Chapter 8-9 Flashcards
Uses only two primary neurotransmitters, acetylcholine and norepinephrine .
ANS
Contains powerful networks of inhibitory neurons that are constantly active in modulating the rate of neuronal transmission
CNS
How do neurons in the CNS and ANS function similarly?
Both involve the release of neurotransmitters that diffuse across the synaptic space to bind to specific receptors on the postsynaptic neuron.
What triggers intracellular changes in neurons?
The recognition of the neurotransmitter by the membrane receptor of the postsynaptic neuron.
What is a major difference between the CNS and ANS?
The circuitry of the CNS is much more complex than that of the ANS.
How does the number of synapses in the CNS compare to that in the ANS?
The number of synapses in the CNS is far greater than in the ANS.
Neurotransmitters can be classified a either ____ or ____ depending on the nature of the action they elicit
Excitatory or inibitory
Stimulation of this neuron causes the release of neurotransmitter molecules such as glutamate or acetylcholine
Excitatory neurons
footnote
Stimulation of excitatory neurons cases a movement of ions that results in a depolarization of the postsynaptic membrane.
The stimulation of this neurons cases movement of ions that resultss in a hyperpolarization of the postsynaptic membrane
Inhibitory neurons
When glutamate or acetylcholine bind to receptors what happens
Causes transient increase in the permeablity of Na+ ions
footnote
Influx of ions causes weak depolarization or EPSP that moves the postsynaptic potential towards its firing threshold
Generating an allor-none action potential
Stimulation of inhibitory neurons releases what neurotransmitters
GABA or glyciine - which binds to receptors
footnote
When binded this causes a transient increase in the permeability or ions like K+ and Cl+
Influx of Cl+ and efflux of K+ causes a
Weak hyperpolarization
What are some of he neurodegenerative diseases of the CNS?
Parkinson’s disease
Alzheimer’s disease
MS
ALS
footnote
These illnesses are characterized by the progressive loss of selected neurons in discrete brain areas, resulting in characteristic disorders of movement, cognition, or both
A progressive neurological disorder of muscle movements, characterized by tremors, muscular rigidity, bradykinesia and postural and gait abnormalities
Parkinsonism
footnote
Postural and gait abnormalities refer to deviations from normal walking patterns and body alignment
Slowness in initiating and carrying out voluntary movements
bradykinesia
Part of the extrapyramidal system, the source f dopaminergic neurons that terminate neostriatum
Substantia nigra
Is connected to the substantia nigra by neurons that secrete the inhibitory tranmitter GABA
neostriatum
Destruction of cells in the substantia nigra results in the degeneration of the nerve terminals that secrete dopamine in the neostriatum
Parkinson’s disease
What drugs may produce parkinsonian symptoms (also called pseudoparkinsonism)
Drugs such as phenothiazines ad haloperidol
Major pharmacological action of these drugs is the blockade of dopamine receptors in the brain
Is a metabolic precursor of dopamine
Levidopa
- It ennhance the synthesis of dopamine in the surviving neurons in the substantia nigra restoring dopaminergic neurotransmission in the neostriatum
- an extremely short life which causes fluctuations in plasma concentration
-shoulld be taken 30 mins b4 meal
Levidopa is greatly enhanced by
Carbidopa
A dopamine decarboxylase inhibitor that does not cross the blood brain barrier
carbidopa
An efficacious drug regimen for the treatment of parkinson’s disease
Levidopa carbidopa
Reduces the severity of symptoms for the first few years of treatment.
