Pharmacotherapy and Calcium's Role in Alzheimer's Disease

This report provides a comprehensive overview of Alzheimer's disease pharmacotherapy, with a specific focus on the involvement of calcium ions in the disease's progression and potential therapeutic interventions. The report begins by explaining how calcium ions act as signaling molecules and neurotransmitters in the nervous system, including their role in neuronal excitability and synaptic function. It then delves into the dysregulation of calcium homeostasis in Alzheimer's disease, highlighting the link between familial Alzheimer's mutations and endoplasmic reticulum calcium leakage, as well as the influence of amyloid proteins on neuronal calcium influx. The core of the report examines the pharmacotherapy used to treat Alzheimer's disease, focusing on two main classes of drugs: cholinesterase inhibitors and memantine. Each drug's mechanism of action, pharmacokinetics, side effects, and precautions are detailed, including Donepezil, Rivastigmine, and Memantine. The report concludes by emphasizing the relevance of the topic for nurses and the potential for further research, as well as the importance for patients and healthcare professionals to understand the available treatment options and their implications.

ALZHEIMER'S DISEASE
PHARMACOTHERAPY AND
CA2+ INVOLVEMENT

Calcium as a regulatory and
signalling ion
 Calcium ions can act as neurotransmitters signals either
directly or indirectly(Popugaeva, Vlasova and Bezprozvanny,
2015) .
 Action potential usually stimulate calcium ions enabling them
to open voltages dependant calcium Channels (Hsu, Lane and
Lin, 2018)
 In neurons, calcium ions acts as transmitters where they can
alter the electrical conductivity by modifying the closing of
sodium and potassium channels in order to stimulate the
release of a neural transmitter substances(Popugaeva,
Pchitskaya and Bezprozvanny, 2017) .
 Calcium can later lead to regulation of metabolic activities,
cell growth, and long term change in synaptic efficiency thus
leading to destruction of neurones (Hsu, Lane and Lin, 2018).

Calcium Ions and Alzheimer's
disease
 The Familial Alzheimer’s disease mutations in the
presenilins are directly linked endoplasmic reticulum
calcium ions leaked function presenilins.
 As a result, calcium ions dysregulation is involved in
Alzheimer's disease(Small, 2009) . Various amyloid
proteins have been proved to be involved in the
induction of calcium ions influx into neurons,
making this calcium reflux alters neurological
excitability (Amidfar, Kim and Wiborg, 2018).
 In that case, therefore, calcium ions might be the key
to the step of studying the pathogenesis of
Alzheimer's disease(Popugaeva, Pchitskaya and
Bezprozvanny, 2017) .

Core pharmacology used in
treatment of Alzheimer's disease
 There are various drugs used in the
treatment of the disease namely
Cholinesterase inhibitors and memantine
(Downey, 2013).
 Cholinesterase inhibitors prevent the break
down of acetylcholine, delay worsening and
are generally tolerated.
 Memantine helps to improve memory,
reasoning, language and increase people
performance of little tasks (Downey, 2013).

Cholinesterase inhibitors
 These class of drugs prevent the break
down of acetylcholine which is usually
crucial in learning and memory (Downey,
2013).
 The drug also slow worsening of the
symptoms and their complications are
well tolerated(Small, 2013) .
 These drugs include Donepezil,
rivastigmine and galatamine.

Donepezil
 This drug is approved to treat all stages
of Alzheimer (Dyer et al., 2017).
mechanism of action
This medication acts as an enzyme blocker
in order to restore the balance of
neurotransmitters. The drug improve
awareness, memory and ability to function
(Downey, 2013)

Pharmacokinetics
 Donepezil is well absorbed in the body with a
bioavailability of 100% where it reached the peak
plasma concentration 3 to 4 hours after intake
(Dyer et al., 2017).
 The drug well distribute with a volume of
distribution of 12l/kg and a protein biding of more
than 96% (Alzheimer's Association, 2018)
 The medication is metabolised in the liver using CYP
450 isoenxymes and undergoes a glucuronidation.
 The drug have a half life of 70 hours and it is
eliminated through the urine (Alzheimer's
Association, 2018).

Side effects and
precautions
 Side effects include nausea, vomiting,
diarrhoea, weight loss, weakness, weight
loss, muscle cramps, tremor and dizziness.
These side effects normally last between 1-
3 weeks then lessen (Alzheimer's
Association, 2018)
 Precautions includes anybody allergic to
the drug, people with breathing problems,
fainting, seizures, stomach ulcers and
bleeding and people who have trouble in
urinating (Alzheimer's Association, 2018).

Rivastigmine
 The drug is approved to treat moderate
and mild Alzheimer
 Mode of action
The medication acts by inhibiting both
acetylcholinesterase and
butyrychonesterase.

Pharmacokinetics
 The extent of absorption of this drug is
not well known but have a distribution
rate of 1.8 to 2.7 l / kg with a protein
biding of 40%
 The drug is metabolized through
cholenesterase mediated hydrolysis with
a half life of i.5 hours.
 The medication is excreted majorly by
renal excretion with less than 1%
excreted in the faeces.