Pharmacology Test 1
Afferent System: transmits information to the CNS from Receptors
Somatic Sensory: Sensory Information received from skin, fascia, joints, skeletal muscles, eyes, ears, nose, and tongue
Visceral Sensory: Sensory Information received from viscera
Efferent System: Sends information from the CNS to the body
Somatic Motor: Voluntary muscle movement
Autonomic: controls organs such as heart, lungs, stomach, and intestines
Autonomic Nervous System: Involuntary activities: respiration, circulation, digestion, body temperature, metabolism, blood glucose, sweating
Somatic nervous system: Acetylcholine only neurotransmitter between CNS and skeletal muscles
CNS
Acetylcholine (Ach)
Dopamine
Norepinephrine
GABA (gamma-aminobutyric acid)
Glutamate
Serotonin
PNS
Acetylcholine (Ach)
Norepinephrine
Chemical Signal is received on cell body and dendrites
Chemical Signal is converted to electrical signal or
Impulse travels down axon to the axon terminal
Axon terminal releases neurotransmitters
Acetylcholine: stimulates skeletal muscle, inhibits cardiac muscle, inhibits and excites smooth muscle and glands (CNS & PNS)
Gamma-Aminobutyric Acid: Primary inhibitory neurotransmitter in the brain; can impact muscle tone (CNS)
Dopamine: Inhibitory role; important in cognition, motivation, behavior, mood
Epinephrine: Effects in thalamus, hypothalamus, spinal cord
Norepinephrine: Modulates sympathetic part of the autonomic nervous system
Serotonin: Functions related to sleep, appetite, cognition, mood
Glutamate: Excitatory role; promotes cognitive function; most common neurotransmitter in the brain
ACh and GABA
ACh acts on receptors in smooth and cardiac muscle, skeletal muscle, and exocrine glands
ACh receptors blocked by anticholinergics
GABA regulates message delivery system of the brain
Dopamine, Epinephrine, and Norepinephrine
Dopamine acts on receptors in the CNS and kidneys
Epinephrine acts on cardiac and bronchodilator receptors
Norepinephrine acts on alpha and beta receptors
Serotonin and Glutamate
Serotonin acts on smooth muscle and gastric mucosa
Causes vasoconstriction which decreases blood flow
Emotional responses: depression, anxiety
Glutamate may be crucial to some forms of learning and memory
Alpha: vasoconstriction, raises blood pressure
Beta-1: increases heart rate and contrastive force of the heart
Beta-2: influences bronchodilation
Response of various adrenergic receptors to epinephrine/norepinephrine
Alpha receptors
Constriction of blood vessels
Decongestion
Beta-1 receptors
Increases heart rate and contrastive force of heart
Beta-2 receptors
Dilation of bronchial tubes and blood vessels
Drug Effects on the receptors (Nervous System)
Neurotransmitter binding causes cell membrane to be more permeable to various ions.
Activate enzyme systems that promote chemical reaction
Blocking, preventing transmitters from binding to receptors
Anticholinergics
Side Effects of Anticholinergics
Decreased GI motility (constipation)
Decreased sweating
Decreased urination
Dilated pupil and blurred vision
Dry eyes
Dry mouth
Seizure: Results from excessive firing of a small number of neurons with spread to adjacent neurons
Conscious periods and loss of control over movements or distortion of the senses
Convulsion: An involuntary contraction or series of contractions of voluntary muscles
Seizures and convulsions are not interdependent
Epilepsy: Neurologic disorder characterized by sudden and recurring seizures
Involves disturbances of neuronal electrical activity that
interfere with normal brain function
All epilepsy patients have seizures but not all patients with
seizures have epilepsy.
Seizures: Factors which influence the firing of neurons
• Positively charged ions increase firing.
• Negatively charged ions inhibit firing.
•Glutamate, an excitatory neurotransmitter, increases firing.
•GABA, an inhibitory neurotransmitter, decreases firing.
