chapter 15 CNS

Question 1

use of anorexiants

Answer 1

• prescription weight-loss drugs are used for pt. BMI >30 or BMI>27 with DM, HTN, dyslipidemia
• serious side effects-cardiac, pulmonary ADRs-possibly fatal
• avoid in patients with cardiac hx, drug/ETOH abuse
• difficult to monitor pts with diabetes-increased glucose uptake from skeletal muscles

Question 2

Anorexiants

Answer 2

-for short term use only
-related to amphetamines-suppresses appetite
-Diethylpropion (Tenuate, Tenuate Dospan Cat-IV)
-Orlistat (Xenical, Alli OTC)-only non-stimulant-lipase inhibitor; preg. cat. X
-phentermine (Adepex-P)
-Sibutramine (meridia)
-

Question 3

pharmacodynamics of anorexiants

Answer 3

• release of norepi/dopamine from storage sites in lateral hypothalmic feeding center
• decreases appetite

Question 4

pharmacokinetics of anorexiants

Answer 4

• lipid soluble with wide distribution
• crosses BBB
• metabolized by liver and excreted by kidneys
• duration of action 4-6 yrs

Question 5

pharmacotherapeutics of anorexiants

Answer 5

• high risk of dependence (avoid pts with ETOH/drug dependence)
• avoid pt who abuse cocaine/methamphetamines-d/t additional adrenergic stimulation

Question 6

ADRs for anorexiants

Answer 6

• overstimulation of CNS-agitation, insomnia, dizziness, HTN, etc
• may cause withdrawal symptoms if suddenly stop
• increased glucose uptake from skeletal muscles

Question 7

drug interactions for anorexiants

Answer 7

• off label in combo with SSRI: “Phen-Pro” (prozac and phentermine)
• with serotonergic meds-blks seratonin production and causes seratonin syndrome (severe muscle rigidity can lead to death)
  
  • cyproheptadine anecdote
• MAO inhibitors could lead to HTN crisis
• lithium toxicity
• cautious with: adrenergic blks, insulin sulfonylureas, phenothiazines
• Orlistat decreases level of levothyroxine and increases warfarin

Question 8

ADHD

Answer 8

• persistent hyperactivity and impulsivity
• tx: behavior therapy and medication therapy (stimulant and non-stimulant options; used to help with alertness, focus, attention
• most common drug: MPH (methylphenidate)
• all stimulants are controlled substance

Question 9

MPH

Answer 9

MAO: blks dopamine reuptake
M: de-esterification to inactive metabolite
AE: insomnia, decreased appetite, weight loss
Rare AE: tics, visual hallucinations
Caution: hx psychosis, mania, drug addiction
DI: carbamazepine, clonidine, warfarin, phenobarb, phenytoin, TCAs
-short and long acting available
* concerta with pt with esophageal motility issues-may increase risk of obstruction

Question 10

Adderall and Vyvanse

Answer 10

• amphitamines for ADHD
• ? vyvanse less abuse potential
• ADRs: decreased appetite, insomnia, abd pn
• risk of sudden cardiac death

Question 11

non-stimulant meds for ADHD

Answer 11

• atomoxetine (Strattera)
• MAO: inhibitor of norepi reuptake
• metabolized in CYP2D6
• ADRs: dyspepsia, decreased appetite, wt. loss, no tics
• can cause severe liver injuries, suicidal ideation

Question 12

adjunct meds for ADHD

Answer 12

• buproprion
• clonidine: cautious for sedation
• TCA: monitor EKG first
• guafacine: less sedation longer action
• modanifil-not recommended-hallucinations, Stevens Johnson syndrome

Question 13

parkinsons disease

Answer 13

• loss of neurons in substantia nigra
• presence of Lewy bodies
• loss of dopamine 1 and 2-leading to increased cholinergic activity
• symptoms: bradykinesia, resting tremor, postural instability
• progression: depression and psychosis

Question 14

dopaminergics/dopamine agonist

Answer 14

• choice of tx for parkinson’s
• attempt to restore functional balance of dopamine and acetylcholine-both responsible for smooth movements and balance
  
