Psychopharmacology

Presented by : Cantos Peter Cinco, Carla Corpus, Blaine Maxine Cruz, Kimberly Anne B. De Borja , Jose Paolo

Psychopharmacology
Is the use of medications to treat mental illness.

Neurotransmitters
are chemical substance manufactured in the neuron to aid in transmission of information throughout the body.
  

 

Dopamine generally excitatory Serotonin mostly inhibitory Acetylcholine synthesized in dietary holine found in red meat and vegetables. Found to affect sleep/wake cycles and signal muscles to be active. Norepinephrine GABA (Gamma-amino butyric acid) major inhibitory neurotransmitter. Found to modulate other neurotransmitters rather than to provide direct stimulus

Neurotransmitter and related mental disorders

    

Inc. Dopamine ( Schizophrenia ) Dec. Norepinephrine ( Depression ) Dec. Serotonin ( Depression ) Dec Acetylcholine ( Alzheimers disease) Dec. GABA ( Anxiety )

Efficacy-maximal

therapeutic effect that a

drug can achieve

Potency

describes the amount of the drug needed to achieve the maximum effect.
Half-life

is the time it takes for half of the drug to be removed in the blood stream.

Off label use- A drug that proves effective for a disease that differs from the one involved in the original testing and FDA approval. e.g. anticonvulsants approved to prevent seizures are prescribed for their effects in stabilizing the moods fo clients with bipolar disorder ( off label )

Black box warning ( black label warning ) a type of warning that appears on the package insert for prescription drugs that may cause serious adverse effects. It is so named for the black border that usually surrounds the text of the warning.

Antipsychotic Drugs
Prepared by : Cruz, Kimberly Anne B.

Psychosis - inability to recognize reality, complicated severe thought disorder and inability to relate with others.

Antipsychotics


Also known as Neuroleptics Used to treat symptoms of psychosis such as delusions and hallucinations seen in schizophrenia, schizoactive disorders, and manic phase of bipolar disorders.

Off label uses : Anxiety and insomnia ; aggressive behavior and other disruptive behaviors that sometimes accompany Alzheimers disease

D1- Motor neurons in the basal ganglia and may be principal dopamine stimulating receptor for motor functions - influence D2 function - has no direct role in controlling psychotic symptoms

D2 overactivation causes positive symptoms ( e.g. hallucinations ). It is modulated when D1 is blocked ( except in schizophrenia D3 and D4- overstimulation of D3 may be assoc. with negative symptoms. D4 may be related to positive symptoms. D5-found only in limbic regions. May be an important dopamine-stimulating receptor for behavior.

Mode of Action:


Blocking receptors of neurotransmitter dopamine (Neurochemical Theory of Schizophrenia). Dopamine generally excitatory neurotransmitter Classified into subcategories : D1 D2 D3 D4 and D5 D2 D3 D4 have been associated with mental illness. Typical antipsychotic drugs are potent antagonists of D2 D3 D4 , making an effective treatment of target symptoms however extrapyramidal side effects may be produced. This is due to the blockage of D2 receptors.

   

Dopamine system stabilizers (DSS ) are drugs that stabilize dopamine output. Preserve and enhance when dopaminergic transmission is too low and reduce it where it is too high. Depot injection is a time-release form of medication for maintenance therapy. Vehicle : sesame oil . Medication is absorbed slowly over time thus less frequent administration is needed to maintain desired therapeutic effects .

Typical Antipsychotic
               

Low potency Chlorpromazine (Largactil, Thorazine) Thioridazine (Mellaril) Mesoridazine Medium potency Loxapine (Loxapac, Loxitane) Molindone (Moban) Perphenazine (Trilifon) Thiothixene (Navane) Trifluoperazine (Stelazine) High potency Haloperidol (Haldol, Serenace) Fluphenazine (Prolixin) Droperidol Zuclopenthixol (Clopixol) Prochlorperazine

Chlorpromazine ( Thorazine)considered the first antipsychotic drug. It was synthesized in 1950 by French scientists while attempting to develop a new antihistamine. It came from phenothiazine family of drugs, is

Thioridazine (Mellaril)


Also used for short-term marked depression accompanied by anxiety,tension, sleep disturbance Maximum upper limit of 800 mg due to pigementary retinopathy( pigment deposits on the fundus characterized by decreased visual acuity and impaired night vision )

Fluphenazine (Prolixin)
High potency antipsychotic  Fluphenazine decanoate , a long acting form is beneficial for patients who do not comply with daily oral medication regimen  Injection can be given 2-4 wks


Trifluoperazine (Stelazine)


I: Excessive anxiety,tension, agitation as well as for psychotic manifestation

Perphenazine ( Trilafon )


I: Depression and psychotic

Butyrophenone : Haloperidol
Haloperidol ( Haldol ) high potency that tends to cause more EPSEs and fewer anticholinergic side effects than do low potency drugs.  Can be used alone or in combination with benzodiazepine, lorazepam (Ativan )  Is a long-acting form can be given at 2-4 weeks intervals


Atypical antipsychotic drugs

Have greater effect on negative symptoms  Blockade of serotonin receptors that , in turn, is thought to liberate dopamine in cortex explaining the reduction of negative symptoms.


