PH SCI 310 Exam 3 Questions With
Correct Solution
Dementia - ANSWER progressive deterioration of memory and cognitive function
Reversible: can treat underlying cause and reverse - causes - hypothyroidism,
depression, b12 deficiency, sleep apnea, alcohol
Irreversible: incurable condition caused by alzheimers and stuff and strokes
Alzheimer's disease (AD) - ANSWER Most common type of dementia
Proposed to be a continuum from preclinical (no symptoms but brain changes) to full
symptoms
Early onset dementia - ANSWER 5-10% of AD
diagnosed before 65
half of cases are familial by inherited gene
some have no obvious cause
increased risk in down syndrome
late onset alzheimers - ANSWER most common AD
after age 65
may be influenced by genetics
may be influences by environment, lifestyle, trauma, etc.
Alzheimers in US - ANSWER 65-74: 5%
75-84: 13.1%
85+: 33%
200,000 early onset
predicted that 14 million by 2060
Alzheimers neuropathy - ANSWER Brain atrophy -- caused by cell death and loss of
neurons can be seen via MRI
Histological: plaques and tangles that can now be seen by imaging and biomarkers
,amyloid plaques - contain primarily aggregated (fibrillary) forms of beta-amyloid (AB)
which are caused by clumped proteins
Neurofibrillary tangles (NFTs) - primarily abnormal tau
Approved drugs to treat AD - ANSWER Acetylcholinesterase inhibitors
Glutamate receptor partial antagonists
AB targeting antibodies
Acetylcholinesterase inhibitors to treat AD - ANSWER Donepezil (aricept)
Stop the breakdown of acetylcholine which is needed for memory
only modest impact on cognition, function and behavior, do not impact disease course
not all patients see a benefit
side effects due to effect in periphery (nausea, loss of appetite etc.)
Glutamate receptor partial antagonist to treat AD - ANSWER Memantine (namenda) -
moderate to severe AD - glutamate NMDA non-competitive partial antagonist
glutaminergic excitotoxicity
modest effects, does not alter disease course
dizziness, headache, confusion, and constipation
NMDA Channel Stuff - ANSWER When glutamate is absent, NMDA receptor blocked by
Mg ions
Normal excitatory transmission: glutamate is released
NMDA (Ca2+ channel) opens if: neuron is depolarized, glutamate is bound,
co-transmitter glycine is also bound
Chronic block of NMDA receptors can interfere with memory formation and
neuroplasticity
Memantine - ANSWER un competitive (binds at Mg site) open channel receptor
antagonist
Basically only blocks channel when it is open, that bock is quickly reversible
May have actions at other receptors too
Usually given in combo with AChE inhibitor
Namzaric - single, extended release pill combo of memantine and donepezil
, prevents excess glutamate from damaging the brain
Immunotherapy for AD - ANSWER Clear or prevent worsening of AB plaque forms that
are proposed to cause the disease
Antibody - protein complex made and used by immune system to neutralize foreign
invaders, each antibody recognizes a specific protein sequence
Lecanemab (leqembi) - ANSWER antibody that binds with high affinity to AB protofibrils -
FDA approved early 2023 for MCI or early dementia in AD - reduced plaque hella in
clinical trial and had modest impacts on cognitive decline - side effects of amyloid
related imaging abnormalities like edema or micro hemorrhage
Controversies - only 3% black, ARIA risk, some interactions with blood thinning drugs,
only moderate effect for cost and patient burden.
Histamine - ANSWER Small signaling molecule found in many tissues
produced by mast cells, basophils (stored)
produced by certain cells in gastric mucosa
produced by certain CNS neurons
Histamine receptors - ANSWER 4 types (H1, H2, H3, H4)
Different expression patterns
different downstream signaling mechanisms
selective antagonists and agonists have been identified
H1 anti used clinically, H2 used clinically for reducing acid, H3 used clinically for
narcolepsy
Histamine Effects (H1 receptor) - ANSWER H1 found primarily on smooth muscle,
vascular endothelium and sensory nerves
H1 stimulation results in: smooth muscle in intestine, bronchi, and uterus contractions,
vasodilation and edema at small blood vessels, and sensory nerve stimulation
CNS neurons: increases wakefulness inhibits appetite, regulates emesis
Type 1 Hypersensitivity - stimulus is not noxious but promotes an immune response
(allergen) - evokes the production of specific type of protein (IgE antibody) by cells of
immune system - subsequent exposure causes mast cell activation and histamine
release
Allergies - ANSWER urticaria (rash), conjunctivitis (puffy/ red eyes), and rhinitis (hay
fever)
Correct Solution
Dementia - ANSWER progressive deterioration of memory and cognitive function
Reversible: can treat underlying cause and reverse - causes - hypothyroidism,
depression, b12 deficiency, sleep apnea, alcohol
Irreversible: incurable condition caused by alzheimers and stuff and strokes
Alzheimer's disease (AD) - ANSWER Most common type of dementia
Proposed to be a continuum from preclinical (no symptoms but brain changes) to full
symptoms
Early onset dementia - ANSWER 5-10% of AD
diagnosed before 65
half of cases are familial by inherited gene
some have no obvious cause
increased risk in down syndrome
late onset alzheimers - ANSWER most common AD
after age 65
may be influenced by genetics
may be influences by environment, lifestyle, trauma, etc.
