Psychotropic Drugs

Bryan Mae H. Degorio

Review on Neurobiological Theory

A.Neurotransmitters- are the chemical substances that

are being manufactured in the neuron that aid in the transmission of information throughout the body.

They either excite or stimulate an action in the cells (excitatory) or inhibit or stop an action (inhibitory).

After neurotransmitters are released into the synapse (point of contact between the dendrites and the next neuron) and relay the message to the receptor cells, they are either transported back from the synapse to the axon to be stored for later use (reuptake) or are metabolized and inactivated by enzymes, primarily monoamine oxidase (MAO).

1. Dopamine

- a neurotransmitter located primarily in the brain stem. Dopamine is generally excitatory and is synthesized from tyrosine, a dietary amino acid.

Antipsychotic medications work by

blocking dopamine receptors and reducing dopamine activity.

2. Norepinephrine and Epinephrine - Norepinephrine, the most prevalent

neurotransmitter, is located primarily in the brain stem. It plays a role in mood regulation.

Epinephrine is also known as noradrenaline and adrenaline. Epinephrine has limited distribution in the brain but controls the fight-or-flight response in the peripheral nervous system.

3. Serotonin A neurotransmitter found only in the brain, is

derived from tryptophan, a dietary amino acid. The function of serotonin is mostly inhibitory,

involved in the control of food intake, sleep and wakefulness, temperature regulation, pain control, sexual behavior, and regulation of emotions.

Some antidepressants block serotonin reuptake, thus leaving it available longer in the synapse, which results in improved mood.

4. Histamine The role of histamine in mental illness is under

investigation.  

5. Acetylcholine Acetylcholine is a neurotransmitter found in the

brain, spinal cord, and peripheral nervous system. It can be excitatory or inhibitory. It is synthesized from dietary choline found in red meat and vegetables and has been found to affect the sleep-wake cycle and to signal muscles to become active.

Studies have shown that people with Alzheimer’s disease have decreased acetylcholine secreting neurons.

6. Glutamate Glutamate is an excitatory amino acid that

at high levels can have major neurotoxic effects.

7. Gamma-Aminobutyric Acid (GABA) GABA is a major inhibitory neurotransmitter

in the brain and has been found to modulate other neurotransmitter systems rather than to provide a direct stimulus.

Drugs that increase GABA function such as benzodiazepines are used to treat

anxiety and to induce sleep.

Theories of Psychopharmacology Efficacy refers to the maximal therapeutic effect

that a drug can achieve. Potency describes the amount of the drug

needed to achieve that maximum effect; low-potency drugs require higher doses to achieve efficacy, whereas high-potency drugs achieve efficacy at lower doses.

Half Life is the time it takes for half of the drug to be removed from the bloodstream. Drugs with shorter half-life may need to be given three or four times a day, but drugs with a longer half-life may be given once a day.

The FDA may issue a black-box warning when a drug is found to have serious or life-threatening side effects. This means that package inserts must have a highlighted box, separate from the text, which contains a warning about the serious side-effects.

 

Sedative Hypnotics and Anti-anxiety Drugs- these drugs are use to treat anxiety and anxiety disorders, OCD, depression, post-traumatic stress disorder, and alcohol withdrawal- it induces sedation, relax muscles and inhibit convulsion- previously called: Minor tranquilizer- 2 Major Groups:

a. Benzopdiazipinesb. Barbiturates

Benzodiazepines- mediates the action of actions of the amino acid GABA, the major inhibitory neurotransmitter in the brain- it increases the action of the GABA thus opening the chloride channel rendering the neurons in hyperpolarized state which reduces the neurons excitability- Indications:

a. Anxiolytic d. Anestheticsb. Hypnotics e. Muscle

Relaxantc. Anticonvulsant

- Adverse Reaction:a. Physical dependence or psychological

dependenceb. CNS: drowsiness, sedation, poor coordination,

and impaired memory or clouded sensoriumc. When used for sleep, may complain of next-

day sedation or a hangover effectd. Use cautiously among elderlye. CI: Among pregnant client and are not

recommended among nursing mothers- Drug Interaction

a. Alcohol and other CNS depressant- respiratory depression

b. Tobacco, caffeine and sympathomimetics- decrease the effect of benzodiazipinesExamples:

a. Chlodiazepoxide (librium)b. Diazepam (Valium)c. Lorazepam (Ativan)d. Oxazepam (Serax)e. Alprazolam (Xanax)f. Prazepam (Xentrax)d. Chlorazepate (Tranxene)

Non-Benzodiazipines

- often used for the relief of anxiety acts as partial agonist at serotonin receptors,

which decreases serotonin turnover Has a lesser CNS side effects Examples: Buspirone

