CNS Pharm Flashcards
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
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
2 drugs for neuropathic pain and MOA
Carbamazepine and oxcarbazine
Na+ channel blockers (especially Na v 1.3 channels)
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
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
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)
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
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
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
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
amitriptyline, nortriptyline
Neuropathic Pain
TCAs (amitriptyline, nortriptyline) blocks both Na+ channels and ↓ NE and 5HT reuptake
duloxetine, venlafaxine
Neuropathic Pain
SNRI (serotonin/ NE reuptake inhibitors) inhibits 5HT and NE reuptake
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
lidocaine
Topical agents (lidocaine) reversibly blocks Na+ channels and prevents generation of action potential responsible for nerve conduction (pain)
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
dextromethorphan, ketamine
NMDA receptor antagonists (dextromethorphan, ketamine) may be used for chronic pain and postoperative pain
Both may produce psychomimetic side effects
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
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.
name three viruses that acyclovir can be used against
HSV
EBV
VZV
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.
Two indications for famciclovir
For the management of acute herpes zoster and for the suppression of recurrent genital herpes
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
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.
