Wk 8 - Drugs Acting on Central Nervous System

Central Nervous System

• Brain & Spinal Cord

• very important structure of the CNS is its protective mechanisms that not all chemicals can pass through it, this affects the pharmacodynamics of drugs because some of them cannot penetrate the CNS.

• One vital protective structure is the Blood Brain Barrier (BBB). This represents therapeutic challenge to drug treatment of brain related disorders because a large percentage of drugs are carried bound to plasma proteins and are unable to cross the brain.

Anxiolytic and Hypnotic Drugs

• Anxiety

  • a feeling of tension, nervousness, apprehension or fear that usually involves unpleasant reactions to a stimulus, whether acutal or unknown.

  • Is classified as mild, moderate, severe and panic

    • Mild Anxiety - Typically doesn't significantly interfere with daily life. Can be managed with coping mechanisms or stress-reduction techniques. (Worry, unease)

    • Moderate Anxiety - Can disrupt daily activities and make it challenging to function normally. May require professional help or medication. (fear, dread)

    • Panic Anxiety - Can be debilitating and significantly interfere with daily life. Often requires professional treatment to manage. (sense of impending doom)

• Sedation

  • the loss of awareness and reaction to environmental stimuli

• Hypnosis

  • Extreme sedation resulting in further CNS depression and sleep

• These conditons occur due to increase excitatory neurotansmitters causing rapid brain impulse conduction causing restlessness, irritability, loss of concentration, loss of mental focus and sympathetic responses like palpitations, tremors, diaphoresis, increase breathing and increase blood pressure.

• Classified into Three

  • Barbiturate

  • Benzodiazepines

  • Non-Benzodiazepines

Mechanism of Action

• to enhance the effect of GABA (Gamma Amino Butyric Acid), therefore decreasing conduction of rapid impulses causing symptoms of anxiety.

• GABA (Gamma Amino Butyric Acid) - an inhibitory neurotransmitter to decrease impulses in the synapses of the brain

Barbiturates

• drug action is to enhance GABA effect.

• CNS depressants

• Inhibit neuroral impulse conduction in the ascending RAS

• Depress cerebral cortex

• Depress motor output

• This used to be the drug of choice to manage anxiety but its depressant effect may cause severe respiratory depression that this is not primarily used for anxiety today

• Indication

  • Relief of the signs and symptoms of anxiety

  • Sedation

  • Insomnia

  • Preanesthesia

  • Seizures

• Pharmacokinetics

  • Barbiturates are absorbed well, reaching the peak levels in 20 to 60 minutes.

  • It is metabolized in the liver and excreted in the urine

• Contraindications and Cautions

  • Barbiturates are more addicting than other anxiolytic drugs.

  • May cause severe CNS depression and respiratory dysfunction.

  • Contraindicated in pregnant women and clients with heaptic and renal dysfunction

• Adverse Effects

  • CNS depression, paradoxical excitement, anxiety and hallucinations.

  • Gastrointestinal signs and symptoms like nausea, voimiting, constipation, diarrhea and epigastric pain.

  • Cardiovascular effects include bradycardia, hypotension and syncope

• Drug-Drug Interactions

  • Increase CNS depression when given with alcohol, antihistamines, and other tranquilizers

  • Altered response to phenytoin

  • MAO cause increase serum levels and effect

  • Decrease effectiveness of the following drugs: anticoagulants, digoxin, tricyclic antidepressants, corticosteroids and oral contraceptives

• Drug Samples (…barbital)

  • Phenobarbital

  • Secobarbital

  • Amobarbital

Benzodiazepines

• drug action is to enhance GABA effect to cause inhibition of impulse transmission

• Act in the limbic system and the RAS

• Causes interference with neurons firing

• Lower doses assist with anxiety o Higher doses cause sedation and hypnosis

• Indications

  • Anxiety Disorders

  • Alcohol Withdrawal

  • Hyperexcitability and Agitation

  • Preoperative relief of anxiety and tension

• Pharmacokinetics

  • this is well absorbed in the GIT with peak levels achieved in 30 minutes.

  • This is lipid soluble and well distributed in the body crossing the BBB, placenta and breast milk.

  • Metabolized in the liver and excreted in the urine

• Contraindications and Cautions

  • Contraindicated in Clients with allergy to benzodiazepines, psychosis, clients with acute narrow angle glaucoma, shock, acute alcohol intoxication which may exacerbate the depressant effects of the drugs.

  • Contraindicated in pregnancy as this is known to possible cause cleft lip or palate, inguinal hernia, cardiac defects, microcephaly or pyloric stenosis if taken during the first trimester.

