PHARM 1 EXAM #3 Flashcards
Neurotransmitters (NTs) + Receptors + Enzymes in Sympathetic vs Parasympathetic Nervous Systems
Sympathetic Nervous System (SNS)
NTs: Norepinephrine, Epinephrine, Dopamine
Receptors: a1, a2, b1, b2
Enzymes: Monoamine Oxidase (MAO), Catechol-O-Methyltransferase (COMT)
Parasympathetic Nervous System (PNS)
NTs: Acetylcholine (ACh)
Receptors: muscarnic, nicotinic
Enzymes: Acetylcholinesterase (ACh-ase)
What is Alzheimer’s Disease (AD)?
Alzheimer’s disease (AD) is characterized by progressive memory loss, impaired thinking, personality changes (neuropsychiatric symptoms), and inability to perform routine tasks of daily living.
Symptoms of Alzheimer’s Disease
— Memory loss
— Confusion
— Inability to communicate
— Aggressive behavior
— Depression
— Psychoses
— Progression to loss of memory, logical thinking, and judgment; time disorientation; personality changes; hyperactivity; tendency to wander; inability to express oneself; and later hostility, paranoia
Pathophysiology of Alzheimer’s disease
— Incurable dementia illness
— Chronic, progressive neurodegenerative conditions
— Marked cognitive dysfunction
— Onset usually occurs between ages 45 and 65 years, risk increases after 65.
— Neuritic plaques form (outside of neurons)
— Neurofibrillary tangles are in neurons.
— Cholinergic neurotransmitter abnormality
Which are the most common degenerative diseases of nerves?
1st = Alzheimer’s Disease
2nd = Parkinson’s Disease (PD)
Summarize the pathophysiology of Parkinsonism
Parkinson’s:
– Chronic neurologic disorder
– Imbalance of the neurotransmitters dopamine (DA) and acetylcholine (ACh)
– Marked by degeneration of neurons of the
extrapyramidal motor tract
– Reason for the degeneration of neurons is
unknown
Characteristics of Parkinsonism
– Tremors of head, neck, and limbs
– Rigidity (increased muscle tone)
– Bradykinesia (slow movement)
– Postural changes: head and chest thrown forward
– Shuffling walk
– Lack of facial expression
– Pill-rolling motion of hands
– Common non-motor symptoms: depression,
psychosis, dementia, sleep disturbances
Differences between depression vs. psychosis
Depression — lack of motivation, disinterest; “blah” feeling..don’t care
Psychosis — lack of being in touch with reality; hallucinations, paranoia present
What are the treatments (Tx) regimens for Parkinsonism?
– Anticholinergics
– Dopaminergics
– Dopamine agonists
– MAO-B inhibitors
– COMT inhibitors
Action of Anticholinergics in treatment of Parkinson’s Disease
oldest drugs used as treatment
— Inhibits release of acetylcholine (ACh); parasympatholytic
— Blocks cholinergic receptors in order to push the ACh influence down in CNS, which helps to restore the balance of ACh + Dopamine in the body
— Reduce the rigidity and some of the tremors characteristic of parkinsonism
— Minimal effect on bradykinesia
— Used to treat drug-induced parkinsonism, or pseudoparkinsonism
NON-DRUG Tx for Mirgraines
Adequate sleep
Exercise
Avoiding triggers
Once headache begins
Quiet, dark room with ice pack to neck
Supplements
Riboflavin (Vitamin B2)
Coenzyme Q-10
Feverfew
Butterbur
Interventions for taking Anticholinergic Drugs
— Counsel patients who take an anticholinergic to have routine eye exams because anticholinergics are contraindicated in patients with glaucoma.
— Encourage patients to relieve a dry mouth with hard candy, ice chips, or sugarless gum.
— Monitor urine output (I&Os) for early detection of urinary retention.
— Increase fluid intake, fiber, and exercise to avoid constipation.
Antiparkinsonism Drugs RN Interventions
— Monitor for orthostatic hypotension.
— Administer drug with low-protein foods.