Atypical antipsychotic drugs

Amisulpride (Solian) Aripiprazole (Abilify) Asenapine (Saphris) Blonanserin (Lonasen) Clotiapine (Entumine) Clozapine (Clozaril) Iloperidone (Fanapt) Mosapramine (Cremin) Olanzapine (Zyprexa) Paliperidone (Invega) Perospirone (Lullan) Quepin (Specifar) Quetiapine (Seroquel) Remoxipride (Roxiam)

Dibenzodiazepine: Clozapine
 

Clozapine ( Clozaril ) was the first new an Has greater affinity to Dopamine D-1, Dopamine D-4 , and serotonin(5H2T) receptors Agranulocytosis

Benzisoxazole : Risperidone
Greater affinity to D2 receptor and similar antagonism to serotonin 5HT  Doesnt appear to cause agranulocytosis, EPSE, tardive dyskenisia or NMS


Sertindole (Serlect )
    

Potent Dopamine D2 and serotonin 5HT2 antagonism Both positive and negative schizophrenia Prolonged QT interval Withdrawn from the market due to number of cardiac arrythmia and deaths caused. 12-24 mg /day

Side effects Extrapyramidal side effects  Neuroleptic Malignant Syndrome  Tardive dyskinesia  Anticholinergic side effects


weight gain  mild ECG changes



Extrapyramidal Side Effects



Serious neurologic symptoms caused by blockage of Dopamine (D2) receptor located in the midbrain. They are major side effects of antipsychotic drugs. Acute dystonia Pseudoparkinsonis Akathisia

Acute dystonia (most likely 1st week of treatment)

Acute

muscular rigidity and crampting, a stiff or thick tongue with difficulty swallowing, in severe cases laryngospasm and respiratory difficulties

twisted head and neck Opisthotonus tightness of entire body with head back and arched neck Oculogyric crisis eyes rolled back and in locked position.
Torticolis

Treatment: Benztropine mesylate(Cogentin) Dophenhydramine ( Benadryl )

Oculogyric crisis Torticolis

Opisthotonus

Pseudoparkinsonism
 

Also known as drug-induced Parkinsonism Symptoms resemble Parkinsonism:

        

Stiff stoop posture Masklike facies Decreased arm swing A shuffling, festinating gait ( with small steps) Cogwheel rigidity (ratchet-like movements of joints) Drooling Tremor Bradycardia Coarse pin-rolling movement of the thumb and fingers while at rest

Treatment : Changing antipsychotic medication that has lower incidence of EPS Additional oral anticholinergic agent or Amantadine ( Dopamine agonist )

Akathisia


Inform client about the types of side effects and encourage to report such problems. Drink sugar free fluids and eating sugar free candy ( dry mouth ) Sunscreen ( photosensitivity ) Avoid driving and performing potentially dangerous activities If missed a dose, client can take it if its 3-4 hours late.

 

Treatment :
Changing

antipsychotic medication that has lower incidence of EPS

Additional

oral agent such as beta-blocker , anticholinergic or benzodiazepine

Tardive dyskinesia (TD)

 

 

Tardive means late appearing ( usu. After months or years) Dyskinesia refers to abnormal voluntary skeletal muscle movements which usually produce a jerky motion. Anticholinergic drugs such as trihexyphenidyl and benztropine may aggravate TD. Three times more likely to have an impaired gag reflex Treatment : Bromocriptine ( Parlodel )

Signs and Symptoms

    

Lip smacking Grinding of teeth Rolling or protrusion of tongue Tics Diaphragmatic movements

Note : Involuntary movements are generally coordinated , fluctuate in severity and disappear during sleep. TD is IRREVERSIBLE. Discontinuing antipsychotic can arrest its progression

Prevention of TD Keeping medication dosages as low as possible  Changing medications  Monitoring periodically for signs of TD using standardized assessment tool such as AIMS ( Abnormal Involuntary Movement Scale )


Once the client have acquired TD he/she may be given atypical antipsychotic which does not have been found to cause TD

Neuroleptic Malignant Syndrome (NMS)

Typical

onset : 3-9 days after initiation of

therapy

S/Sx:

increased temperature ( chief sign ) muscular rigidity , tremors , impaired ventilation, muteness, altered consciousness, autonomic hyperactivity Dantrolene ( Dantrium) Bromocriptine ( Parlodel )

Treatment:

Note : Antipsychotics should not be reinstituted for at least 2 weeks after complete resolution NMS symptoms

Droperidol , Thioridazine,Mesoridazine


May lengthen QT interval leading to potentially life treatening cardiac dysrhythmias or CARDIAC ARREST.

Clozapine
 

Agranulocytosis - POTENTIALLY FATAL Develops suddenly characterized by:

A. fever B. malaise C. Ulcerative sore throat D. Leukopenia NOTE: Drug must be discontinued IMMEDIATELY if WBC count drops by 50% or to less than 3,000

Before initiation of treatment: Must have a baseline WBC count and differential Throughout the treatment and 4 wks after discontinuation : WBC count every week

    

Inform client about the types of side effects and encourage to report such problems. Drink sugar free fluids and eating sugar free candy ( dry mouth ) Sunscreen ( photosensitivity ) Avoid driving and performing potentially dangerous activities If missed a dose, client can take it if its 3-4 hours late.

