Medications Flashcards
Pyridostigmine
MOA and SE
MOA: AChE inhibitor
SE: twitching and hyperesthesia, diarrhea, abdominal pain, urinary frequency, xeroderma, myalgias, ambylopia, epistaxis, diaphoresis, urinary incontinence, increased salivation.
beware cholinergic crisis in MG patients who are dosed >120mg q 3 hours
Acetylcholinesterase Inhibitors (AChE inhibitors)
Main uses
AD and PD: DRG: donepezil, rivastigmine, galantamine
MG: pyridostigmine, neostigmine, edrophonium
2 Drugs for organophosphate poisoning and their MOA
__Pralidoxime (2-PAM):__ reactivates AChE if given before “aging” makes organophosphate AChE inhibition permanent.
__Atropine__
muscarinic receptor antagonist in peripheral nervous system. Does NOT affect nicotinic receptors at the NMJ or autonomic ganglia
- blocks M2 receptors at SA node causing increase in HR
- prevents vagal stimulation of AV node which increase AV conduction (useful in heart block)
- blocks M3 receptors in bronchial smooth muscle causing vasodilation
- inhibits M3 mediated glandular secretion which reduces respiratory secretions
- blocks M3 receptors in pupillary sphincter muscle causing pupil dilation
- inhibits ciliary muscle contraction causing paralysis of accommodation (cycloplegia)
- inhibits M3 receptors in GI tract decreasing peristalsis and GI secretions
- inhibits M3 receptors in bladder detrusor muscle causing urinary retention (used for intestinal spasms)
- Crosses BBB, at high doses causes CNS stimulation, used as antidote for organophosphate poising to offset CNS and PNS muscarinic effects
Statins
- MOA of muscle toxicity
- genetic susceptibility gene
- which other lipid med increases risk of statin muscle toxicity
- does hypo or hyper thyroidism increase risk of muscle toxicity?
direct toxic effect or immune mediated myopathy, abs include: anti-HMG-CoA and anti-SRP.
Resolution does NOT usually occur with drug discontinuation.
SLC01B1 changes susceptibility to statin myopathy
Fibrates - gemfibrozil - increases risk of statin muscular toxicity
Hypothyroidism increases risk of muscle toxicity
Myopathy, weakness, may occur w or w/o increased CK
Medications that cause peripheral neuropathy
isoniazid
tacrolimus
didanosine, zalcitabine, and stavudine are nucleoside analogs used in HIV therapy
simvastatin
discontinuation leads to improvement or resolution
Leviteracitam
MOA and se
MOA: Inhibits synaptic vesicle glycoprotein 2A
SE: neuro-psych - aggressive, cognitive, GI, suicidal ideation (all AEDs), SJS, TENs, DRESS
Ethosuximide
MOA
SE
Decreases T type calcium channels in thalamus
GI, hyperactive, ataxia, hiccups,
Aplastic anemia, agranulocytosis, leukopenia, SJS, TENs, DRESS
Topiramate
MOA SE
blocks voltage-dependent sodium channels, enhances the activity of GABA at a nonbenzodiazepine site on GABA(A) receptors, antagonizes an N-methyl-D-aspartic acid (NMDA)-glutamate receptor, and weakly inhibits carbonic anhydrase
Side effects of topiramate include appetite suppression and sometimes weight loss, paresthesias in the digits, cognitive slowing and word-finding difficulty, nephrolithiasis (calcium phosphate crystals), and acute angle-closure glaucoma (rare).
Higher doses of topiramate (> 200 mg) can decrease the plasma concentration of estrogen and progestins in patients taking oral contraceptives (OCPs). Topiramate also can be used to treat essential tremors.
Common Side Effects of Topiramate
- Central Nervous System (CNS) Effects
• Cognitive impairment (“Dopamax” effect):
• Slowed thinking
• Difficulty concentrating
• Memory problems
• Sedation or fatigue
• Dizziness
• Coordination issues (ataxia)
• Paresthesia (tingling, especially in the extremities)
• Speech and language problems (e.g., word-finding difficulty)
• Mood changes:
• Irritability
• Anxiety or depression - Gastrointestinal Effects
• Nausea
• Loss of appetite
• Weight loss (beneficial in some cases, but can become problematic in underweight individuals) - Other Common Effects
• Metallic taste or altered taste sensation
• Dry mouth
• Visual disturbances (e.g., blurred vision)
Severe Side Effects of Topiramate
- Kidney and Metabolic Effects
• Kidney stones (nephrolithiasis, calcium phosphate):
• Due to topiramate’s effects on renal bicarbonate excretion and urine alkalinization.
