pharmacology CNS disorders and seizure drugs

psychiatric disorders categories

• psychoses

• affective disorders

• anxiety disorders

psychoses

• Schizophrenia is the most common of this class of mental illness

  • Disturbance of patient’s personality

  • Loss of perception of reality

  • Derived from word that means “splitting” referring to splitting from reality, not multiple personalities

• Positive symptoms: Add to person’s perception of reality

• Negative symptoms: Take away from person’s perception of reality

positive symptoms of psychoses

• hallucinations, auditory

• delusions

• unwanted thoughts

• disorganized behavior

• agitation

• distorted speech, communication

negative psychoses symptoms

• flat affect

• unemotional lack of emotion

• apathetic, passively

• abstract thinking difficult

• spontaneity and goals lacking

• thought and speech impaired

• lack of pleasure

• social withdrawl

affective disorders

• Depression

  • Exogenous: results from external situations

  • Endogenous: results from internal issues (lack of NE, Serotonin, Dopamine)

  • Debated whether two separate issues. Treated similarly

• Bipolar Disorder

  • Exhibit a manic phase and a depressive phase

  • Also called manic-depressive disorder

anxiety disorders

Generally, less severe than psychoses

• Examples

  • Anxiety

  • Panic Disorder

  • Phobias

  • Obsessive compulsive disorder

• Personality disorders can overlap

  • Sexual deviance

  • Alcoholism

  • Addiction

• Treated with antidepressants due to concern of addiction if benzodiazepines used

• Before medication many physical methods were used. Electroconvulsive therapy is the only one still used

general precautions

• When treating patients with mental disorders use some precautions

  • Communication: Consider what, or how, you say to the patient.  Do not speak with other co-workers in their presence as they may perceive you are talking about them

  • Compliance: Thorough health history to determine if patient takes medication as prescribed. Some do not

  • Suicide: Be aware that some depressed patients consider suicide. Also consider that in the beginning of new medication the medication has not completely controlled the depression, and suicidal thoughts may encroach the patient’s thoughts.

• Show some empathy and think about what is said to patient.

antipsychotic agents

•Treat: schizophrenia, schizoaffective disorder, delusional disorder, and other psychoses

•First generation mostly treated positive symptoms

•Chronic schizophrenia may take weeks or months to respond to medication

•2^nd generation meds used more frequently today as they seem to be better tolerated than 1^st

antipsychotic agents mechanism of action

•1^st generation medications were primarily dopamine antagonists

•2^nd generation medications have action at more than one receptor

•Dopamine

•Serotonin

•Norepinephrine

•2^nd generation medications tend to have less side effects

•While 1^st generation medications treat the positive symptoms, 2^nd generation agents are effective against the positive and negative effects

first generation pharmacologic effects antipsychotic

• Antipsychotic effect: Suppress positive effects of psychosis

• Antiemetic effect: Depresses chemoreceptor trigger zone, area in brain that causes nausea and vomiting

• Adverse Reactions: can negatively affect oral health

  • Sedation: differs depending on drug. Tolerance develops to sedative effects

  • Extrapyramidal: (a special network of nerve cells in the brain responsible for posture and controlling involuntary movements) Muscle spasms, Parkinsonism, Increased compulsive motor activity (akathisia). Tardive dyskinesia (repetitive body movements involving tongue, lips, face, jaw. Exacerbated by drug withdrawal. Can cause severe, intermittent pain in TMJ. Should not force patient’s mouth open for treatment

  • Orthostatic hypotension

  • Tachycardia

  • Xerostomia

  • Seizures

second generation pharmacologic effects antipsychotic

•Relatively low extrapyramidal effects.

•Less likely to cause tardive dyskinesia

•Clozapine, olanzapine, quetiapine can cause significant weight gain

•Agranulocytosis: clozapine mainly. Weekly blood cell count monitoring required. Use of clozapine has decreased, and it’s a last resort

•Higher risk of hyperglycemia, diabetes, and metabolic syndrome. Healthy diet is recommended

•Tachycardia

drug interactions antipsychotic

•1^st generation have additive effects with CNS depressants

•Epinephrine in local anesthetics is safe to use

•Anticholinergic agents are used to control extrapyramidal stimulation. The combination of the antipsychotic and the anticholinergic can exacerbate antimuscarinic peripheral effects such as xerostomia, urinary retention, constipation, blurred vision, and inhibition of sweating

antipsychotic dental implications

• use caution with patient interactions (may misinterpret verbal or nonverbal actions)

• check for xerostomia

• emphasize oral hygiene instruction

• extrapyramidal dyskinesia may make oral hygiene more difficult

• check the temporomandibular joint for extrapyramidal side effects

• sedation is additive with other agents

• epinephrine is safe to use

antidepressant agents

• Used for depression as well as chronic pain, and migraine headache prophylaxis.