Anticholinergic Side effects



Often occur with the use of antipsychotic drugs Orthostatic hypotension, dry mouth, constipation, urinary hesitance / retention, blurred near vision, dry eyes ,photophobia , nasal congestion and decreased memory.

Side effect Peripheral Nervous System Constipation Dry mouth Nasal congestion Blurred vision

Nursing intervention

Encourage high dietary fiber and increased water intake ; give laxatives as ordered Advise to take sips of water frequently , Give over the counter nasal congestants if approved by physician Advise to avoid potentially dangerous tasks,. Reassure that normal vision returns in few weeks, when tolerance in side effects develops . Advise to report eye pain immediately Advise to wear sunglasses outdoors Advise the patient to get out of the bed or chair slowly. Sit on the side of the bed for 1 full minute whle dangling feet , then slowly rise. Measure BP before each dose.

Mydriasis Photophobia Hypotension/ Orthostatic hypotension

Tachycardia

Is usually a reflex response to hypotension. With clozapine, hold dose if PR>140 bpm Encourage frequent voiding and voiding when urge is present. Monitor I and O Provide privacy. Run water in sink. Run warm water in the perineum Help patient get up early and get the day started Help patient order an appropriate diet; diet pills should not be taken If WBC <2000 cells/mm3 and granulocyte count <1000 cells /mm3 stop therapy. Give antibiotics as ordered if infection develops

Urinary Retention Urinary hesitation Sedation Weight gain Agranulocytosis

Central Nervous system Akathisia Be patient and reasssure the patient who is jittery that you undersand the need to move. Switching to new antipsychotic drug may be necessary for compliance since akathisia is a chief cause of this. If severe, give antiparkinson drugs immediately as needed or antihistamine and offer assurance. More likely an order for intramuscular administration will not have been written so call the physician at once to obtain order. Assess for tremors , rigidity and bradykinesia and report physician. Antiparkinsonism drugs will probably indicated Assess using AIMS. Be alert for this is potentially fatal. Routine temperature taking. Encourage adequate water intake.Assess for rigidity , tremor and similar symptoms Discontinue drugs Seizure precautions

Dystonias

Pseudoparkinsonism

Tardive dyskinesia NMS

Seizures

Thank You !

Anti Depressants or Mood Elevators



Used to treat depressive disorders caused by emotional or environmental stressors, frustrations, losses, drugs. These drugs are classified as Tricyclic Antidepressants, Monoamine Oxidase Inhibitors (MAOIs) and Atypical Antidepressants.

Tricyclic Antidepressants


Increase the level of neurotransmitters, serotonin or norepinephrine in the space between nerve endings. Used to treat symptoms of depression such as insomia, decreased appetite, decrease libido, excessive fatigue, indecisiveness, difficult thinking and concentrating, somatic symptoms, irritability and feeling of worthlessness. Considered effective in 85% of those who exhibit symptoms of depression

Those receiving tricyclic agents generally show an increase mental alertness and physical activity with mood elevation within a few days after initial therapy is begun.

CONTRAINDICATIONS:
Pregnant and lactating women  Persons recovering from myocardial infarction  Persons with severe liver disease and kidney disease


SIDE EFFECTS:
Dry mouth  Blurred vision  Tachycardia  Urinary retention  Constipation  Increase intraocular pressure  Increase seizure susceptibility in epileptic patients  Acute toxicity due to overdose.


NURSING IMPLICATIONS:
Assess the level or severity of patient's depression.  Monitor for drug interactions  Note any side effects  Avoid excessive exercise and high temperatures on patient  Instruct patient to take drug as prescribed. No attempt should be made to alter the dosage.


Monoamine Oxidase Inhibitor (MAOIs)

 

Antidepressants that prevents metabolism of neurotransmitters. Effective in treating depression with acute anxiety attacks, phobic attacks, or many physical complaints or patients who fail to respond to tricyclic agents and patients who are in depressive phase of manic depressive illness.

CONTRAINDICATIONS:
Asthma  Congestive heart failure  Hypertension  Cardiac Arrhythmias  Impaired kidney function  Hypernatremia  Cerebral Vascular Disease  Hyperthyroidism  Liver Disease


SIDE EFFECTS:
Abnormal heart rate  Orthostatic hypotension  Nausea and Vomiting  Drowsiness or Insomia  Headache  Vertigo  Blurred Vision  Constipation  Weakness  Loss of appetite


PATIENT EDUCATION:
Avoid tyramine rich food, caffeine containing foods or alcoholic beverages  Do not alter dosage or discontinue the drug  Have vision checked periodically  Avoid overactivity


 

First line agents to treat anxiety Probably the most effective, as well as the safest, agents for prophylaxis and long-term treatment of panic attacks

Venlafaxine (Effexor, Effexor XR)

   

First drug approved for both GAD and major depression At lower doses: blocks the reuptake of serotonin At medium to higher doses: blocks the reuptake of norepinephrine Doses at higher range are believed to be more effective

Have four basic clinical uses

1. 2.

3. 4.

