SKELETAL 2 Flashcards
Is characterized by the loss of cholinergic neurons in the nucleus basalis of Meynert
Alzheimer’s disease
Is associated with a loss of dopaminergic neurons in the substantia nigra.
Parkinson’s disease
The most prevalent of Neurodegenerative Diseases
Alzheimer’s disease
2nd most prevalent neurodegenerative disorder
Parkinson’s disease
Is a progressive neurological disorder of muscle movement, characterized by tremors, muscular rigidity, bradykinesia (slowness in initiating and carrying out voluntary movements), and postural and gait abnormalities. Most cases involve people over the age of 65.
Parkinsonism
Parkinsonism is correlated with destruction of ___ in the substantia nigra with a consequent reduction of dopamine actions in the corpus striatum parts of the brain’s basal ganglia system that are involved in motor control. Genetic factors do not play a dominant role of this, although they may exert some influence on an individual’s susceptibility to the disease.
dopaminergic neurons
The substantia nigra, part of the extrapyramidal system, is the source of dopaminergic neurons that terminate in the striatum. The dopaminergic system appears to serve as a tonic, sustaining influence on motor activity rather than participating in specific movements.
Substantia nigra
Normally, it is connected to the substantia nigra by neurons that secrete the inhibitory transmitter GABA at their termini in the substantia nigra.
neostriatum
Cells of the substantia nigra send neurons back to the neostriatum, secreting the inhibitory transmitter ___ at their termini.
dopamine
Destruction of cells in the substantia nigra results in the degeneration of the nerve terminals responsible for secreting dopamine in the neostriatum.
Parkinson’s disease
Parkinsonian symptoms infrequently follow viral encephalitis or multiple small vascular lesions.
Secondary parkinsonism
Drugs whose major pharmacologic action is blockade of dopamine receptors in the brain, may also produce parkinsonian symptoms. These drugs should not be used in parkinsonian patients.
phenothiazines and haloperidol
Is a metabolic precursor of dopamine. It restores dopaminergic neurotransmission in the corpus striatum by enhancing the synthesis of dopamine in the surviving neurons of the substantia nigra. Uses in early disease.
Levodopa
Side effects of Levodopa in large doses.
- nausea,
- vomiting,
- cardiac arrhythmias, and
- hypotension
A dopa decarboxylase inhibitor that does not cross the blood-brain barrier. It diminishes the metabolism of levodopa in the gastrointestinal tract and peripheral tissues; thus, it increases the availability of levodopa to the CNS.
Carbidopa
Decreases the rigidity, tremors, and other symptoms of parkinsonism.
Levodopa
Large, neutral amino acids (for example, leucine and isoleucine) compete with it for absorption from the gut and for transport across the blood-brain barrier. Thus, it should be taken on an empty stomach, typically 45 minutes before a meal.
levodopa
Adverse effect of Levodopa and carbidopa in the peripheral.
- Anorexia
- nausea
- vomiting
- tachycardia
- ventricular systoles
- hypotension
- mydriasis
- blood dyscasias
- brownish saliva and urine
CNS eefects of Levodopa and carbidopa
- visual and auditory hallucinations
- dyskinesias
- overactivity of dopaine
- mood changes, depression, psychosis and anxiety in levodopa
increases the peripheral breakdown of levodopa and diminishes its effectiveness
Vitamin pyridoxine (B6)
Concomitant administration of levodopa and ___, such as phenelzine, can produce a hypertensive crisis caused by enhanced catecholamine production; therefore, caution is required when they are used simultaneously.
monoamine oxidase (MAO) inhibitors
Are generally contraindicated in parkinsonian patients, because these potently block dopamine receptors and produce a parkinsonian syndrome themselves.
Antipsychotic drugs
Also called deprenyl, selectively inhibits MAO Type B (which metabolizes dopamine) at low to moderate doses but does not inhibit MAO Type A (which metabolizes norepinephrine and serotonin) unless given at above recommended doses, where it loses its selectivity.
Selegiline
Selegiline has little potential for causing hypertensive crises but if taken at high doses, the selectivity of the drug is lost, and the patient is at risk
severe hypertension
Selegiline is metabolized to ___, whose stimulating properties may produce insomnia if the drug is administered later than midafternoon.
methamphetamine and amphetamine
an irreversible and selective inhibitor of brain (MAO) Type B, has five times the potency of selegiline. Unlike selegiline, it is not metabolized to an amphetamine-like substance.
Rasagiline
inhibits Catechol-O-methyltransferase (COMT) → decreased plasma concentrations of 3-O-methyldopa → increased central uptake of levodopa → greater concentrations of brain dopamine
Entacapone or tolcapone
Differs from entacapone in that the former penetrates the blood-brain barrier and inhibits COMT in the CNS. However, the inhibition of COMT in the periphery appears to be the primary therapeutic action.
Tolcapone
does not exhibit this toxicity and has largely replaced tolcapone.