• Enzymes control neurotransmitter levels
• Disruption in enzymes = disruption of neurotransmitters
Causes of seizures
• Alcohol or drug withdrawal/use
• Epilepsy
• High fever
• Hypoglycemia and hyperglycemia
• Infection
• Brain tumors
• Trauma or head injury
Symptoms vary from staring to unconsciousness
localized in a specific area of the brain
almost always results from injury to cerebral cortex
occurs in about 65% of people with epilepsy
can progress to generalized seizures
Involves both hemispheres of the brain, no specific location
Four types
tonic-clinic
absence
myoclonic
atonic
Partial Seizure in a specific hemisphere
Simple partial seizure: twitching and sensory hallucination with no loss of consciousness (focal motor)
Complex partial seizure: blank stare, post seizure amnesia with impaired consciousness (psychomotor)
Generalized Seizures
Tonic-Clonic seizure: muscle rigidity followed by muscle jerks with shallow breathing, loss of bladder control, excess salivation (Grand Mal)
Tonic: body becomes rigid, patient may fall, lasts a minute or less
Clonic: starts with muscle jerks, may be accompanied by shallow breathing, loss of bladder control, and excess salivation; lasts a few minutes
Status Epilepticus: continuous tonic-Clonic convulsions, high fever, lack of oxygen; with or without loss of consciousness
lasts at least 30 minutes
high fever and lack of oxygen that can cause brain damage or death
Absence seizure (petit Mal): interruption of activities by black stare, rotating eyes, uncontrolled facial movements, rapid eye blinking, twitching or jerking of an arm or leg
no generalized convulsions
30 seconds or less
typically stops at the age of 10 or develop tonic-Clonic
Myoclonic seizure: occurs with sudden, massive brief muscle jerks which may throw patient down or nonpassive, quick jerks of the arms, hands, legs, or feet: consciousness not lost
can occur during sleep
Ten percent of patient who suffer from status epilepticus die regardless of treatment
Two goals of Antiepileptic Therapy
Seizure control or lessen the frequency
Prevent emotional and behavioral changes that may result from seizures
About 30% of patient do not comply due to side effects such as sedation and loss of cognitive processes
Principles of treatment- Different seizure types require different drugs
Initiate monotherapy at a low dose.
Increase dose gradually over 3-4 weeks
Monitor plasma concentrations, must be maintained at steady therapeutic levels
If insufficient response, polytherapy can be considered (severe cases).
Periodically evaluate continued need for therapy.
Monitor for drug interactions.
Watch for “dispense as written” on prescription.
Dispense with medication guide.
Newer drugs are seizure-specific
high potential for drug interactions
Anticonvulsants have narrow therapeutic ranges
prescribers often write for the brand name medications
Sedatives with anticonvulsant action
inhibit nerve impulse conduction and depress neurons in the brain
ex. Phenobarbital
oldest drug in the class
still used
sedation
more drugs Depakene and Epival are not interchangeable; Sabril is last chance drug
many clinical uses
potential for abuse
one use is as an anticonvulsant – acts on receptors in the brainstorm
ex. diazepam
Characterized by muscular difficulties and postural abnormalities
Signs
tremors while resting, rigidity, akinesia
manifests as poor posture control. shuffling gait, loss of overall muscle control
Cause
Alterations in the extrapyramidal system which controls movement
Imbalance between the neurotransmitters dopamine and Ach
Part of the CNS that controls motor activities
Made up of the basal nuclei (basal ganglia)
Chronic, degenerate condition
part of the CNS that controls motor activities
made up of basal nuclei (basal ganglia)
Most common extrapyramidal disease
Usually affects people over 60
Parkinson has no definitive test, diagnosed by symptoms
For normal muscle movement to be performed, 2 main neurotransmitters must be in balance
dopamine (inhibitor)
acetylcholine (stimulator)
In Parkinson disease, there neurotransmitters are not in balance
In the substania nigra, insufficient dopamine is released to counteract effects of Ach
This causes excessive motor nerve stimulation
Improves functional ability, clinical status, temporary remission
Does not alter disease process
side effects may necessitate numerous medication changes
tolerance develops easily
need larger doses
more side effects
Drug holiday
lower dose required
less side effects
may be taken off completely for a couple weeks so it stays effective
does not cross the blood brain barrier
not useful therapeutically
precursor- Levodopa (L-Dopa)
converted to Dopamine
Drugs that increase or enhance the action of dopamine in the brain
Drugs that inhibit the effect of acetylcholine
Multiple Sclerosis: An autoimmune disease in which the myelin sheaths around nerves degenerate
Causes loss of muscle control
can affect eyesight
can result in severe trembling in later stages
no cure but medications used to slow progression
Alzheimer’s Disease and Drug treatment:A degenerative brain disorder that leads to progressive dementia(symptom) and changes in personality and behavior, changes in personality and behavior, wandering, irritability or hostility
symptoms include loss of memory, intellect, judgment, orientation, speech
depression and anxiety are common
in early stages, patient complain of memory deficit, forgetfulness, misplacement of ordinary items
In final stages, disease progresses to incapacitation, disorientation, and failure to thrive.
Causes include insufficient ACh and hyperactive glutamate receptors
Drug therapy slows the disease but does not cure or reverse it.