For chronic anxiety For time-limited periods in people going through crises For presurgery nervousness For treatment of panic disorder

Mode of Action


Enhance the effects of the inhibitory neurotransmitter GABA

GABA attaches to GABA receptors, which trigger the opening of chloride channels. Chloride has a hyperpolarizing effect on the neuron, which makes the neuron less responsive to excitatory neurons.

Inhibit the anxiety response to stressors

Overall effect: slowing down or halting of neuronal firing Neuronal inhibition: a brain without the inhibition of GABA can produce thought acceleration, autonomic dysfunction, excessive anxiety, panic, or even seizure activity.

Pharmacologic Effects
 

Depressing effect on the CNS 5 major effects

1. 2. 3. 4. 5.

Reduce anxiety Relax muscles Promote sleep Prevent seizures Produce amnesia

Because benzodiazepines depress the reticular activating system, incoming stimuli are muted and evoke less reaction. As the antianxiety agent decreases environmental input, a general relaxing effect takes places. The ability to mute incoming stimuli gives a great potential for abuse

  

Can cause several levels of CNS depression, from sedation to anesthesia. Accomplished by depressing the inhibitory neurons that affect the arousal Causes a state of disinhibition, which results in feelings of euphoria and excitement that, in turn, can lead to poor judgment.

 

Inhibiting effect accounts for their anticonvulsive activity. Intravenous diazepam (Valium) and lorazepam (Ativan) are first-line agents for status epilepticus clonazepam (Klonopin) is regularly prescribed orally

Pharmacokinetics


Absorption:

Readily absorbed after oral ingestion Slow and inconsistent IM administration (except for lorazepam [Ativan])

 

Distribution: highly lipid-soluble, therefore, readily cross the blood-brain barrier Metabolism: liver

Active metabolites can exert an effect for up to 10days

Excretion: urine

Short half-lives
 

20 hours or less Preferable for use in older adults

lorazepam (Ativan) oxazepam (Serax) temazepam (Restoril)

Long half-lives
 

Longer than 20 hours Therefore, has an extended duration of action

clorazepate (Tranxene) chlordiazepoxide (Librium) diazepam (Valium)

PNS SEs

Constipation Double vision Hypotension Incontinence Urinary retention Can exacerbate narrow-angle glaucoma

Side Effects


CNS SEs

Sedation and mental alertness (a 20-mm Hg drop of systolic level while the patient is standing warrants withholding the drug and notifying the physician)
Drowsiness Fatigue Ataxia Mental impairment Slowing of reflexes Confusion Depression Headache

Can cause a physical dependence (state in which the body functions normally when the drug is present), tolerance (needs an increasing amount of the drug to achieve the same effect) and produce a withdrawal syndrome. Discontinuance should be tapered gradually.

Relatively safe drugs when taken alone but can be deadly if mixed with other CNS depressants (alcohol) Signs and symptoms of overdose:

Somnolence, confusion, coma, diminished reflexes and hypotension

Treatment: emptying the stomach with induced vomiting and gastric lavage, followed by activated charcoal. Monitor BP, PR and RR and provide supportive care

Benzodiazepine Receptor Antagonist



Flumazenil (Romazicon) blocks the benzodiazepine-binding site on the GABA receptor It selectively blocks benzodiazepine receptors but does not block adrenergic or cholinergic receptor Thus, because it does not stimulate the CNS and does not block other receptors, it can be given when benzodiazepine overdose is suspected

  

If patient responds to flumazenil, the benzodiazepines are present Response typically occurs within 30-60 secs. 2 important considerations:
1.

2.

Does not speed up metabolism or excretion of benzodiazepines Has a short duration of action

Thus, repeated doses of flumazenil as the body eliminates benzodiazepines from the system is needed Furthermore, it might not reverse benzodiazepine-induced respiratory depression and can precipitate seizures

Use during pregnancy

Might be associated with cleft lip and cleft palate in 1st trimester  Floppy infant syndrome has been asc. with benzodiazepine use during labor  Also known to be found in breat milk


! Discontinue or taper to
lowest possible dose

Patient Education
1.

2.

3.

4.

Not intended for the minor stresses of everyday life OTC drugs might enhance the actions of benzodiazepine Driving should be avoided until tolerance develops Prescribed dose should not be exceeded

5.

6.

7.

Alcohol and other CNS depressants exacerbate the effects of benzodiazepines Hypersensitivity to one benzodiazepine might mean hypersensitivity to another These drugs should not be stopped abruptly

 

Buspirone (BuSpar) is a first-line agent Advantages:

It is not sedating It is not a drug that causes a high, so it has no abuse potential It has no cross-tolerance with sedatives or alcohol It does not produce dependence, withdrawal or tolerance It does not cause muscle relaxation It takes 1 to 6 weeks to be effective

Disadvantages:

 

Provides relief from anxiety within 7-10 days, but maximal therapeutic gain in not achieved until 3 to 6 weeks after treatment is initiated Has a relatively short half-life Effective in reducing symptoms of worry, apprehension, difficulties with concentration and cognition, and irritability Does not depress the CNS

Side Effects
     

Dizziness Nausea Headache Nervousness Light-headedness Excitement

Nonbenzodiazepines with antianxiety qualities

      

buspirone (BuSpar) clomipramine (Anafranil) clonidine (Catapres) hydroxyzine hydrochloride (Atarax) hydroxyzine pamoate (Vistaril) meprobamate (Equanil) propanolol (Inderol)

IMPLICATIONS FOR NURSING ACTIONS

 1.