  • Caution should be used in the elderly or debilitated patients an those with hepatic and renal functions

• Adverse Effects

  • Sedation, drowsiness, depression, lethargy

  • anticholinergic effects like drying of mount, constipation, orthostatic hypotension, urinary retention, dysrhythmias, blood dyscrasias and phlebitis.

  • Withdrawal syndrome may occur with abrupt cessation characterized by nausea, headache, vertigo, malaise and headache.

• Drug-Drug Interactions

  • Increase CNS depression when taken with alcohol

  • Increase in effect when taken with cimetidine, oral contraceptives, or disulfiram

  • Decrease in effect if given with theophylline or ranitidine

• Drug Samples (…zepam)

  • Diazepam

  • Lorazepam

  • Clonazepam

Non-Benzodiazepines

• Other Drugs used for anxiety that do not fall under Benzodiazepine

1. Paraldehyde

   • Old drug used for Delerium Tremens, seizures, absorbed and metabolze in the liver.

   • It has a distinctve odor and cannot be stored in plastic containers

2. Meprobamate

   • An old drug used to manage anxiety for 4 months, works in the limbic system.

   • metabolized in the liver and excreted in the urine

3. Chloral Hydrate

   • Frequently used to produce nocturnal sedation or preoperative sedation. Unknown mechanis of action.

   • absorned in the GIT, metabolized in the liver and excreted in the urine

4. Zolpidem

   • Used to treat insomnia.

   • Metabolized in the liver and excreted in the urine

5. Anti-Histamines

   • Dipenhydamine (Benadryl)

   • Promethazine (Phenergan)

   • Used or its drowsiness effect in anxiety.

   • With anticholinergic effect. Used during preoperatively or postoperatively to decrease use of narcotics

6. Buspirone

   • No sedative,anticonvulsant, or muscle relaxant properties, unknown mechanism of action, reduces anxiety without many CNS effects.

   • Absorbed in the GIT, metabolized in the liver an excreted in the urine

7. Beta-Blockers

   • Propranolol

   • Metoprolol

   • Decreasing sympathetic effect to lessen signs nd symptoms of anxiety

Nursing Considerations

• Do not administer intraarterially because of possible serius areriospasm and gangrene may develop

• Do not mix IV drugs with other drugs

• Give parenteral forms if oral forms are not feasible and switch to oral which is safer

• Give IV drugs slowly to avoid hypotension effects

• Promote safety measures

• Monitor hepatic and kidney function

• Taper dose of drugs gradually o

• Provide comfort measures to help patient tolerate the effects of drugs

• Provide thorough health teaching about drug effects and adverse reactions

• Offer support and encouragement

• For overdose of Benzodiazepine, Flumazenil must be ready as its antidote.

Antidepressant Drugs

• Depression being an affective disorder is recognized by its clnical manifestations such as sleep disturbances, they have little energy, inability to perform daily activity.

  • Affect - People’s feelings in response to their environment

  • Affective Disorder - A person’s mood goes far beyond the usual, normal “ups and downs”

• They may describe overwhelming feelings of sadness, despair, hopelessness and disorganization.

• Pharmacology explains depression by Biogenic Amine Theory.

Biogenic Amine Theory

• This theory explains that depression occurs due to decreasing neurotransmitters, norepinephrine, serotonin and dopamine.

• When impulses travel across the synapses, neurotransmitters are released into the symapse, they bind in the receptors in the post synaptic neural membrane and help impulse to be conducted. After which, neurotransmitters are removed by enzymes or they may go back to the presynaptic neuron:

  

• Limbic System

  • area responsible for over all emotion and behavior

• In the Limbic System, there are 3 neurotransmitters being released (Norepinephrine, Serotonin and Dopamine)

• After impulse is transmitted across the synpase, and enzyme called Mono Amine Oxidase will remove them.

• Some however may go back to the pre synaptic neuron the process called reuptake of Neurotrnasmitters. If they are not available in the synapse, there will be no more impulse transmission

• depression results from decreasing neurotransmitter in the limbic system which may happen due possibly to:

  1. Overused of neurotransmitters ( Norepinephrine, Dopamine and Serotonin)

  2. Increase effect of Mono Amine Oxidase ( MAO ) enzyme

  3. Increase reuptake of neurotransmitter back to presynaptinc neuron

Mechanisms of Action

• Inhibit the enzyme Mono Amine Oxidase (MAO), leading to increased NE or 5HT in the synaptic cleft

• Inhibit Reuptake of Neurotransmitters, leading to increased neurotransmitter levels in the synaptic cleft

• Regulate receptor sites and breakdown of neurotransmitters, leading to an accumulation of neurotransmitters in the synaptic cleft

Tricyclic Antidepressants (TCA)

• inhibit presynaptic reuptake of neurotransmitter, norepinephrine and serotonin, which leads to accumulation of these neurotransmitters in the synaptic cleft and increased stimulation of post synpatic receptors

• Pharmacokinetics

  • it is abosrbed in the gastrointestinal tract, reaching the peak in 2 to 4 hours.