— Avoid vitamin B6, alcohol, other depressants.
— Do not abruptly discontinue
— Warn of harmless brown discoloration of urine and sweat.
— Assess for suicidal tendencies.
— Assess symptom status and “on-off” phenomenon.
— Monitor blood cell counts, liver and kidney function.
Correlation with protein-rich foods + Medication + Parkinson’s Disease
— Food does slow drug absorption.
— High-protein foods interfere with drug transport to CNS.
— Foods high in vitamin B6 include lima, navy, kidney beans; cereals.
— Vitamin B6 inhibits conversion of levodopa to dopamine.
— A conservative amount of vitamin B6 is needed to prevent vitamin B6 deficiency (peripheral neuritis, muscle weakness).
— want low protein foods with PD medications
Actions of Dopaminergics in treatment of Parkinson’s Disease
— Converts to dopamine
— A mimetic that mimics dopamine and becomes dopamine in the body
Centrally Acting Anticholinergics: Benztropine (Cogentin) + Trihexyphenidyl (Artane)
— Reduce tremor and possibly rigidity
— No reduction of bradykinesia
— Less effective than levodopa or the dopamine agonists but better tolerated
— Used as second-line therapy for tremor
— Most appropriate for younger patients with mild symptoms
— Avoided in the elderly, who are intolerant of CNS side effects (for example, sedation, confusion, delusions, hallucinations)
Action of Dopamine Agonists in treatment of Parkinson’s Disease + Drugs
— Converted to dopamine and stimulates receptors to increase mobility
E.g. Carbidopa-levodopa (Sinemet)
Advantages of combining Carbidopa/Levodopa
More dopamine reaches the basal ganglia and that smaller doses of levodopa are required to achieve the desired effect
Contraindications to Dopaminergic therapy (carbidopa/levodopa (Sinemet))
— Narrow-angle glaucoma; severe cardiac, renal, hepatic disease; and suspicious skin lesions (activates malignant melanoma).
— Has a short half-life and must be taken 3-4 times per day
Side effects of Dopaminergics In Antiparkinsonism drugs
— Fatigue, insomnia
— Dry mouth
— Blurred vision
— Orthostatic hypotension, palpitations, dysrhythmias
— Urinary retention
— GI disturbance: nausea, vomiting
— Dyskinesia, psychosis, severe depression
Drug interaction with Carbidopa-levodopa (Sinemet) in Dopaminergics
Decrease levodopa effect with:
— Anticholinergics
— Phenytoin
— Tricyclic antidepressants
— MAO inhibitors
— Benzodiazepines (works in CNS)
— Phenothiazines (works CNS)
— Vitamin B6
Because PD patients have too much ACh, there will be an imbalance of ACh + dopamine levels r/t dopamine becoming less effective if taken concurrently
Side effects for Anticholinergics
Dizziness, drowsiness, anxiety, headache
Insomnia, paresthesia, restlessness
Blurred vision, ocular hypertension
Weakness, dry mouth, GI distress
Anhidrosis, urinary retention
”Can’t see, can’t spit, can’t pee, can’t sht!”*
Action of MAO-B Inhibitors in treatment of Parkinson’s Disease
MAO-I = Monoamine Oxidase B Inhibitors
— Inhibit MAO-B enzyme that interferes with dopamine
— MAO = enzyme that breaks down NTs in the peripheral nervous system (PNS)
— MAO-B = enzyme that breaks down dopamine, therefore if we inhibit the enzyme —> an increase availability of dopamine in the CNS
COMT inhibitors in the treatment of Parkinson
— Inhibit COMT enzyme that inactivates dopamine
— By stopping the breakdown of dopamine in the CNS + peripheral[P]NS in order to improve the effects of dopamine bioavailability
Side Effects for MAO-Is Selegiline + Parkinson’s Disease
— Dizziness, headache, nausea, dry mouth
— Orthostatic hypotension, hypertension
— Impulse control disorder, suicidal ideation
— Not as popular, but an option
_Interaction: foods high in tyramine can cause hypertensive crisis; hard to manage