2.

Before administering: The nurse should assess the persons mental and physical status to avoid the risk of adverse side effects Pregnant women or those breast-feeding should not be placed on antianxiety agents because of the risk of these side effects

3.

4.

If a patient complains of sleep disturbance, the causative factor should be identified if possible. Appropriate nursing measures to promote relaxation such as a warm drink or a backrub, should be first be tried as alternatives to the administration of hypnotics.

 1.

2.

When administering, the nurse should: Give the daily dose at bedtime to promote sleep, minimize adverse reactions, and allow more normal daytime activities to occur. Administer IM dosages deeply and slowly into large muscle masses because they are irritating to tissues and can cause pain at the site of injection. The Z-track method is generally used to avoid irritation of tissue.

3. 4.

Observe for therapeutic effects. Observe for side effects such as oversedation, hypotension, pain at the injection site, skin rashes, and paradoxic excitement. Symptoms of paradoxic excitement include hostility, rage, confusion, depersonalization, or hyperactivity. Rare side effects include GI discomfort, nausea, vomiting, menstrual irregularities, blood dyscrasias, photosensitivity and nonthrombocytopenic purpura

5.

6.

Observe for symptoms of drug interactions, especially with elderly patients who often are taking a variety of medications. Lorazepam (Ativan) can be given sublingually for rapid absorption.

PATIENT EDUCATION
Patients should be told the name of the drug, dose, and schedule of treatment, as well as the course of treatment. Patients should not alter the dose of medication nor should they drive or operate hazardous equipment. Instructions to patients and family members include the following:

1.

2.

Avoid mixing alcoholic beverages, antihistamines, or antipsychotic drugs with antianxiety agents because they can increase the depressant effects of those agents, possibly causing death. Avoid ingesting large amounts of beverages containing caffeine, a stimulant, because it can decrease the effects of hypnotic agents.

3.

4.

5.

6.

Report symptoms of fever, malaise, sore throat, petechiae, easy bruising or bleeding and skin rash. Sudden cessation of these agents can cause REM or rebound effects of insomnia, dreams, nightmares, hyperexcitability, agitation or convulsions. Avoid excessive use of these drugs to prevent the onset of substance abuse or addiction. Hypnotics are ineffective as analgesics.

Antimanic Agents (Lithium Salts)

Administration of lithium is considered the treatment of choice for the manic phase of the bipolar disorder formerly termed manic-depressive illness and for the long-term prophylaxis of this bipolar disorder. It has also been used in the treatment of depressive and schizoaffective disorders, aggression, and uncontrolled rage reaction.

What is Lithium?
   

Exact therapeutic effects: unknown Not metabolized in the body 80% of lithium dose is reabsorbed in the proximal renal tubules and excreted by the kidneys. Believed to level out the activity of neurotransmitters in the area of the brain that controls emotions, thus preventing a decreased activity of nerve impulses, resulting in depression, or an increased activity, resulting in anemia maintains a constant sodium concentration in the brain, regulation in mood swings as well as impulses traveling along nerve cells

General Contraindications and Side Effects:

 

Not prescribed: -pregnancy -severe impaired kidney function Caution: -heart disease -diaphoresis -on a sodium-restricted diet -hypotensive -epilepsy -parkinsonism -other CNS disorders -dehydration
*Serum lithium concentration may increase in the presence of extreme vomiting, diarrhea, or perspiration, resulting in the lithium toxicity.

Common side effects:

         

Nausea Metallic taste Abdominal discomfort Polydipsia Polyuria Muscle weakness Fine hand tremors Fatigue Mild diarrhea Edema: feet, hands, abdominal wall, face

*These effects may occur as early as two(2) hours after the first does was taken.

DRUG INTERACTIONS


Drugs that increases the effects of lithium: -diuretics -anti-inflammatory agents such as Indocin Drugs that decreases the effects of lithium: - Acetazolamide (Diamox) -Sodium Bicarbonate -Excessive amounts of Sodium chloride -Drugs with high sodium contents -Theophylline compounds

TYPES OF ANTIMANIC DRUGS

LITHIUM CARBONATE
A.) Mode of Action *The precise mechanism by which lithium produces its therapeutic effect is complex and poorly understood.


1. 2.

Postulated mechanisms of therapeutic effects:

Decreased neurotransmitter postsynaptic receptor activity. Stimulates exit of Na+ from cells where intracellular Na+ is elevated (as in depression) by stimulating the Na+/K+ pump mechanism. Stimulates entry of Na+ into cells where intracellular Na+ is reduced (as in mania). Influences Ca2+ and Na+ transfer across cell membranes including the Ca2+ -dependent release of neurotransmitters. Inhibits both cyclic AMP and inositol phosphate second messenger systems in the membrane- this mechanism mediates the long-term side-effects of nephrogenic diabetes insipidus and hypothyroidism. Interacts with Ca2+ and Mg2 +, thereby increasing cell membrane permeability.

3. 4. 5.

6.

