Pharmacology Study Materials - Week 6: Key Terminology and Definitions

migraine

may have nausea/vomiting

pain on one or both sides of head

activity of slight head movement makes pain worse

pain lasts hours to days

cluster headaches

pain for minutes, but may repeat

excruciating pain

redness or tearing of eyes, stuffy or runny nose (typically on side with pain)

occurrence of types of primary headache

tension (69%)

migraine (16%)

cluster (0.1%)

most common cause of secondary headache

systemic infection (63%)

diagnostic alarms of headaches

"first" or "worst" headache ever

onset of headache after age 50

focal neurological sx or papilledema

in pts with cancer or HIV infection

migraine triggers

bright lights or loud noises

exhaustion

hormonal changes

diet

stress

genetics

clinical presentation of migraines

aura (most often visual and frequently affects half the visual field)

pain is gradual in onset, peaks within minutes to hours, and lasts b/w 4 and 72 hrs

migraine resolution phase

fatigue, irritability, listlessness, impaired concentration, scalp tenderness, and mood changes

migraine tx goals

acute: consistent and rapid relief, allow pt to manage own headaches w/o a medical visit

chronic: reduce migraine frequency, severity, and disability, reduce reliance on chronic pharmacotherapy

tx of migraine

headache diary, general healthy lifestyle, nonpharmacological tx, drug tx (analgesics, ergot alkaloids, serotonin-1 receptor agonists)

non pharmacological tx of migraines

women: pay attn to estrogen level increases (catamenial)

relaxation therapy, apply ice to forehead, sleep/rest in a dark, quiet place

acute migraine tx

migraine non-specific agents (mil/mod HA w/o disability)

- analgesics, NSAIDs, opioids

migraine specific agents (more severe)

- ergot derivatives, triptans, CGRP antagonists

adjunctive agents

- antiemetics/dopamine antagonists, corticosteroids, intranasal lidocaine, IV valproate and mag sulfate

NSAIDs

non steroidal anti-inflammatory drugs, effective for menstrual migraines and in combination with triptans

NSAIDs MOA

prevention of inflammation by inhibition of prostaglandin synthesis

NSAIDs AE

GI side effects

IM ketorolac (Toradol)

same GI side effects, related to PG inhibition

acetaminophen for migraines

not recommended as monotherapy

aspirin/acetaminophen/caffeine (Excedrin) AE

possibility of acetaminophen OD

caffeine side effects (jitters, increased BP, heart palpitations)

sleep aid to enhance NSAID use for migraines

butalbital (barbiturate, depresses sensory cortex and motor fn [GABA])

opiate analgesic to enhance NSAID use for migraines

codeine

opiate analgesics for migraine

reserved for mild to moderate migraines that cannot take/are inadequately treated using NSAIDs or acetaminophen

rescue medication, delivered intranasally

risk of hyperalgesia

presynaptic 5HT1B/D autoreceptors

block serotonin release when activated

dihydroergotamine

DHE 45

nonspecific serotonin-1 agonist

DHE 45 AE

nausea and vomiting (chemoreceptor trigger zone -> pretreat with anti-emetics)

vascular constriction and occlusion

do not use within 24 hrs of triptan administration

DHE 45 advantages

fast onset, non-oral routes of administration, effective for severe migraine requiring hospital admission

serotonin-1 B/D agonists (triptans)

eletriptan (Relpax)

rizatriptan (Maxalt, Maxalt MLT)

sumatriptan (Imitrex)

serotonin-1 B/D agonists MOA

inhibits vasodilation and inflammation in some areas, vasoconstriction in others

more selective 5HT1B/D agonist (fewer side effects)

DOC for abortive therapy

serotonin-1 B/D agonists

serotonin-1 B/D agonists non-oral routes

sumatriptan and zolmitriptan (does not work faster than PO)

triptan for recurrent HA

slow onset/longer duration: naratriptan, frovatriptan

failing to respond to one triptan

try another triptan (others in class may be effective)

triptans key counseling point

take as soon as possible at onset of headache

serotonin-1 B/D agonists AE

cardiac effects (chest pressure syndrome), tingling, flushing, dizziness, and drowsiness

serotonin-1 B/D agonists contraindications

cardiac or vascular disease (uncontrolled HTN, peripheral/cerebral vascular dz, CAD, previous MI, Prinzmetal angina, coronary vasospasm)

MAOI use within 14 days

used selectively with SSRIs (counsel on serotonin syndrome)

ergot use within 24 hrs (enhanced vasoconstriction effect)

other triptan use within 24 hrs

overuse of triptans

may increase frequency of migraines, discontinue triptan, spontaneous improvement

how to avoid medication overuse HA

limit use of acute migraine therapy to < 2 days/week

first an only "ditan"

lasmiditan (Reyvow)

lasmiditan (Reyvow) MOA

5-HT1F receptor agonist (same as triptans, just different receptor)

CV

migraine prophylaxis

considered if any of the following are met:

3 or more migraine days/month

frequent migraines requiring abortive therapy > 2 times/week

inefficacy or inability to use acute therapy

pt preference

cost of acute meds is problematic

adverse effects w acute therapies

uncommon migraine presentation

principles of migraine prophylaxis

use lowest effective dose

base drug choice on co-morbidities

give adequate trial (3-6 mon)

monitor progress with HA diary

should see 50% decrease in # of migraines

continuous migraine prophylaxis

beta-adrenergic blockers

antidepressants (TCAs)

anticonvulsants

calcium channel blockers

NSAIDs

CGRP receptor antagonist

anticonvulsant drugs for migraines

most effective in migraine sufferers with comorbid seizures, anxiety, or bipolar (manic-depressive) d/o

topiramate (Topamax)

onabotulinumtoxin A (Botox)

chronic migraine injection directly into specific muscles

CGRP receptor antagonist options

monoclonal antibodies

non-MAB

erenumab (Aimovig)

administered SQ monthly for prophylaxis

AE: constipation, Ab development, injection site run, muscle cramps/spasms

rimepepant (Nurtec)

acute migraine tx: 75mg PO PRN x 1

migraine prophylaxis: 75mg PO every other day

cheaper migraine tx option

vitamin B2 (Riboflavin) and magnesium

400mg daily for both

what to do if migraine tx fails

look at meds -> is rebound or drug toxicity possible?