Progressive and irreversible
Progression
Memory deficit, forgetfulness, misplacements of ordinary items
Inability to complete complex tasks
Complete incapacitation, disorientation, and failure to thrive
Alzheimer’s= disease
dementia= a symptom
also symptoms of Parkinson’s, vascular dementia, AIDS dementia
Dementia: progressive and irreversible loss of mental capabilities
Treatment: use limited to disease stage
expensive and controversial
Cholinesterase inhibitors and memantine
Antipsychotics:
to treat dementia associated with AD
ex. olanzapine (Zyprexa)
Myasthenia Gravis: a disorder of the interface between nerves and muscles in which the muscles cannot respond to the nerve signal in order to contract
Cause
autoimmune damage to ACh receptors at the connection between a nerve and a muscle (neuromuscular junction); ACh receptors are destroyed at the motor end plate
Symptoms
weakness and fatigue especially of skeletal muscles
ptosis (upper eyelid drooping)
diplopia (double vision)
dysarthria (imperfect articulation of speech
dysphagia (difficulty swallowing)
respiratory difficulty
Treatment
Acetylcholinesterase drugs can produce improvement in all forms of myasthenia gravis
drug therapy doesn’t inhibit or reverse the immunologic flaw
Description
Lou Gehrig’s disease: a progressive degenerative disease of the nerves that leads to muscle weakness, paralysis, and eventually death
Symptoms
muscle weakness, muscle paralysis
Cause
excessive levels of glutamate which causes nerve damage
riluzole (Rilutek)
The only drug that prolongs ALS patient survival
Works by inhibiting the release of glutamate and inactivating sodium channels
Side effects include weakness, dizziness, gastrointestinal effects, liver enzyme elevation.
Seems to improve survival rate by 3 months in some patients
Restless leg syndrome: Severe pain or unpleasant sensations in the leg
Usually occurs at bedtime, can cause sleep disturbances
Cause unknown, may be worsened by stress
Symptoms may be related to withdrawal from sedatives, or to use of lithium, calcium channel blockers, or caffeine.
Non drug treatment includes stretching exercises, massage, and warm baths.
Drug therapy includes gabapentin (Neurontin), pramipexole (Mirapex), and ropinirole (Requip).
Fibromyalgia
Long-term pain over entire body; tenderness in joints, muscles, and tendons
Linked to sleep problems, fatigue, headaches, anxiety, and depression
Cause unknown; may be triggered by trauma, sleep disturbances, infection
Nondrug treatment includes physical therapy, exercise, light massage, and relaxation techniques.
Drug therapy includes duloxetine (Cymbalta) or pregabalin (Lyrica).
Symptoms include inattention, impulsivity, hyperactivity
Diagnosis involve documenting > 6 symptoms of inattention and > 6 symptoms of hyperactivity/impulsivity that impair life in > 2 settings for at least 6 months
Onset by age three, decline in hyperactivity with age but potential for persistence of inattention and impulsivity into adulthood
Coexisting conditions include learning disabilities, depression, anxiety
Inattention, hyperactivity, and impulsivity are used to diagnose ADHD
Yoga
Used in epilepsy and ADHD
5-hydroxytryptophan
Used in Parkinson’s disease to improve motor symptoms
Music therapy
Used in Parkinson’s disease to improve motor symptoms, speech, and bradykinesia
Ginkgo biloba
May provide slight benefit patients with early Alzheimer’s disease
Questionable benefit in preventing Alzheimer’s disease
Risks include variability in content of products; anti-platelet effects; interaction with warfarin, aspirin, anticonvulsants.
