Dopamine Releasers

AMANTADINE (Gocovri,Symmetrel)

Dopamine Releasers

⬆ Increased dopamine level at postsynaptic receptor sites by ⬇ dec reuptake and enhance dopamine synthesis and release

AMANTADINE (Gocovri,Symmetrel) MOA

(Gocovri,Symmetrel)

AMANTADINE BN

AMANTADINE (Gocovri,Symmetrel)

○ Also an antiviral agent

○ Have anticholinergic effect

○ Decreases TRAP (cardinal signs)

○ Given in combination with L-dopa

peak concentration: W/in approx 4 hrs

AMANTADINE (Gocovri,Symmetrel) Absorption

Crosses the placenta and the blood-brain barrier; enters breast milk.

AMANTADINE (Gocovri,Symmetrel) Distribution

3-8 L/kg

AMANTADINE (Gocovri,Symmetrel) Volume of distribution:

Approx 67%

AMANTADINE (Gocovri,Symmetrel) Plasma protein binding

mainly by N-acetylation

AMANTADINE (Gocovri,Symmetrel) Metabolism

Via urine (80-90% as unchanged drug and small amounts of an acetylated metabolite).

AMANTADINE (Gocovri,Symmetrel) Excretion

15 hrs

AMANTADINE (Gocovri,Symmetrel) half life

Livedo Reticularis (netlike rashes)

A skin condition. Reddish blue skin discoloration. Legs are commonly affected. Swollen blood vessels. Worsen in cold temperature.

AMANTADINE (Gocovri,Symmetrel) ADR

History of seizures and Heart failure

AMANTADINE (Gocovri,Symmetrel)

CONTRAINDICATIONS

Anticholinergics

More effective for tremor/rigidity

Anticholinergics

Used for mild symptoms, tremors

Anticholinergics

Less effective for bradykinesia and less effective for postural imbalance

Peripheral anticholinergic effects (Hypohydrosis, urinary constipation, dry retention, mouth, tachycardia, increase intraocular tension leading to glaucoma and nausea)

Anticholinergics ADR

Dizziness, Delirium, Disorientation, Anxiety, Agitation, Orthostatic Hypotension / Syncope, Impaired Memory

Anticholinergics other effects

Dryness

Anticholinergics toxicity

Benign Prostatic Hyperplasia (BPH) - can also cause urinary retention caused by enlargement of the prostate gland.

Anticholinergics Contraindications

Tremor

Huntington’s Disease

Ballismus

Tourette’s Syndrome

Athetosis

Restless Legs Syndrome

Wilson’s Disease

Other Movement Disorder

Tremor

May be alleviated by B-blockers including Propranolol but caution with cardiac heart failure, asthma, diabetes, hypoglycemia

Tremor

Consist of rhythmic oscillatory movements or repeating movements

Metoprolol

has been used with patients with concomitant pulmonary disease.

primidone and Topiramate

Antiepileptic drugs including

have been used to treat essential tremor

Intention Tremor

Postural Tremor

MAIN TYPES OF TREMOR i

Postural Tremor

occurs when your muscles try to hold parts of your body still against gravity.

Intention Tremor

occurs when you reach something and your hand starts shaking

PHYSIOLOGIC POSTURAL TREMOR

ESSENTIAL TREMOR

INTENTION TREMOR

REST TREMOR

TYPES OF TREMOR

REST TREMOR

Due to parkinsonism

INTENTION TREMOR

Present during movement

A postural tremor, sometimes familial (inherited)

PHYSIOLOGIC POSTURAL TREMOR

Normal phenomenon, enhanced amplitude by anxiety, fatigue, thyrotoxicosis (condition in which you have too much thyroid hormone in your body), and IV epinephrine

Huntington’s Disease

Inherited disorder characterized by progressive chorea (jerking movements) and dementia that begins at adulthood

Huntington’s Disease

Related to imbalance of neurotransmitters Dopamine, Acetylcholine, GABA, and perhaps other neurotransmitter in the basal ganglia

haloperidol, tetrabenazine

Huntington’s Disease Tx

Ballismus

Violent movements of the limbs, as in chorea, sometimes affecting only one side of the body

Tics

Tourette’s Syndrome manifested by

pimozide

Tourette’s Syndrome Tx

Tourette’s Syndrome

Unknown cause that frequently responds to haloperidol and other dopamine D2 receptor blockers, pimozide.

Athetosis

A continuous stream of slow, sinuous writhing movements (worm-like movement, rolling and twisting), typically of the hands and feet

athetoid movements

Movements typical to athetosis called

corpus striatum of the brain

Athetosis is said to caused damage by

Restless Legs Syndrome

➔ Unknown causes

➔ Unpleasant creeping discomfort in the limbs that occurs particularly when the Patient is at rest

Restless Legs Syndrome

More common in pregnant and uremic women, diabetic patients

Dopaminergic therapy is the preferred treatment and ropinirole, a long- acting drug

Restless Legs Syndrome preferred tx & drug

Opioid analgesics and benzodiazepine

Restless Legs Syndrome tx

Wilson’s Diseas

Progressive; may cause liver disease when left untreated

Wilson’s Diseas

Inherited disorder of copper metabolism results in deposition of copper salts in the liver and other tissues.

Wilson’s Diseas

Hyperkinetic movements

Wilson’s Diseas

Copper toxicity

Penicillamine

the antidote to remove the copper excess.

★ A chelating agent.