Transcript Pharmacology and Pathophysiology II

Neurological Pharmacology
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Norepinephrine (NE)
◦ Triggers sympathetic response
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Acetylcholine (Ach)
◦ Release in multiple locations
◦ Opposite effect of NE when released from
parasympathetic neurons
◦ Transmitted at the end of all presynaptic neurons
(ganglia)
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Adrenergic Nerves
◦ Comes from the word adrenaline
 Adrenaline is closely related to NR
 Same chemical structure as epinephrine
 Epinephrine and NE are released under extreme stress
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Cholinergic
◦ Comes from
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Cholin – acetylcholine
Erg - work
Ic related to
Nerves that release Ach are cholinergic
Neurotransmitter
Receptor
Primary Locations
Responses
Acetylcholine
Muscarinic
Parasympathetic
target:
Organs other than
the heart
Stimulation of
smooth muscle
contractions and
gland secretions
Heart
Decreased HR and
contraction force
Cell Bodies of
postganglionic
neurons
Stimulation of
smooth muscle
contractions and
gland secretions
Nicotinic
Neurotransmitter
Receptor
Primary Locations
Responses
Norepinephrine
Alpha 1
All sympathetic
target organs
except the heart
Constriction of
blood vessels,
dilation of pupils
Alpha 2
Presynaptic
adrenergic neuron
terminals
Inhibits NR release
Beta 1
Heart and kidneys
Increase HR and
contraction force,
release of renin
Beta 2
All sympathetic
target organs
except the heart
Inhibits smooth
muscle
contractions
Beta 3
Adipose Tissue
Breakdown of fat
Bladder
Suppresses
emptying
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Urecholine (bethanechol)
◦ Stimulation of urine
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Ocusert (pilocarpine)
◦ Treatment of dry mouth
◦ Glaucoma
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Aricept (donepezil)
◦ Alzheimer’s
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Prostigmin (neostgmine)
◦ Myasthenia Gravis
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Adverse Effects
◦ Excessive muscarinic stimulation
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Increased GI motility
Increased GI secretions
Bradycardia
Urinary urgency
Can be treated with atropine
◦ Cholinergic Crisis
 Excessive muscarinic stimulation and respiratory
depression from neuromuscular blockade
 Treated with emergency respiratory care
 Monitor those receiving atropine
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Dosages begin low and are increased until
individual desired effects
Encourage patients to participate in selfdosage adjustments
◦ Take notes on administration and effects
◦ Recognize sx. Of inadequate dosing
◦ Do not change dosages themselves
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Dopaminergics
◦ Levodopa (Dopar)
◦ levodopa and carbidopa (Sinemet)
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Dopamine Agonists
◦ pramipexole (Mirapex)
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These medications do not stop the
progression of PD
Offer relief of symptoms from dyskinesias
and increase the ability to perform ADLS
(maintain the balance between dopamine and
Ach)
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Levodopa
◦ Crosses blood brain barrier
◦ Taken up by dopaminergic terminals
◦ Converted to dopamine (DA) and is released,
causing stimulation of DA receptors
◦ First Line Medication for PD
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Carbidopa
◦ Used to augment levodopa
◦ Decreases the amount of levodopa that is converted
to DA in the intestine and periphery
◦ Results in an increase of levodopa reaching the CNS
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Adverse Reactions
N/V
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Dyskenesias
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◦ Administer with food in small doses
◦ Reduce the dose
 May result in resumption of PD sx.
