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NR 565 Week 4 Study Guide , NR 565: Advanced Pharmacology Fundamentals
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NR 565 Week 4 Study Guide , NR 565: Advanced Pharmacology Fundamentals
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Chapter 15: Drugs Affecting the Central Nervous SystemAnorexiants (p. 226): Short-term adjuncts to calorie limiting, cognitive-behavioral,
weight-loss programs for severely obese individuals. Nonamphetamine appetite
suppressants are commonly used today but are chemically and pharmacologically related
to amphetamines. (Phendimetrazine, Benzphetamine, Diethylpropion HCl, Phentermine,
Lorcaserin)
Precautions and Contraindications: High risk of tolerance and dependence. Should be
used in caution with patients who have a history of alcohol or drug dependence. Use
should be limited to 6 months and discontinued at any sign of tolerance.
Substance Abuse: Patients who abuse substances such as cocaine, phencyclidine,
and methamphetamine should not be prescribed anorexiants because of the
potential for excessive adrenergic stimulation.
Alcoholics: Actively drinking alcoholics taking anorexiants have experienced
depression, paranoia, and psychosis.
Diabetes: Patients with diabetes may experiences altered insulin or oral
hypoglycemic dosage requirements.
Lorcaserin: Serotonergic drug. Patients may develop serotonin syndrome or
Neuroleptic Malignant Syndrome like reactions if coadministered with
serotonergic drugs. Pregnancy Category X and is not approved in children under
18.
Anticonvulsants (p. 227):
Hydantoins: First line treatment of choice for tonic-clonic and partial complex seizures
and the lease sedating drugs used to treat seizure disorders of any type. (phenytoin-
Dilantin, ethotoin-Peganone, fosphenytoin-Cerebyx).
Pharmacodynamics: Inhibit and stabilize electrical discharges in the motor cortex
of the brain by affecting the influx of sodium ions into the neuron during
depolarization and repolarization, slowing the propagation and spread of
abnormal discharges.
Metabolism and Excretion: Metabolism takes place in the liver and
, excretion via the kidneys. Plasma half-lives range from 6-24 hours.
Precautions and Contraindications: Contraindicated under conditions of
hypersensitivity. Phenytoin induced hepatitis is a common hypersensitivity
reaction. Other hypersensitivity reactions include fever, rash, arthralgias, and
lymphadenopathy.
Phenytoin: May cause severe cardiovascular events and death has resulted
from too-rapid IV administration. Phenytoin has a Black-Box Warning
that IV administration should not exceed 50mg/minute in adults and 1-3
mg/kg/minute in pediatric patients owing to risk of cardiovascular
reactions associated with a too rapid rate of administration.
Contraindicated in sinus bradycardia, sinoatrial block, second-and third-
degree AV block, and Stokes-Adams syndrome. Should be used
cautiously in patients with hepatic or renal disease.
Ethotoin: Contraindicated in the presence of hepatic or hematological
disorders.
Fetal Defects: Pregnancy Category D. About 10% of babies have defects
in Mother’s who take phenytoin during pregnancy. Newborns exposed to
phenytoin is utero may experience decreased levels of Vitamin K-
dependent clotting factors and the mother should receive Vitamin K before
delivery and the newborn at birth.
Adverse Drug Reactions: CNS effects (agitation, ataxia, confusion, dizziness,
drowsiness, headache, and nystagmus), Cardiovascular effects (hypotension,
tachycardia, atrial and ventricular conduction depression, and ventricular
fibrillation), GI effects (nausea, vomiting, anorexia, altered taste, constipation, dry
mouth, and gingival hyperplasia), GU effects (urinary retention and reddish-
brown discoloration of urine), Dermatologic reactions (Stevens-Johnson
Syndrome and toxic epidermal necrolysis).
Drug Interactions: Interactions that increase hydantoins effect because of
increased metabolism, competition for binding sites or for unknown reasons occur
with benzodiazepines, cimetidine, disulfiram, TCAs, salicylates, and valproic
acid. Interactions that decrease hydantoin’s effect include barbiturates, rifampin,
theophylline, influenza vaccine, pyridoxine, and antacids. Oral contraceptives
, effect is decreased with use of hydantoins. Acute alcohol intake may increase
phenytoin serum levels, whereas chronic alcohol use may decrease levels. IV
phenytoin should only be mixed with normal saline.
