CNS Pharm Flashcards by Levi Daugherty

Triptans

Suma, riza, zolmi, nara, almo, etc.. are the first line Tx for severe migraines.

Affect the 5-HT1B/1D and inhibit the release of vasodilating neuropeptides.

Chest pain reported in 1-5% of cases due to coronary vasospasm.

Triptan duration of action is often shorter than duration of migraine

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Prophylaxis for migraines: criteria and 5 drugs

2 or more attacks/month

Tx vacation every 4-6 months to evaluate

Propranolol: Beta-blocker
Amitriptyline: TCA
Verapamil: Ca2+ channel blocker
Valproic acid and topiramate: anti-seizure

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2 drugs for neuropathic pain and MOA

Carbamazepine and oxcarbazine

Na+ channel blockers (especially Na v 1.3 channels)

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Methadone

Higher bioavailability than morphine

Its isomers can also block both NMDA receptors and monoaminergic reuptake transporters

Very effective for difficult-to-treat pain (neuropathic, cancer pain)

Long T1/2 (25-52 hours) Slower development of tolerance than morphine, Long lasting relief of pain

Widely used for treatment of opioid abuse, Abrupt cessation yields milder withdrawal signs

Unlike other opioids, is associated with prolonged QT syndrome

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Meperidine

Has significant antimuscarinic effects.

Unlike other opioids, causes mydriasis rather than miosis; IV administration frequently increases heart rate

Two severe reactions may result in patients also taking MAO inhibitors
Serotonin syndrome – can block neuronal reuptake of 5HT, resulting in serotonergic overactivity
Acute narcotic overdose – due to inhibition of hepatic CYPs by MAO inhibitors

Metabolized to normeperidine, which can cause increased CNS excitability and seizures

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Fentanyl

Subgroups include su-, al-, remi-fentanil

Most widely used in anesthesia applications

Most lipid soluble (partition coefficient: 9550)

Relatively short time to peak analgesic effects
High abuse potential
Rapid termination

Cardiovascular safety (do not release histamine)

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Codeine, hydrocodone, oxycodone

Given in formulations containing acetaminophen or aspirin

Codeine metabolism is variable, not recommended for cancer pain management

Oxycodone is available in sustained-release form. Contains large quantities of oxycodone for prolonged action. Abuse potential due to modification of the tablets for injection or snorting

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Tramadol

Mixed mechanism opioid

Synthetic codeine analog that works centrally. Mechanism of action is based on both (weak) MOR activity and NE and 5HT reuptake blockade

Can cause seizures; contraindicated in patients taking MAO inhibitors, SSRIs or other drugs that lower seizure threshold

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Nalbuphine
Butorphanol
Buprenorphine

Nalbuphine- no mu, lots kappa
Butorphanol- some mu, lots kappa
Buprenorphine- mu, no kappa

Effects of these drugs are not easily reversible with μ receptor antagonistsAll have ceiling effect for analgesia and respiratory depression
Butorphanol (less with nalbuphine) causes psychoto-mimetic side effects (dysphoria, racing thoughts, and distortions of body image)
Analgesia through KOR is more effective in women
Similar to methadone, buprenorphine has a long duration of action and is effective for treatment of opioid abuse; unlike methadone, high dose results in μ receptor antagonist action

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Opioid Overdose

μ receptor antagonists are used for OD and to reverse opioid-induced respiratory depression
Both drugs have high affinity for MOR and lower affinity for DOR and KOR

Naloxone
Short duration of action (1-2 hours)
Administered parenterally in-clinic
Patient has to be monitored until it is certain that the offending opioid is no longer in system

Naltrexone
Long half-life (10 hours)
Administered orally in outpatient settings
Used in maintenance programs

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amitriptyline, nortriptyline

Neuropathic Pain

TCAs (amitriptyline, nortriptyline) blocks both Na+ channels and ↓ NE and 5HT reuptake

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duloxetine, venlafaxine

Neuropathic Pain

SNRI (serotonin/ NE reuptake inhibitors) inhibits 5HT and NE reuptake

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gabapentin, pregabalin

Neuropathic Pain

Calcium channel α2δ ligands (gabapentin, pregabalin) inhibit voltage-gated Ca2+ channels

Both are GABA analogs that increase presynaptic GABA release. Gabapentin bioavailability is unpredictable; pregabalin is more potent, has faster onset of action, and more predictable bioavailability

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lidocaine

Topical agents (lidocaine) reversibly blocks Na+ channels and prevents generation of action potential responsible for nerve conduction (pain)

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carbamazepine, lamotrigine

Antiepileptic (carbamazepine, lamotrigine) blocks Na+ channels

Carbamazepine is 1st line for trigeminal neuralgia
Associated with risk of aplastic anemia

Lamotrigine is used in combination with carbamazepine for trigeminal neuralgia but has a high incidence of skin reactions which requires slow dose titration to mitigate these reactions

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dextromethorphan, ketamine

NMDA receptor antagonists (dextromethorphan, ketamine) may be used for chronic pain and postoperative pain

Both may produce psychomimetic side effects

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clonidine

Adrenergic Agonist (clonidine) acts on α2 receptors in the dorsal horn of the spinal cord to produce anti-nociceptive state

Associated postural hypotension limits its usefulness in pain management

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why is acyclovir more selectively toxic than other antivirals?

It attacks the viral kinases rather than the host cell kinases. This gives it more selective toxicity, but also renders it susceptible to resistance if the viral kinase is mutated.