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Orothostatic HTN
Cardiovascular effects (beta 1 stimulation)
◦ Tachycardia, irregular HR
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Psychoses
Discoloration of sweat or urine
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Activation of malignant melanoma
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◦ Harmless side effect
◦ Do not use in patients with undiagnosed skin lesions
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Do not use Levodopa within 2 weeks of MAOI
(cause antihypertensive crisis)
Contraindicated with malignant melanoma
Use caution with cardiovascular disease and
psychiatric patients
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Levodopa Interactions
◦ Proteins
 Interfere with levodopa absorption and transport
across blood – brain barrier
 “off eipsode”
 Avoid high protein meals
◦ Compazine and Haldol
 Decrease therapeutic effects
◦ Vitamin B6 (pyridoxine)
 Decrease therapeutic effects
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AEDs control seizure disorders by
◦ Slowing the entrance of Na and Ca back into the
neuron and extending the time it takes for the
nerve to return to its active state
◦ Suppressing neuronal firing
◦ Enhances the inhibitory effects of gamma butyric
acid (GABA)
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Barbituates
◦ phenobarbitol (Luminal)
◦ primidone (Mysoline)
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phenytoin (Dilantin)
carbamazepine (Tegretol)
valproic acid (Depakote)
Benzodiazepines
◦ diazepam (Valium)
◦ lorazepam (Ativan)
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ethosuximide (Zarontin)
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Phenobarbitol
◦ Partial seizures and tonic-clonic seizures
◦ Not effective against absent seizures
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Phenytoin
◦ All major forms of epilepsy except absent seizures
◦ IV route for status epilepticus
◦ Use for dysrhythmias with QT prolongation
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Carbamazepine
◦ Partial seizures, tonic-clonic seizures, bipolar
disorder
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Ethosuximide
◦ Only for absent seizures
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Valproic Acid
◦ Partial, generalized and absence seizures
◦ Bipolar disorder
◦ Migraine headaches
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Gabapentin
◦ Single agent for control of partial seizures
◦ Prevention of migraines
◦ Neuropathic pain
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Diazepam and lorazepam
◦ IV Route for status epilepticus
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Adverse Effects
◦ Barbiturates
 CNS Effects
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Drowsiness
Sedation
Confusion
Anxiety
Irritability and hyperactivity (children)
Toxicity
 Nystagmus, ataxia, respiratory depression, coma, pinpoint
pupils, hypotension, death
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Hydantoins (phenytoin)
◦ CNS effects
 Nystagmus, sedation, ataxia, cognitive impairment, double
vision
◦ Gingival hyperplasia
 Softening and overgrowth of gum tissue
◦ Skin Rash
◦ Teratogenic
 Cleft palate, heart defects
◦ Cardiovascular
 Dysrhythmias and hypotension
 Do not administer with patients in sinus bradycardia, SA
blocks, 2nd or 3rd degree AV Blocks
◦ Endocrine
 Coarsening of facial features, hirsutism
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Carbamezapine
◦ CNS Effect
 Nystagmus, double vision, vertigo, staggering gait, HA
◦ Blood Dyscrasias
◦ Hypo-osmolarity
 Promotes secretion of ADH
 CHF – risk of fluid overload
◦ Skin
 Dermatitis, rash
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Ethosuximide
◦ GI Effects
 N/V
 Administer with food
 CNS Effects
 Sleepiness, lightheadedness, fatigue
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Valproic Acid
◦ GI Effects
 N/V, Indigestion
◦ Hepatoxicity
 Anorexia, abdominal pain, jaundice
◦ Pancreatitis
 N/V and abdominal pain
◦ Thrombocytopenia
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Gabapentin
◦ CNS Effects
 Drowsiness
 Nystagmus
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Diazepam
◦ Respiratory Depression
◦ Amnesia
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Interactions
◦ Phenytoin
 Decreases effects of oral contraceptives, Coumadin
and glucocorticoids
 Phenytoin levels are decreased by ETOH, valium,
Tagamet and valproic acid
 Phenytoin levels are increased by Tegretol,
phenobarbital and chronic ETOH levels
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Interactions
◦ Carbamazepine
 Decreases effects of contraceptives and Coumadin
 Grapefruit juice inhibits metabolism and increases
carbamazepine levels