Some of the adverse effects of levodopa
Anorexia
Nausea
vomiting
Positive reaction to coombs test
Saliva and urine are brownish
Mydriasis
Mood swings
Depression
anxiety
This drugs are generally contraindicated in parkinson’s disease
Antipsychotic drugs
What are sometimes used to treat levodopa-induced psychotic symptoms
Low doses of atypical anipsychotics
What vitamin increases the peripheral breakdown of levodopa and diminishes its effectiveness
Vitamin pyridoxine (b6)
What produces a hypertensive crisis cause by cathecolamine production
Levodopa and nonselective MAOIs (phenelzine)
Seleginline is also called
deprenyl
Selectively inhibits monoamine oxidase type B at lw moderate doses
selegiline
MAO type B - metabolizes dopamine
MAO type A - metabolizes norepinephrine and serotonin
Selegiline is metabolized to
Methamphetamine and amphetamine
Stimulating properties may produce insomnia if the drug is administered later than mid-afternoon
An irreversible and selective inhibitor of brain MAO type B
rasagiline
- Has five times the potency of selegiline
- not metabolized to a amphetamine like substance
What is the minor pathway for levodopa metabolism
Levodopa by catechol-O-methyltransferase to 3-O-methyldopa
Selectively and reversibly inhibit COMT
Entacapone and tolcapone
Leads to decrease plasma concentration of 3-0-methyldpa
Increased uptake of levodopa
Greater concentrations of brain dopamine
What anti parkinsonian compounds are ergot derivative
Bromocriptine
This toxicity does not exhibit in entacapone. It is associated with tolcapone use
Fulminating hepatic necrosis
Liver cell death
Nonergot derivatives that are orally active agents
Pramipexole and ropinirole
What are the nonergot drugs
Ropinirole
Pramipexole
Rotigotine
Apomorphine
These agents have a longer duration of action than that f levodopa
An injectable dopamine agonist that is used in severe and advanced stags of the disease
apomorphine
Used for the acute management of the hypomotility “off” phenomenon in advanced
Apomorphine
Off - times when it drops?
It is administered as a once daily transdermal patch that provides even drug levels over 24 hours
rotigotine
Inhibits Rena tubular secretion of organic bases and may increase the half-life of pramipexole
cimetidine
What may inhibit the metabolism of ropinirole that may require adjusting the dosage of it
Fluoroquinolone antibiotics and other inhibitors of the CTP450 1A2 isoenzyme
An antiviral drug that has an anti parkinsonian action
amantadine
It s used to treat influenza
- at high doses it may induce acute toxic psychosis
Also hypotension, urinary retention, peripheral edema, dry mouth
TRUE OR FALSE
If dopamine release is already at a maximum, amantadine has still an effect
FALSE
## footnote
Amantadine has no effect
Antimuscarinic agents used in parkinson’s disease
Benztropine, trihexyphenidyl, procyclidine, biperiden
These agents can induce mood changes and produce xerostomia
Contraindicated in patients with glaucoma, prostatic hyperplasia, pyloric stenosis
3 features of Alzheimer’s disease
Accumulation of senile plaques - b-amylois accumulations
Formation of numerous neurofibrillary tangles
Loss of cortical neurons
What are the AChE inhibitors approved for treatment of mild to moderate Alzheimer’s disease?
Donepezl
Galantamine
Rivastagmine
This may also augment the action of acetylcholine at nicotinic receptors in the CNS
Galantamine
The only agent approved for the management of dementia associated with parkinson’s disease
Rivstigmine
Also the only AChE inhibitor available as a transdermal formulation
- hydrolyzed by AChE to a carbamylate metabolite
It acts by blocking the NMDA receptor and limiting Ca2+ influx into the neuron
Memantine
- an NMDA receptor antagonist for moderate to severe Alzheimer’s
- often give with AChEE inhibitor
An autoimmune inflammatory demyelinating disease of the CNS
Multiple sclerosis
What has been used to treat acute exacerbation of MS
Corticosteroids
Dexamethasone
Prednisone
What are the chemotherapeutic agents that is also used in MS
Cyclophosphamide
Azathioprine
Help diminish the inflammatory response that lead t demyelination of the axon sheaths
Interferon B1a and B1b
Adverse effects may include depression, injection site reactions, hepatic enzyme increase and flu like symptoms
A systhentic polypeptide that resembles myelin protein and may act as a decoy to T-cell attack
Glatiramer
Adverse effects
Flushing
Chest paint
Itching
Anxiety
An oral drug that alters lymphocyte migration, resulting in fewer lymphocytes I the CNS
Fingolimod
May cause first-dose bradycardia
Associated with increased risk of infection and macular edema
An oral pyimidne synthesis inhibitor that leads to lower concentration of active lymphocytes in the CNS
Teriflunomide
## footnote
Cause elevated liver enzymes
Should be avoided in pregnancy
Oral agent that may alter the cellular response to oxidative stress to reduce disease progression
Dimethyl fumarate
Flushing and abdominal pain - adverse effects
Monoclonal antibody indicated for MS in patients who have failed first-line therapies
natalizumab
Cytotoxic anthracycline analog that kills t cells and may also be used for MS
Mitoxantrone
An orall potassium channel blocker that improves walking speeds with patients with MS
Dalfampridine
Progressive degeneration of motor neurons resulting inabilty to initiate orcontrolmuscle movement
ALS - amyotrophiclateral sclerosis
An NMDA receptor antagonist
Only drug for ALS
Act by inhibiting glutamate release and blocking sodium channels
Riluzole
## footnote
May improve survival time and delay the need fr ventilator support
Which one of the following combinations of antiparkin
sonian drugs is an appropriate treatment plan?