Depression: feelings of pessimism worry, intense sadness, loss of concentration, slowing of mental processes, problems eating and sleeping
Mania: mental and physical hyperactivity, disorganized behaviour, elevated mood; mood of extreme excitement, excessive elation, hyperactivity, agitation, increased psychomotor activity
Bipolar disorder: alternating episodes of depression and mania; mood swings that alternate between periods of major depression and periods of mild to severe chronic agitation
Post Traumatic Stress Disorder: Triggered by a traumatic event that leaves a person with intense, disturbing thoughts and feelings long after the event; Persistent anxiety or recurrent fear after a terrifying event
Seasonal Affective Disorder: depression which occurs in the fall and winter and remits in the spring and summer
Neurotransmitters
produced by a nerve cell and transmit information
ie. serotonin, norepinephrine, dopamine
psychiatric and mood disorders
deficiency of neurotransmitters
dysfunction of neurotransmitters
Antidepressants
goal of therapy is to change neurotransmitter levels
take 10-21 days to start working
medication Guide required
Overview of Disorders
hard to diagnose
often occur together in same patient
Need multiple medications for treatment
Good communication essential among patient family or caregivers. prescriber, pharmacist
Antidepressants
delay of onset of 10-21 days
not used on “as needed” basis
Depression
underlying causes: exogenous vs. endogenous sources
signs: crying, loss of interest in life or social activities, increased focus on death, significant weight loss or gain
symptoms: low self-esteem, pessimism, sleep disturbances, loss of energy and ability to think, feelings of worthlessness and guilt, poor memory, thoughts of suicide
neurotransmitters involved in mood: norepinephrine, serotonin, dopamine
Drug Regimens and Treatments for Depression
Patient response to drug therapy
response not immediate
may take 3-6 weeks for full response
drug therapy trial of at least 3-4 weeks
Risk for suicide
teens and young adults
highest risk is when starting drug therapy
monitor for worsening signs of depression, suicidal thoughts, unusual behaviours
Stopping Therapy
risk of facute withdrawal symptoms if stopped abruptly
worsened depression symptoms if dose not tapered
Clinical depression is the most severe psychiatric disorder
women more likely than men to have depression
depression occurs later in life in men
Selective Serotonin Reuptake Inhibitors (SSRI): block reuptake of serotonin, little effect on norepinephrine
Serotonin Norepinephrine Reuptake Inhibitors (SNRI): increase both serotonin and norepinephrine
Tricyclic Antidepressants (TCA): prevent reuptake of serotonin and/or norepinephrine
Monoamine Oxidase Inhibitors (MAOIs): inhibit enzymes that break down serotonin and norepinephrine
Serotonin syndrome
cause: presence of too much serotonin
Signs: racing heart, fever, high blood pressure, headache
risk factors: taking more than one antidepressant, taking St. John’s wort
Prognosis: potentially fatal
Selective Serotonin Reuptake Inhibitors: block the reuptake of serotonin
classified effects: Nausea, vomiting, dry mouth, drowsiness, insomnia, headache, diarrhea, sexual dysfunction, serotonin syndrome
Patients wish antidepressants worked immediately, but it is important to realize that it may take four weeks for these medications to achieve full effect. Antidepressants should help with sleep problems within a week or so, but other psychiatric effects may take longer to achieve full efficacy.
Additional uses for SSRIS Obsessive-compulsive disorder (OCD) A form of anxiety Obsessive thoughts impair function.
Repetitive behaviors relieve fears and anxiety. Premenstrual dysphoric disorder (PMDD) Emotional and behavioral changes during second half of a woman's menstrual cycle Similar symptoms to PMS but more severe Posttraumatic stress disorder (PTSD), fibromyalgia, anxiety, panic disorder, nerve pain (duloxetine)
Often confused
Celexa
Celebrex (arthritis)
Look-a-like
Prozac
Proscar (prostrated enlargement)
not alcohol
do not stop abruptly
Serotonin and norepinephrine Reuptake inhibitors work by blocking the reuptake of serotonin and norepinephrine
side effects: nausea, vomiting, insomnia, agitation, drowsiness
2 Weeks washout period before starting new class of antidepressants
severe hypertensive reactions with food containing high levels of tyramine
Periods of depression alternating with periods of mania, a state of overly high energy, excitement, hyperactivity, optimism, and increased psychomotor activity
Increased psychomotor activity can involve irritability, excessive involvement in work or other activities, grandiose ideas, racing thoughts, decreased need for sleep
Goals of Therapy
Treat acute episodes and prevent subsequent attacks
Mania: mood of extreme excitement, excessive elation, hyperactivity, agitation, and increased psychomotor activity
Bipolar Disorder: mood swings that alternate between major depression and mania
Unipolar Depression: major depression with no previous occurrence of mania
