2. Anti-anxiety, Sedative, Hypnotic Drugs Flashcards
Increasing Levels of CNS Depression • Anxiolysis – take the \_\_\_\_ off • Sedation – feel \_\_\_\_ • Hypnosis - induce sleep but \_\_\_\_ • General Anesthesia – A \_\_\_\_ state of patient unresponsiveness, analgesia and muscle \_\_\_\_ that allows the goals of surgery to be accomplished
edge drowsy rousable pharmacological relaxation
Uses of ASH Drugs in Dentistry
• ____ before so anxious patient gets good night of sleep
• ____ patient both before and during procedure
• Muscle relaxation as in ____ patient
night
calm
TMD
Categories of ASH Drugs • Barbiturates • Benzodiazepines • Carbamates • Antihistamines (H-1 receptor blockers) • Alcohols • Others
Barbiturates are rarely used today
◦ They have a ____ therapeutic index (about 4-10), easy to unintentionally overdose
‣ Benzodiazepines have a ____ therapeutic index (about 20-60) so they’re used more often
• BTW, if you take these with alcohol of opioids, all bets are off
• The higher the therapeutic index, the safer the drug is
Carbamates are highly promoted as muscle ____
◦ Flexeril (cyclobenzaprine) was one of the few drugs that has shown, in a clinical trial, some efficacy in ____ pain. but there’s a lot of side effects.
low
higher
relaxant
musculoskeletal TMJ
Antihistamines. This makes sense. ◦ They've shown up in Parkinson's and an alternative for patients with local anesthetic allergy ◦ They are \_\_\_\_, pediatric dentists love them ◦ [tells story about his grandson taking this for tx] ◦ BTW, if a kid is totally uncooperative, you gotta bring them to the OR ‣ Otherwise, all you end up doing is throwing too many drugs into them which can get you in trouble, like the kid stops breathing
Alcohols. This makes sense, having a glass of wine is a little sedating
◦ ____ is an old drug that pediatric dentists use. It goes on and off the market
‣ It’s related to an industrial solvent, ____
• In a test tube, trichloroethylene is mutagenic
◦ But guess what? If you put a Coors Light in a test tube, that’s mutagenic too “There’s a couple of Others that I may mention…”
sedating
chloral hydrate
tricholorethylene
Barbiturate Structures
• These are some of the classic Barbiturates
◦ [red circle] This makes it a barbiturate, this is the barbiturate ____
• ____ was mainly used to knock people out, but there are drugs with better therapeutic indices
• If a patient is on chronic Phenobarbital, what do they probably have?
◦ ____ disorder, that’s its major use
◦ It kinda makes sense that drugs that dull the brain have anti-seizure activity
‣ BTW, these more-so than opioids because these indirectly affect ____ channels
nucleus
thiopental
seizure
chloride
Barbiturate vs. Benzodiazepine Dose Response Curves
The dose response curve for a ____ (Phenobarbital) is much steeper than a ____ (Diazepam or Midazolam)
◦ With a barbiturate, it’s much ____ transition to transition from Sedation and Hypnosis into Coma and Death
BTW, the type of respiratory depression you get from barbiturates is usually a little different than opioids
◦ With opioids, you’re not responding to ____
◦ With barbiturates, you tend to lose ____ reflexes, like the ability to keep the airway open
• Benzos have a much ____ dose response curve
◦ Easier to stay in
Sedation/Hypnosis and not
bring pt to Coma/Death
◦ This is another way to show how ____ have a higher therapeutic index
barbiturate benzodiazepine easier CO2 protective flatter benzos
Other Barbiturate Limitations
• ____ and physical dependence can rapidly appear
• Withdrawal if dependent is life-threatening-____
• Some drugs DEA schedule ____–seco and pento
• Lots of drug interactions –____ inducers
• Depress ____ sleep
• No ____ for overdose
• ____ compounds
tolerance seizures 2 CYP REM antagonist hyperalgesic
Molecular Pharmacology Differences Between Benzodiazepines and Barbiturates/Alcohols
• Benzodiazepines increase frequency of ____ channel openings
• Barbiturates and alcohols:
– increase duration of ____ channel opening
– physically open ____ channels w/o ____
– depress action of excitatory amino acids like ____
chloride chloride chloride GABA glutamate
Thiopental (Pentothal®) and Methohexital (Brevital®)
- Given for ultrashort acting ____
- “Cocktailed” with other intravenous sedation drugs to produce deep ____ or twilight anesthesia
- No ____ agent (no antagonist)
- More about these in injectable GA lecture
general anesthesia
sedation
reversal
Secobarbital (Seconal®) and Pentobarbital (Nembutal®)
• Available ____ and intravenous formulations
• DEA Schedule ____ drugs
• ____ therapeutic index
– Therapeutic blood levels = ____ ug/ml
– Coma/respiratory depression = ____ ug/ml
oral and intravenous 2 low 1-3 10
Phenobarbital (Luminal®)
• Considered ____ in class
– Therapeutic blood levels – ____ ug/ml
– Coma/respiratory depression – ____ ug/ml
- DEA Schedule ____
- Major use today is in control of ____ disorders
- Chronic use can produce both ____ and pharmacodynamic tolerance
safest
5-10
50
4
seizure
metabolic
Benzodiazepines
- diazepam
- midazolam
- triazolam
- flumazenil (benzo antag)
- benzos- main reason replaces barbs as anti- anxiety sedative hypnotic drugs (hypnotic–> sleeping aid) is bc they’re ____ is much higher if you take them alone of 20-50
- even w the most powerful need a 20 fold OD to get into trouble. If drink w booze and opioids all bets are off. then you may have additive effects (1+1= 20)
- for benzo to be agonist- need bottom 6 membered ring * points to the arrows*. won’t have to draw structures, just get CONCEPT!
- btw the benzo antagonist ____- for diazepam, mid, triaz. BUT doesn’t have the bottom ring and its ____ on the side chain (why its an antagonist) binds receptor but doesn’t activate it
- naloxone (morphine, fentanyl, heroin)
TI
flumazenil
bulky
Benzodiazepines
• the other thing you can do w this is add more HALOGENS (Cl, Fl) –> increase ____ and ____! doesnt mean better just need less
• ex. IV sedation of diaz. diff for everyone cuz titrate to effect, usually 10-12 mg vs mida. 3-4mg (3x more powerful, doesnt mean its better). like oxycodone and coding (oxy is just more powerful)
• add 5 membered ring–> decrease production of ____ metabolites
• diaz.- 1/2 life in young adult of 24 hrs, but few ____ metabolites (methydiazepam, oxazepam–> extent duration of action). take to prevent seizures then its good just 1 dose vs pt for dental appt its bad (tired all day)
• triaz.- orally taken over. also w potency- halogenating, oral dose of diaz. in an adult (for anxiety) need 5-10mg vs .25-.5mg-
triaz. that additional Cl makes the difference.
lipid solubility
potency
active
active
- EXAM: ask- what could flumazenil fix an OD of? ____, ____, ____
- what wouldn’t it reverse? pick answer thats not a benzo
diazepam
midaxolam
triazolam
Advantages of Benzodiazepines vs. Barbiturates 1
• Much ____ therapeutic index
• More ____ than barbiturates as anti- anxiety agents
– In animal studies doses needed to calm animal 1/10 that needed to induce ataxia and sleep
– With barbiturates in animals see ____ and sedation with anti-anxiety doses
higher
selective
ataxia