B.) Indications 1. Treatment of depressive disorders: (i) Treatment can be justified in the acute stages of depressive disorders, when other measures have failed. (ii) Treatment of resistant depression- ex: effective in patients who have failed to respond to cyclic antidepressant drug. (iii) Enhances the effects of TCAs and MAOIs. (iv) Enhances the effects of of SSRIs- however, lithium should be introduced cautiously because of the risk of the serotonin syndrome developing (owing to enhanced serotonergic activity); this risk appears to be lowest with fluvoxamine. 2. Preventing relapse of depressive disorders: (i) In unipolar affective disorders: Lithium reduces the rate of relapse After the first episode- treatment should be prolonged for 6 months post-clinical recovery. After 2 or more episodes- treatment should be prolonged for several (1-3) years post-clinical recovery; lithium is particularly useful in the prophylaxis of recurrent unipolar depression. Continuing treatment with lithium reduces the rate of relapse after treatment of ECT. (ii) In bipolar affective disorders- prolonged administration of lithium (5 years) prevents relapses into depression.

3. Treatment of mania: Lithium is effective in high doses (1000 mg nocte), but the therapeutic response usually only occurs in the second week of treatment; thus, the response to lithium is slower than the response to antipsychotic drugs. 4. Preventing relapse of mania: In bipolar affective disorders, prolonged administration of lithium (5 years) prevents relapses into mania. 5. Treatment of mixed affective states. 6. Prophylaxis of schizoaffective disorders- in combination with an antipsychotic depot injection. 7. Treatment of aggressive or self-mutilating behaviour.

C.) Adverse effects 1.Short-term side-effects: (i) GI disturbances (N/V, diarrhea) (ii) Fine tremor (iii) Muscle weakness (iv) Polydipsia 2. Long-term side-effects: (i) Nephrogenic diabetes insipidus (ii) Hypothyriodism (iv) Cardiotoxicity (v) Oedema (vi) Weight gain (vii) Tardive dyskinesia and other movement disorders. 3. Toxic effects: (i) Increasing GI disturbances (anorexia, vomiting, diarrhea). (ii) Increasing CNS disturbances (coarse tremor, drowsiness, ataxia, nystagmus, incoordination, slurring of speech, convulsions, coma). (iii) The effects of lithium overdosage may be fatal- hence it is important that the serum lithium level be closely monitored to ensure that it lies within the therapeutic range of 0.4-1.0 mmol/L (the lower end of this range is for maintenance therapy; the higher end of this range is for treatment in the acute stages of illness) in blood samples taken 12 hours after the last dose of lithium; serum lithium levels over 1.5 mmol/L may be fatal. (iv) Once stabilized on lithium carbonate, the following should be monitored: - Every 3 months- serum lithium levels and serum urea and electrolytes. -Every 6 months- thyroid functions test -Every 12 months- ECG.

4.) Drug interactions: (i) Na+ depletion raises the serum lithium levels and may result in lithium toxicity- therefore the concurrent use of diuretics (particularly thiazides) should be avoided. (ii) The concurrent use of carbamazepine with lithium may result in neurotoxicity without raising the serim lithium level- hence if carbamazepine is added to lithium, it should be done so with caution. (iii) NSAIDs raise the serum lithium levels and may result in lithium toxicity- therefore their concurrent use with lithium should be avoided. (iv) ACE inhibitors raise the serum lithium level.

5.) Contraindications: (i) Pregnancy (ii) Breast feeding (iii) Renal impairment

Lithium toxicity occurs when serum lithium levels exceeds 1.5 to 2.0 mEq/liter and includes the following symptoms:
    

Drowsiness Slurred speech Muscle spasms Blurred vision Diarrhea

    

Dizziness Stupor Convulsions Coma Death

Pictures of lithium carbonate

Can be a in a form of a capsule or tablet

Implications for Nursing Actions:

 

Lithium therapy should be given during or after meals to decrease gastric irritation. Serum lithium levels should be taken at least twice a week during the initiation of therapy before stabilization of the manic intervals. Serum samples should be drawn 12 hours after a dose is administered; desired levels should reach 1.0 to 1.5 mEq/L. Patient should be observed for decreases in manic behavior and mood swings, adverse side effects, and drug interactions.

Patient Education: (Lithium Therapy)

Take the drug as directed. Do not alter the dosage or cease taking the prescribed drug. Lithium may require three to five weeks to be effective. Do not decrease dietary salt intake unless restricted to do so by the physician because it increases the risk of adverse effects from lithium. Maintain a high intake of fluids (three liters daily) unless contraindicated because of a physical disorder. Avoid crash or fad diet. Avoid excessive exercise in warm weather.

 

Patient Education: (Lithium Therapy)



Regular blood lithium levels are necessary for safe, effective therapy. Blood samples should be taken 12 hours after previous dose of lithium; therefore, do not take the morning dose until the serum sample has been taken. Avoid taking other medications without the physician's knowledge because these may increase or decrease the effects of lithium. Report any unusual symptoms, illness, or loss of appetite immediately to the physician. Continue to take the drug despite an occasional relapse. Some patients respond slowly to lithium therapy. Notify the doctors whenever a change in diet occurs because this may affect the lithium level. Women should not breast-feed while taking lithium. Schedule an annual physical examination. Carry a Medic Alert card or wear a Medic Alert bracelet.

