Pharm exam 3

parkinsons disease

neurogenerative disorder associated with movement disorders and cognitive health decline

pathogenesis of parkinsons

reduced dopaminergic activation of D1 and D2 receptors and the sequential downstream effect on signaling pathways results in a net inhibitory tone on the thalamus

decline in dopamine

kinds of parkinson disease drugs

domaine agonists

MAO-B inhibitors

COMT inhibitors

DDC inhibitors

COMT inhibitors

parkinsons assessment: no significant impairment

consider MAO-B inhibitors

parkinsons assessment: tremor

anticholinergic: carbidopa/levodopa

parkinsons assessment: bradykinesia and rigidity

less than 65: domaine agonist

older than 65: carbidopa/levodopa

parkinsons assessment: postural instability

less than 65: dopamine agonist

older than 65: carbidopa/levodopa

MAO B inhibitors name

monoamine oxidase B inhibitors

MAO B I MOA

block dopamine breakdown and modestly extend duration of action of levodopa

irreversible or reversible inhibition of MAO

may decrease presynaptic reuptake of DA in brain

MAO B drugs

selegiline

rasagiline

safinamide

selegiline is what kind of parkinson drug

MAOB-I

rasagiline is what kind of parkinson drug

MAOB-I

safinamide is what kind of parkinson drug

MAOB-I

selegiline MOA

irreversible inhibition of MAO

may decrease presynaptic reuptake of DA in brain

rasagiline MOA

irreversible inhibition of MAO

safinamide MAO

reversible inhibition of MAO

MAOB-I role in therapy

neuroprotective: may delay need for levodopa by 9 months and has sympotomatic effects

no firm evidence tht it will slow neurogeneration

duration of benefit of MAOB-Is

limited to one year

selegiline and rasagiline indications

may be used as monotherapy in early parkinsons disease to dealy the need for other agents

safinamide indication

only to be used in combination with levodopa

MAOB-I ADEs

nausea

abdominal pain

agitation

confusion

insomnia

hallucinations

orthostatic hypotension

worsening dyskinesias

dry mouth

MAOB-I ADE management

administer with food

reduce dose

administoer dose earlier in the day

reduce dose of levodopa

manage symptomatically

MAOB-I drug interactions

combining with serotonergic activity drugs may precipitate serotonin syndrome

such as antidepressants, opiates, amphetamines and other sympathomimetics

ciprofloxacin: inhibits CYP1A2 metabolism of rasagiline

anticholinergic agents for parkinsons MOA

inhibiting the action of acetylcholine at the muscarinic receptor may normalize the balance between DA and ACh

anticholinergic agents role in therapy

primarily beneficial in improving tremor

some dystonic symptoms may also improve

not beneficial for bradykinesias or rigidity

anticholinergic ADEs

dry mouth

constipation

urinary retention

blurred vision

impaired memory

hallucination

anticholinergic agents for parkinsons drugs

benztropine

trihexylphenidyl

amantadine MOA

weak NMDA receptor antagonist that blocks glutamate

promotes DA release

anticholinergic like activity

amantadine role in therapy

most effectve against tremors

may have some improvement in rigidity and braydkinesias

managment of levodopa induced dyskinesias

amantadine ADEs

sedation

vivid dreams

depression

dizziness

confusion

hallucinations

psychosis

livedo reticularis - mottling of the skin

ankle edema

levodopa MOA

decarboxylated to dopamine to increase domaine concentration in the synapse

carbidopa MOA

inhibits peripheral decarboxylation of levodopa

decreases its conversion to dopamine in peripheral tissues

results in higher plasma levels of levodopa and an increased availability of levodopa for transport across the blood brain barrier

levodopa role in therapy

in combination with peripherally aciting L amino acid decarboxylase inhibitor makes it the most effective

used for symptomatic PD treatment

carbidopa role in therapy

reduces the occurrence of nausea, vomiting, arrhythmias, and hypotension with levodopa

carbidopa/levodopa ADEs

dyskinesias

periods of unpredictable loss of mobility

nausea: take with non protein small snack

kinds of dopamine agonists classes for PD

ergotamine derivatives

non-ergotamine non selective dopamine agonists

non-ergotomine selective agonists

ergotamine derivatives

bromocriptine

non-ergotomine non selective dopamine agonist

apomorphine

non-ergotamine selective dopamine agonists

pramipexole

ropinirole

rotigotine

dopamine agonists MOA

directly stimulates central dopaminergic receptors thereby increasing the effect, reducing the dosage requirements, or prolonging the duration of action of levodopa

ergotamine derivatives MOA

stimulates post synaptic D2 receptors

non-ergotamine non selective dopamine agonist MOA

stimulates post-synaptic D2 receptors

non-ergotamine selective dopamine agonists MOA

stimulates post synaptic D2 receptors in the striatum

non ergotamine selective dopamine agonists role in therapy

decrease symptoms or reduce dosage of levodopa in patients with controlled symptoms

dopamine agonists ADEs

nausea

vomiting

postural hypotension

confusion

sedation

hallucinations

dyskinesias due to levodopa

pramipexole pharmacokinetics

well absorbed

food decreases rate of absorption

minimal hepatic metabolism

primarily renal excretion

ropinirole pharmacokinetics

extensively metabolized in the liver by CYP1A2 to inactive metabolites

ropinirole drug interactions

decreases ropinirole clearance: ciprofloxacin, oral estrogens, fluvoxamine, mexiletine

increases ropinirole clearance: smoking, omeprazole

dopamine antagonists: phenothiazines, butyrtophenones, metoclopramide

catecholo-o-methyltransferase inhibitors (COMT) MOA

enhances the effect of levodopa by slowing the degradation by the enzyme catechol-O-methyltransferase