A. Amantadine, carbidopa, and entacapone.
B. Levodopa, carbidopa, and entacapone.
C. Pramipexole, carbidopa, and entacapone.
D. Ropinirole, selegiline, and entacapone.
E. Ropinirole, carbidopa, and selegiline.
Correct answer = B.
## footnote
To reduce the dose of levodopa and its
peripheral side effects, the peripheral decarboxylase inhibitor,
carbidopa, is coadministered. As a result of this combination,
more levodopa is available for metabolism by catechol-O
methyltransferase (COMT) to 3-0-methyldopa, which com
petes with levodopa for the active transport processes into
the CNS. By administering entacapone (an inhibitor of
COMT), the competing product is not formed, and more
levodopa enters the brain. The other choices are not appro
priate, because neither peripheral decarboxylase nor COMT
nor monoamine oxidase metabolizes amantadine or the
direct-acting dopamine agonists, ropinirole and pramipexole.
Peripheral adverse effects of levodopa, including
nausea, hypotension, and cardiac arrhythmias, can be
diminished by including which of the following drugs in
the therapy?
A. Amantadine.
B. Ropinirole.
C. Carbidopa.
D. Tolcapone.
E. Pramipexole.
Correct answer = C.
## footnote
carbidopa inhibits the peripheral
decarboxylation of levodopa to dopamine, thereby dimin
ishing the gastrointestinal and cardiovascular side effects of
levodopa. The other agents listed do not ameliorate adverse
effects of levodopa.
3 Which of the following antiparkinsonian drugs may cause
vasospasm?
A. Amantadine.
B. Bromocriptine.
C. Carbidopa.
D. Entacapone.
E. Ropinirole.
Correct answer = B.
Bromocriptine is a dopamine receptor
agonist that may cause vasospasm. It is contraindicated in
patients with peripheral vascular disease. Ropinirole directly
stimulates dopamine receptors, but it does not cause vaso
spasm. The other drugs do not act directly on dopamine
receptors.
Modest improvement in the memory of patients with
Alzheimer’s disease may occur with drugs that increase
ransmission at which of the following receptors?
À. Adrenergic.
B. Cholinergic.
C. Dopaminergic.
D. GABAergic.
E. Serotonergic.
Correct answer = B.
AChE inhibitors, such as rivastigmine,
increase cholinergic transmission in the CNS and may
cause a modest delay in the progression of Alzheimer’s dis
ease. Increased transmission at the other types of recep
tors listed does not result in improved memory.
Which medication is a glutamate receptor antagonist that
can be used in combination with an acetylcholinesterase
inhibitor to manage the symptoms of Alzheimer’s disease?
A. Rivastigmine.
B. Ropinirole.
C. Fluoxetine.
D. Memantine.
E. Donepezil.
Correct answer = D.
When combined with an acetylcholin
esterase inhibitor, memantine has modest efficacy in keep
ing patients with Alzheimer’s disease at or above baseline
for at least 6 months and may delay disease progression.
Which of the following agents is available as a patch
for once-daily use and is likely to provide steady drug
levels to treat Alzheimer’s disease?
A. Rivastigmine.
B. Donepezil.
C. Memantine.
D. Galantamine.
E. Glatirame-
Correct answer = A.
Rivastigmine is the only agent avail
able as a transdermal delivery system for the treatment of
Alzheimer’s disease. It may also be used for dementia asso
ciated with Parkinson’s disease.
Which of the following is the only medication that is
approved for the management of amyotrophic lateral
sclerosis?
A. Pramipexole.
B. Selegiline.
C. Galantamine.
D. Riluzole.
E. Glatiramer.
Correct answer = D. Riluzole continues to be the only agent
FDA approved for the debilitating and lethal illness of ALS.
It is used to, ideally, delay the progression and need for ven
tilator support in severe patients.
Which of the following medications reduces immune
system-mediated inflammation via inhibition of
pyrimidine synthesis to reduce the number of activated
lymphocytes in the CNS?