  • Widely distributed in the tissue including the brain.

  • Metabolized in the liver and excreted in the urine. They cross the placenta and the breast milk.

• Contraindications and Caution

  • Contraindicated to those with known allergy to TCA.

  • Clients with recent myocardial infarction because of its cardiovascular effects.

  • Caution should be used in clients with Gastrointestinal and Genitourinary tract disorders.

  • The presence of hepatic and renal impairment increases toxicity of the drugs.

• Adverse Effects

  • CNS effects like sedation, hallucinations, fatigue, cardiovascular effects, unstable blood pressure, abnormal rhtyhms, myocaridal infarction, anticholinergic effects like drying of the mouth, constipation, urinary retention

  • Remember Mnemonic

  • C - Cardiovascular Effects

  • A - Anticholinergic Effects

  • S - Sedation

  • H - Hypotension or Hypertension

• Drug-Drug Interactions

  • The effects of TCA may increase if combined with Ranitidine, Fluoxetine and Cimetidine especially the anticholinergic effects

  • Oral anticoagulant level may increase if combined with TCA and risk for bleeding increases.

  • Increase effect with sympathomimetic drugs especially its cardiovascular effects

• Drug Samples

  • Imipramine

  • Amitryptilline

  • Clomipramine

Mono Amine Oxidae Inhibitors

• these drugs inactivate the enzyme MAO to increase the neurotransmitters in the synapses.

• Pharmacokinetics

  • absorbed in the GIT, reaching peak levels in 2 – 3 hours.

  • metabolized in the liver and excreted in the urine.

  • They pass the placenta and breast milk and not used in pregnancy

• Contraindications and Cautions

  • Contraindicated in clients with cardiovascular disease, hepatic and renal disease.

  • Caution should be used in psychiatric patients

• Adverse Effects

  • More adverse effects than other antidepressant drugs.

  • Dizziness, excitement, nervousness, mania, hyperfexia, tremors, confusion, insomina, agitation and blurred vision.

  • Liver toxicity, Cardiovascular toxicity.

  • Anticholinergic effects

• Drug-Drug Interaction

  • Drug interaction with other antidepressant drugs include hypertensive crisis, coma and severe convulsion.

  • A period of 6 weeks should elapse after stopping SSRI and beginning MAOI.

• Drug-Food Interactions

  • Tyramine-rich food which normally broken down by MAO enzymes in the GIT maybe absorbed in high concentration in the resence of MAOI and may cause hypertensive crisis.

  • Fermented Foods

  • Aged Foods

  • Cured Foods

  • Overripe Foods

• Drug Samples

  • Isocarboxazid - Used for patients who did not respond to or could not take newer, safer antidepressants

  • Phenelzine - Used for some patients who did not respond to newer, safer antidepressants

  • Tranylcypromine - Used for adult outpatients with reactive depression

Selective Serotonin Reuptake Inhibitors

• these drug specifically block the reuptake of serotonin with little or no effect on Norepinpehrine. SSRIs do not have the many adverse effects of TCAs and MAOIs

• Indications

  • Depression

  • Obsessive Compulsive Disorders (OCD) Panic attacks

  • Bulemia

  • Post Traumatic Stress Disorder (PTSD)

• Pharmacokinetics

  • well absorbed in the GIT, metabolized in the liver and excreted in the urine or feces.

  • SSRIs are associated with congenital abnormalities. They passed the placenta and the breastmilk

• Contraindications & Caution

  • Those with allergy to SSRIs

  • pregnancy and lactation.

• Adverse Effects

  • CNS effects like headache, drowsiness, dizziness, insomnia, anxiety, tremor, agitation and seizures.