Post-traumatic stress disorder: Disorder characterized by persistent agitation or persistent,
recurrent fear after the end of a traumatic event and lasting for over a month or impairing work or relationship
Seasonal Affective Disorder: Form of depression that recurs in the fall and winter and remits in the spring and summer
The two-fold objective of drug therapy is to treat acute episodes and prevent subsequent attacks
Schizophrenia: A chronic mental health disorder characterized by delusions, disorganized speech and behavior, decrease in emotional range, neurocognitive deficit
Cause excessive dopamine levels in the limbic system
Positive symptoms include hallucinations and delusions
Negative symptoms are withdrawal, ambivalence, behaviour changes, memory loss and confusion
Treatment
Typical antipsychotic
Block dopamine receptors in all four dopamine pathways
Lead to unfavorable side effects extrapyramidal symptoms (EPS)
Atypical antipsychotics
Block dopamine receptors in the limbic system pathway instead of all four pathways
Improved efficacy and fewer side effects
Goals of Therapy: reduce symptoms such as thought disorder, hallucination, delusions
Afferent System: transmits information to the CNS from Receptors
Somatic Sensory: Sensory Information received from skin, fascia, joints, skeletal muscles, eyes, ears, nose, and tongue
Visceral Sensory: Sensory Information received from viscera
Efferent System: Sends information from the CNS to the body
Somatic Motor: Voluntary muscle movement
Autonomic: controls organs such as heart, lungs, stomach, and intestines
Autonomic Nervous System: Involuntary activities: respiration, circulation, digestion, body temperature, metabolism, blood glucose, sweating
Somatic nervous system: Acetylcholine only neurotransmitter between CNS and skeletal muscles
CNS
Acetylcholine (Ach)
Dopamine
Norepinephrine
GABA (gamma-aminobutyric acid)
Glutamate
Serotonin
PNS
Acetylcholine (Ach)
Norepinephrine
Chemical Signal is received on cell body and dendrites
Chemical Signal is converted to electrical signal or
Impulse travels down axon to the axon terminal
Axon terminal releases neurotransmitters
Acetylcholine: stimulates skeletal muscle, inhibits cardiac muscle, inhibits and excites smooth muscle and glands (CNS & PNS)
Gamma-Aminobutyric Acid: Primary inhibitory neurotransmitter in the brain; can impact muscle tone (CNS)
Dopamine: Inhibitory role; important in cognition, motivation, behavior, mood
Epinephrine: Effects in thalamus, hypothalamus, spinal cord
Norepinephrine: Modulates sympathetic part of the autonomic nervous system
Serotonin: Functions related to sleep, appetite, cognition, mood
Glutamate: Excitatory role; promotes cognitive function; most common neurotransmitter in the brain
ACh and GABA
ACh acts on receptors in smooth and cardiac muscle, skeletal muscle, and exocrine glands
ACh receptors blocked by anticholinergics
GABA regulates message delivery system of the brain
Dopamine, Epinephrine, and Norepinephrine
Dopamine acts on receptors in the CNS and kidneys
Epinephrine acts on cardiac and bronchodilator receptors
Norepinephrine acts on alpha and beta receptors
Serotonin and Glutamate
Serotonin acts on smooth muscle and gastric mucosa
Causes vasoconstriction which decreases blood flow
Emotional responses: depression, anxiety
Glutamate may be crucial to some forms of learning and memory
Alpha: vasoconstriction, raises blood pressure
Beta-1: increases heart rate and contrastive force of the heart
Beta-2: influences bronchodilation
Response of various adrenergic receptors to epinephrine/norepinephrine
Alpha receptors
Constriction of blood vessels
Decongestion
Beta-1 receptors
Increases heart rate and contrastive force of heart
Beta-2 receptors
Dilation of bronchial tubes and blood vessels
Drug Effects on the receptors (Nervous System)
Neurotransmitter binding causes cell membrane to be more permeable to various ions.
Activate enzyme systems that promote chemical reaction
Blocking, preventing transmitters from binding to receptors
Anticholinergics
Side Effects of Anticholinergics
Decreased GI motility (constipation)
Decreased sweating
Decreased urination
Dilated pupil and blurred vision
Dry eyes
Dry mouth
Seizure: Results from excessive firing of a small number of neurons with spread to adjacent neurons
Conscious periods and loss of control over movements or distortion of the senses
Convulsion: An involuntary contraction or series of contractions of voluntary muscles
Seizures and convulsions are not interdependent
Epilepsy: Neurologic disorder characterized by sudden and recurring seizures
Involves disturbances of neuronal electrical activity that
interfere with normal brain function
All epilepsy patients have seizures but not all patients with
seizures have epilepsy.
Seizures: Factors which influence the firing of neurons
• Positively charged ions increase firing.
• Negatively charged ions inhibit firing.
•Glutamate, an excitatory neurotransmitter, increases firing.
•GABA, an inhibitory neurotransmitter, decreases firing.