• Metabolic acidosis:
• Due to inhibition of carbonic anhydrase.
• Symptoms: Hyperventilation, fatigue, confusion.
• Hypohidrosis (decreased sweating):
• Can lead to hyperthermia, especially in children and during hot weather. - Vision Problems
• Acute myopia and secondary angle-closure glaucoma:
• Rare but serious condition requiring urgent ophthalmologic evaluation.
• Visual field defects:
• Can occur even without angle-closure glaucoma. - Neuropsychiatric Effects
• Suicidal ideation and behavior:
• A general risk with antiepileptic drugs, including topiramate.
• Psychosis or hallucinations:
• Rare but documented. - Hematologic Effects
• Rare cases of pancytopenia or leukopenia have been reported. - Teratogenicity
• Fetal harm:
• Associated with an increased risk of oral clefts and low birth weight when used during pregnancy. - Seizure Exacerbation
• Paradoxical worsening of seizures in rare cases.
Vigabatrin
MOA
SE
irreversible inhibitor of GABA-T leading to increased GABA levels
Vigabatrin is an antiepileptic drug primarily used for infantile spasms (West syndrome) and refractory focal seizures. It works by irreversibly inhibiting gamma-aminobutyric acid transaminase (GABA-T), leading to increased GABA levels in the brain. While effective in certain conditions, vigabatrin has a significant side effect profile, including serious visual and systemic effects.
Common Side Effects of Vigabatrin
These are typically dose-related and may improve with dose adjustment:
- Visual Effects
• Blurred vision (non-permanent)
• Photophobia - Central Nervous System (CNS) Effects
• Drowsiness
• Fatigue
• Dizziness
• Headache
• Irritability or agitation
• Cognitive slowing - Gastrointestinal Effects
• Nausea
• Vomiting
• Weight gain - Behavioral and Mood Changes
• Depression
• Anxiety
• Hyperactivity (especially in children) - Other Mild Effects
• Peripheral edema
• Arthralgia (joint pain)
Severe Side Effects of Vigabatrin
These effects are rare but clinically significant and require careful monitoring:
- Visual Field Defects
• Irreversible bilateral concentric visual field constriction (tunnel vision):
• Occurs in up to 30–50% of patients with prolonged use.
• Risk increases with higher cumulative doses.
• Mechanism: Vigabatrin-induced retinal toxicity.
• Retinal damage:
• May result in progressive loss of peripheral vision.
Monitoring:
• Baseline and periodic visual field testing is mandatory (e.g., Humphrey visual field test).
• Regular ophthalmologic exams, including retinal imaging.
- Neuropsychiatric Symptoms
• Psychosis or hallucinations:
• Reported in predisposed individuals or at higher doses.
• Suicidal ideation and behavior:
• Risk inherent to many antiepileptic drugs, including vigabatrin. - CNS Effects
• Encephalopathy:
• Rare but may present with confusion, somnolence, or stupor.
• Exacerbation of seizures:
• Paradoxical seizure worsening is rare but possible. - Hematologic and Metabolic Effects
• Anemia or eosinophilia:
• Rare hematologic abnormalities.
• Peripheral neuropathy:
• Occurs in a small subset of patients.
• Hyperammonemia:
• Rare, but associated with altered mental status in severe cases. - Pediatric Risks
• In children with infantile spasms:
• Increased risk of developmental delay or worsening of preexisting delays.
Monitoring and Management of Side Effects
- Visual Field Defects:
• Prevention:
• Limit cumulative dose and duration of therapy.
• Screening:
• Baseline and regular visual field testing (every 3–6 months).
• Management:
• Discontinue if significant visual field loss is detected. - Neuropsychiatric Symptoms:
• Management:
• Dose adjustment or discontinuation if psychosis or mood changes are severe. - CNS and Metabolic Side Effects:
• Monitor for symptoms of encephalopathy, and check ammonia levels if mental status changes occur. - Pediatric Monitoring:
• Close developmental assessments and cognitive monitoring in children receiving vigabatrin for infantile spasms.
Clinical Considerations
Advantages:
• Highly effective for:
• Infantile spasms, especially those associated with tuberous sclerosis.
• Refractory focal seizures that fail to respond to other AEDs.
Disadvantages:
• Risk of irreversible visual field defects limits long-term use.
• Requires frequent monitoring, increasing the burden on patients and caregivers.