• Healthcare provider should determine why patient is taking the antidepressant rather than assuming it is for depression

• Classes of antidepressant agents

  • SSRI (selective serotonin reuptake inhibitors)

  • SNRI (serotonin-norepinephrine reuptake inhibitors

  • TCA (tricyclic antidepressants)

  • MAOI (monoamine oxidase inhibitors)

  • Buproprion

  • Mirtazapine

  • Nefazodone

selective serotonin reuptake inhibitors

•First-line therapy for treatment of major depression

•No evidence of one being better than another

•Similar antidepressant action to Tricyclic Antidepressants with different adverse reaction

SSRI adverse reactions

• CNS effects: stimulation

  • Headache, dizziness, tremor, agitation, sweating, and insomnia

  • Weight loss or stabilization

  • Fatigue has been reported

• GI effects:

  • Nausea and diarrhea

  • Anorexia

• Oral effects:

  • Xerostomia

  • Taste changes

  • Aphthous stomatitis

  • Glossitis

• Other effects:

  • Sexual dysfunction

  • Excessive sweating

examples of SSRIs

• Citalopram (Celexa)

• Escitalopram (Lexapro)

• Fluoxetine (Prozac)

• Paroxetine (Paxil)

• Sertraline (Zoloft)

serotonin-norepinephrine reuptake inhibitors

• Unclear if they offer an advantage over SSRIs

• Inhibit reuptake of serotonin and norepinephrine, more selective for serotonin than NE

• Adverse effects:

  • Sweating

  • Tachycardia

  • Elevated BP

  • Urinary retention

• Must taper off of drug. Cannot stop cold turkey

examples of serotonin-norepinephrine reuptake inhibitors

• Desvenlafazine (Pristiq)

• Venlafaxine

• Venlafaxine, extended release (EffectorXR)
  Duloxetine (Cymbalta)

• Levomilnacipran (Fetzima)

tricyclic antidepressants (TCAs)

• First generation of antidepressants, but no longer first line

• Block the reuptake of both serotonin and NE to varying degrees

• Adverse reactions

  • CNS: some degree of sedation

  • Anticholinergic effects: xerostomia, blurred vision, constipation, and urinary retention

  • Cardiac effects: tachycardia, orthostatic hypotension. Cardiac toxicity. More dangerous in an overdose situation

TCAs Drug interactions

• Potentiate:

  • Behavioral actions of amphetamines and other CNS stimulants

  • Pressor effect of injected sympathomimetics such as epinephrine

  • Interact with MAOIs resulting in severe toxicity

  • Additive anticholinergic effects

tricyclic antidepressant examples

• Amitriptyline

• Desipramine (Norpramin)

• Imipramine (Tofranil)

• Nortiptyline (Pamelor)

Monoamine Oxidase inhibitors (MAOIs)

• Have many adverse effects, and overdose leads to severe toxic reaction

  • Sleep disturbances

  • Orthostatic hypotension

  • Sexual dysfunction

  • Weight gain

• Interact with many drugs (amphetamines) and foods (cheese, wine, fish) leading to hypertensive crisis or death

• Last choice for treating depression

• Patient taking an MAOI should not be given any drug  without consulting a drug reference for drug interactions

MAOIs examples

• Isocarboxazid (Marplan)

• Phenelzine (Nardil)

• Tranylcupromine (Parnate)

other antidepressants

• Buproprion (Wellbutrin): a dopamine-NE reuptake inhibitor

  • Can develop seizures at  high doses

  • Reserved for patients who are not responsive to other agents

  • Dry mouth, headache, excessive sweating, and tremors have been reported

• Trazodone (Desyrel): Serotonin modulator chemically unrelated to TCAs but has similar antidepressant effects.