A. Riluzole.
B. Rotigotine.
C. Teriflunomide.
D. Dexamethasone.
Correct answer =C. Teriflunomide is believed to exert its
disease modifying and anti-inflammatory effects by inhibit
ing the enzyme dihydro-orotate dehydrogenase to reduce
pyrimidine synthesis.
Which of the following agents may cause tremors as
a side effect and, thus, should be used with caution in
patients with Parkinson’s disease, even though it is also
indicated for the treatment of dementia associated with
Parkinson’s disease?
A. Benztropine.
B. Rotigotine.
C. Rivastigmine.
D. Dimethyl fumarate.
Correct answer = C. Though rivastigmine is an acetyl
cholinesterase inhibitor, which can cause tremors as an
adverse effect, its use is not contraindicated in patients with
Parkinson’s disease, as this agent is also the only medi
cation approved for dementia associated with Parkinson’s
disease. It should be used with caution, as it may worsen
the parkinsonian-related tremors. A risk-benefit discussion
should occur with the patient and the caregiver before rivastigmine is used.
(10 Which of the following agents exerts its therapeutic
effect in multiple sclerosis via potassium channel
blockade?
A. Dalfampridine.
B. Donepezil.
C. Riluzole.
D. Bromocriptine.
Correct answer = A. Dalfampridine is a potassium channel
blocker and is the only agent that is indicated to improve
walking speed in patients with MS.
An unpleasant state of tension,apprehension, or uneasiness
Anxiety
Symptoms include tachycardia sweating trembling palpitations
Antianxiety drugs are also called
anxiolytics
Widely used anxiolytic drugs
benzodiazepines
Not necessarily best choice for insomnia and anxiety
Targets for benzodiazepines receptors
GABA receptors
A muscle relaxant that is believed to affect GABA receptors at the level of the spinal cord
Baclofen
Log acting benzodiazepine
Clorazepate
Chlordiazepoxide
Diazepam
Flurazepam
quazepam
Intermediate acting benzodiazepine
Alprazolam
Estazolam
Lorazepam
temazepam
Short acting benzodiazepine
Oxazepam
triazolam
Drug for patients experiencing frequent wakening
Temazepam
- occurs 1 to 3 hours after an oral dose
Effective in treating individuals who have difficulty in ginng to sleep
triazolam
A benzodiazepine used to facilitate amnesia while causing sedation prior to anesthesia
midazolam
Used as a adjuctinve therapy for certain types of seizures
clonazepam
DOC in terminating status epilepticus
Lorazepam and diazepam
Useful in the acute treatment of alcohol withdrawal and reduce the risk of withdrawal related seizures
Chlordiazepoxide
Clorazepate
Diazepam
Lorazepam
Oxazepam
Useful in the treatment of skeletal muscle spams
diazepam
Benzodiazepines are rapidly absorbed because they are
Lipophilic
A GABA receptors antagonist that can rapidly reverse the effects of benzodiazepine
flumazenil
- IV administration only
- may precipitate withdrawal in dependent patients or cause seizures
May be used alone or combination with a low dose of a benzodiazepine during the first weeks of treatment
SSRIs and SNRIs
Useful for the chronic treatment of GAD
Buspirone
- mediated by serotonin
- lacks anticonvulsant and muscle relaxant properties
Ultra short acting barbiturate that induce anesthesia
Thipental
May be used for the treatment of refractory status epilepticus
Phenobarbital
- has a specific anticonvulsant activity
Used as a sedative to assist in the management of tension-type or migraine headaches
Butalbital
Combined with butalbital
Acetaminophen
Caffeine
Aspirin
caffeine
Selectively benzodiazepine , no anticonvulsant or muscle relaxing properties
zolpidem
May shorten shor-lfie of zopidem
rifampin
Similar to zolpidem , causes fewer residual effects
zaleplon
A nonbenzodiazepine hypnotoc effective for insomnia, rapidly absorbed
eszopiclone
A selective agonist at the MT1 and MT2 subtypes of melatonin receptors
ramelteon
Treatment of insomnia, difficulty falling sleep
Antihistamine with setting prperties
Diphenhydramine, hydroxyzine and doxylamine
- treating mild types of situational insomia
Sedating antidepressants with strong antihistamine profiles
Doxepin
Long acting barbiturates
phenobarbital
Short acting barbiturates
Pentobarbital
Secobarbital
amobarbital
Ultra short acting
Thiopental