Summary Table
Category Common Effects Severe Effects
Visual Blurred vision, photophobia Irreversible visual field defects, retinal damage
CNS Drowsiness, fatigue, dizziness Psychosis, encephalopathy, seizure worsening
Behavioral Irritability, hyperactivity, depression Severe mood changes, suicidal ide
ACTH
ACTH is the first line treatment for Infantile Spasms, except for patients with Tuberous Sclerosis where Vigabatrin has shown to be superior.
Adrenocorticotropic hormone (ACTH) is used as a diagnostic agent for adrenal insufficiency and as a treatment for conditions such as infantile spasms (West syndrome) and other inflammatory or autoimmune disorders. ACTH stimulates the adrenal cortex to release cortisol, aldosterone, and androgens, resulting in therapeutic and adverse effects, many of which overlap with those seen with systemic corticosteroids.
Common Side Effects of ACTH
These are primarily related to its stimulation of adrenal corticosteroid production and the resultant increase in cortisol levels:
- Endocrine and Metabolic Effects
• Weight gain (fluid retention, increased appetite).
• Hyperglycemia (glucose intolerance due to cortisol’s effects on metabolism).
• Electrolyte disturbances:
• Hypokalemia (due to mineralocorticoid activity).
• Hypernatremia (fluid retention).
• Cushingoid appearance:
• Moon face, central obesity, striae. - Musculoskeletal Effects
• Muscle weakness (catabolic effects of cortisol on muscle).
• Myopathy (especially in chronic use).
• Bone loss (osteopenia/osteoporosis). - Gastrointestinal Effects
• Increased appetite.
• Dyspepsia or gastric irritation. - Behavioral and Psychiatric Effects
• Irritability.
• Mood swings.
• Insomnia. - Immune Suppression
• Increased susceptibility to infections due to corticosteroid-mediated suppression of the immune system.
Severe Side Effects of ACTH
The severe side effects are often dose- and duration-dependent and primarily result from excessive cortisol production or other systemic effects of ACTH.
- Endocrine and Metabolic
• Adrenal suppression (prolonged ACTH use can suppress the hypothalamic-pituitary-adrenal axis, leading to adrenal insufficiency when stopped abruptly).
• Hyperglycemic crisis:
• In patients with underlying diabetes or impaired glucose tolerance.
• Hypertensive crisis:
• Secondary to fluid retention and cortisol-induced vascular sensitivity to catecholamines. - Cardiovascular
• Heart failure exacerbation:
• Due to fluid retention and hypertension.
• Edema (peripheral or generalized). - Neurologic and Psychiatric
• Severe psychiatric symptoms:
• Psychosis.
• Severe depression or euphoria.
• Suicidal ideation. - Gastrointestinal
• Peptic ulcers or gastrointestinal bleeding:
• Cortisol can impair the gastric mucosal barrier and increase acid secretion.
• Pancreatitis:
• Rare, but potentially life-threatening. - Immunosuppression and Infection
• Opportunistic infections:
• Fungal infections (e.g., candidiasis).
• Reactivation of latent infections (e.g., tuberculosis).
• Sepsis:
• Due to significant immunosuppression. - Other Severe Reactions
• Anaphylaxis or hypersensitivity reactions:
• Rare but reported with exogenous ACTH administration.
• Severe hypokalemia:
• Leading to arrhythmias or muscle paralysis.
JME first line RX
Valproic Acid is the 1st line treatment for JME.
What is the first line treatment for infantile spasms in patients with tuberosclerosis
Vigabatrin
ACTH is a treatment of choice and infantile spasms, except for patients with tuberous sclerosis in which vigabatrin is the treatment of choice
What other epilepsy medication causes lamotrigine levels to rise significantly?
If valproic - increased risk of lamotrigine-associated rashes, including Stevens–Johnson syndrome.
Chlorpromazine
FGA
Fluphenazine
FGA
Haloperidol
FGA
Loxapine
FGA
Perphenazine
FGA
Pimozide
FGA
Thiothixene
FGA
Trifluoperazine
FGA
Aripiprazole
SGA
Asenapine
SGA
Brexpiprazole
SGA
Cariprazine
SGA
Clozapine
SGA
Iloperidone
SGA
Lurasidone
SGA
Olanzapine
SGA
Paliperidone
SGA
Quetiapine
SGA
Risperidone
SGA
Ziprasidone
SGA
FGA mnemonic 9 drugs in order of prescribing frequency
“Happy Friendly Cats Prefer Lounging Together, Taking Their Pills.”
Happy = Haloperidol
Friendly = Fluphenazine
Cats = Chlorpromazine
Prefer = Perphenazine
Lounging = Loxapine
Together = Trifluoperazine
Taking = Thiothixene
Their = Thioridazine
Pill = Pimozide
High potency FGA: 5 drugs
“High Flyers Try Perfect Tricks.”