  • Fewer incidences of xerostomia and cardiac toxicity

  • Highly sedative

  • Has been associated with priapism requiring surgery

other anitdepressants

• Nefazodone, Mirtazapine, Vilazodone, Vortioxetine

  • Newer antidepressants

• Nefazodone

  • Xerostomia, sexual dysfunction

  • Raises blood serum levels of alprazolam, triazolam, and digoxin

  • Can lead to life threatening hepatic failure

• Mirtazapine causes somnolence, weight gain, constipation and dry mouth

• Vilazodone and vortioxetine have similar adverse effects as SSRIs

suicide and antidepressants

• All Antidepressants carry a black box warning about suicidal ideation and behavior.

• Increased risk in children, adolescents, young adults.

• All depressed individuals under 24 years of age should be carefully monitored.

dental implications of antidepressants

• Sympathomimetic Agents

  • Vasoconstrictors in local anesthesia s hould be administered with caution to patients taking TCAs. May potentiate the increased blood pressure response to epinephrine. Use cardiac dose

• Xerostomia

  • Anticholinergic effects of sympathomimetic amines is additive with other agents

management of patient taking antidepressants

• use caution in patient interactions

• an antidepressant is used for other than depression; ask why taking medication

• check for xerostomia and its management

• epinephrine may increase the vasopressor response. limit dose of epinephrine to 0.04 mg if blood pressure is a concern

• limit total amount of any potentially lethal drugs prescribed if patient is depressed

• increase motivation for good oral hygiene

antiepileptic drugs

• In the treatment of bipolar depression several antiepileptic agents have been used

  • Carbamazepine

  • Lamotrigine

  • Valproate

  • Gabapentin

epilepsy

• A group of disorders that involve chronic stereotyped recurrent attack of involuntary behavior or experience or changes in neurologic function caused by electrical activity in the brain that can be recorded by EEG

• Seizure may be accompanied by:

  • Motor activity: convulsions

  • Neurologic changes: sensory or emotional

uTwo major groups:

uGeneralized seizures

uTonic-clonic

uAbsence

uPartial seizures

uSimple

uComplex

two major groups of seizures

• Generalized seizures

  • Tonic-clonic

  • Absence

  • consciousness lost in both tonic-clonic and absence

• Partial seizures

  • Simple

  • Complex

absence seizures

•Brief loss of consciousness with little movement

•Begin during childhood; disappear in middle age

•Patient usually unaware seizures occur; body tone not lost

•Ethosuximide drug of choice; long term use can have adverse effects

•No problems for dental team

tonic-clonic seziures

•Longer periods of loss of consciousness

•Major motor activity of large muscles of body

•Body becomes rigid, then patient falls to floor

•Tonic rigidity is followed by Clonic jerking of face, limbs, and body

•Patient may bite tongue or cheek

•Patient becomes limp and comatose, then consciousness returns

•Valproate, lamotrigine and levetiracetam drugs of choice

status epilepticus

•Limbs and face begin to jerk that last more than five minutes, can produce hypoxia

•Parenteral benzodiazepines drugs of choice

partial (focal) seizures

•Activation of only part of the brain

•Location of activity in brain determines clinical manifestations

•Simple Partial Attack when consciousness is not impaired

•Complex Partial Attack when consciousness is imparited

•While absence seizures last a few seconds, complex partial last several minutes

•Lamotrigine, Carbamazepine, Levetiracetam and Oxcarbazepine are used as drugs of choice

drug therapy of patients with epilepsy

• variable efficacy from complete control to reduction in frequency

• may be used alone or in combination

dental management of patients taking antiepileptic agents

• review emergency management of epiletic patients (remove hands and dental instruments from mouth, turn head to side)

• take a thorough medical and drug history, including medications and frequency of seizures

• additive central nervous system depression- use additional CNS depressants cautiously

• additive GI adverse reactions (use NSAIDs cautiously)

• drug interactions- induction of hepatic microsomal enzymes, metabolizes certain drugs more quickly (lowers blood level and effect)

• dental drugs affects- propoxyphene, doxycycline

general adverse reactions of antiepileptic agents

• CNS Depression

  • Common side effect of antiepileptic agents

  • Tolerance often develops to the sedative effects

  • Impairment of learning and cognitive abilities occur in some

  • Can exacerbate a seizure type not being treated

• GI Distress

  • Anorexia, nausea, vomiting

  • Minimized by taking medication with food

  • Avoid NSAIDs, opioids or other drugs that cause GI irritation

other adverse reactions of antiepileptic agents

• Drug interactions

  • Some antiepileptic agents can interact with other antiepileptic agents

  • Most important drug interaction involved stimulation of hepatic microsomal enzymes. Results in reduction of the affected drugs (those metabolized by liver enzymes) in the blood