• Enzymes control neurotransmitter levels
• Disruption in enzymes = disruption of neurotransmitters
Causes of seizures
• Alcohol or drug withdrawal/use
• Epilepsy
• High fever
• Hypoglycemia and hyperglycemia
• Infection
• Brain tumors
• Trauma or head injury
Symptoms vary from staring to unconsciousness
localized in a specific area of the brain
almost always results from injury to cerebral cortex
occurs in about 65% of people with epilepsy
can progress to generalized seizures
Involves both hemispheres of the brain, no specific location
Four types
tonic-clinic
absence
myoclonic
atonic
Partial Seizure in a specific hemisphere
Simple partial seizure: twitching and sensory hallucination with no loss of consciousness (focal motor)
Complex partial seizure: blank stare, post seizure amnesia with impaired consciousness (psychomotor)
Generalized Seizures
Tonic-Clonic seizure: muscle rigidity followed by muscle jerks with shallow breathing, loss of bladder control, excess salivation (Grand Mal)
Tonic: body becomes rigid, patient may fall, lasts a minute or less
Clonic: starts with muscle jerks, may be accompanied by shallow breathing, loss of bladder control, and excess salivation; lasts a few minutes
Status Epilepticus: continuous tonic-Clonic convulsions, high fever, lack of oxygen; with or without loss of consciousness
lasts at least 30 minutes
high fever and lack of oxygen that can cause brain damage or death
Absence seizure (petit Mal): interruption of activities by black stare, rotating eyes, uncontrolled facial movements, rapid eye blinking, twitching or jerking of an arm or leg
no generalized convulsions
30 seconds or less
typically stops at the age of 10 or develop tonic-Clonic
Myoclonic seizure: occurs with sudden, massive brief muscle jerks which may throw patient down or nonpassive, quick jerks of the arms, hands, legs, or feet: consciousness not lost
can occur during sleep
Ten percent of patient who suffer from status epilepticus die regardless of treatment
Two goals of Antiepileptic Therapy
Seizure control or lessen the frequency
Prevent emotional and behavioral changes that may result from seizures
About 30% of patient do not comply due to side effects such as sedation and loss of cognitive processes
Principles of treatment- Different seizure types require different drugs
Initiate monotherapy at a low dose.
Increase dose gradually over 3-4 weeks
Monitor plasma concentrations, must be maintained at steady therapeutic levels
If insufficient response, polytherapy can be considered (severe cases).
Periodically evaluate continued need for therapy.
Monitor for drug interactions.
Watch for “dispense as written” on prescription.
Dispense with medication guide.
Newer drugs are seizure-specific
high potential for drug interactions
Anticonvulsants have narrow therapeutic ranges
prescribers often write for the brand name medications
Sedatives with anticonvulsant action
inhibit nerve impulse conduction and depress neurons in the brain
ex. Phenobarbital
oldest drug in the class
still used
sedation
more drugs Depakene and Epival are not interchangeable; Sabril is last chance drug
many clinical uses
potential for abuse
one use is as an anticonvulsant – acts on receptors in the brainstorm
ex. diazepam
Characterized by muscular difficulties and postural abnormalities
Signs
tremors while resting, rigidity, akinesia
manifests as poor posture control. shuffling gait, loss of overall muscle control
Cause
Alterations in the extrapyramidal system which controls movement
Imbalance between the neurotransmitters dopamine and Ach
Part of the CNS that controls motor activities
Made up of the basal nuclei (basal ganglia)
Chronic, degenerate condition
part of the CNS that controls motor activities
made up of basal nuclei (basal ganglia)
Most common extrapyramidal disease
Usually affects people over 60
Parkinson has no definitive test, diagnosed by symptoms
For normal muscle movement to be performed, 2 main neurotransmitters must be in balance
dopamine (inhibitor)
acetylcholine (stimulator)
In Parkinson disease, there neurotransmitters are not in balance
In the substania nigra, insufficient dopamine is released to counteract effects of Ach
This causes excessive motor nerve stimulation
Improves functional ability, clinical status, temporary remission
Does not alter disease process
side effects may necessitate numerous medication changes
tolerance develops easily
need larger doses
more side effects
Drug holiday
lower dose required
less side effects
may be taken off completely for a couple weeks so it stays effective
does not cross the blood brain barrier
not useful therapeutically
precursor- Levodopa (L-Dopa)
converted to Dopamine
Drugs that increase or enhance the action of dopamine in the brain
Drugs that inhibit the effect of acetylcholine
Multiple Sclerosis: An autoimmune disease in which the myelin sheaths around nerves degenerate
Causes loss of muscle control
can affect eyesight
can result in severe trembling in later stages
no cure but medications used to slow progression
Alzheimer’s Disease and Drug treatment:A degenerative brain disorder that leads to progressive dementia(symptom) and changes in personality and behavior, changes in personality and behavior, wandering, irritability or hostility
symptoms include loss of memory, intellect, judgment, orientation, speech
depression and anxiety are common
in early stages, patient complain of memory deficit, forgetfulness, misplacement of ordinary items
In final stages, disease progresses to incapacitation, disorientation, and failure to thrive.
Causes include insufficient ACh and hyperactive glutamate receptors
Drug therapy slows the disease but does not cure or reverse it.
