Why are most unbound, ionized drugs NOT able to penetrate the CNS?
The capillary beds are not leaky enough to permit passage
What is the relative order of permeability of between the placenta, kidney, liver, muscle, and brain?
Liver > Kidney > Muscle = Placenta > Brain
The addition of _________ to the hydrocarbon backbone of chloroform increases the potency and decreases the flammability
Which halogen can participate in H-bonding with O and N?
Which halogenated anesthetic contains bromine?
What is the metabolism of halothane?
20% metabolized in liver and the rest is eliminated via exhalation
Why would you avoid enflurane in labor?
It relaxes the uterus
What are the properties of an IDEAL anesthetic agent?
Rapid, pleasant onset
Adequate relaxation of smooth muscle
Wide margin of safety
Nonflammable and nonreactive
The addition of ________ to the hydrocarbon backbone of anesthetics increases the potency and decreases the flammability
Which halogenated anesthetic undergoes very little metabolism?
Which halogenated anesthetic undergoes extensive metabolism
What opioid analgesic is 50-100X more potent than morphine?
What IV anesthetic is a derivative of fentanyl, is 10X more potent than fentanyl, and has a short onset and DOA?
What class of drugs slow activity in the CNS?
What class of drugs are used to relax, calm, or transquilize?
What class of drugs are used to induce sleep?
What are some characteristics of the IDEAL hypnotic drug?
Gentle decrease in consciousness
No potential to depress respirations
No potential for abuse, addiction, tolerance
What are some problems with barbiturates?
On the barbiturate SAR, all four hydrogens must be _______.
Which hydrogens on the barbiturate SAR must be replaced for activity?
BOTH hydrogens at position 5--then the compound can tautomerize
What does an increase in alkyl length on C-5 of barbiturates do?
It increases the onset and decreases the DOA
What should the total number of carbons be under on barbiturate C-5 chains?
Should be under 9 carbons
_______ groups abolish barbiturate activity
Polar (OH, NH, C=O)
Which intermediate-acting barbiturate has no active metabolites?
What is the onset and DOA of short-acting barbiturates?
What is the Key SAR for tertiary acetylenic alcohols?
An acetylene group
What is the metabolism for all benzodiazepines?
N-dealkylation and hydroxylation
What's special about the metabolism of Quazepam?
The S is lost and replaced with an O to become an active metabolite
Which 1st generation benzodiazepine doesn't have any active metabolites?
Which 2nd generation benzodiazepine has an ultra-short half life due to metabolism to an inactive metabolite?
Which binding site for benzodiazepines produces hypnotic effects?
(BZ-2 produces anxiolytic effects)
What is the metabolism of Zolpidem?
Extensive metabolism to inactive metabolite via CYP3A4 hydroxylation of the aryl methyl groups
What is the metabolism of Eszopiclone (Lunesta)?
The carbamate is hydrolyzed first, then the N makes the compound a hemi-animal which is unstable and falls apart into an inactive metabolite
What class of drug is Ramelteon?
Metatonin receptor agonist
What are some characteristics of an IDEAL anticonvulsant?
Suppress seizures without sedation or organ damage
Well-tolerated and highly effective against various seizures
Rapid onset and long duration
What converts fosphenytoin to its active form?
Is Primidone a prodrug?
Which form of valproic acid derivatives are inactive?
The oxidized forms are inactive
How is Gabapentin transported into the CNS?
Active transport by L-aromatic amino acid transport (LAAT)
What GABA mimetic is used in Europe for alcohol and cocaine abuse?
How does Vigabatrin inhibit the GABA-T?
Where does Pregabalin bind to?
Voltage-gated Ca channels to block release of NTs
Which metabolite of Carbamazepine is active and which is inactive?
What is the metabolism of Felbamate?
Esterase, aldehyde dehydrogenase, aldehyde intermediate, then becomes a Michael acceptor which is toxic
What drug is a GABA uptake inhibitor?
What is the major metabolite of Methocarbamol?
Para-hydroxy substitution of the phenyl ring into INACTIVE compound
What is the metabolic route for Chlorphenesin?
Hydrolysis of the carbamate
Which propanediol carbamate is cyclic?
Which benzodiazepine is also a 2nd-generation SkMR?
Which GABA derivative acts as a GABAb agonist?
How does Dantrolene act?
Direct-acting SkMR that acts peripherally
How does Tizanidine act?
Central alpha2-adrenergic agonist
What is the DA biosynthesis?
L-tyrosine is converted to L-DOPA via tyrosine hydroxylase
L-DOPA is converted to DA via dopa decarboxylase
What drug(s) constitute Levodopa therapy?
Levodopa is used with Carbidopa. Carbidopa inhibits the peripheral decarboxylase activity to allow Levodopa to work in the brain
What is the MOA of Pergolide?
Direct D1 partial agonist and D2 full agonist
How does an inverse agonist benzodiazepine work?
It binds allosterically to induce opposite actions of GABA and block GABA from binding
What are the positions that canbe substituted in benzodiazepines?
1, 2, 2', 3, and 7
What does the addition of a S on the 2 position of a benzodiazepine do?
It decreases the potency, but is further metabolized to an O which increases the potency
What is essential for benzodiazepine activity at the C-5 position?
A phenyl group (with Cl or F substitutions at the 2' position)
Which 1st generation benzodiazepine contains an N-oxide group?
What substitutions on the aromatic ring of Lorazepam make it more potent and lipophilic?
Which benzodiazepine can be dealkylated to Lorazepam?
Which benzodiazepine is 10X as potent as Valium and is known as the date-rape drug?
How is Flurazepam activated?
Substituted with triethylamine that needs to be removed in order to be activated
What is the metabolism of 2nd-generation benzodiazepines?
Benzylic oxidation followed by conjugation
What other indications can Midazolam be used for?
General anesthetics and anticonvulsant
What drug is used as a benzodiazepine antidote?
(When used alone, it has some anxiogenic and pro-convulsant activity
How do azaspirones act?
When full agonists are present, partial agonists must compete with them for receptors. When full agonists are displaced, NT release is decreased. They are considered functional agonists.
Who developed Buspirone?
Dr. Davis Temple
What are analeptics?
Have stimulant effect on the autonomic centers
Where do Xanthine alkaloids work?
Antagonism of adenosine receptors
What is the SAR of beta-phenethylamines?
Branched chain at alpha-position reduces MAO attack
The amine must be basic