Entacapone
Is associated with tolcapone use. Therefore, it should be used along with appropriate hepatic function monitoring only in patients in whom other modalities have failed.
fulminating hepatic necrosis
An ergot derivative alkaloid and partial agonist at dopamine D2 receptors in the brain. The drug increases the functional activity of dopamine neurotransmitter pathways, including those involved in extrapyramidal function. It causes pulmonary and retroperitoneal fibrosis.
bromocriptine
Effect of Bromocriptine in patients with peripheral vascular disease, a worsening of the ___ occurs, and in patients with peptic ulcer, there is a ___ of the ulcer.
- vasospasm
- worsening
Non-ergot alkaloid. Has high affinity for the dopamine D3 receptor. Effective as monotherapy in mild parkinsonism & can be used together with levodopa in more advanced disease.
Pramipexole
- Mental disturbances (confusion, delusions, hallucinations, impulsivity) are more common with pramipexole than with levodopa.
- In rare cases, an uncontrollable tendency to fall asleep may occur.
- may be neuroprotective because it is reported to act as a scavenger for hydrogen peroxide.
Pramipexole
- Non-ergot alkaloid
- Has high affinity for the dopamine D2 receptor.
- It is effective as monotherapy and can be used with levodopa to smooth out response fluctuations.
- Metabolized by hepatic CYP1A2
Ropinirole
- A potent dopamine receptor agonist, apomorphine injected subcutaneously may provide rapid (within 10 min) but temporary relief (1–2 h) of “off-periods” of akinesia in patients on optimized dopaminergic therapy.
- Because of severe nausea, pretreatment for 3 days with antiemetics is necessary.
- Other side effects of apomorphine include dyskinesias, hypotension, drowsiness, and sweating.
Apomorphine
Increasing the release of dopamine, blockading cholinergic receptors, and inhibiting the N-methyl-D-aspartate (NMDA) type of glutamate receptors. The drug may cause restlessness, agitation, confusion, and hallucinations, and at high doses, it may induce acute toxic psychosis.
Amantadine
Antimuscarinic agents
- benztropine,
- trihexyphenidyl,
- procyclidine, and
- biperiden
- All of these drugs can induce mood changes and produce xerostomia (dryness of the mouth) and visual problems, as do all muscarinic blockers.
- They interfere with gastrointestinal peristalsis and are contraindicated in patients with glaucoma, prostatic hyperplasia, or pyloric stenosis.
Antimuscarinic agents
Blockage of ___ produces effects similar to augmentation of dopaminergic transmission
cholinergic transmission
Dementia of the Alzheimer’s type has three distinguishing features:
1) accumulation of senile plaques (β-amyloid accumulations)
2) formation of numerous neurofibrillary tangles
3) loss of cortical neurons particularly cholinergic neurons
Currently, four reversible AChE inhibitors are approved for the treatment of mild to moderate Alzheimer’s disease:
➢donepezil
➢galantamine
➢rivastigmine
➢tacrine
Competitive and may also be acting as an allosteric modulator of the nicotinic receptor in the CNS and, therefore, secondarily increase cholinergic neurotransmission through a separate mechanism.
Galantamine
Is associated with hepatotoxicity for AD drugs unlike the other drugs.
tacrine
Stimulation of ___ in the CNS appears to be critical for the formation of certain memories but overstimulation suggested a mechanism for neurodegenerative or apoptotic.
glutamate receptors
A dimethyl adamantane derivative that acts by physically blocking the NMDA receptor-associated ion channel partially. Often given in combination with an AChE inhibitor.
Memantine
Which occupy and block nearly all NMDA receptor-associated ion channel channels.
phencyclidine
NMDA-receptor antagonist is indicated for the management of amyotrophic lateral sclerosis (ALS). It blocks glutamate, sodium channels and calcium channels. It may improve the survival time and delay the need for ventilator support in patients suffering from ALS.
Riluzole
Bradykinesia has made drug treatment necessary in a 60-year-old male patient with Parkinson’s disease, and therapy is to be initiated with levodopa. Regarding the anticipated actions of levodopa, the patient would not be informed that
(A) A netlike reddish to blue discoloration of the skin is a possible side effect
(B) Dizziness may occur upon standing up
(C) He should take the drug in divided doses to avoid nausea
(D) The drug will probably improve his symptoms for a period of time but not indefinitely
(E) Uncontrollable muscle jerks may occur
A netlike reddish to blue discoloration of the skin is a possible side effect
The prescribing physician will (or should) know that levodopa
(A) Causes less severe behavioral side effects if given together with a drug that inhibits hepatic dopa decarboxylase
(B) Fluctuates in its effectiveness with increasing frequency a treatment continues
(C) Prevents extrapyramidal adverse effects of antipsychotic drugs
(D) Protects against cancer in patients with melanoma
(E) Has toxic effects, which include pulmonary infiltrates
Fluctuates in its effectiveness with increasing frequency a treatment continues
Modest improvement in the memory of patients with Alzheimer’s disease may occur with drugs that increase transmission at which receptors?
Cholinergic