Progressive and irreversible
Progression
Memory deficit, forgetfulness, misplacements of ordinary items
Inability to complete complex tasks
Complete incapacitation, disorientation, and failure to thrive
Alzheimer’s= disease
dementia= a symptom
also symptoms of Parkinson’s, vascular dementia, AIDS dementia
Dementia: progressive and irreversible loss of mental capabilities
Treatment: use limited to disease stage
expensive and controversial
Cholinesterase inhibitors and memantine
Antipsychotics:
to treat dementia associated with AD
ex. olanzapine (Zyprexa)
Myasthenia Gravis: a disorder of the interface between nerves and muscles in which the muscles cannot respond to the nerve signal in order to contract
Cause
autoimmune damage to ACh receptors at the connection between a nerve and a muscle (neuromuscular junction); ACh receptors are destroyed at the motor end plate
Symptoms
weakness and fatigue especially of skeletal muscles
ptosis (upper eyelid drooping)
diplopia (double vision)
dysarthria (imperfect articulation of speech
dysphagia (difficulty swallowing)
respiratory difficulty
Treatment
Acetylcholinesterase drugs can produce improvement in all forms of myasthenia gravis
drug therapy doesn’t inhibit or reverse the immunologic flaw
Description
Lou Gehrig’s disease: a progressive degenerative disease of the nerves that leads to muscle weakness, paralysis, and eventually death
Symptoms
muscle weakness, muscle paralysis
Cause
excessive levels of glutamate which causes nerve damage
riluzole (Rilutek)
The only drug that prolongs ALS patient survival
Works by inhibiting the release of glutamate and inactivating sodium channels
Side effects include weakness, dizziness, gastrointestinal effects, liver enzyme elevation.
Seems to improve survival rate by 3 months in some patients
Restless leg syndrome: Severe pain or unpleasant sensations in the leg
Usually occurs at bedtime, can cause sleep disturbances
Cause unknown, may be worsened by stress
Symptoms may be related to withdrawal from sedatives, or to use of lithium, calcium channel blockers, or caffeine.
Non drug treatment includes stretching exercises, massage, and warm baths.
Drug therapy includes gabapentin (Neurontin), pramipexole (Mirapex), and ropinirole (Requip).
Fibromyalgia
Long-term pain over entire body; tenderness in joints, muscles, and tendons
Linked to sleep problems, fatigue, headaches, anxiety, and depression
Cause unknown; may be triggered by trauma, sleep disturbances, infection
Nondrug treatment includes physical therapy, exercise, light massage, and relaxation techniques.
Drug therapy includes duloxetine (Cymbalta) or pregabalin (Lyrica).
Symptoms include inattention, impulsivity, hyperactivity
Diagnosis involve documenting > 6 symptoms of inattention and > 6 symptoms of hyperactivity/impulsivity that impair life in > 2 settings for at least 6 months
Onset by age three, decline in hyperactivity with age but potential for persistence of inattention and impulsivity into adulthood
Coexisting conditions include learning disabilities, depression, anxiety
Inattention, hyperactivity, and impulsivity are used to diagnose ADHD
Yoga
Used in epilepsy and ADHD
5-hydroxytryptophan
Used in Parkinson’s disease to improve motor symptoms
Music therapy
Used in Parkinson’s disease to improve motor symptoms, speech, and bradykinesia
Ginkgo biloba
May provide slight benefit patients with early Alzheimer’s disease
Questionable benefit in preventing Alzheimer’s disease
Risks include variability in content of products; anti-platelet effects; interaction with warfarin, aspirin, anticonvulsants.