  

Daily Dosage of Lithium Salts:

Generic Name Lithium carbonate Trade Name Eskalith Lithane Lithobid Eskalith CR Lithium citrate CibalithCibalith-s Dosage Range (mg/day) 900900-1800 mg in divided doses until serum levels reach 1.0-1.5 mEq/L 1.0- mEq/L

Begins with 300 mg BID and gradually increase by 300 mg increments to achieve desired serum lithium level

Anticonvulsants


Used to treat seizure disorders, which are not uncommon among individuals with psychiatric disorders. For example, individuals experiencing acute substance abuse withdrawal are given sedatives and anticonvulsant medications to prevent or treat seizures and delirium tremens. Other examples include individuals with organic mental disorders associated with Axis III physical disorders or conditions such as brain tumor, history of head injury, explosive personality, or epilepsy. According to Maxmen, 1991, it can also treat bipolar disorders, especially mania.

Commonly used anticonvulsants

     

Depakene (valproic acid) Dilantin (phenytoin) Klonopin (clonazepam) Mysoline (primidone) Tegretol (carbamazepine) Zarontin (ethosuximide)

General Contraindications and Side Effects

 

   

There are several chemical classifications of anticonvulsants: longacting barbiturates, benzodiazepines, hydantions, and succinimides. They are utilized to control seizure activity such as potit mal ( absence seizures), grand mal (tonic-clonic), psychomotor, akinetic and myolonic, focal epileptic, oe seizures associated with neurosurgery (Handbook of Psychotropic Agents, 1990). Anticonvulsants are contraindicated or must be used cautiously in patients with CNS depression. Also contraindicated with patients having hepatic or renal damage, liver disease, or bone marrow depression. Increased incidence of birth defects may occur if utilized during pregnancy. Mothers who are breast-feeding should not take anticonvulsants.

CARBAMAZEPINE


Available as standard formulation requiring three times a day dosing, and a modified-release formulation (Tegretol Retard) to allow twice daily dosing up (up to 800 mg BID).

A.) Mode of Action - Structurally similar to the tricyclic antidepressant imipramine, however, carbamazepine has no effect on monoamine reuptake. - Thought to mediate its therapeutic effect by inhibiting kindling phenomena in the limbic system.

B.) Indications 1.) Treatment of depressive disorders - Treatment of resistant depression, i.e. worth a trial in patients who have failed to respond to a cyclic antidepressant drug and lithium carbonate. - Enhances the effects of TCAs and SSRIs.

2.) Preventing relapse of depressive disorders: -it prevents relapses into depression in both recurrent unipolar affective disorders and recurrent bipolar affective disorders. -it is the mood stabilizer of choice in patients with both epilepsy and bipolar affective disorder.

3.) Treatment of mania -Carbamazepine is effective in high doses (600 mg bd- 800 mg bd), but the therapeutic response usually only occurs in the second week of treatment; thus, the response to carbamazepine is slower than the response to antipsychotic drugs.

4.) Preventing relapse of mania: - In patients who fall to respond to lithium carbonate- carbamazepine can either be substituted for, or added to lithium; the two drugs appear to have a a synergistic effect when used in combination (but see earlier note on their concurrent use). - In patients with the rapid-cycling form of bipolar affective disorder (i.e. four or more affective episodes per year)- carbamazepine is a better prophylactic agents than lithium carbonate.

5.) Treatment of all forms of epilepsy- except absence seizures. 6.) Treatment of trigeminal neuralgia. 7.) Treatment of behavioral disorders secondary to limbic epileptic. 8.) Treatment of aggressive behavior (including after head injury). 9.) Treatment of acute alcohol withdrawal.

C.) Adverse Reactions 1.) Side-effects: -Dizziness and drowsiness -Generalized erythematous rash (3%) -Visual diturbances (esp. double vision) -GI disturbances (anorexia and constipation) -Leucopenia and other blood disorders -Hyponatremia

2.) Carbamazepine should be initiated at a dosage of 200 mg bd and increased after 1 week to the usual therapeutic dosage of 200 mg mane, 400 mg nocte required for prophylaxis (some patients may require 400 mg bd)carbamazepine is a less toxic drug than lithium carbonate and regular serum level estimation appears to be unnecessary; however, because of the slight risk of leucopenia and other blood disorders, it is important that full blood count is monitored periodically.

3.) Carbamazepine is an inducer of the liver enzyme cytochrome P450 2D6- thus it lower plasma haloperidol levels by half. 4.) It also decreases the plasma concentration of: -Oral contraceptives -Warfarin

5.) The plasma concentration of carbamazepine is increased by: -Erythromycin -Cimetidine -Calcium channel blockers -Isoniazid

Pictures of carbamazepine
Can be in a form of a capsule or a tablet

VALPROIC ACID
-also known as Sodium Valproate or Valproate Semisodium -it is available as a standard formulation requiring three times a day dosing, and a modifies-release formulation (Epilim Chrono) to allow twice daily dosind (maximum of 2.5 g daily in divided doses.

A.) Mode of Action

-Sodium vaproate is thought to mediate its therapeutic effect through indirect effects of GABA-ergic succinic semialdehyde dehydrogenase), implying a possible underlying biochemical disturbance of GABA deficiency in some affective disorders. -Valproate semisodium is thought to permeate the blood-brain barrier more easily.

