cns i drug notes

8/8/2019 CNS I Drug Notes

1/9


2/9


3/9

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)


4/9

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)


5/9

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


6/9

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.


7/9


8/9

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


9/9

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

cns i drug notes

Documents