  • Anti cholinergic effects on the gastrointestinal tract and genitourinary tract

• Drug Samples

  • Sertraline

  • Paroxetine

  • Fluoxetine

Nursing Considerations

• Limit drug access to potentially suicidal patients to decrease the risk of overdose

• Monitor the patient for 2 – 4 weeks to ascertain onset and full effects

• Monitor blood pressure and orthostatic blood pressure carefully

• Monitor liver function

• Withold medication dose in client with severe headache that may due to severe hypertension and cerbrovascular effects

• Have phentolamine or another adrenergic blocker for hypertensive crisis

• Provide comfort measures to help the client tolerate drug effects

• Provide list of food that is low or no tyramine to clients on MAOI therapy

• Offer support and encouragement to help patients cope with the disease and drug regimen

Psychotherapeutic Drugs

• Mental disorders have several classifications. For this course, discussion include only drugs used for Schizophrenia and Mania, two of the most common psychiatric disorders.

• Schizophrenia

  • the most common type of psychotic disorders.

  • This prevents an individual in functioning in the society.

  • Some clinical manifestations include, hallucinations, delusions, paranoia, speech abnormalities and affcetive problems

• Mania

  • associated with Bipolar illenss

  • Mania is characterized by periods of extreme overactivity and excitement

• Narcolepsy

  • daytime sleepiness and sudden periods of loss of wakefulness

  • Caused by problems with stimulation of the brain by the reticular activating system (RAS)

  • problems with response to that stimulation

• Attention Deficit Disorder (ADHD)

  • inability to concentrate on one activity for longer than a few minutes

  • state of hyperkinesis

  • usually diagnosed in school-aged children but can occur in adults

• Drugs for mental disorders are called Psychotherapeutic drugs.

  • Drugs for Schizophrenia are called Anti Psychotic Drugs

  • Drugs for Mania are called Anti Manic Drugs

Antipsychotic Drugs

Mechanism of Action

• Typical Antipsychotic Drugs

  • block Dopamine receptors in the limbic system, in the reticular activating system and the brain.

  • This group of antipsychotic may block all dopamine receptors including those not associated with psychoses

• Atypical Antipsychotic Drugs

  • block Dopamine and Serotonin receptors.

  • This group will lock only the receptors of Dopamine and Serotinin which are responsible for occurrence of psychosis making them more specific drugs for Psychotic disorders

Drug Classifications

• Typical Antipsychotic Drugs

  • once known as major tranquilizers

  • primarily dopamine receptor blockers

  • used to treat disorders involving thought processes

  • Older drugs, they are less potent and associated with more adverse effects

    → Chlorpromazine

    → Fluphenazine

    → Thioridazine

    → Haloperidol

• Atypical Antipsychotic Drugs

  • block both dopamine receptors and serotonin receptors

  • may alleviate some of the unpleasant neurological effects and depression of typical antipsychotics

    → Clozapine

• Pharmacokinetics

  • Antipsychotic drugs are erratically absorbed in the GIT, metabolized in the liver and excreted in the bile and urine.

  • Widely distributed in the tissues, being released up to 6 months after they are discontinued.

  • Drugs cross the placenta and breast milk so they are not given to pregnant and lactating mothers

• Contraindications and Cautions

  • Contraindicated in patients with Parkinson’s disease, cardiovascular disease, severe hypotension and bone marrow suppresion

• Adverse Effects

  • Anti cholinergic effects like drying of the mouthe, constipation and urinary retention, Sedation effect, Orthostatic hypotension and extra pyramidal symptoms.

  • Remember Mnemonic

    • A – Anti cholinergic effect

    • S – Sedation

    • H – Hypotension

    • E – Extra pyramidal Symptoms

  • Extra Pyramidal Symptoms

    • Parkinson’s like syndrome, Dystonia, Akathisia, Tardive dyskinesia (happen because of dopmaine blocking effect in the basal ganglia altering its function of coordination and fine motor function.)

Nursing Considerations

• Do not allow patients to crush or chew the tablet as it decreases absorption of the drugs

• Monitor for orthostatic hypotennsion

• Consider warning the patient or the patient’s guardian on the risk of tardive dyskinesia

• Monitor CBC to check signs of bone marrow suppression

• Provide positioning of legs to decrease discomfort of dyskinesia

• Provide sugarless candies for drying of the mouth

• Encourage the patient to void before taking the dose if urinary retention is a problem

• Provide safety measures such as side rails and assistance in ambulation if there are CNS effects

• Provide vison examination to determine ocular changes

• Conduct thorough health teaching on the effects and adverse effects of the drugs

• Offer support and encouragement to help patients cope with their drug regimen

Anti Manic Drugs - Lithium

Mechanism of Action

• Lithium alters sodium transport in the nerve and muscle, inhibit the release of norepinephrine and dopamine slightly and decreases intraneuronal content of second messengers.

• The last action may modulate impulses to control hyperactive state in mania

• Pharmacokinetics

  • Lithium is absorbed in the GIT. It slowly crosses the BBB.