 Carbamazepine levels are decreased by phenytoin and
phenobarbital
◦ Valproic Acid
 Levels of phenytoin and phenobarbital are increased
with use of valproic acid
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diazepam
alprazolam (Xanax)
lorazepam (Ativan)
clonazepam (Klonopin)
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Adverse Reactions
◦ CNS Depression
 Sedation, lightheadedness, ataxia, decreased cognitive
function
◦ Anterograde amnesia
◦ Acute Oral Toxicity
 Drowsiness, lethargy and confusion
 Gastric lavage and activated charcoal
◦ Paradoxical response
 Insomnia, excitation, euphoria, anxiety, rage
◦ Withdrawal symptoms (infrequent)
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SSRIs selectively inhibit serotonin reuptake
and allowed more serotonin to stay in the
junction of the neurons
Paroxetine (Paxil)
Sertraline (Zolft)
Escitalopram (Lexapro)
Fluoxetine (Prozac)
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Uses
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Depression
PTSD
OCD
Panic Disorder
Social Anxiety Diorder
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Adverse Reactions
◦ Early effects
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Nausea
Diaphoresis
Tremor
Fatigue
Drowsiness
◦ Later effects
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 Sexual dysfunction
Weight gain
GI Bleeding
Hyponatremia (more likely with older patients taking diuretics)
Serotonin Syndrome
 Agitation, Confusion, Disorientation, Difficulty Concentrating, Anxiety,
Hallucinations, Tremors, fever, diaphoresis
 Usually begins 2 – 72 hours after initiation
◦ Bruxism
 Teeth grinding
◦ Withdrawal syndrome
 Really a discontinuation syndrome, not withdrawal
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Amitriptyline (Elavil)
Imipramine (Tofranil)
Block reuptake of NE and Serotonin in the
synaptic space
◦ Intensifies the effects of the neurotransmitters
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Used for depression and depressive episodes
of bipolar patients
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Adverse Reactions
◦ Orthostatic Hypotension
◦ Anticholinergic Effects
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Dry Mouth
Blurred Vision
Photophobia
Urinary Hesitancy or retention
Constipation
Tachycardia
◦ Sedation
◦ Toxicity
 Cholinergic blockade and cardiac toxicity result
 Dysrhythmias, mental confusion, agitation, seizures, coma,
death
◦ Decreased seizure threshold
◦ Excessive Sweating
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Interactions
◦ Serotonin syndrome with concurrent use of MAOIs
and St. John’ Wort
◦ Antihistamines have additive anticholinergic effects
◦ Increased effects of epinephrine and dopamine
◦ ETOH, benzos, opioids and antihistamines cause
additive CNS depression when used with TCAs
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phenelzine (Nardil)
selegiline (Emsam)
◦ Transdermal
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Block MAO A in the brain
◦ Increase NE, Dopamine and Serotonin available foor
transmission
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Used for Atypical Depression
Bulimia Nervosa
OCD
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Adverse Effects
◦ CNS Stimulation
◦ Orthostatic Hypotension
◦ Hypertensive crisis
 Results from dietary intake of tyramine
 HA, nausea, increased HR and BP
◦ Rash (transdermal patch)
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Do not take with SSRIs
Contraindicated with cardiovascular disease,
cerebral vascular disease and severe renal
insufficiency
Emsam is contraindicated in those taking
Tegretol or Trileptal
◦ Increases blood levels of Emsam
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Interactions
◦ TCAs
 Hypertensive crisis
◦ SSRIs
 Serotonin Syndrome
◦ Antihypertensive
 Additive hypotensive effect
◦ Demerol
 Hyperpyrexia
◦ Tyramine Rich Foods
 Hypertensive crisis
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bupropion (Wellbutrin)
◦ Inhibits dopamine uptake
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Venlafaxine (Effexor) and duloxetine (Cymbalta)
◦ Inhibit serotonin and NE reuptake
◦ Some dopamine blockade
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Alternative to SSRIs because of side effects
◦ Primarily sexual dysfunction
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Aid to quit smoking
Prevention of seasonal affective disorder (SAD)
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Adverse Effects
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HA
Dry Mouth
GI Distress
Constipation
Increased HR
Nausea
Insomnia and Restlessness
Appetite Suppressant
Seizures
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Interactions
◦ MAOIs
 Increase risk of toxicity
 Discontinue MAOIs 2 weeks before starting Wellbtrin