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name three viruses that acyclovir can be used against

HSV
EBV
VZV

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two indications for valacyclovir

Recurrent genital or zoster infections.

longer acting ester of acyclovir. converted to acyclovir when taken orally and gives 3-5 times the serum levels.

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Two indications for famciclovir

For the management of acute herpes zoster and for the suppression of recurrent genital herpes

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Apply the early symptoms and DOC for herpes encephalitis to a clinically-relevant case scenario

Any age, acute onset of fever, headache, decreased consciousness, and seizures

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how is ganciclovir metabolized to an active form inside host cells?

A guanosine analog.

Acts as an antimetabolite, which is phosphorylated first by viral (monophosphorylation) and then by cellular kinases (di –and tri phosphorylation) to form a nucleotide that inhibits DNA polymerase of CMV.

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how does cidofovir have selective toxicity

1000-fold more effective against the DNA polymerases of viruses such as herpes virus than against the DNA polymerase of the host cell

what is unique about the metabolism requirement of foscarnet

Inhibits (in vitro) viral DNA polymerase, RNA polymerase, or HIV RT directly, without requirement for activation by phosphorylation.

List four viruses attacked by foscarnet

HSV HHV-6 VZV HBV CMV HIV EBV

Give the CDC guideline treatments for influenza in adults

Start treatment within 48 hours of symptom onset

Explain the MOA of neuraminidase inhibitors

Inhibit viral cleavage of sialic acid Inhibit the release of newly formed viruses Reduce duration of uncomplicated influenza A and B infection symptoms by 1 day if started within 2 days of the onset of symptoms. May prevent up to 84% of influenza infections

Explain the site of action for palivizumab

Binds to fusion (F) protein of RSV Prevents infection of host cell, reduce replication of RSV and spread to other cells

Explain the dosing and timing of palivizumab treatment for RSV

Dosing- 15 mg/kg IM monthly x up to 5 doses during RSV season with 1st dose given just prior to RSV season Kinetics- t ½ 13-27 days (approximates human IgG t ½) Onset: within 48 hrs

Explain who should avoid contact with people receiving ribavirin and why

Planning to get pregnant or pregnant should avoid direct care of patients receiving inhaled ribavirin (it is teratogenic)

Phenobarbital

Barbiturate For pre-op sedation Has slow onset Produces hyperactivity in children

Secobarbital

Barbiturate For short term insomnia (less that 2 wks) Also used for acute psychosis

Zolpidem

Ambien Z-hypnotic acts on GABA-A type 1 receptor Sedative hypnotic with rapid onset

Zaleplon

Sonata Z-hypnotic acts on GABA-A type 1 receptor Short acting and rapid onset anxiolytic

Propofol

Stimulated GABA release Drug of choice for ambulatory Sx Rapid metabolism and 99% changed before excretion

Etomidate

Similar to propofol Good for elderly pts as it doesn't lower BP NOT analgesic, and not as rapid as propofol

Buspirone

acts on the 5-HT 1A receptor and decreased 5TH release and increases NE and DA For long term anxiety- not for panic attacks Not for use with BZ, so BZ must be tapered before use No potential for abuse or withdrawal can be taken with ETOH

Ramelteon

melatonin receptor agonist Shortens latency to sleep w/o rebound insomnia or withdrawal

Fun facts for BZs

BZs are for short term use Pt must be educated about sleep driving Don't take with ETOH If pt doesn't respond to a BZ don't try others

Alprazolam

BZ | For panic disorders

Lorazepam

BZ- Ativan For generalized anxiety disorder

Meprobamate

BZ Short term anxiety and sedative hypnotic Decrease in REM sleep

Midazolam

BZ | Can be used for pediatric pre-op

Selegiline

Selective, irreversible MAO-B inhibitor -prevents DA breakdown! Prolongs the effect of L-dopa, thereby allowing for smaller doses May reduce the "on-off" effect AE=insomnia

Resagiline

Selective, irreversible MAO-B inhibitor -prevents DA breakdown! Similar to selegiline, but also has a neuroprotective effect Can be used as a mono therapy early in PD

Entacapone

Selective COMP inhibitor Prolongs the L-dopa activity- "on time" Several adverse effects: Dyskinesias Nausea Confusion Orange peepee

Tolcapone

Selective COMP inhibitor, like entacapone, but has increased liver toxicity

Stalevo

L-dopa + carbidopa + etacapone

Sinemet

L-dopa + Carbidopa

Amantadine

Antiviral that just so happens to have anti parkinson effects! Unknown MOA, but it enhances the DA function Less potent than L-dopa Tx only lasts a few weeks Reduces all symptoms

Bromocriptine

D2 receptor agonist ergot derived For parkinson disease No enzymatic conversion needed No toxic metabolite No competition to cross the BBB Few adverse effects

Promipexole

D3 receptor agonist Monotherapy for mild Parkinson disease Adjunct therapy for severe PD Dose adjustment needed for renal function No enzymatic conversion needed No toxic metabolite No competition to cross the BBB Few adverse effects

Ropinerol

D2 receptor agonist For parkinson disease No enzymatic conversion needed No toxic metabolite No competition to cross the BBB Few adverse effects

Propranolol

``` Beta blocker (B1+B2) Tx of essential tremor ```

Metoprolol

Beta- blocker (B1)

Tetrabenazine

For Tx of Huntington disease Inhibits vessicular monoamine transporter 2 Precise MOA unknown

Riluzole

Only drug specifically approved for ALS