  • Dehydration and sodium depletion may cause the kidneys to reabsorb more Lithim thus increasing serum levels and toxicity.

  • Lithium crosses the palcenta and breastmilk

• Contraindications and Cautions

  • Contraindicated to those with allergy to the drug, dehydration, hyponatremia and leukemia

• Adverse effects

  • Toxicity associated with serum level of Lithium. ( Therapeutic level 0.6 – 1.2 mmol/L)

  • Serum level less than 1.5 mmol/L

    • CNS problems including lethargy, slurred speech, muscle weakness, fine tremor; poluria, beginning gastric toxicity

  • Serum level 1.5 – 2 mmol/L

    • Intensification of the above plus ECG changes

  • Serum levels of 2.0 – 2.5 mmol/L

    • Progression of CNS symptoms to ataxia, hyperreflexia and seizure, hypotension

  • Serum levels more than 2.5 mmol/L

    • complex multi organ toxicity and death

Other Drugs for Mania

• Aripiprazole – atypical antipsychotic drug

• Lamotrigine – anti convulsive drug

• Olanzapine – atypical antipsychotic drug

• Quetiapine – atypical anti psychotic drug

Nursing Considerations

• Daily monitoring of lithium serum levels

• Give the drug with food to alleviate GI irritation

• Ensure that the patient have adequate intake of salt nd fluid

• Monitor closely especially during the initial stage of therapy

• Arrange for small and frequent meals with sugarless lozenges for drying of mouth

• Provide safety measure like siderails and assistance with ambulation if CNS effects occur to prevent potential injury

• Offer support and encouragement ot help patient cope with drug regimen

Anti-Seizure Drugs

• Seizure

  • collection of different syndromes characterized by abnormal and excessive impulse transmission in the brain

  • may be primary or secondary.

  • Primary Seizure - Disorder has no known cause this is often called Epilepsy

  • Secondary Seizure - may be caused by Cerebrovascular accident, Infections, Brain Tumor, Traumatic Brain Injury, Fever and a lot more conditions that may alter impulse transmission in the brain

• Convulsion

  • seizure manifesting motor symptoms like tonic clonic seizure.

  • All convulsions are seizure but not all seizures are convulsions

Classifications of Seizure

1. Generalized Seizure - beigns in one area of the brain and rapidly spread to both hemispheres of the brain.

   • Tonic – Clonic Seizure (Grand Mal Seizure) - dramatic (loss of conscious)

   • Absence seizures (petit mal seizures) - brief (loss of attention)

   • Myoclonic seizures - brief muscle jerks often on limbs

   • Febrile seizures - in children usually when having a fever

   • Status epilepticus - medical emergency, seizure more than 5 mins

2. Partial Sezure - Partial seizures or focal seizures involve one area of the brain and do not spread throughout the entire organ

   • Simple partial seizures

     • Occur in a single area of the brain and may involve a single muscle movement or sensory alteration

   • Complex partial seizures

     • Involve complex sensory changes

     • Motor changes may include involuntary urination, chewing motions, diarrhea, etc.

The problems of seizure is excessive impulse transmission in the brain, so the action of the drug is to decrease impulse transmission, anti seizure drugs cause CNS depression.

Mechanisms Of Action

1. Suppressing sodium influx or deporalarization in the neuron

2. Suppressing calcium influx, preventing electric current generated by calcium ions

3. Increasing the action of the Gamma Amino Butyric Acid ( GABA ) an inhibitory neurotransmitter in the brain

   
   

   • Action potential happen by sodium influx and potassium efflux

   • calcium channels open causing release of calcium that generate electrical activity and nurotransmitters both excitatory and inhibitory regulate impulse transmission.

   • Excitatory neurotransmitters allow impulses to travel while inhibitory neurotransmitters stop impulses.

   • The mechanisms of action of anti seizure drugs occur in the neuronal synapse.

   • Drugs for Seizures are called Anti – seizure drugs or Anti – convulsive drugs (Anticonvulsant drugs) or Anti – Epileptic Drugs.

Drug Classifications

Hydantoins

• inhibit sodium influx or depolarization along the nerve fiber.

• Pharmacokinetics

  • Hydantoins are absorbed in the GIT.

  • It is higly protein bound up to 95%.

  • A decrease in serum albumin or proteins increases free phenytois serum levels.

  • Average half life is 24 hour.

  • Hydantoins are metabolized to inactive metabolites and excreted in the liver.

  • Hydantoins are less sedating than Barbiturates and Benzodiazepines.

• Adverse Effects

  • Neurologic and psychiatric effect which include slurred speech, confusion, depression.

