Intro to Prescription Writing and Antiepileptic Pharm Flashcards
In terms of prescription writing, what aspects does a designation as a scheduled/controlled substance impact?
Dispense quantity
Refills allowed
Prescription lifespan
9 legal requirements of prescriptions
- Name/address of prescriber
- Name/address of patient
- Date prescription was written
- Name, strength, dosage
- Directions for use
- Quantity to be dispensed
- Number of refills allowed
- Prescriber’s signature
- Prescriber’s DEA number (controlled drugs only)
Lifespan of non-controlled legend drug prescriptions
12 months, or number of refills (whichever occurs first)
Lifespan of controlled/scheduled legend drug prescriptions
6 months or number of refills (exception is C-V which has lifespan of 12 months)
Legal limit on number of refills for controlled/scheduled legend drugs
C-II = None
C-III or C-IV = 5 refills over 6 months
C-V = no limit on refills
Legal limit on quantity dispensed for controlled/scheduled legend drugs
C-II = 30 day supply (up to 90 days with documented medical reason)
C-III and C-IV = 90 day supply
Partial filling for C-II is not permitted except under what circumstances?
Pharmacist does not have full quantity
Long-term care/hospice
Law on prescription transfers of scheduled drugs
Not allowed for C-II
C-III through C-V can be transferred only once
What can NEVER be changed/added on a controlled substance prescription?
Patient’s name
Drug name
Prescriber’s name
Prescriber’s signature
Definition of “emergency” for controlled drugs
Immediate administration is necessary for proper tx of intended user and no appropriate alternative tx is available
note that 72 hours are allowed for delivery of Rx to the dispensing pharmacy and quantity is limited to amount needed during emergency time period
Laws on self-prescribing and prescribing to family
Self-prescribing of controlled substances is illegal in most states; self-prescribing of non-controlled substances is legal but discouraged
Physicians may prescribe all legend drugs for a family member as long as same records are maintained as for any other patient
One way that anti-epileptic drugs (AEDs) target epileptic-transmitter systems is by suppressing excitatory (glutamate) tranmission.
This may be done by suppressing voltage-gated ____ channels, or by suppressing ligand-gated ______ and _____ channels
Na+; AMPA; NMDA
AED’s that work by suppressing activation of voltage-gated Na+ channels bind at the _______ side of the channel pore, thus the ______ gate must be open for the drug to work
Interior; activation
[note that voltage-gated sodium channels can be affected during open state or during fast-inactivated state]
What is the explanation for the fact that voltage-gated Na+ channel blockers act preferentially on neurons involved in seizure activity?
The probability of Na(v) blockade is proportional to the frequency of Na(v) chanel opening and dose — epileptic seizures involve neurons firing at higher frequency than normal so they are more likely to attract the drug
Which of the Na(v) blockers can do its job irrespective of open-close of channels — meaning it can both prolong fast inactivation and enhance slow inactivation of Na(v) channels?
Lacosamide
[whereas other AED Na(v) blockers just prolong fast inactivation state of Na(v) ion channels]
What are the AEDs that act on voltage-gated Na+ channels to enhance fast inactivation?
Carbamazepine Oxcarbazepine Lamotrigine Phenytoin Rufinamide Topiramate Valproic acid Lacosamide Zonisamide
AEDs that are AMPA receptor antagonists
Topiramate
Perampanel
AED that is an NMDA receptor antagonist
Felbamate
AEDs that affect pre-synaptic GABA-ergic transmission and their MOAs
Vigabatrin inhibits GABA metabolism by GABA-T
Valproic acid promotes formation of GABA via activation of glutamic acid decarboxylase; also inhibits GABA metabolism by SSD
Tiagabine inhibits GABA reuptake by GAT-1
AED that affects post-synaptic GABA-ergic transmission by binding to a distinct allosteric site that potentiates GABA binding so that Cl- channels open with greater frequency
Benzodiazepines (lorazepam, diazepam, clonazepam)
AED that affects post-synaptic GABA-ergic transmission by binding to a distinct site on the receptor and increasing the duration of Cl- channel opening
Barbiturates (phenobarbital, primidone)
Which has higher lethality, benzodiazepines or barbiturates?