Monitoring: Patients should be assessed for phenytoin hypersensitivity syndrome
(fever, skin rash, lymphadenopathy), which usually occurs at 3-8 weeks. Baseline
CBC, urinalysis, and LFTs should be assessed prior to onset of treatment, with
frequent reassessment during the first few months of treatment. Plasma levels
should be monitored, especially when drugs that increase plasma hydantoin, such
as ibuprofen, are used.
Patient Education: Abrupt withdrawal may lead to status epilepticus. Advise the
patient to wear a medical identification bracelet, to avoid hazardous situations if
drowsiness occurs, and to report adverse effects to the clinician. Patients should
avoid alcohol use. Maintain good oral hygiene to prevent tenderness, bleeding,
and gingival hyperplasia. Phenytoin may color the urine red, pink, or reddish
brown but the color change is not a cause for alarm. Advise diabetic patients to
monitor blood glucose levels and report significant changes to the clinician.
Iminostilbenes (p. 235): (Carbamazepine-Tegretol and oxcarbazepine-Trileptal).
Structurally related to TCAs. Used to treat epilepsy, bipolar affective disorder, aggressive
and assaultive behavior, and some neuralgias.
Pharmacodynamics: Thought to affect the sodium channels, slowing influx of
sodium in the cortical neurons and slowing the spread of abnormal activity.
Carbamazepine exerts its effect by depressing transmission in the nucleus
ventralis anterior of the thalamus. This area is associated with the spread of
seizure discharge.
Metabolism and Excretion: Carbamazepine is metabolized in the liver and
has the unique ability to induce its own metabolism (autoinduction). Due
to autoinduction, initial concentrations within a therapeutic range may
later fall despite good compliance. It also induces the metabolism of many
CYP450 enzymes and other substrates. Excretion is through urine and
feces. Oxcarbazepine is metabolized into an active metabolite 10-
monohydroxy metabolite, which is responsible for the pharmacologic
effect of the drug. The metabolites of oxcarbazepine are excreted 95% in
, urine, 4% in feces, and 1% unmetabolized oxcarbazepine.
Precautions and Contraindications:
Carbamazepine: Contraindications include hypersensitivity to
carbamazepine or TCAs, history of bone marrow suppression, and current
administration with MAOIs. Carbamazepine is Pregnancy Category D;
tetratogenic defects have occurred including spina bifida. Black-Box
Warning regarding serious dermatological reactions, particularly among
patients of Asian ethnicity (Stevens-Johnson Syndrome, toxic epidermal
necrolysis and risk of developing aplastic anemia and agranulocytosis).
Patients of Asian ethnicity should be screened for presence of the HLA-
B*1502 genetic variant prior to starting carbamazepine. Caution is advised
in patients with a history of previous adverse hematological reactions to
any drugs and in those with cardiac, renal, or hepatic impairment.
Oxcarbazepine: Pregnancy Category C; it crosses the placenta and adverse
effects have been noted in animal studies. Contraindicated with
hypersensitivity to oxcarbazepine.
Adverse Drug Reactions: Carbamazepine has a Black Box Warning regarding the
development of Stevens-Johnson Syndrome and toxic epidermal necrolysis in
patients of Asian ethnicity. Carbamazepine has a Black Box Warning due to its
potential to cause blood dyscrasias, some potentially lethal. Carbamazepine can
depress the bone marrow and lead to leukopenia, thrombocytopenia,
agranulocytosis, and aplastic anemia. For that reason, a baseline CBC, chemistry,
LFTs, and TSH should be obtained, followed by periodic monitoring. Follow up
studies should be more frequent initially, decreasing to every 3-4 months if the
results remain normal. Other adverse reactions to carbamazepine include hepatic
damage and impaired thyroid function. Less serious adverse events include
drowsiness, dizziness, blurred vision, ataxia, nausea, vomiting, dry mouth,
diplopia, and headache. The most common adverse effects observed in patients
taking oxcarbazepine were dizziness, diplopia, somnolence, fatigue, N/V, ataxia,
abdominal pain, tremor, and dyspepsia. Hyponatremia may occur, particularly in
the first 3 months of therapy.
Drug Interactions:
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