  • Low platelet count and WBC may happen and gingival hyperplasia (overgrowth of gum tissue or reddened gums that easily bleeds).

  • Hyperglycemia and less severe adverse effcts such as nausea, vomiting, constipation, drowsiness, headache and alopecia

• Drug-Drug interactions

  • Hydantoins must not be taken with other anti seizure drugs because it may increase its CNS depressant effects.

  • Increase effects of Hydantoins happen in combination with Aspirin, anticoagulants, Barbiturates, Rifampicin and chronic ingestion of ethanol.

  • Decreased Hydantoins absorption occur when combined with Antacids, calcium preparations, sucralfate and some anti cancer drugs.

• Drug Samples (…toin)

  • Phenytoin

  • Fosphenytoin

  • Ethotoin

Barbiturates

• enhance GABA effect.

• These drugs are highly sedating and they may cause severe CNS depression.

• Indications

  • Anxiety, General Anesthesia and most commonly used for Generalized Tonic – Clonic Seizure

Benzodiazepines

• enhanced GABA effect.

• Indications

  • For status epilepticus and benign febrile seizure.

  • Diazepam is not used for long term treatment of seizure. Clonazepam is good for treatment of Petit Mal Seizure and Myoclonic Seizure

Succinimides

• enhanced effect of GABA, an inhibitory neurotransmitter.

• Drug Samples

  • Ethosuximide - the drug of choice for Petit – Mal or Absence Seizure (fewer adverse effects)

  • Methosuximide

Valproate or Valproic Acid

• reduces electrical acivity by suppressing calclim influx and enhancing GABA effects the drug of choice for treating myoclonic seizure

Other Anti-seizure Drugs

• Carbamazepine

• Gabapentin

• Lamotrigine

• Levetiracetam

• Topiramate.

• Some of these drugs used for partial seizure may also be used for treatment of neuropathic pain

• Carbamazepine is used for treatment of Trigeminal Neuralgia.

Nursing Considerations

• Administer the drug with food to alleviate GI irritations

• Monitor CBC to detect possible bone marriw suppresion

• Evaluate therapeutic blood level to prevent toxicity

• Provide safety measures

• Provide thorough health teaching, including drug name, prescribed dosage and avoidance of adverse effects

• Suggest that clients wear Medic Alert Bracelet to alert health care workers about the use of anti epiletpic drugs

• Offer support and encouragement to help the partient cope with the drug regimen.

Anti-Parkinson Drugs

• Parkinson’s Disease

  • a degenerative disorder of the central nervous system. There is no known cause.

  • This is common among elderly 60 years old and above.

  • The disease is characterized by degeneration of the substantia nigra in the midbrain. Therefore there is tremendous decrease of dopamine in the brain especially affecting the basal ganglia

• Substantia Nigra

  • A dopamine secreting neurons in the brain.

• Basal Ganglia

  • responsible for coordinating fine motor movement of the body

  • Alterations in the basal ganglia function results to lack of coordination, tremors, rigidity and bradykinesia

• The neurons of the basal ganglia function normally when there is a balance between excitatory and inibitory neurotransmitters.

  • Dopamine in the basal ganglia acts as the inhibitory neurotransmitter

  • Acetylcholine produced by higher neuron in the cerebral cortex act as excitatory neurotransmitter.

• In Parkinson’s disease an imbalance of neurotransmitters, decreased dopamine and increased acetylcholine

• Results to clinical manifestions causing incoordination for unconscious muscle movements including those that control position, posture and movement

• Anti – Parkinson’s drugs should balance the effects of the neurotransmitters.

  • These Drugs do not cure the disease but control the symptoms, hence the use is for palliative treatment.

Mechanism of Action

• To increase dopamine effect

• To supress acetylcholine effect

Drug Classifications

Dopaminergic Drugs

• increase the effect of Dopamine at the receptor sites by increasing the levels of dopamine in the substantia nigra or directly stimulating the receptors

• Pharmacokinetics

  • These drugs are absorbed in the GIT, metabolized in the liver and excreted in the urine.

  • They cross the placenta and the breast milk

• Contraidication and Caution

  • Contraindicated to clients with allergy to the drugs and glaucoma as the drug can exacerbate glaucoma.

  • Caution should be used with any condition that could be exacerbated by dopamine receptor stimulation such as cardiovascular disease, bronchial asthma, peptic ulcer disease, urinary tract obstrution and psychiatric disorders.

• Adverse Effects

  • CNS effects include anxiety, nervousness, headache, malaise, fatigue, confusion, mental changes, blurred vision, muscle twitching and ataxia.