Nursing Implication1.Administer IM route slowly in large muscles2.Observe for S.E.3.Monitor vitals signs (hypotension and bradycardia)4.Do not mix diazepam with other drugs5.For Benzodiazepines overdose

- Antagonist: flumazenil IV (Romazicon)- if conscious: administer emetic (follow with

activated charcoal- if unconscious: Gastric lavage- Maintain airway, give O2

7. Client teaching- do not drive or operate machine- do not consume alcohol, CNS

depressant- Effective response may take 1-2

weeks- strictly follow drug regimen- prevent

withdrawal symptoms

Barbiturates- are drugs use to treat insomnia, anxiety,

tension and apprehension- Mechanism of Action:

a. Depress the reticular activating system by promoting the inhibitory synaptic action of the GABA

- Indicationsa. Sedative hypnoticsb. Anestheticsc. Anti-convulsant

- Adverse Reaction:a. Mild side effect:

- confusion and irritability- Rare: agranulocytosis,

thrombocyopenia and megaloblastic anemia

Allergic reactionb. Withdrawal symptoms

- nightmares, daytime agitation and shaky feelings

c. Overdose: Respiratory and cardiovascular depression

Examples:a. Amobarbital (amytal)b. Aprobarbital (Alurate)c. Butabarbetal (Butisol)d. Pentobarbital (Nembutal)e. Phenobarbital (Luminal)f. Secobarbital (Seconal)

Barbiturates are classified in four categories

1. Long acting- Phenobarbital2. Short acting- Butobarbital , Pentobarbital3. Ultra short acting- Thiopental, Methohexitone

Anti-Psychotic- also known as Neuroleptic or Major

Tranquilizer- used to treat symptoms of psychosis,

such as delusions and hallucinations seen in schizophrenia, schizoaffective disorder, and

manic phase of bipolar disorder- work by blocking receptors of the

neurotransmitter dopamine - 2 Categories:

A. Classic/Typical AntipsychoticB. Atypical Antipsychotic

Classic/Typical Antipsychotic- the largest group under this category are

the PhenotiazinesMechanism of Actiona. As Dopamine Receptor Agonist

- it blocks dopamine receptor in various parts of the brain

- Dopamine receptors are classified into 5 (D1, D2, D3, D4, D5)

- it blocks : D2, D3, D4- relieving psychotic manifestation- blocking of D2 leads to EPS manifestations

b. As Adrenergic and Cholinergic Receptor Antagonist

- it blocks the receptors of norepinephrine and dopaminec. CNS effect and Adrenergic Receptors

- neurons containing norepinephrine in the reticular activating system of the brain is associated with alertness

- blockade can lead to sedative effect- blockade of norepinephrine receptor in

the center can lead to hypotension

Indications:- to treat manifestations associated by the

Dopamine theory of pscyhosis- Gilles de la Tourette’s Syndrome- Emesis and dopamine

Adverse Reaction:1.Extrapyramidal Syndrome (EPS)

- this is the most important side effect of the antipsychotic drugs

- it arises from the blockade of the D2 receptors in the certain nuclei of the basal ganglia which is responsible for the coordinated movement

- can be manifested by: Acute dystonia Akathisia Tardive dyskinesia Pseudoparkinsonism

Acute Dystonia- is a spasm of the muscles of the tongue,

face, neck or back and may mimic seizures- can be manifested by: torticollitis, oculygric crises and opisthonos posture- can be treated by anticholinergic drugs

Akathisia- is a motor restlessness - is reported by the client as an intense

need to move about- The client appears restless or anxious

and agitated often with a rigid posture or gait and a lack of spontaneous gestures.

- can be treated with : anticholinergic drugs or muscle relaxant

Pseudoparkinsonism- is marked by motor retardation and

rigidity- often referred to by the generic label of EPS- symptoms resemble those of Parkinson’s

disease and include: a. A stiff and stooped postureb. Mask-like faces, decreased arm swing, a

shuffling, festinating gait, cogwheel rigidity, drooling, tremors,

c. Bradycardia, and coarse pill-rolling movements of the thumb and fingers while at rest

- can be treated by: oral anticholinergic drugs or amantidine (a dopamine agonist)

Tardive Dyskinesia- is associated with long term, high doses of

antipsychotic therapy- syndrome of permanent involuntary

movements commonly caused by the long-term use of conventional antipsychotic drugs

- symptoms of TD include involuntary movements of the tongue , facial and neck muscles, and upper and lower extremities