  • either by increasing synthesis, increasing receptors, release from storage, or inactivating MAO leading to more amounts available
    i. e.: amantadine, bromocriptine, levodopa (carbidopa-levodopa), pramipexole, ropinirole
• many drug intereactions
• can not stop abruptly
• cautious with patients with impulse-control disorders (pathologic gambling, binge eating, hypersexuality, excessive shopping etc)
• “sleep attacks”-suddenly fall asleep
• confusion and toxic psychosis

Question 15

cabidopa/levodopa

Answer 15

-combination enhances transmission of levodopa across BBB
-levodopa precursor to dopamine
-carbidopa: increases CNS penetration, prevents peripheral dopamine metabolism
ADRs: n/v, arrhythmias, postural hypotension, nightmares
-always given in combination
-absorption: levodopa protein bound, food delays gastric emptying
-controversial when to start tx, enhances neuron degradation, builds dose tolerance

Question 16

catechol-O-methyltranserase inhibitor (COMT)

Answer 16

• blocks degradation of levodopa
• entacopone-may have sleep attacks
• tolcapone-hepatotoxicity-monitor LFTs
• decreases levodopa requirements
• adrs: dyskinesias, n/d, discolored urine

Question 17

ergot derivatives for parkinsons

Answer 17

• bromocriptine: limited efficacy, risk of pulmonary fibrosis
• pergolide: removed from market d/t cardiac valve regurg

Question 18

MAO-B inhibitors for parkinsons

Answer 18

• selegiline, rasagiline
• inhibits catabolism and reuptake of dopamine
• can be mono or adjunctive therapy
• caution with SSRIs, meperidine, tramadol
• lower dose than for depression
• adrs: nausea, orthostatic hypotension, may enhance adrs of levodopa

Question 19

anticholinergics for parkinsons

Answer 19

• trihexyphenidyl, benztropine, ethopropazine
• limited role d/t ADRs
• used for tremors and drooling

Question 20

drugs associated with seizure activity

Answer 20

• antidepressants: SSRIs, TCA, buproprion
• quinolones
• high dose pcn
• cabepenems
• theophylline
• tramadol
• cyclosporins
• ETOH, drug, benzo withdrawal

Question 21

anticonvulsants

Answer 21

• seizures are result of abnormal discharge off neurons-anything that disrupts stability of neurons may cause
• can be used for tx of mood disorders
• precipitating factors: stress, high intake of caffeine, sleep deprivation, infection, sensory stimuli, hormonal change, metabolic disorders
• classes: hydantoins, iminostilbenes, succinimides
• main actions: stimulating influx of chloride ions-assoc. with GABA neurotransmitter
  - delaying influx of Na+
  - delaying influx of Ca+
• may cause suicide ideation and depression
• consider levels-toxicity and compliance
• there are many drug interactions

Question 22

hydantoins

Answer 22

• phenytoin-most commonly used, ethotoin, fosphenytoin
• inhibit and stabilize electrical discharge in motor cortex of brain
• first line tx for tonic-clonic and partial complex seizures

Question 23

phenytoin (Dilantin)

Answer 23

• stabilize Na+ channels
• dose: loading: 15-20mg/kg, maintenance: 4-7mg/kg/day
• metabolized: non-linear kinetics enzyme inducer
• many drug interactions
• caution: hypothyroidism, carbohydrate intolerance, peripheral neuropathy
• toxicity: n/v, tachycardia,
• adrs: nystagmus, ataxia, drowsiness, cognitive impairment (dose related)
  
  • gingival hyperplasia, hirsutism, acne, rash, coarse facial features, osteomalacia, vit D and folic acid deficiency

Question 24

levetiracetam (Keppra)

Answer 24

• for epilepsy and partial seizures/mono or adjunct therapy
• prevents epileptiform burst firing
• propagation of seizure activity
• dose 500mg BID (max of 3g/day)-adjust for renal impairment
• not largely metabolized-non-hepatic hydrolysis
• adrs: sedation, fatigue, agitation, lethargy
• levels: 12-46 mcg/ml
• pregnancy C

