *-drug names:
- clinical use?
- MOA?
- pharmacokinetics:
- **-eszopiclone, zolpidem
- -management of insomnia
- selectively bind to BZ receptors on GABA_A receptor and is agonist (only to Alpha1 subunit)
- rapidly acting
- short duration -rapid metabolism with in-active metabolites
-also reversed by flumazenil
Barbiturates
- drugs names?
- clinical uses?
phenobarbital
pentobarbital
thiopental
anesthesia, sedative/hypnotic, anticonvulsant, medically induced coma –> OLDER AND NOT REALLY USED ANYMORE
phenobarbital used mainly for what?
anticonvulsant
pentobarbital used mainly for waht?
medically induced coma
thiopental used mainly for what?
anesthesia
barbiturates - pharmacokinetics:
- absorption and distribution - varies with lipid solubility
- metabolism - liver and is slow - has NO active emtabolites unlike benzos
- excretion - via kidney - needs to be metabolized except phenobarbital to some extent
- duration of effect - depends on metabolism except thiopental where redistribution limits duration
barbiturates vs benzodiazepines MOA
- benzos increase freqency of opening of the GABA gated Cl channel
- barbsopen the same channel for longer
Barbiturates MOA:
***-inc the duration of the GABA-gated chloride channel opening
= membrane hyperpolarization
=neuronal inhibition
Ultra short acting - intermediate - long acting barbiturates:
short=thiopental
med=pentobarbital
long=phenobarbital
- melatonin receptor agonist
- drug name?
- use?
- MOA?
- metabolism?
- *-ramelteon
- *-induces sleep onset if pateint cant falls asleep - no dependence!
- -MOA: melatonin receptor agonist - MT1 (sleep onset); MT2 (circadian pattern)*
- met: extensive first pass - active met with even longer t1/2
serotonin receptor agonist:
- drug name?
- use?
- MOA?
- metabolism?
- AE?
-buspirone
-non-sedating anxiolytic - less psychomotor impairment compared to benzos - does not affect driving skills! little abuse potential
NO AMNESIA OR MUSCLE RELAXATION
-MOA: Partial agonist at 5HT1A receptors (autoreceptors)
-Met: 2-4 halflive - extensive first pass
-nonspecific chest pain, tachycardia, palpitations, dizziness, nervousness, tinnitus, GI distress
- *beta blockers
- Drug name?
- uses?
- propranolol
- NOT an anxiolytic but diminishes some of the somatic manifestations of anxiety
- *antihistamines
- drug names
- use?
- hydroxyzine, diphenhydramine
- used as mild sedative/relaxant for procedures
- anxiolytic via sedative action
carbamates - dont worry so much here
- drugs?
- use?
- meprobamate
- CNS acting muscle relaxant
- like intermediate acting barbs - potential for abuse
- alcohols:
- drugs?
- uses?
- ethanol
- anxiolytic via sedative action
- ethanol is probably the oldest and most commonly used anxiolytic