- tongue thrusting and protruding, lip smacking, blinking, grimacing, and other excessive, unnecessary facial movements are characteristic

- once it has developed, TD is irreversible, although decreasing or discontinuing antipsychotic medication can arrest its progression

Neuroleptic Malignant SyndromePotentially fatal reaction to antipsychotic

drugsmajor symptoms of NMS are rigidity, high

fever, autonomic instability (such as unstable BP, diaphoresis, and pallor), delirium, and elevated levels of enzymes (particularly

creatinine phosphokinase)clients with NMS usually are confused and

often mute, may fluctuate from agitation to stupor

Anticholinergic Action- atropine like effects- dry mouth, blurred vision, delayed

micturation, and constipation- CNS reaction: is beneficial because it used to

treat pseudoparkinsonism manifestationsSeizure Potential

- it lowers the convulsive thresholdEndocrine Disturbances

- blockade of the dopamine receptors can lead to hypersecretion of prolactin and endocrine

disturbances in the reproductive system

- can lead to: increase blood prolactin levels causing breast

enlargement and tenderness (both in men and women)

diminished libido erectile and orgasmic dysfunction menstrual irregularities weight gain (obesity common in schizophrenic

clients, increasing risk for DM II and CVD) minor cardiovascular adverse effects such as

postural hypotension, palpitations, and tachycardia

Allergic Reaction:- photosensitivity and cholestatic

hepatitisDrug Interaction

a. It potentiates the action of drugs that depresses the CNS: sedative-hypnotics, narcotic analgesic and anesthetic agent

Nursing Implication:

1.Inform client of side effects and encourage to report problems instead of discontinuing medication

2. teach client methods of managing or avoiding unpleasant side effects and maintaining medication regimen:

dry mouth – sugar-free fluids and sugar-free hard candy

* client should avoid calorie-laden beverages and candy

constipation – exercise, increase water and bulk-forming foods; stool softener permissible but avoid laxatives

photosensitivity – sunscreen

3. Client should monitor amount of sleepiness and drowsiness they feel; avoid driving and

potentially dangerous activities until response time and reflexes seem normal

Examples of Drugs:A. Phenothiazine

Alipathic- Chlorpromazine (thorazine)- Promazine (Sparine)- Trifulpromazine (Vesporin)

Piperazines- Fluphenazine (Prolixin)- Perphenazine (Trilafon)

Piperidines- Thioridazine (Meliaril)- Mesoridazine (Serentil)

B. Non-Phenothiazide Haloperidol (haldol) Loxapine (loxatane) Molindone (Moban) Pimozide (Orap)

Atypical Antipsychotic- are new agents used of treatment of

severe schizophrenia- they have minimal EPS side effects- are effective in treating negative

symptoms of schizophrenia (apathy, social withdrawal, blunted affect

- Mechanism of action:a. Blocks the Dopamine D2 but not as effective as the traditional antipsychotic b. Block the serotonine 5-HT2A receptors

Indication:a. Patients who are unresponsive to

typical antipsychotic drugsAdverse Reaction:

a. Increase risk for seizureb. Clozapine

- CV: orthostatic hypotension and tacycardia

- agranulocytosis- dizziness and sedation

Examples:a. Olanzapine (Clorazil)b. Olanzapine (Zyprexia)c. Respiridone (Risperdal)

Nursing Implication: Monitor VS Remain with client while he takes the medication. Avoid skin contact with liquid concentrates. Protect liquid prep from light & dilute with juice. Administer oral dose with food or milk.

Administer IM drug deep. Observe for EPS. Monitor for signs of neuroleptic malignant

syndrome. Client teachings:

- take drug exactly as ordered.- Meds take 6 wks or longer to achieve

full clinical effect.- WBC monitored for 3 months. (WOF

signs of infection)- Avoid driving & operating machineries.

Avoid driving & operating machineries. Avoid direct sunlight. Avoid extremes in temperatures & increased

exercise. Change positions slowly. Alipathic phenothiazines pink-red brown urine. Suggest lozenges, hard candy for dry mouth. Changes to sexual functioning & menstruation.

