cns i drug notes
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Nonopioid Centrally Acting Analgesics MOA
Relieve pain by mechanisms largely or completely unrelated to opioid
receptors; do not cause resp depression, dependence, or abuse.Tramadol: WEAK agonist of mu rec. mostly works by blocking uptake of NE and
5HT3 thereby activating the monoaminergic spinal inhibition of pain.
Naloxone will partially block Tramadols effect.
Clonidine: Pain relief is delivered through continuous epidural infusion.
Relieves pain by binding to pre & postsynaptic 2 rec in the spinal
cord & blocks pain signals from the periphery to the brain.
Ziconotide: Centrally acting analgesic w/ intrathecal admin. NOT 1st
line agent
due to adverse rxn (hallucinations, confusion, muscle injury)
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Muscle Relaxants MOA (says he wont ask MOA) Adverse Effects Uses/Other2 Groups:
For Muscle Spasm (1) Unclear. May result primarily
from sedative properties, not by
specifically controlling muscle
tone.
Used to relieve localized spasm
resulting from muscle injury. Not
used for spasticity or other
muscle disorders resulting from
CNS pathology (except Diazepam).
Diazepam (Valium) Promotes presynaptic inh by
enhancing effects of GABA
CNS depression sedation,
lightheaded, dizzy; physicaldependence with life-threatening
withdrawal if not done slowly
(see above)not muscle relaxer is
benzodiazepine; can give you high
Tizanidine Agonist at the presynaptic 2 rec Same as above + hepatotoxic
check LFT prior to use.
(see above)
Metaxalone Also hepatotoxic
Chlorzoxazone Marginally effective & can cause
fatal hepatic necrosis
Others: Cyclobenzaprine, Cyclo: causes marked drowsinessCarisoprodol, Methocarbamol Caris: just became ctrled subst.
Orphenadrine, Baclofen
Drugs for Spasticity (2) Used for movement disorders of
CNS origin (spasticity); disorders
w/ heightened muscle tone,
spasm, & loss of dexterity
Baclofen Acts w/in the spinal cord tosuppress hyperactive reflexes
involved in reg of muscle movemt
Abrupt d/c of intrathecal dose cancause rhabdomyolysis, multi-
organ failure, death
MS, usually SCI, cerebral palsy
Diazepam (listed in 1st
group) (listed in 1st
group) Preferred in pts w/ marginal
strength
Dantrolene Acts directly on skeletal muscle;
does not allow muscle to
contract; can decrease strength
Hepatotoxicity MS, SCI, cerebral palsy; treats
malignant hyperthermia (life-
threatening increase in temp)
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Sedative-Hypnotics:
Class & Specific Agents MOA Adverse Effects Uses/OtherBarbiturates Bind to and enhance GABA rec
Thiopental, Secobarbital
Phenobarbital
High abuse potential; rarely used
anymore
Strong resp dep, tolerance,
dependence, DOC for suicide
dec response to other drugs (inc
hepatic synthesizing enzymes)
Benzodiazepines
Diazepam, Lorazepam,
Midazolam, Clonazepam,
Clorazepate, Alprazolam
Enhance effects of GABA Confusion, anterograde amnesia Uses: anxiety, insomnia, general
anesthesia, seizure disorders,
muscle spasm, panic disorders,
alcohol withdrawal
Benzo-like Drugs
Zolpidem (Ambien)
Enhances GABA, but does not
bind to benzo receptors
Some daytime drowsiness insomnia
Eszopiclone (Lunesta)CIV E: only drug with no limit to how
long it can be taken
Pyrazolopyrimidines
Zaleplon (C IV)
Works the same way as zolpidem
but quick onset and short DOA
Approved only for short-term
insomnia
Melatonin Agonist
Ramelteon
Activates MT1 & MT2 rec for
melatonin; can inc levels of
prolactin & dec levels of
testosterone
Amenorrhea, Galactorrhea,
reduced libido, fertility problems
Avoid during preg/lact
Miscellaneous Sed-Hyp
Chloral Hydrate (C IV) CNS dep similar to barbs Tolerance, withdrawal w/ sleep
disruption and nightmares
Prodrug that is rapidly
metabolized to active form in liver
Trazodone Used for induction of sleep
Antihistamines
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Benzodiazepines
Classification benzodiazepines
Drug Names Diazepam, Lorazepam, Midazolam, Clonazepam, Clorazepate, Alprazolam, Triazolam, Oxazepam
MOA (brief) Potentiate the actions of GABA (intensify GABAs effects only, not direct GABA agonists)
MOA (detailed) Enhance the actions of GABA by binding to specific rec in the supramolecular structure known as the GABA rec-
chloride channel complex. Since the amount of GABA in the CNS is finite, there is a built-in limit to the depth of CNS
depression the benzodiazepines can produce. This is why they are much safer than barbiturates, which directly
mimic GABA. Benzos readily cross the bbb (lipid soluble). Benzos metabolites are pharmacologically active, so the
effects of the drugs persist long after the parent drug has disappeared.