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Used for Bipolar Disorder
◦ Controls episodes of acute mania
◦ Prevents the return of mania or depression
◦ Decrease incidence of suicide
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Also used for
◦ ETOH abuse
◦ Bulima
◦ Schizophrenia
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Adverse reactions
◦ GI Distress
◦ Hand Tremors
 Exacerbated by stress and caffeine
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Polyuria
Weight Gain
Renal Toxicity
Goiter and hypothyroidism with long term use
Hypotension, bradycardia and electrolyte
imbalances
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Signs and Symptoms of Toxicity
◦ Early
 Less than 1.5mEq/L
 N/V/D, polyuria, thirst, muscle weakness, slurred speech
◦ Advanced
 1.5 – 2.0mEq/L
 GI Distress, Mental Confusion, Poor Coordination
◦ Severe
 2.0 – 2.5mEq/L
 Extreme polyuria of dilute urine, tinnitus, blurred vision, ataxia,
seizures, severe hypotension, coma, respiratory complications, death
 Gastric Lavage
◦ End Stage
 More than 2.5mEq/L
 Rapid Progression of symptoms
 Coma and Death
 Hemodialysis needed
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Interactions
◦ Diuretics
 Lithium toxicity (reduced sodium)
◦ NSAIDs
 Increase renal reabsorption of lithium
 Toxicity
◦ Anticholinergics
 Antihistamines, TCA
 Induce urinary retention and polyuria
 Abdominal discomfort
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Chlorpromazine (Thorazine)
Haloperidol (Haldol)
Fluphenazine (Prolixin)
Used for
Psychoses
Schizophrenia
Manic Phase of Bipolar
Dementia
Tourettes
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Adverse Reactions
◦ Acute Dystonia
 Treat with anticholinergic agents
 Cogentin or Benadryl
◦ Parkinsonism
 Treat with benztropine, Benadryl or Symmetrel
◦ Akathisia
 Inability to sit or stand still
 Continual pacing and agitation
 Treat with beta-adrenergic blockers, benzos or
anticholinergic meds
◦ Anticholinergic Effects
 Dry mouth, blurred vision, photophobia, urinary hesitancy,
constipation and tachycardia
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Adverse Reactions
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Orthostatic Hypottension
Sedation
Seizures
Skin Effects
 Photosensitivity resulting in severe sunburn
◦ Agranulocytosis
◦ Prolonged QT interval
 May lead to fatal dysrhythmias
◦ Neuroendocrine effects
 Gynecomastia (breast enlargement), menstrual
irregularities
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ETOH, opioids and antihistamines
◦ Additive CNS Depressant Effects
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Levodopa
◦ Counteracts antipsychotic effects (activates
dopamine receptors)
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Cas, amiodarone, erythromycin
◦ Further prolongation of QT intervaal
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Atypical Medications
risperidone (Risperdal)
olanzapine (Zyprexa)
quitiapine (Seroquel)
aripiprazole (Abilify)
ziprasidone (Geodon)
Block serotonin and some deopamine receptors
Also block recptors for NE, histamine and Ach
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Used for Schiz., psychoses (caused by levodopa) relief of
psychotic episodes
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Abilify also labeled for depression
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Adverse Reactions
◦ New onset of DM or loss of glucose control in
diabetics
◦ Weight gain
◦ Hypercholesterolemia
◦ Orthostatic Hypotension
◦ Agitation, Dizziness, Sedation, Sleep Disturbances
◦ Mild EPS such as tremor
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Contraindicated for dementia patients
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Interactions
◦ May cause death due to CVA
◦ Immunosuppressive medications
 Increased immunosuppression
◦ ETOH, Opioids, antihistamines
 Additive CNS Depressant effects
◦ Levodopa
 Counteracts antipsychotic agents
◦ TCAs, amiodarone, clarithromycin
 Prolonged QT interval
◦ Barbituates and Dilaantin
 Stimulation of hepatic medication metabolizing enzymes
 Decreases drug levels of antipsychotics
◦ Diflucan
 Inhibits hepatic metabolism
 Increases levels of antipsychotics
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Lithium
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◦ 0.8 – 1.2mEq/L
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Valproic Acid
◦ 5 – 12mcg/mL
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Desipramine
◦ 150 – 300ng/mL
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Amitriptyline
◦ 120-150ng/mL
Phenobarbital
◦ 10 – 30mcg/mL
◦ 50 – 100mcg/mL
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Carbamazepine
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Phenytoin
◦ 10 – 20mcg/mL