High = Haloperidol
Flyers = Fluphenazine
Try = Trifluoperazine
Perfect = Pimozide
Tricks = Thiothixene
High binding affinity for D2 receptors. So need lower dose to achieve therapeutic effect.
Higher risk of extrapyramidal side effects (EPS):
- dystonia: spams and abnormal posture
- akathisia: feeling of inner restlessness accompanied by mental distress and/or an inability to sit still
- Parkinsonism
Low potency FGA: 2 drugs
chlorpromazine
thioridazine
Three things that inhibit CYP 450 (3A4) and increase carbamazepine levels
Ketoconozole, grapefruit, and erythromycin
Drug Metabolism: Phase II metabolism. Drugs that go directly to Phase II so are less affected by liver disease: 5
Lorazepam, temazepam, oxazepam, lamotrigine, olanzapine
Drugs not metabolized by liver: 3
lithium, gabapentin, 70% of topiramate
Valproate inhibits phase II enzymes (UGT1A4) important in ….
lamotrigine, valproate causes increased levels of lamotrigine, so decrease lamotrigine dose.
Side effects of using Valproate in a patient already taking Lamotrigine
skin rash, restlessness, seizures, tremors, muscle weakness, and staggering walk.
Eculizumab
rx nmo
complement inhibitor, meningococcal vaccination
Ravulizumab
rx nmo
compliment inhibitor, meningococcal vaccination
Inebilizumab
rx nmo
CD 19 ab, Heb B, quant serum immunoglobin, TB screening
Sartalizumab
rx nmo
IL-6 ab, Heb B, TB and LFT sreening
Interferon
rx MS
injectable
Interferes with viral replication; may reduce the inflammatory pathway and help, Injection site reactions, depression, flu-like symptoms
No apparent long-term SEs and no opportunistic infections
Glatiramer acetate
RX MS
injectable
unknown moa, Injection site reactions, chest pain (non-cardiac), focal lipoatrophy. The “easiest” MS therapy to prescribe as it requires no baseline testing or
monitoring, excellent long term safety data, minimal side effect profile
No apparent long-term SEs and no opportunistic infections
Glatiramer acetate and interferon generally safe during pregnancy
Ofatumumab
RX MS
injectable
Selectively targets CD20 expressing B-cells, Injection reactions, lymphopenia
Fat Albert wearing costume nose glasses
Fingolimod
RX MS
oral
- sphingosine 1-phosphate (S1P) receptor modulator
- sequestors lymphoctyes in lymph nodes,
- monitoring: VSV abs testing, fundus, ecg for type II heart block,
SE:
- Transient bradycardia,
- macular edema, lymphopenia (unclear significance)
- APPROVED for PEDS
PML cases have been reported as has cryptococcal meningitis
PRES, Rebound (?–more likely yes than no)
Siponimod
RX MS
oral
S1P, CYP2C9 genotype testing for dosing, macualr edema, sometimes FDO
Ponesimod
RX MS
oral
S1P, NO macular edema NO FDO
Ozanimod
RX MS
oral
S1P, macualr edema, no FDO
Dimethyl fumarate
oral
unknown MOA, Early GI side effects, transient flushing, PML w lymphopenia, new version: diroximal fumarate less GI
Teriflunomide
RX MS
oral
blocks DHODH,
Moniitoring: quantiferon gold/ppd for TB reactivation risk. LFTs monthly for six months.
Transient hair thinning, peripheral neuropathy, elevated LFTs,
teratogenic for women AND men EASY oral therapy (safe bc no PML no lymphopenia),
can rapidly eliminate w cholestyramine if skin reaction or patient becomes pregnant. v long half life becasue hepatically recycled so need to elimiate w cholestyramine.
