Intro to Prescription Writing and Antiepileptic Pharm

Question 1

In terms of prescription writing, what aspects does a designation as a scheduled/controlled substance impact?

Answer 1

Dispense quantity
Refills allowed
Prescription lifespan

Question 2

9 legal requirements of prescriptions

Answer 2

1. Name/address of prescriber
2. Name/address of patient
3. Date prescription was written
4. Name, strength, dosage
5. Directions for use
6. Quantity to be dispensed
7. Number of refills allowed
8. Prescriber’s signature
9. Prescriber’s DEA number (controlled drugs only)

Question 3

Lifespan of non-controlled legend drug prescriptions

Answer 3

12 months, or number of refills (whichever occurs first)

Question 4

Lifespan of controlled/scheduled legend drug prescriptions

Answer 4

6 months or number of refills (exception is C-V which has lifespan of 12 months)

Question 5

Legal limit on number of refills for controlled/scheduled legend drugs

Answer 5

C-II = None

C-III or C-IV = 5 refills over 6 months

C-V = no limit on refills

Question 6

Legal limit on quantity dispensed for controlled/scheduled legend drugs

Answer 6

C-II = 30 day supply (up to 90 days with documented medical reason)

C-III and C-IV = 90 day supply

Question 7

Partial filling for C-II is not permitted except under what circumstances?

Answer 7

Pharmacist does not have full quantity

Long-term care/hospice

Question 8

Law on prescription transfers of scheduled drugs

Answer 8

Not allowed for C-II

C-III through C-V can be transferred only once

Question 9

What can NEVER be changed/added on a controlled substance prescription?

Answer 9

Patient’s name
Drug name
Prescriber’s name
Prescriber’s signature

Question 10

Definition of “emergency” for controlled drugs

Answer 10

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

Question 11

Laws on self-prescribing and prescribing to family

Answer 11

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

Question 12

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

Answer 12

Na+; AMPA; NMDA

Question 13

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

Answer 13

Interior; activation

[note that voltage-gated sodium channels can be affected during open state or during fast-inactivated state]

Question 14

What is the explanation for the fact that voltage-gated Na+ channel blockers act preferentially on neurons involved in seizure activity?

Answer 14

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

Question 15

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?

Answer 15

Lacosamide

[whereas other AED Na(v) blockers just prolong fast inactivation state of Na(v) ion channels]

Question 16

What are the AEDs that act on voltage-gated Na+ channels to enhance fast inactivation?

Answer 16

Carbamazepine
Oxcarbazepine
Lamotrigine
Phenytoin
Rufinamide
Topiramate
Valproic acid
Lacosamide
Zonisamide

Question 17

AEDs that are AMPA receptor antagonists

Answer 17

Topiramate

Perampanel

Question 18

AED that is an NMDA receptor antagonist

Answer 18

Felbamate

Question 19

AEDs that affect pre-synaptic GABA-ergic transmission and their MOAs

Answer 19

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

Question 20

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

Answer 20

Benzodiazepines (lorazepam, diazepam, clonazepam)

Question 21

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

Answer 21

Barbiturates (phenobarbital, primidone)

Question 22

Which has higher lethality, benzodiazepines or barbiturates?

Answer 22

Barbiturates — because high doses are GABA-independent

Question 23

MOAs of Topiramate

Answer 23

GABA-A agonist — increases frequency of GABA-A receptor activation

Fast inactivation of Na(v) channels

AMPA receptor antagonist

Question 24

Hallmark of absence (petit mal) seizures

Answer 24

T-type Ca++ channels mediate 3 Hz spike and wave activity in the thalamus

Question 25

What drug is ONLY used for absence seizures because it only limits excitation at T-type Ca++ channels?

Answer 25

Ethosuximide

Question 26

Other than ethosuximide, what are 2 other drugs used that antagonize T-type Ca++ channels?

Answer 26

Valproic acid | Zonisamide

Question 27

All MOAs of valproic acid

Answer 27

T-type Ca2++ channel antagonist Fast inactivation of Na(v) channels GABA-T inhibitor

Question 28

All MOAs of zonisamide

Answer 28

T-type Ca++ channel antagonist Fast inactivation of Na(v) channels

Question 29

Which AED has the MOA involving inhibition of synaptic vesicle 2A protein in presynaptic neuron?

Answer 29

Levetiracetam (and other -acetams)

Question 30

Which AEDs have the MOA of inhibiting alpha-2-delta subunit of P/Q-type Ca2+ channels on presynaptic neuron?

Answer 30

Gabapentin | Pregabalin

Question 31

AED indications for partial onset seizures, both simple and complex

Answer 31

``` Lamotrigine Oxcarbazepine Perampanel Primidone Lacosamide ```

Question 32

AED indications for generalized onset absence seizures

Answer 32

Ethosuximide Clonazepam Valproic acid

Question 33

AED indications for generalized onset myoclonic seizures

Answer 33

Clonazepam

Question 34

AED indications for generalized onset tonic/clonic seizures

Answer 34

Primidone | Phenytoin

Question 35

AED indications for broad-spectrum seizures (minus absence)

Answer 35

Carbamazepine Phenobarbital Topiramate Valproic acid

Question 36

AED indications for Lennox-Gastaut seizures (adj. therapies)

Answer 36

``` Rufinamide Topiramate Clobazepam Clonazepam Lamotrigine Felbamate ```

Question 37

AED indications for status epilepticus

Answer 37

``` Lorazepam Diazepam Phenobarbital Phenytoin Valproic acid Levetiracetam ```

Question 38

Broad warning/risk of ALL AEDs

Answer 38

Abrupt withdrawal may precipitate status epilepticus Suicidal behavior and ideation

Question 39

What are some known issues with Phenytoin?

Answer 39

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

Question 40

Osteopenia/osteoporosis are associated with what AEDs due to their induction of CYP450-dependent vitamin D catabolism?

Answer 40

Phenytoin Carbamazepine Phenobarbital Valproic acid

Question 41

Issues with Carbamazepine

Answer 41

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

Question 42

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?

Answer 42

Lamotrigine

Question 43

Analogue of carbamazepine with fewer CNS/hematological side effects due to formation of an alternative active metabolite; also a less-potent CYP450 inducer

Answer 43

Oxcarbazepine

Question 44

Issues with phenobarbital

Answer 44

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

Question 45

Issues with vigabatrin

Answer 45

Toxicities — progressive, permanent, bilateral, concentric vision loss Only prescribable via REMS program

Question 46

Drug-drug interactions associated with hepatic CYP450 induction by carbamazepine, phenytoin, phenobarbital, and valproate

Answer 46

Oral contraceptives — risk of unplanned pregnancy Anticoagulants — risk of arterial/venous thrombosis Antivirals — risk of HIV replication

Question 47

Valproic acid + lamotrigine interaction

Answer 47

Inhibits conjugation of drugs by UGT causing accumulation of parent drug

Question 48

Non-CYP450 drug interactions with phenytoin, carbamazepine, and phenobarbital

Answer 48

Induce conjugation of drugs by UGT, causing reduction of parent drug

Question 49

Renal insufficiency requires dose adjustments of what AEDs?

Answer 49

``` Levetiracetam Topiramate Oxcarbazepine Gabapentin Pregabalin Vigabatrin ```

Question 50

Initial therapy protocol for convulsive status epilepticus in adults

Answer 50

In first IV: Lorazepam (alternative is diazepam) In second IV: Fosphenytoin, phenytoin, valproic acid, or levetiracetam If no IV access: midazolam