Barbiturates — because high doses are GABA-independent
MOAs of Topiramate
GABA-A agonist — increases frequency of GABA-A receptor activation
Fast inactivation of Na(v) channels
AMPA receptor antagonist
Hallmark of absence (petit mal) seizures
T-type Ca++ channels mediate 3 Hz spike and wave activity in the thalamus
What drug is ONLY used for absence seizures because it only limits excitation at T-type Ca++ channels?
Ethosuximide
Other than ethosuximide, what are 2 other drugs used that antagonize T-type Ca++ channels?
Valproic acid
Zonisamide
All MOAs of valproic acid
T-type Ca2++ channel antagonist
Fast inactivation of Na(v) channels
GABA-T inhibitor
All MOAs of zonisamide
T-type Ca++ channel antagonist
Fast inactivation of Na(v) channels
Which AED has the MOA involving inhibition of synaptic vesicle 2A protein in presynaptic neuron?
Levetiracetam (and other -acetams)
Which AEDs have the MOA of inhibiting alpha-2-delta subunit of P/Q-type Ca2+ channels on presynaptic neuron?
Gabapentin
Pregabalin
AED indications for partial onset seizures, both simple and complex
Lamotrigine Oxcarbazepine Perampanel Primidone Lacosamide
AED indications for generalized onset absence seizures
Ethosuximide
Clonazepam
Valproic acid
AED indications for generalized onset myoclonic seizures
Clonazepam
AED indications for generalized onset tonic/clonic seizures
Primidone
Phenytoin
AED indications for broad-spectrum seizures (minus absence)
Carbamazepine
Phenobarbital
Topiramate
Valproic acid
AED indications for Lennox-Gastaut seizures (adj. therapies)
Rufinamide Topiramate Clobazepam Clonazepam Lamotrigine Felbamate
AED indications for status epilepticus
Lorazepam Diazepam Phenobarbital Phenytoin Valproic acid Levetiracetam
Broad warning/risk of ALL AEDs
Abrupt withdrawal may precipitate status epilepticus
Suicidal behavior and ideation
What are some known issues with Phenytoin?
Zero-order (saturable) pharmacokinetics
Required serum-drug level monitoring (10-20 mcg/mL)
Well known inducer of CYP450 enzymes
Select toxicities: gingival hyperplasia, hypothyroidism, CV risk, hypocalcemia—>osteoporosis
Osteopenia/osteoporosis are associated with what AEDs due to their induction of CYP450-dependent vitamin D catabolism?
Phenytoin
Carbamazepine
Phenobarbital
Valproic acid
Issues with Carbamazepine
Serum drug level monitoring (4-12 mcg/mL)
Known inducer of CYP450 enzymes, also induces auto-induction (self-metabolism)
Toxicities: leukopenia/neutropenia/thrombocytopenia, hypocalcemia —>osteoporosis
Carbamazepine induces its own metabolism at certain serum levels, resulting in potential loss of efficacy and recurrence of seizures. What other drug does this occur with, though to a lesser extent?
Lamotrigine
Analogue of carbamazepine with fewer CNS/hematological side effects due to formation of an alternative active metabolite; also a less-potent CYP450 inducer
Oxcarbazepine
Issues with phenobarbital
C-IV agent— can’t prescribe as often/as many refills
Serum drug level monitoring (10-40 mcg/mL) — coma, respiratory depression, fatality risk at high concentrations
Known inducer of CYP450
Toxicities: CNS depressant, hypocalcemia —> osteoporosis
Issues with vigabatrin
Toxicities — progressive, permanent, bilateral, concentric vision loss
Only prescribable via REMS program
Drug-drug interactions associated with hepatic CYP450 induction by carbamazepine, phenytoin, phenobarbital, and valproate
Oral contraceptives — risk of unplanned pregnancy
Anticoagulants — risk of arterial/venous thrombosis
Antivirals — risk of HIV replication
Valproic acid + lamotrigine interaction
Inhibits conjugation of drugs by UGT causing accumulation of parent drug
Non-CYP450 drug interactions with phenytoin, carbamazepine, and phenobarbital
Induce conjugation of drugs by UGT, causing reduction of parent drug
Renal insufficiency requires dose adjustments of what AEDs?
Levetiracetam Topiramate Oxcarbazepine Gabapentin Pregabalin Vigabatrin
Initial therapy protocol for convulsive status epilepticus in adults
In first IV: Lorazepam (alternative is diazepam)
In second IV: Fosphenytoin, phenytoin, valproic acid, or levetiracetam
If no IV access: midazolam