  • Peripheral effects include anorexia, nausea, vomiting, diarrhea, constipation, cardiac arrythmias, urinary retention and bone marrow suppresion

• Drug – Drug interaction

  • Dopaminergic drugs combined with MAOI may increase hypertensive crisis.

  • The combination of levodopa with Vitamin B6 and phenytoin and dopamine antagonists may lead to decrease effect of dopaminergic drugs.

• Drug Samples

  • Levodopa

    • a precursor of Dopamine.

    • Once levodopa enters the BBB, it becomes dopamine and will replace the loss od dopamine.

    • When this drug was develop, there was a dramatic reduction in the signs and symptoms of Parkinson’s disease, however it was found out later that levodopa can be destroyed by and enzyme called dopa decarboxylase before they cross the BBB resulting to decreasing the level of levodopa that may cross the BBB.

    • Levodopa is combined with Carbidopa (Sinemet) to increase the level of levodopa entering BBB by inhibiting the enzyme

    • Best drug used for Parkinson’s

  • Amantadine

    • drug that can increase the release of dopamine.

    • This drug can be effective as long as there is a possibility of more dopamine release.

  • Bromocriptine

    • acts a direct dopamine agonists on dopamine receptor sites in the substantia nigra.

Anti-Cholinergic Drugs

• oppose the effects of acetylcholine at receptor sites in the substantia nigra.

• These anticholinergic drugs have greater affinity with the receptors of acetylcholine in the CNS than those in the periphery

• However, they still block some receptors at the autonomic nervous sytem.

• Blocking the acetylcholine effect help to normalize the dopamine – acetylcholine imbalance in the basal ganglia.

• Pharmacokinetics

  • drugs absorbed in the GIT, metabolized in the liver and excreted by cellular pathways.

  • They pass the placenta and the breast milk

• Contraindications and Cautions

  • Contraindicated in clients with Gastro intestinal or Genito urinary obstruction.

  • Caution should be used in clients with cadiovascular conditions because of its blocking effect of parasympathetic nervous system

• Adverse Effects

  • Blocking CNS actylcholine may cause disorientation, confusion and memory loss.

  • Peripheral anticholinergic effect include drying of the mouth, constipation, urinary retention and orthostatic hypotension.

• Drug-Drug interaction

  • These drugs should not be combined with other drugs with anti – cholinergic effects like anti – psychotic, anti – depressant drugs.

• Drug Samples

  • Diphenhydramine ( Benadryl )

  • Benztropine ( Cogentin )

  • Biperiden ( Akineton )

  • Trihexyphenidyl ( Artane )

  • These drugs are famous by their brand names. Most often used for treatment of Parkinson’s like syndrome, an adverse effect of anti – psychotic drugs

Nursing Considerations

• Provide sugarless lozenges to relieve drying of the mouth

• Give the drugs with caution in hot weather or with exposure to hot environemtn because of increase risk for heat prostration

• Give drugs with meals as they may cause GI irritation

• Monitor bowel functions

• Establish safety precautions

• Ensure that the patient voids before taking the drugs if urinary retention is a problem

• Provide thorough patient teaching about topics such as the drug name and prescribed dosage, measures help to avoid averse effects, warning signs that may indicate problems and need for pwriodic monitoring and evaluation to enhance patient knowledge about drug therapy and to promote compliance

• Offer support and encouragement to help the patient cope up with the disease and drug regimen

Muscle Relaxants

• Types of Spinal Reflexes

  1. Simple - Involving an incoming sensory neuron and an outgoing motor neuron

  2. Complex - Involving interneurons that communicate with the related centers in the brain

Mechanism

• Most relaxants

  • Work in the brain and spinal cord

  • Interfere with cycle of muscle spasm and pain

• Botulinum toxins and dantrolene

  • Enter muscle fibers directly

• Work in the upper levels of the CNS to interfere with the reflexes that are causing the muscle spasm

  • Possible depression anticipated with their use

• Lyse or destroy spasm - Often referred to as spasmolytics

• Fibers in the CNS Controlling Different Types of Movements

  • Pyramidal tract - Controls precise intentional movements

  • Extrapyramidal tract - Modulates unconsciously controlled muscle activity - Allows the body to make automatic adjustments in posture, position, and balance

Neuromuscular Abnormalities

• Muscle spasm

  • Often results from injury to the musculoskeletal system

  • Caused by the flood of sensory impulses coming to the spinal cord from the injured area

• Muscle spasticity

  • Result of damage to neurons within the CNS

  • May result from an increase in excitatory influences or a decrease in inhibitory influences within the CNS