B.) Indications 1.) Treatment of depressive disorders 2.) Preventing relapse of depressive disorders: 3.) Treatment of mania -effective in high doses- 600 mg bd-1200 mg bd) 4.) Preventing relapse of mania 5.) Treatment of all forms of epilepsy.

C.) Adverse Effects 1.) Side-effects: -Recent concern over severe hepatic and pancreatic toxicity. -Haematological disturbances (thrombocytopenia, inhibition of platelet aggregation). -Drowsiness, weight gain and hair loss.

2.)Sodium valproate is initiated at a dosage of 200 mg bd and increased after 1 week to 400 mg bd and again after another week to 600 mg bd, the usual theraeutic dosage required for prophylaxis (some patients may require 800 mg bd)- sodium valproate is a less toxic drug than lithium carbonate and regular serum level estimation appears to be unnecessary, however, because of the slight risk of severe hepatic and pancreatic toxicity, and haematological disturbance of platelet function, it is important that liver function test s, serum amylase level and full blood count are monitored periodically.

Pictures of valproic acid

Can be in a form of a capsule, syrup, or a tablet

Implications for Nursing Actions:



Abrams (1991) cites the following nursing actions for anticonvulsant drug therapy: 1. Give on a regular schedule to maintain therapeutic blood levels. 2. Give oral anticonvulsant drugs with meals or fluid to reduce gastric irritation and decrease GI side effects. Zantac (ranitidine) is often prescribed to eliminate gastric irritation. 3. Observe for therapeutic effects, which occur approximately seven to ten days after drug therapy is started. 4. Monitor for adverse effects including CNS changes (drowsiness, sedation, ataxia), GI irritation, skin disorders, blood dyscrasias, respiratory depression, liver damage, gingival hyperplasia, hypocalcaemia, and lymphadenopathy. 5. Observe for drug interactions.

Patient Education:


Patient receiving anticonvulsant drug therapy should be instructed to 1. Inform the physician/psychiatrist of any known physical illnesses or pregnancy. 2. Inform the physician/psychiatrist of any medication or OTC drug he or she is presently taking. 3. Take medications with food or glass of fluid at the same time each day. 4. Ask for the same brand and form of drug when renewing prescriptions. 5. Follow directions when taking a liquid preparation of phenytoin (Dilantin). 6. Discuss monitoring blood levels of type prescribed drug to avoid reaching toxic levels. 7. Report any adverse side effects to physician/psychiatrist

Daily Dosage of Used Anticonvulsants

Generic Name Carbamazepine Clonazepam Ethosuximide Phenytoin Primidone Valproate Valproic acid Trade Name Tegretol Klonopin Zarotonin Dilantin Mysoline Depakote Depakene Dosage Range (mg/day) 600600-1200 mg 1.51.5-20 mg 500500-1500 mg 500500-625 mg 500500-2000 mg 60 mg/kg in divided doses 10001000-3000 mg

Anticholinergic/ Antiparkinson Drugs

Anticholinergic/Antiparkinson Agents


An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is gabapentindicyclomine, and the classic example is atropine. Anticholinergics are administered to reduce the effects mediated by acetylcholine on acetylcholine receptors in neurons throughcompetitive inhibition. Therefore, their effects are reversible.

Indications


Anticholinergic/antiparkinson agents are the drugs of choice to treat extra pyramidal disorders, to treat idiopathic or post encephalitic Parkinsons disease, or to use as an adjunct to levodopa. Anticholinergic drugs are utilized to decrease salivation, spasticity, and tremors in people who have minimal symptoms or cannot tolerate levodopa. They may also be prescribed in combination with other antiparkinson drugs.

Contraindications


Anticholinergic drugs are contraindicated in the presence of glaucoma, myasthenia gravis, gastrointestinal obstruction, prostatic hypertrophy, and urinary bladder neck obstruction. They must be used in caution with patients exhibiting symptoms related to cardiovascular disorders.

Implications for Nursing Actions



Give antiparkinson agents with or immediately following food intake to prevent or reduce gastrointestinal stress. Observe for therapeutic effects such as decreased salivation, tremor, and drooling (anticholinergic effects). Observe for improvement in gait, balance, posture, speech, and self-care ability.

Monitor for adverse effects due to anticholinergic drugs (atropine like effects) such as dry mouth, drowsiness, and constipation. Monitor for adverse reactions to antiparkinson agents.

Patient Education


Maintain an adequate amount of fluid intake (unless contraindicated) to prevent excessive dryness of the mouth. Taking the medication just before meal, chewing gum, or sucking on hard candies may alleviate this side effect. Avoid operating potentially hazardous machinery or driving an automobile if symptoms of blurred vision or drowsiness occur.

 

Report any side effects or unusual symptoms to the physician/psychiatrist. Use caution when rising from a sitting or reclining position because of the possibility of postural hypotension and drowsiness. Limit strenuous activities in hot weather since anticholinergic drugs may cause anhidrosis.

 

Have routine vision examinations to eliminate the possibility of the presence of glaucoma. Limit use of alcohol, high protein foods, and vitamin B6 as they decrease therapeutic effect of levodopa.