Cladribine
oral
- inhibits DNA synthesis by blocking adenosine deaminase leading to programmed cell death of T and B cells, malignancy, lymphopenia,
- teratogenic (no pregnancy for six months after stopping)
Dalfampridine
RX MS
oral
K blocker, NOT DISEASE MODIFYING improves walking in MS patients BUT contraindicated in those with epilepsy bc it is a stimulant, and/or renal insufficiency
Natalizumab
RX MS
infusion
anti alpha-4 integrin abs, PML, rebound, infusion rxn, MOST effective
Alemtuzumab
RX MS
infusion
binds to CD52 and depletes T and B cells, monitoring: quantiferon gold, vzv, SE: infusion rxn/cell lysis syndrome, stroke during infusion, thyroid dysfunction (hypo or hyper), ITP, rapdily progressive glomerularnephritis, shingles. HIGHLY EFFECTIVE BUT V HIGH TREATMENT BURDEN
Ocrelizumab
RX MS
infusion
Targets CD20 leading to immediate and prolonged reduction in B-cell counts, Infusion reactions
PML (?; has been rare in isolation)
Breast cancer(? Not seen in post-marketing analysis)Has become a major “go-to” therapy for MS due to effectiveness and
convenience. Some patients are reporting a “crap gap” around 5 month
(increasing symptoms; unclear if it is a real phenomenon)
Valproic Acid
MOA
SE
Drug interactions
MOA: Increases GABA, Na+ channel blocker, inhibits T-type Ca2
Levetiracetam
Binds SV2A, reduces glutamate release, modulates calcium channels stabilizing neuronal firing
Lamotrigine
Na+ channel blocker, ↓ glutamate release
Ethosuximide
T-type Ca2+ channel blocker
Topiramate
Na+ channel blocker, ↑ GABA, ↓ glutamate (inhibits AMPA/kainate receptors), carbonic anhydrase inhibition
Clobazam
GABA-A agonist
Zonisamide
Na+ channel blocker, inhibits T-type Ca2+ channels, carbonic anhydrase inhibition
Valproate
MOA, SE, SSE, Drug interactions, Black Box
MOA: Increases GABA, Na+ channel blocker, inhibits T-type Ca2+
SE: Weight gain, tremor, GI uspet, sedation, alopecia
SSE: Hepatotoxicity, pancreatitis, teratogenicity, thrombocytopenia, hyperammonia, PCOS exacerbation
Drug interactions: inhibits CYP enzymes (↑ lamotrigine, phenobarbital, carbamazepine), highly protein bound and can displace phenytoin leading to toxicity
Black box: Hepatotoxicity, pancreatitis, teratogenicity
Lamotrigine
MOA, SE, SSE, Drug interactions, Black Box
MOA: Na+ channel blocker, ↓ glutamate release
SE: Rash, dizziness, diplopia,
SSE: Stevens-Johnson syndrome, TEN, aseptic meningitis (rare)
Drug interactions: Valproate ↑ levels (risk of rash); OCPs, carbamazepine and phenytoin all ↓ lamotrigine levels
Black box: Stevens-Johnson syndrome, TEN
Levetiracetam
MOA, SE, SSE, Drug interactions, Black Box
MOA: Binds SV2A, reduces glutamate release, modulates calcium channels stabilizing neuronal firing
SE: Sedation, mood changes
SSE: Depression, suicidality, psychosis, SJS (rare)
Minimal drug interactions
No black box warning
Ethosuximide
MOA, SE, SSE, Drug interactions, Black Box
MOA: T-type Ca2+ channel blocker
SE: Nausea, headache, sleep disturbances (insomnia or drowsiness), hyperactivity
SSE: Agranulocytosis (and other blood dysrasias), Stevens-Johnson syndrome, lupus like syndrome
Drug interactions: CYP3A4 metabolism (so impacted by inducers and inhibitors)
Balck box: None
Topiramate
MOA, SE, SSE, Drug interactions, Black Box
MOA: Na+ channel blocker, ↑ GABA, ↓ glutamate (inhibits AMPA/kainate receptors), carbonic anhydrase inhibition
SE: Cognitive impairment, weight loss, paresthesias (tingling)
SSE: Acidosis, kidney stones, cleft palate in pregnancy, angle closure glaucoma
Drug interactions: ↓ Oral contraceptive efficacy, ↓ valproic acid levels, excessive sedation w alcohol
Black box: None
Clobazam
MOA, SE, SSE, Drug interactions, Black Box
MOA: GABA-A agonist
SE: Drowsiness, dizziness
SSE: Respiratory depression, dependence, suicidal ideation
Drug interactions: CYP3A4 metabolism (interacts w inducers like rifampin and phenytoin), additive sedation w alcohol, optiods, CNS depressants
Black box: Respiratory depression, dependence
Zonisamide
MOA, SE, SSE, Drug interactions, Black Box
MOA: Na+ channel blocker, inhibits T-type Ca2+ channels, carbonic anhydrase inhibition
SE: Sedation, dizziness, weight loss, kidney stones
SSE: Stevens-Johnson syndrome, metabolic acidosis, oligohydrosis (reduced sweating)
Drug interactions: CYP3A4 metabolism, additive CNS depression with other AEDs
Black box: None