Alzheimers in US - ANSWER 65-74: 5%
75-84: 13.1%
85+: 33%
200,000 early onset
predicted that 14 million by 2060
Alzheimers neuropathy - ANSWER Brain atrophy -- caused by cell death and loss of
neurons can be seen via MRI
Histological: plaques and tangles that can now be seen by imaging and biomarkers
,amyloid plaques - contain primarily aggregated (fibrillary) forms of beta-amyloid (AB)
which are caused by clumped proteins
Neurofibrillary tangles (NFTs) - primarily abnormal tau
Approved drugs to treat AD - ANSWER Acetylcholinesterase inhibitors
Glutamate receptor partial antagonists
AB targeting antibodies
Acetylcholinesterase inhibitors to treat AD - ANSWER Donepezil (aricept)
Stop the breakdown of acetylcholine which is needed for memory
only modest impact on cognition, function and behavior, do not impact disease course
not all patients see a benefit
side effects due to effect in periphery (nausea, loss of appetite etc.)
Glutamate receptor partial antagonist to treat AD - ANSWER Memantine (namenda) -
moderate to severe AD - glutamate NMDA non-competitive partial antagonist
glutaminergic excitotoxicity
modest effects, does not alter disease course
dizziness, headache, confusion, and constipation
NMDA Channel Stuff - ANSWER When glutamate is absent, NMDA receptor blocked by
Mg ions
Normal excitatory transmission: glutamate is released
NMDA (Ca2+ channel) opens if: neuron is depolarized, glutamate is bound,
co-transmitter glycine is also bound
Chronic block of NMDA receptors can interfere with memory formation and
neuroplasticity
Memantine - ANSWER un competitive (binds at Mg site) open channel receptor
antagonist
Basically only blocks channel when it is open, that bock is quickly reversible
May have actions at other receptors too
Usually given in combo with AChE inhibitor
Namzaric - single, extended release pill combo of memantine and donepezil
, prevents excess glutamate from damaging the brain
Immunotherapy for AD - ANSWER Clear or prevent worsening of AB plaque forms that
are proposed to cause the disease
Antibody - protein complex made and used by immune system to neutralize foreign
invaders, each antibody recognizes a specific protein sequence
Lecanemab (leqembi) - ANSWER antibody that binds with high affinity to AB protofibrils -
FDA approved early 2023 for MCI or early dementia in AD - reduced plaque hella in
clinical trial and had modest impacts on cognitive decline - side effects of amyloid
related imaging abnormalities like edema or micro hemorrhage
Controversies - only 3% black, ARIA risk, some interactions with blood thinning drugs,
only moderate effect for cost and patient burden.
Histamine - ANSWER Small signaling molecule found in many tissues
produced by mast cells, basophils (stored)
produced by certain cells in gastric mucosa
produced by certain CNS neurons
Histamine receptors - ANSWER 4 types (H1, H2, H3, H4)
Different expression patterns
different downstream signaling mechanisms
selective antagonists and agonists have been identified
H1 anti used clinically, H2 used clinically for reducing acid, H3 used clinically for
narcolepsy
Histamine Effects (H1 receptor) - ANSWER H1 found primarily on smooth muscle,
vascular endothelium and sensory nerves
H1 stimulation results in: smooth muscle in intestine, bronchi, and uterus contractions,
vasodilation and edema at small blood vessels, and sensory nerve stimulation
CNS neurons: increases wakefulness inhibits appetite, regulates emesis
Type 1 Hypersensitivity - stimulus is not noxious but promotes an immune response
(allergen) - evokes the production of specific type of protein (IgE antibody) by cells of
immune system - subsequent exposure causes mast cell activation and histamine
release
Allergies - ANSWER urticaria (rash), conjunctivitis (puffy/ red eyes), and rhinitis (hay
fever)