Baclofen

• Prototype

• Indication

  • Alleviation of signs and symptoms of spasticity; use in spinal cord injuries or diseases

• Actions

  • GABA analog; inhibits monosynaptic and polysynaptic spinal reflexes; CNS depressant

• Oral route

  • Onset 1 hour; peak 2 hours; duration 4–8 hours

• Intrathecal route

  • Onset 30–60 min; peak 4 hours; duration 4–8 hours

• T½

  • 3–4 hours; excreted in the urine

Dantrolene

• Indications

  • Treatment of spasticity directly affecting peripheral muscle contraction

  • Management of spasticity associated with neuromuscular diseases

• Contraindications

  • Presence of any known allergy to the drug

  • Spasticity that contributes to locomotion, upright position, or increased function

  • Active hepatic disease

  • Lactation

Botulinum Toxin Type A

• Prescription drug approved by the FDA in 2002

• Temporarily improves the appearance of glabellar lines between the eyebrows

• Four units of the drug are injected between eyebrows

• Adverse effects include headache, respiratory infections, flu-like symptoms, and droopy eyelids

Nursing Considerations

• Monitor patient response to the drug (improvement in muscle spasm and relief of pain; improvement in muscle spasticity)

• Monitor for adverse effects (CNS changes, GI depression, urinary urgency)

• Evaluate the effectiveness of the teaching plan

• Monitor the effectiveness of comfort measures and compliance with the regimen

Neuromuscular Junction Blocking Agents

• NMJ - point of communication between a nerve and a muscle

• Sarcomere the functional unit of a muscle

• Categories of NMJ Blockers

  • used when clinical situations require muscle paralysis

  • not broken down by acetylcholinesterase, hence longer effect than Ach

  • PREVENTS skeletal muscle function

Nondepolarizing

• Act as antagonists to acetylcholine (ACh) at the NMJ

• prevent depolarization ( contraction ) of muscle cells

• eg. curare ( poison used to on tips of arrows or spears )

• Tubocurarine

  • General anesthesia; skeletal muscle relaxation; reduce intensity of muscle contractions in ECT; management of mechanical ventilation

  • Occupies the muscular cholinergic receptor site, preventing ACh from reacting with the receptor; does not cause activation of muscle cells; causes a flaccid paralysis

Depolarizing

• Act as an ACh agonist, causing stimulation of the muscle cell

• causes prolonged contraction, hence prevents repolarization

• Succinylcholine

  • Adjunct to general anesthesia; to facilitate endotracheal intubation; to induce skeletal muscle relaxation during surgery or mechanical ventilation

  • Combines with ACh receptors at the motor endplate to produce depolarization; this inhibits neuromuscular transmission, causing a flaccid paralysis

Action of NMJ Blockers

• Both are used to cause paralysis (loss of muscular function)

  • For performance of surgical procedures

  • To facilitate mechanical ventilation

• Similar in structure to ACh

• Occupy the muscular cholinergic receptor site, preventing ACh from reacting with the receptor

• Do not cause activation of muscle cells; muscle contraction does not occur

• Not broken down by acetylcholinesterase; effect is more long-lasting than that of ACh

• Used when clinical situations require muscle paralysis

• Indications

  • As an adjunct to general anesthetics during surgery

  • To facilitate mechanical intubation by preventing resistance to the respirator

  • To facilitate electroconvulsive therapy

• Evaluation of Patient Receiving NMJ

  • Monitor patient response to the drug (adequate muscle paralysis)

  • Monitor for adverse effects

  • Evaluate the effectiveness of the teaching plan

  • Monitor the effectiveness of comfort measures and compliance with the regime

• Adverse Effects

  • Respiratory depression

  • Hypotension / cardiac arrythmias

  • Bronchospasm
    → due to histamine release of many NMJ blockers causing respiratory obstruction

  • GI slowdown

  • Skin breakdown
    → Decubitus Ulcer = lost of reflex muscle movement that protects body from pressure sores

  • Fear related to helplessness and inability to communicate

  • Hyperkalemia
    → due to muscle membrane alterations

  • Malignant Hyperthermia
    → massive muscle contractions, sharply ↑ body temperature, severe acidosis and death
    → due to succinylcholine

• Care for Patients

  • Support and reassurance – Communication is decreased with paralysis

  • Vigilant maintenance of airways and respiration

  • Prevention of skin breakdown

  • Monitoring for return of function

  • Pain relief as appropriate

  • Reassurance

  • Support

  • Orientation

  • Skin care and turning

  • Supportive care