tension HA clinical presentation

"hatband," dull, nonpulsatile pain, tightness or pressure

tension-type HA physical interventions

cold packs, exercise, massage, e-stim

tension-type HA pharmacologic therapy

simple analgesics and NSAIDs (if inadequate -> combination of NSAIDs with sleep aids or opiates may be needed)

TCA antidepressants may be best for prophylaxis

cluster HA abortive therapy

O2 (100%)

ergotamines or triptans

epilepsy

recurrent seizures (abnormal neuron discharge) or convulsions

neuronal signal propagation

synchronous hyperexcitability

neurotransmitter imbalance: glutamate -> excitatory, GABA -> inhibitory

mechanisms of seizure initiation and propagation

influx of intracellular calcium

opening of voltage-dependent sodium channels, influx of sodium and generation of repetitive action potential

recruitment of surrounding neurons

seizure classification

partial (focal): originates in one cerebral hemisphere, highly localized

generalized: diffuse and often involves both cerebral hemispheres

absence seizures

motionless stare

myoclonic seizures

sudden, brief, shock-like muscle contractions

tonic-clonic seizures AKA grand-mal

tonic phase first, clonic phase follows

post-ictal period after

therapeutic goal of epilepsy tx

complete seizure control, minimal side effects, optimal quality of life

epilepsy drug selection

as therapy may be very long-term, tx cost should be considered, drug should be effective against demonstrated seizure, dose determined by pt and response

non adherence is the leading cause of tx failure (60% noncompliance)

epilepsy monotherapy

up to 70% adequately treated with one drug

epilepsy polypharmacy

should be considered only after three single agents have proven ineffective, all drugs must be effective, never abruptly discontinue a drug used for more than two weeks

pt counseling on missed anti-epileptic dose

take dose as soon as possible (w/in ~4hrs), resume normal schedule with next dose, do not double dose

when to stop epilepsy therapy

seizure-free for 2-4 yrs

slow process: each drug can be slowly withdrawn one at a time, monitor for seizures or convulsions

anti-epileptic general MOAs

affecting ion channel kinetics: sodium channel (major mechanism for generalized and partial)

augmenting inhibitory neurotransmission: GABA (major for myoclonic)

modulating excitatory neurotransmission: glutamate and aspartate, T-type calcium (major for absence)

therapeutic drug monitoring

used to confirm compliance

used for carbamazepine (Tegretol), phenytoin (Dilantin), and valproate sodium (Depakote, Depakene)

carbamazepine

Tegretol

phenytoin

Dilantin

valproate sodium

Depakote, Depakene

gabapentin

Neurontin

lamotrigine

Lamictal

levetiracetam

Keppra

oxcarbazeoine

Trileptal

phenobarbital

Luminol

pregabalin

Lyrica

topiramate

Topamax

carbamazepine MOA

blocks sodium channels, auto-inducer with active metabolite

carbamazepine AE

bone marrow depression, hepatotoxicity, life-threatening rash in Asian pts

carbamazepine indications

first line drug for partial and generalized

can be used for augmentation in other disease states (psych)

autoinduction

potent inducer of its own metabolism by hepatic enzymes

recommend weekly titration of smaller dose than the dose required for maintenance

gabapentin MOA

inhibits calcium channels

really excreted (altered mental status with accumulation)

gabapentin AE

withdrawal characterized by anxiety, insomnia, sweating and pain

gabapentin indications

chronic pain/neuropathic pain

gabapentin max absorbable dose

3600mg

lamotrigine MOA

sodium channel reactivation

lamotrigine AE

rash early in therapy, may become severe (life-threatening) and dose-limiting (BBW), super additive toxicity with other antiepileptic drugs

lamotrigine indications

augmentation of other disease states

lamotrigine dosing indications

titrate up slowly

CYP substrate (increase dose when taken with CYP inducers)

pts on valproate: titrate even slower and lower maintenance dose (valproate decreases lamictal metabolism)

levetiracetam MOA

unknown, but antiepileptic activity is very general and broad

levetiracetam AE

some cognitive disruption in adults

some behavioral disruption in children

oxcarbamazepine MOA

blocks sodium channels, calcium channels, and potassium activity

oxcarbamazepine AE

rash

contraceptive failure is common (increased metabolism of steroid)

phenobarbital MOA

enhancement of GABA inhibition

CIV

phenobarbital AE

sedation, respiratory and cardiac depression

primidone MOA

prodrug of phenobarbital (not a controlled substance)

phenytoin MOA

disruption of sodium channel activation

auto-inducer

protein binding, adjust for low albumin (regular level shows bound and unbound drug)

phenytoin AE

CNS depression early in therapy, gingival hyperplasia, vitamin D deficiency, osteomalacia, elevated cardiac toxicity when used by IV route (BBW)

rare hypersensitivities: rashes (Stevens-Johnson syndrome), bone marrow suppression

phenytoin dosing considerations

mild dose increases can exponentially increase blood concentrations of drug -> toxicity

fosphenytoin

Cerebyx