Depression: feelings of pessimism worry, intense sadness, loss of concentration, slowing of mental processes, problems eating and sleeping
Mania: mental and physical hyperactivity, disorganized behaviour, elevated mood; mood of extreme excitement, excessive elation, hyperactivity, agitation, increased psychomotor activity
Bipolar disorder: alternating episodes of depression and mania; mood swings that alternate between periods of major depression and periods of mild to severe chronic agitation
Post Traumatic Stress Disorder: Triggered by a traumatic event that leaves a person with intense, disturbing thoughts and feelings long after the event; Persistent anxiety or recurrent fear after a terrifying event
Seasonal Affective Disorder: depression which occurs in the fall and winter and remits in the spring and summer
Neurotransmitters
produced by a nerve cell and transmit information
ie. serotonin, norepinephrine, dopamine
psychiatric and mood disorders
deficiency of neurotransmitters
dysfunction of neurotransmitters
Antidepressants
goal of therapy is to change neurotransmitter levels
take 10-21 days to start working
medication Guide required
Overview of Disorders
hard to diagnose
often occur together in same patient
Need multiple medications for treatment
Good communication essential among patient family or caregivers. prescriber, pharmacist
Antidepressants
delay of onset of 10-21 days
not used on “as needed” basis
Depression
underlying causes: exogenous vs. endogenous sources
signs: crying, loss of interest in life or social activities, increased focus on death, significant weight loss or gain
symptoms: low self-esteem, pessimism, sleep disturbances, loss of energy and ability to think, feelings of worthlessness and guilt, poor memory, thoughts of suicide
neurotransmitters involved in mood: norepinephrine, serotonin, dopamine
Drug Regimens and Treatments for Depression
Patient response to drug therapy
response not immediate
may take 3-6 weeks for full response
drug therapy trial of at least 3-4 weeks
Risk for suicide
teens and young adults
highest risk is when starting drug therapy
monitor for worsening signs of depression, suicidal thoughts, unusual behaviours
Stopping Therapy
risk of facute withdrawal symptoms if stopped abruptly
worsened depression symptoms if dose not tapered
Clinical depression is the most severe psychiatric disorder
women more likely than men to have depression
depression occurs later in life in men
Selective Serotonin Reuptake Inhibitors (SSRI): block reuptake of serotonin, little effect on norepinephrine
Serotonin Norepinephrine Reuptake Inhibitors (SNRI): increase both serotonin and norepinephrine
Tricyclic Antidepressants (TCA): prevent reuptake of serotonin and/or norepinephrine
Monoamine Oxidase Inhibitors (MAOIs): inhibit enzymes that break down serotonin and norepinephrine
Serotonin syndrome
cause: presence of too much serotonin
Signs: racing heart, fever, high blood pressure, headache
risk factors: taking more than one antidepressant, taking St. John’s wort
Prognosis: potentially fatal
Selective Serotonin Reuptake Inhibitors: block the reuptake of serotonin
classified effects: Nausea, vomiting, dry mouth, drowsiness, insomnia, headache, diarrhea, sexual dysfunction, serotonin syndrome
Patients wish antidepressants worked immediately, but it is important to realize that it may take four weeks for these medications to achieve full effect. Antidepressants should help with sleep problems within a week or so, but other psychiatric effects may take longer to achieve full efficacy.
Additional uses for SSRIS Obsessive-compulsive disorder (OCD) A form of anxiety Obsessive thoughts impair function.
Repetitive behaviors relieve fears and anxiety. Premenstrual dysphoric disorder (PMDD) Emotional and behavioral changes during second half of a woman's menstrual cycle Similar symptoms to PMS but more severe Posttraumatic stress disorder (PTSD), fibromyalgia, anxiety, panic disorder, nerve pain (duloxetine)
Often confused
Celexa
Celebrex (arthritis)
Look-a-like
Prozac
Proscar (prostrated enlargement)
not alcohol
do not stop abruptly
Serotonin and norepinephrine Reuptake inhibitors work by blocking the reuptake of serotonin and norepinephrine
side effects: nausea, vomiting, insomnia, agitation, drowsiness
2 Weeks washout period before starting new class of antidepressants
severe hypertensive reactions with food containing high levels of tyramine
Periods of depression alternating with periods of mania, a state of overly high energy, excitement, hyperactivity, optimism, and increased psychomotor activity
Increased psychomotor activity can involve irritability, excessive involvement in work or other activities, grandiose ideas, racing thoughts, decreased need for sleep
Goals of Therapy
Treat acute episodes and prevent subsequent attacks
Mania: mood of extreme excitement, excessive elation, hyperactivity, agitation, and increased psychomotor activity
Bipolar Disorder: mood swings that alternate between major depression and mania
Unipolar Depression: major depression with no previous occurrence of mania
Post-traumatic stress disorder: Disorder characterized by persistent agitation or persistent,
recurrent fear after the end of a traumatic event and lasting for over a month or impairing work or relationship
Seasonal Affective Disorder: Form of depression that recurs in the fall and winter and remits in the spring and summer
The two-fold objective of drug therapy is to treat acute episodes and prevent subsequent attacks
Schizophrenia: A chronic mental health disorder characterized by delusions, disorganized speech and behavior, decrease in emotional range, neurocognitive deficit
Cause excessive dopamine levels in the limbic system
Positive symptoms include hallucinations and delusions
Negative symptoms are withdrawal, ambivalence, behaviour changes, memory loss and confusion
Treatment
Typical antipsychotic
Block dopamine receptors in all four dopamine pathways
Lead to unfavorable side effects extrapyramidal symptoms (EPS)
Atypical antipsychotics
Block dopamine receptors in the limbic system pathway instead of all four pathways
Improved efficacy and fewer side effects
Goals of Therapy: reduce symptoms such as thought disorder, hallucination, delusions