Question 25

iminostilbenes

Answer 25

• used to treat epilepsy, bipolar affective disorder, aggressive behavior, neuralgias
• carbamazepine (tegretol)

Question 26

carbemazepine (Tegretol)

Answer 26

• structurally related to TCAs
• inhibits Na+ channels-to prevent seizure activity
• metabolized by autoinduction-to induce its own metabolism; CYP3A4, 1A2 inducer
  
  • half life 25-65 hrs decreases to 12-16 hours
    adrs: black box warning blood dyscrasias, rash, ostomalacia, hepatotoxicity, lupus, diplopia, nystagmus
    levels: 4-12 mcg/ml

Question 27

oxcarbazepine

Answer 27

• mono or adjunct therapy for partial seizures
• Na+ channel blker
• metabolized in liver: 3A4 inducers, 2C19 inhibitors
  
  • half life 9 hrs
• adrs: hyponatremiz, rash, less blood dyscrasias than cabazepine
  levels: 3-35 mcg/ml
• pregnancy cat C

Question 28

phenobarbital

Answer 28

• for epilepsy low doses to not have dependence or tolerance
• can be used for tonic-clonic seizures
• increases aminobutyric acid and chloride influx-causing decrease activity and induce sleep
• CYP enzyme inducer; half life 80-100 hrs
• level 15-40 mcg/ml
• drug interactions: other benzos
• adrs: faitugue, depression, cognitive impairment, hyperactivity (pediatrics)
• preg. class D
• enhanced excretion: urinary alkaline, diuretics

Question 29

valproic acid

Answer 29

• used for primary generalized, absent seizures in adults, myclonic, atonic
• potentiates GABA, membrane stabilization, K+ channels
• 10-15 mg/kg/day TID (ER 15% higher)
• metabolized in liver-1 is hepatotoxic, 10 metabolites, CYP 2C9, 2C19
• many drug interactions including antacids
• enzyme inducer
  adrs: GI, derm, wt gain, ataxia, hepatotoxicity, thombocytopenia
• preg. class D
  levels: 40-100 mcg/ml

Question 30

gabapentin

Answer 30

• inhibits Ca+ channels, enhances GABA
• 2nd line for partial seizures
• dose 300-400 mg; titrate, renal dosing
• can be used for neuropathic pn
  adrs: somnolence, sedation
• preg. class C

Question 31

pregabalin

Answer 31

• GABA analog; potency>gabapentin
• used for fibromylagia, postherpetic neuralgia
• dose: 50 mg TID (max 600 mg/day), renal dose
  adrs: wt. gain, dizziness, somnolent
• CNS depressant
• avoid in CHF patients
• controlled substance

Question 32

succinimides

Answer 32

• treatment of absence seizures in children/adults
• decreases nerve impulses/transmission in motor cortex leading to higher seizure threshold
• ethosuximide, mehsuximide

Question 33

ethosuximide

Answer 33

• inhibits Ca+ channels
• dose: 250 mg BID (max 1.5 g/day)
• used for absence seizures
• level: 40-100 mcg/ml
• metabolized in liver, hepatic hydroxylization, 3A4 involvement
  
  • excretion through renal and feces
• half life 60 hrs
• drug interactions with 3A4 meds
  adrs: GI upset, wt loss, CNS depression, derm, abnormal LFTs, blood dyscrasias
• preg. class c

Question 34

adjunctive therapies for seizures

Answer 34

• topiramate and zonisamide
• topiramate-blocks Na+channels, potentiates GABA, blks glutamate, carbonic anhydrase inhibitor; can be used for migraines
• zonisamide: suppresses focus of seizures via Na+ and Ca+ channels; avoid sulfa allergy,
  adrs: nephrolithiasis

Question 35

migraines

Answer 35

3 categories: migraine with aura (classic), without aura (common), complicated migraine-treated by drugs the same

• patho: vascular theory: aura created by vasoconstriction of intracranial vessels and vasodilation of affected vessels-disproven
  
  • sertonin: changes cause release of vasoactive neurotransmitter, causes inflammatory response, excitory serotonin receptors activated
• acute abortive therapy v. prophylactic therapy