  • Older antiepileptic drugs (phenytoin, carbamazepine, valproate) have narrow therapeutic windows. Drug interactions can quickly make these ineffective, or toxic

• Idiosyncratic Reactions

  • Dermatologic effects: rash, Steven-Johnson syndrome, exfoliative dermatitis, erythema multiforme

  • Drug induced systemic lupus erythematosus

  • Hematologic effects

teritogenicity/ growth antiepileptic drugs

• adverse reaction

•Can alter growth

•Profound effects on fetal development

•Sometimes seizures are more damaging to fetus than drug risk/reward decision to be made

withdrawal antiepileptic drugs

•Abrupt withdrawal of drug can precipitate seizures

•Some patients require treatment for life, some will have seizures disappear as they grow older

•Gradual withdrawal of medication if seizures have disappeared

Valproate

• Depakote

• also used for migraine prophylaxis

• bipolar disorder

• additive bleeding is a risk. use caution with drugs that can alter coagulation

• look for signs of hepatotoxicity

lamotrigine

• Sodium-channel-blocking antiepileptic agent

  • As effective as carbamazepine and better tolerated by elderly

  • Preferred over ethosuximide in children with absence seizures

  • FDA approved for bipolar disorder

• Drug interactions

  • Carbamazepine decreases lamotrigine levels

  • Valproate increases levels more than twofold

levetiracetam

•Thought to inhibit presynaptic calcium channels to impede impulse conduction

•Used as a monotherapy for partial or generalized tonic clonic

•May be effective in children with absence seizures

•No clinically significant drug interactions

oxcarbazepine

• Chemically similar to carbamazepine with less induction of hepatic enzymes, and does not induce its own metabolism

• As effective as phenytoin, carbamazepine, and valproate for treatment of partial seizures

• Can increase phenytoin levels by 40%. Active metabolite is reduced in presence of phenobarbital and phenytoin

carbammazepine

• can be used to treat trigeminal neuralgia and bipolar disorder

• dental team should check for petechiae in oral cavity which may indicate presence of a blood dyscrasia

dental management of patients taking carbamazepine

• check for dry mouth, glossitis, and stomatitis

• additive bleeding is a risk; use caution with drugs that alter coagulation

• look for symptoms of blood dyscrasias

• check for flu-like symptoms

• monitor white blood cell counts

• consider drug interactions- doxycycline (reduced dox effects) and erythromycin (increased carbamazepine)

• emphasize oral hygiene; for a child using chewable tablets could have higher caries risk

phenytoin

• Treats both generalized tonic clonic and partial seizures with complex symptomatology

• Used to be drug of choice, but no longer due to adverse effects and many drug interactions

• Associated with gingival enlargement

• Can lead to congenital abnormalities Fetal hydantoin syndrome: craniofacial anomalies, microcephaly, nail/digit hypoplasia, limb defects, growth deficiency, and mental retardation if pregnant mother takes it

• if patient has nausea, avoid drugs that are gastric irritants

• monitor for gingival enlargement and provide extensive oral hygiene instruction

ethosuximide

• Drug of choice to treat absence seizures

• Ineffective in treatment of partial seizures with complex symptoms or tonic clonic seizures

• Can produce gingival enlargement and swelling of tongue

benzodiazepines

• Orally

  • Clonazepam

  • Clabazam

• Parenterally

  • Diazepam

  • Lorazepam

  • Midazolam

• All used to treat recurrent tonic clonic seizures or status epilepticus

dental treatment of epileptic patient

Do not treat patient who has a history of seizure disorders without reviewing the management of patient with epilepsy

• How to handle tonic-clonic seizures

  • Move patient to the floor if possible

  • Tilt head to one side to prevent aspiration

  • Remove objects from patient’s mouth

• Preventive measures

  • Detailed seizure history

  • Treatment planning to avoid excessive stress or missed medications

  • Educate entire dental team

dental hygiene considerations for seizures

• conduct a thorough health history to determine type, duration, and frequency of seizures

• determine when the client had his or her last seizure

• conduct a detailed medication history to avoid drug interactions and adverse effects

• determine whether the patient is experiencing any adverse effects of antiseizure medications

• find out how often the patient takes his or her medication and whether it was taken on the day of the appointment