COMT inhibitors indications

for managing wearing off in combination with carbidopa/levodopa

kinds of COMT inhibitors

tolcapone

entacopone

tolcapone MOA

selective potent peripheral COMPT inhibitor

less potent central reversible COMt inhibitor

entacopone MOA

selective reversible peripheral COMT inhibitor

COMT inhibitor ADEs

tolcapone: hepatotoxicity

hypotension

syncope

diarrhea

hallucinations

dyskinesias

hyperpyrexia withdrawal

motor complications off

refers to periods of poor movement

return of tremor, rigidity, or slowness

motor complications on

refers to periods of good movement

end of dose wearing off

increase frequency of carbidopa/levodopa

add either COMT inhibitor or MAO-B inhibitor or dopamine agonist

add or switch to extended release carbidopa/levodopa

use levodopa inhalation

delayed on or no on response

administer carbidopa/levodopa on an empty stomach

use carbidopa/levodopa ODT

avoid carbidopa/levodopa SR

use apomorphine subQ or levodopa inhalation

start hesitation (freezing)

increase carbidopa/levodopa dose

add a dopamine agonist or MAO-B inhibitor

physical therapy

peak dose dyskineasias

use smaller doses of carbidopa/levodopa

reduce dose of adjunctive dopamine agonist

add amantadine

off period dystonia

usually subside with first dose of carbidopa/levodopa of day

if not: long acting dopamine agonist, carbidopa/levodopa, or baclofen

alzheimer’s disease

most common form of dementing illness

unkown etiology

pathogeneisis of alzheimer’s disease

amyloid plaque formation and neurofibrillary tangles are hallmarks

pharmacotherapy for alzheimer’s disease

does not cure nor arrest

pharmacotherapy focus of alzheimer’s disease

cognition

neuropsychiatric symptoms

functional ability

what should you do before initiating pharmacotherapy for alzheimer’s disease

review currrent medication list for culprits that could be causing cognitive impairment

cholinesterase inhibitors for alzheimer’s disease

donepezil

galantamine

rivastgmine

donepezil is what kind fo alzheimer’s disease drug

cholinesterase inhibitor

galantamine is what kind fo alzheimer’s disease drug`

cholinesterase inhibitor

rivastigmine is what kind fo alzheimer’s disease drug

cholinesterase inhibitor

donepezil MOA

reversible centrally acting cholinesterase inhibitor that inhibits hydrolysis of ACh and increases levels at the synapse

high specificity for acetylcholinesterase and not butyrylcholinesterase which minimizes peripheral effects

donepezil indications

mild to moderate alzheimer’s disease

stabilization of disease for up to 6-12 months followed by gradual decline for up to 5 years

donepezil metabolism

hepatically via CYP2D6 and CYP3A4 isoenzymes to some active metabolites

donepezil ADEs

gastrointestinal: nausea, diarrhea, and vomiting

HA

insomina

galantamine MOA

reversible acetylcholinesterase inhibitor

galantamine indications

mild to moderate alzheimer’s disease

galantamine metabolism

hepatically via CYP2D6 and CYP3A4 isoenzymes

galantamine ADEs

nausea

vomiting

diarrhea

HA

dizziness

rivastigmine MOA

reversible aceytlcholinesterase inhibitor

low activity in the periphery

rivastigmine indications

mild to moderate alzheimer’s disease

rivastigmine elimination

cholinesterase mediated hydrolysis to decarbamylated metabolite

rivastigmine ADEs

nausea→ early, improves with maintence

vomiting

diarrhea

memantine MOA

specific noncompetitive NMDA receptor antagonist

memantine indications

moderate to severe alzheimer’s disease

memantine elimination

renally

memantine ADEs

constipation

HA

insomina

dizzy

hallucinations

confusions

memnatine drug interactions

strong CYP3A4 inducers decrease the concentration of memantine

memantine clinical pearl

combination tablet fo donepezil and memantine

other therapies for alzheimer’s disease

brain vascular health

control HTN diabetes, and obesity

increase physical acitivty

decrease smoking

mediterranean or DASH diet

therapies not recommended for alzheimer’s disease

estrogen

anti-inflammatory agents

lipid-lowering therapy

therapies for alzheimer’s disease with insufficient evidence

vitamin E

vitamin B12

ginkgo biloba

medical foods

peptic ulcer disease

group of ulcerative disorders of the upper GI tract

ulcerations occure most often in the proximal portion of the duodenum and the stomach

two major forms of peptic ulcer disease

duodenal ulcers

gastric ulcers

GERD

gastroesophageal reflux disease

disorder characterized by retrograde movement of gastric contents from the stomach to esophagus

what analgesic can cause PUD

NSAID induced peptic ulcer disease

how do NSAIDs causes ulcers

they block COX 1/2

COX 1- keeps gastrointestinal mucosal integrity, platelet aggregation, and renal function

COX 2- mitogenesis and growth, female repro, bone, renal function

drugs that worsen GERD

anticholinergics

barbiturates

benzodiazepines

caffeine

calcium channel blockers

dopamine

estrogen

ethanol

isoproterenol

narcotic analgesics

nicotine

nitrates

phentolamine

progesterone

theophylline

general treatment of GERD

targeted at reversing pathophysiologic abnormalities

goals of GERD treatment

alleviate/eliminate symptoms

decrease frequency and duration

promote healing

prevent complications

goals of PUD treatment

relieve ulcer pain

accelerate ulcer healing

minimize ulcer related complication