Antidepressant Drugs- primarily used in the treatment of major

depressive illness, anxiety disorders, depressed phase of bipolar disorder, and psychotic depression

- somehow interact with norephinephrine and serotonin which regulate mood, arousal, attention, sensory processing, and appetite

- Theories of the Development of Mood Disorders:a. Deficiency of brain neurotransmitter norepinephrine is associated with depressionb. Reserpine depletes norepinephrine causes depressionc. Inhibition on MAO has antidepressant effect

Classification of Anti-Depressant:a. Selective Serotonine Reuptake Inhibitor (SSRI)b.Tricyclic Anti-depressantc. Monoamine Oxidase InhibitorSelective Serotonine Reuptake Inhibitor

- newest category of antidepressant with fewer side effects and minimal potential lethal overdose

- Mechanism of action:1. Blocks the neuronal reuptake of serotonin but have little effect on norepinephrine and dopamine

Indication:a. major depression (unipolar)b. Obsessive Compulsive Disorders and

eating disordersAdverse Reaction:

a. Headaches, tremors, anxiety and drowsiness, dry mouth, sweating and diarrhea

b. Use cautiously in patient with: - liver and renal impairment- patients with seizure disorders- nursing mothers is not recommended

Drug Interaction:a. Other anti-depressant drug may be

potentiated by SSRI: MOA and tryptophan

b. Use cautiously with anticoagulant and phenytoinExamples:

Flouxetine (Prozac) Sertraline (zoloft) Paroxatine (Plaxil) Fluvoxamine (Luvox) Citalopram (Celexa)

Tricyclic Antidepressant- Have a more pronounced side effects

compared to SSRI- Mechanism of Action:a. Blocks the reuptake of

norepinephrine or serotonin in the presynaptic cleft causing an increase concentration of these

neurotransmitter b. Block cholinergic receptors leading to

anticholinergic side effects

c. Takes 2-3 weeks before the effects can be seen among patients Indications:1. major depression and bipolar disorders2. clomipramine- obsessive compulsive disorders3. Imipramine- enuresisAdverse Reactions:a. Anticholinergic Side Effects:- dry mouth, blurring of vision and constipation- cautiously among client with glaucoma- pt with urinary retention and obstruction

b. Cardiac Effects- increase in heart rate (anticholinergic effects)- postural hypotension (adrenolytic effect)- decrease myocardial contractility and

coronary blood flow (Quinidine like effect)c. Weight gaind. Toxicity:

1. Not addicting2. Overdose of Tricyclic antidepressant

- anticholinergic poisoning- delerium, seizures, hallucination,

pupillary dilation and hyperactive reflexes

- Antidote: Physostigmine (antilirium)Drug Interaction:

a. Can potentiate CNS depressionb. Cemitidine and methylpenidate-

inhibit its metabolismExamples:

Amytriptyline (elavil) Trimipramine (Surmontil) Doxepin (Sinequan) Imipramine (Tofranil)

Monoamine Oxidase Inhibitor- are less commonly used because of

poor safety profile that requires strict adherence to dietary limitations and potential for drug interaction

- Mechanism of Action:a. It inhibits the enzyme MAO thus preventing the degradation of epinephrine and serotonin so that its concentration in CNS is increased

Indications:a. Effective in treatment of depression

exhibit as phobiasSide Effects:

a. Anticholinegic effectsb. Sedationc. insomnia

Toxicity:a. Reflects adrenergic activity:

- tachycardia, anxiety, insomnia and restlessness

Interactions:1. Foods containing Tyramine

- Avocados, Bananas, Beer, Chocolates, Cheese, Liver, Meat extracts, Papaya extracts, Raisins, Salami, Yogurt

- can be manifested by:a. Hypertensive crises- due to

accumulated release of norepinephrine

- Pentholamine- can be given

Examples: Isocarboxacid (Marplan) Phenelzine (Nardil) Tranylcypromine (Parnate)

Mood Stabilizer/Antimanic Drugs- used for treatment of manic episodes in

bipolar disorder- Example: Lithium- Lithium- the most established mood

stabilizer- Mechanism of Action

- it normalizes the reuptake of serotonin, norepinephrine,

acetylcholine, and dopamine- has a narrow therapeutic range: 0.6-

1.5 mEq/L

- excreted in the kidney- Na deficiency- increaser lithium

absorption- Na Excess- lower lithium below

therapeutic range- may reverse manic episode in 1-3

weeks- Indication: Treatment of the manic phase

in bipolar disorders- Adverse Reaction:

a. CI among pregnant clientb. Inhibit thyroxine releasec. Nephrotoxic

Toxicity:a. 1.5-2.0 mEq/L- persistent diarrhea, n

and v, muscle weakness, blurred of vision and tinnitus

b. 2.0- 3.5 mEq/L- excessive urination, tremors and mental confusion

d. > 3.5 mEq/L- seizure, coma, oliguria/anuria, nystagmus, MI and cardiac dys.Treatment: Gastric lavage, correction of fluid imbalance and mannitol

Interaction:a. NASIDS, diuretics, tetracyclines-

increases the risk of lithium toxicity

b. Caffeine product (coffe and tea cole)- aggravate manic phase