Treatments for Wilson Disease: The 2 forms of oral zinc salts are zinc acetate, zinc sulfate and zinc gluconate. Which one has better absorption? Which one is more tolerable?

Best absorption= zinc acetate More tolerable (than zinc sulfate) w/ respect to GI side effects= Zinc gluconate

Movement Disorder 3- MJ Flashcards by Megan Jacobson

Which disease?

•Impaired biliary copper excretion leads to accumulation of copper in several organs (liver, brain, cornea)

Wilson disease

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The following are sxs of which disease?

•Symptoms include liver and CNS

Liver – N/V/fatigue/jaundice/muscle cramps
CNS - tremors or uncontrolled movements, muscle stiffness, problems with speech, swallowing, or physical coordination

Wilson Disease

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What are the 2 treatment options for Wilson Disease?

Chelating agents (D-penicillamine, Trientine)
Oral zinc

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The following describes which tx option for Wilson Disease?

•remove extra copper from the body by releasing it from organs into the bloodstream

Chelating agents (D-penicillamine, Trientine)

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MOA of which med used to tx Wilson Disease?

•Contains a free sulfhydryl group that functions as a copper chelating moiety**

D-penicillamine

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ADEs of which med used to tx Wilson Disease?

•Early onset:

fever
cutaneous eruptions
lymphadenopathy
neutropenia
thrombocytopenia,
proteinuria

•Late onset-months to years: proteinuria

D-penicillamine

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Txs for Wilson Disease:

What should you give patients who are taking D-penicillamine in order to prevent pyridoxal phosphate deficiency**

Pyridoxine

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How does trientine (a copper chelator) differ from D-penicillamine?

by a lack of sulfhydryl group
Chelates copper by forming a stable complex with its four constituent nitrogens

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The following describes which drug used to treat Wilson Disease?

Chelates copper by forming a stable complex with its four constituent nitrogens and is as effective as D-penicillamine
MOA: Functions principally by removing copper from less strongly bound sites on proteins and membranes, and it increases renal copper excretion

Trientine

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What is the pharmacokinetics of Trientine, a med used to tx Wilson Disease?

Poorly absorbed; only 1 percent of the ingested amount is excreted in the urine.

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Treatments for Wilson Disease

T/F: Trientene has more adverse effects than D-penicillamine

FALSE

Trientine has fewer ADEs than D-penicillamine

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Wilson Disease treatments: Trientine

Hypersensitivity reactions and pancytopenia are _____
Neurologic worsening is seen but appears to be ______ common than with D-penicillamine

rare
less

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Treatments of Wilson disease:

Trientine is not specific to copper, it also chelates _____. Because of this, what should you not coadminister with this medication?

Iron

So don’t give iron! The trientine iron complex is nephrotoxic

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Wilson Disease Treatment: Trientine

Copper deficiency induced by trientine can lead to _____ overload in the liver.
This excess______ may potentiate liver injury

iron

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Monitoring:

Adequacy of trientine treatment (for Wilsons Disease) should be determined by measuring _____ _____ ______, which should be in the range of 200 to 500 mcg (3 to 8 micromoles) daily

24-hour copper excretion

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MOA of which med used to tx Wilson Disease?

interferes with the absorption of copper
Induces metallothionein (an endogenous chelator of metals) in enterocytes which has a greater affinity for copper than for zinc, causing it to bind luminal copper and thereby preventing its entry into the circulation
Excreted in stool

Oral Zinc

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Treatments for Wilson Disease:

The 2 forms of oral zinc salts are zinc acetate, zinc sulfate and zinc gluconate.
Which one has better absorption? Which one is more tolerable?

Best absorption= zinc acetate
More tolerable (than zinc sulfate) w/ respect to GI side effects= Zinc gluconate

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What are the 2 adverse effects of oral zinc?

GI upset

2. Elevation in serum amylase (also seen in saliva) and lipase w/o clinical evidence of pancreatitis

What disease?

disorder of the motor neurons of the ventral horn of the spinal cord (lower motor neurons) and the cortical neurons that provide their afferent input (upper motor neurons)
gradual deterioration and death of motor neurons
rapidly progressive weakness, muscle atrophy, fassciculations, spasticity, dysarthria, dysphagia, resp. compromize
Sensory, autonomic and oculomotor function generally spared

ALS

Suspected etiology of which disease?

•Evidence that glutamate reuptake may be abnormal in the disease, leading to accumulation of glutamate and excitotoxic injury

ALS

Which med used to treat ALS?

Presynaptic and postsynaptic effects
Inhibits glutamate release**

•Inactivation of voltage-dependent Na+ channels**

•Ability to interfere with intracellular events that follow transmitter binding at excitatory amino acid receptors**

Riluzole

Which ALS med’s in vitro action is blocked by pertussis toxin?