Pharmacology Reduce anxiety; Promotes sleep; induce muscle relaxation
Dosage/Route PO (have no effect on heart & bv); IV (can produce profound hypotension and cardiac arrest); all benzos can be PO
Adverse Effects Confusion; anterograde amnesia (impaired recall of events that take place after dose) especially w/ Triazolam;
may exacerbate obstructive sleep apnea (OSA); CNS depression with little to no resp dep; paradoxical effects:
insomnia/excitation, euphoria/heightened anxiety & rage; abuse; death from OD has never been documented
When is it used? Anxiety; insomnia; induction of general anesthesia (D,L,M)M is for conscious sedation; seizure disorders (D, L, clona,
clora); muscle spasm (D); panic disorder (A, L, clona); withdrawal from alcohol
Metabolic Effects Certain benzos go through very little hepatic metabolism & can be used in pts w/ liver disease (L,O,T)
Selective Uses Triazolam sleep (b/c rapid onset); Estazolam for someone waking up after falling asleep (slower onset);
Lorazepam (L,O,T) good in elderly b/c it does not accumulate w/ repeated dosing
Overdose - Gastric lavage followed by activated charcoal & saline cathartic & possibly dialysis if Sx are severe.- Flumazenil: competitive benzo rec antagonist & will reverse sedative effects but NOT resp dep. Give IV
slowly over 30 seconds and can be repeated every min PRN. 1st
dose is 0.2 mg, 2nd
dose 0.3 mg 3rd
dose and
all subsequent doses are 0.5 mg.
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AntiepilepticDrugs (AED):
AEDs can suppress discharge of neurons within a seizure focus and suppress propagation of seizure activity from focus area to other areas.
AEDs act through 4 basic mechanisms:
1. Suppression ofNa+ influx: bind to Na+ channels while they are in inactivated state to prolong channel inactivation, thus decreasing theability of neurons to fire at high frequencies. (seizures that depend on high frequency discharge are suppressed)
2. Suppression of Ca2+ influx: calcium influx promotes NT release at axon terminal. Block Ca2+ = block transmission.3. Antagonism ofGlutamate: glutamate is primary excitatory NT in CNS. Block its receptors=suppression of neuronal excitation.4. Potentiation ofGABA: decrease neuronal excitability and suppress seizure activity
Seizure Type Traditional AEDs Newer AEDs
Partial: Simple, complex, and secondary
generalized
Carbamazepine
Phenytoin
Valproic Acid
Primidone
Oxcarbazepine
Gabapentin
Lamotrigine
Levetiracetam
Pregabalin
TopiramateTiagabine
Zonisamide
Primary Generalized:
Tonic-Clonic
Absence
Myoclonic
Same as above & Phenobarbital (rarely)
Ethosuximide (DOC)
Valproic Acid (obtain baseline LFTs)
Valproic Acid
Lamotrigine
Topiramate
Lamotrigine
Topiramate
**red = drugs that suppress Na+
influx. **blue =drugs that suppress Ca++
influx. **green=glutamate antagonist also Felbamate (not listed)
***Valproic Acid has 3 MOAs: sodium, calcium, and GABA
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AEDs that potentiate the effects of GABA:
1.
Barbiturates2. Benzodiazepines3. Gabapentin4. Tiagabine5. Vigabatrin
Phenytoin
Classification AED (most widely used and 1st drug to suppress seizures w/out depressing the entire CNS
MOA (brief) Blockade of hyperactive Na+
channels
Therapeutic Range NARROW (the capacity of the liver to metabolize phenytoin is very limited)
Adverse Effects Gingival hyperplasia (excess swelling, tenderness, bleeding of gums 20% and can be reduced w/ proper hygiene)
Drug Interactions INC plasma levels: Diazepam, Valproic Acid, alcohol (acute). DEC plasma levels: Carbamazepine, phenobarbital,alcohol (chronic)
When is it used? Epilepsy, Cardiac Dysrhythmias
Metabolic Effects life shortens the longer the pt takes the drug