Riluzole

Which med? (used to tx ALS)

absorbed orally and is highly protein bound
High fat meals decrease absorption
extensive metabolism in the liver by both CYP–mediated hydroxylation and glucuronidation

Riluzole

What are the 5 ADEs of riluzole? (drug used to tx ALS) "HANDE"

1. _**HTN\***_ 2. _**Abd pain\***_ 3. _**Neuromuscular and arthralgia, tremor\***_ 4. _**Decreased lung function\***_ 5. _**Elevations of serum transaminases (periodic monitoring recommended)\***_ "HANDE"

Which ALS drug has the following: * Slows decline of physical function- MOA unknown * Free radical scavenger * Prevents oxidative damage to cell membranes

Edaravone

Which drug (Riluzole or Edaravone) is indicated for patients with ALS who: * Have a disease duration of \<2yrs * Living independently * Have an FVC ≥80 percent

Edaravone

What are the 4 ADEs of Edaravone (used to tx ALS) and why should you be cautious of giving this to a pt w/ asthma?

1. Injection site contusion 2. Gait disturbance 3. HA 4. Allergic rxns (b/c of sodium bisulfite) sulfites can cause serious asthmatic reactions in as \<5% of asthmatic pts

What are the 3 meds you can give for symptomatic therapy of ALS, specifically **spasticity**?

1. _**Baclofen \***_ 2. _**Tizanidine \***_ 3. _**Clonazepam \***_

**What does Baclofen do to tx ALS?**

**_•Baclofen acts to restore the lost inhibition by stimulating postsynaptic GABA receptors_** (note- Baclofen works postsynaptically and TIzanidine acts presynaptically)

How does Tizanidine help tx ALS?

•Tizanidine acts presynaptically to **stimulate GABA release** from spinal cord inhibitory interneuron. (note- Baclofen works postsynaptically and TIzanidine acts presynaptically)

MOA of TIzanidine or Baclofen? (used to tx ALS) ## Footnote * GABA_B receptor agonist= \_\_\_\_\_\_ * agonist of α2 adrenergic receptors in the CNS=\_\_\_\_\_\_\_

**_•GABA_B receptor agonist= Baclofen_** (B for Baclofen) **_•Agonist of α2 adrenergic receptors in the CNS= Tizanidine_** * Increases presynaptic inhibition of motor neurons

What is the 1 ADE of Baclofen? (used to tx ALS)

**_Sedation_**

T/F: an Alternative for delivery of Baclofen for tx of ALS is: directly into the space around the spinal cord using a **surgically implanted pump** and an **intrathecal catheter**

True

What are the 3 ADEs of Tizanidine? (used to tx ALS) "DAD"

**_•Drowsiness_** •**_Asthenia_** (abnormal physical weakness or lack of energy) **_•Dizziness_**

Which drug class can be used to tx ALS and are effective **antispasticity agents** but can **contribute to respiratory depression** in pts w/ advanced ALS?

Benzodiazepines (Diazepam or Clonazepam)

What is the MOA of Benzodiazepines (Diazepam/clonazepam) in the tx of ALS

•Enhances the inhibitory effect of GABAA receptors

What are the 4 **_ADEs_** ("CADS") of Benzodiazepines in the tx of ALS? **_What other condition exhibits these effects?_**

1. Amnesia 2. Confusion 3. Drowsiness 4. Slurred speech Other condition: Being Drunk

Which disease? ## Footnote * Neuromuscular disease characterized by **weakness** and **marked fatigability of skeletal muscle** * Exacerbations and partial remissions occur frequently * Defect in the synaptic transmission- **autoimmune** response primarily to the **ACh receptor** at the post-junctional end plate.

Myasthenia Gravis

What are the 2 drugs used to tx Myasthenia Gravis and what is their mechanism?

Anticholinesterase drugs: ("NPs treat Myasthenia Gravis") * Pyridostigmine * Neostigmine

What is the mechanism of Neostigmine and Pyridostigmine, anticholinesterase drugs used to tx myasthenia Gravis

**_Inhibit the action of the metabolizing enzyme acetylcholinesterase_**

Tx of Myasthenia Gravis: What is the drug of choice to reverse too much acetylcholine?

Atropine (anticholinergic)

What are the 6 ADEs of anticholinesterase medications? What 2 are most important because they could be life threatening?

ADEs: "SLUDGE" 1. Salivation 2. Lacrimation 3. Urination 4. Diarrhea 5. GI upset 6. Emesis Most important: 1. **Cardio** 2. **Respiratory** 3. Pupils will be constricted--\> how to judge it