Chapter 18lecture 5

Chapter 18

Anticonvulsants

Anticonvulsants• Epilepsy

* A seizure disorder occurring in about 1% of pop.

* Abnormal electric discharges from cerebral neurons

* Loss or disturbance of consciousness & convulsions

(Abnormal motor rxn)

* 50% = primary or idiopathic (cause unknown)

* 50% secondary to trauma, brain anoxia, infection

* Isolated seizures = febrile, hypoglycemic rxn,

electrolyte imbalance (hyponatremia), ETOH & drug

withdrawal

Anticonvulsants• Classification of seizures

> Generalized - convulsive & nonconvulsive - both

cerebral hemispheres of the brain effected

- Tonic - clonic = grand mal - most common

Tonic = skeletal muscles contract or tighten in a spasm

Clonic = dysrhythmic muscular contraction: jerkiness

- Absence Seizures = petit mal - brief loss of

consciousness

> Partial - One hemisphere of brain. No loss of

consciousness in simple, loss in complex partial

Anticonvulsants

• Action of Anticonvulsants

> Drugs depress abnormal neuronal discharges,

therefore inhibiting seizure activity and

increase the seizure threshold (stabilizes

neuronal membranes.

> Inhibits excitatory nerve impulses; enhances

inhibitory nerve impulses.

Anticonvulsants

• Use - many different types of seizures, but not

all drugs used for all types of seizures

• Side Effects - Not the safest group of drugs;

many very serious side effects: teratogenic =

effects the fetus

• Narrow therapeutic index

• Usually taken throughout a persons lifetime -

compliance issues

AnticonvulsantsHydantoins

• Phenytoin (Dilantin) - since 1938 * Least toxic, nonaddicting, sm. sedating effect

* Dosage varies according to age

* Narrow therapeutic index = monitoring serum drug

levels a must

* Highly protein bound Drug-drug interactions

* Action - Reduces motor cortex activity by altering

transport of ions inhibits spread of seizure activity

* Uses - Grand mal & complex partial seizures

AnticonvulsantsPhenytoin (Dilantin)

• Side effects - Gingival Hyperplasia = overgrowth of the gums - good oral hygiene a must!

* Long term use may elevate blood sugars

• Drug Interactions - Lots!!

AnticonvulsantsBarbiturates

• Phenobarbital - long acting

* Use - grand mal seizures & acute episode of of status epilepticus (rapid succession of seizures)

* Action - Increases seizure threshold in motor cortex

* SE - General sedation & client tolerance

AnticonvulsantsMiscellaneous Agents

• Carbamazepine (Tegretol) -

* Use - Grand mal, psychomotor, mixed seizures, & when other anticonvulsants do not work

* Action - Unknown - Thought to work in Na ions during generation of nerve impulses

* SE - Aplastic anemia (abnormal regeneration of RBC’s), agranulocytosis (great in leukocytes an increase risk of infection

AnticonvulsantsMiscellaneous Agents

• Valproic Acid (Depakote) -

* Use - Petit mal, grand mal, & mixed type of seizures

* Action - Unclear - Probably increases brain levels of GABA which transmits inhibitory nerve impulses in the CNS

* SE - Hepatotoxicity, esp. in young children

* DI - Lots !!

Chapter 19

Antipsychotics, Anxiolytics, and

Antidepressants

Antipsychotics

• Used to treat symptoms of mental disorders• Also known as neuroleptics & psychotropics• Neuroleptic = any drug that modifies plychotic behavior,

thus exerting antipsychotic effect• Psychosis = symptomatic in a variety of mental or

psychiatric disorders

- Characterized by more than one symptom - diff. in processing info., delusions, hallucinations, incoherence, catatonia, aggressive or violent behavior

Antipsychotics

• Schizophrenia - Chronic, major category of psychosis

- Usually occurs in adolescence or early adulhood

- Positive Symptoms = agitation, incoherent speech, hallucination, delusion, & paranoia

- Negative Symptoms = or loss in function & motivation, poverty of speech content, poor self-care, social withdrawl - more chronic & persistent

* Traditional (typical) antipsychotics more helpful for managing poss. symptoms than neg.

* A new group (atypical) more useful in treating both pos. & neg. symptoms of schizophrenia

Antipsychotics

• Comprise the largest group of drugs to treat mental illness• improve the thought processes & behavior• Not used for treating anxiety & depression• Theory - psychotic symptoms result from an imbalance of

the neruotransmitter dopamine in the brain (these drugs sometimes called dopamine agonists)

• Antipsychotics block D2 dopamine receptors in the brain = a dec. in psychotic symptoms.

• Many block the chemoreceptor trigger zone in the brain =

antiemetic effect

Antipsychotics• Side Effects - Pseudoparkinsonism = a major side effect of

typical antipsychotic drugs

- Extrapyramidal symptoms (EPS) - mask-like faces, rigidity, tremors, pill-rolling

* With high doses of drugs symptoms are more pronounced

- Acute dystonia - muscle spasms of face, tongue, neck & back - treat with anticholinergics (Cogentin)

- akathisia - trouble standing still, pacing, constant motion - treat with benzodiazepines or beta blockers

- Tardive dyskinesia - serious with long term use of drug - protrusion/rolling of tongue, sucking/smacking of lips, chewing motion - best to D/C the drug

AntipsychoticsPhenothiazines

• Three groups: Aliphatic, Piperazine, & Piperidine - differ mostly in their side effects

• Most of the antipsychotics can be given orally, IM, or IV• Chlorpromazine (Thorazine) - First drug - aliphatic

- Action - alt. in DA effect on CNS

- Use - psychosis, Hiccups,

- SE - sedation, EPS,

- Adverse rxns - Hypotension, tachycardia ( pulse rate),

tardive dyskinesia, seizures

AntipaychoticsPhenothiazines

• Prochlorperazine (Compazine) - piperazine - low sedative

- Use - antiemetic

- Action - Acts on chemoreceptor trigger zone to inhibit

N & V

- SE - EPS symptoms, orthostatic hypotension• Thioridazine (Mellaril) - piperidine - strong sedative

- Use - Psychosis

- Action - Unknown - probably blocks postsynaptic DA

receptors in the brain

- SE - Low incidence of EPS

AntipsychoticsNonphenothiazines

• Haloperidol (Haldol) - a potent antipsychotic drug whose dose is smaller than less potent drugs - Similar to phenothiazines in pharmacologic action

- Action - Alters the effects of dopamine by blocking dopamine receptors

- Use - Psychoses, Tourette’s syndrome

- SE - EPS symptoms, photosensitivity, hypotension

- CI - Glaucoma, severe hepatic, renal & CV disease

AntipsychoticsAtypical

• New category since early 1900’s• Treats pos & neg symptoms of schizophrenia• Not likely to cause EPS or tardive dyskinesia• clozapine (Clozaril), risperidone (Risperdal), olanzapine

(Zyprexa) & quetiapine (Seroquel)• Clozapine - can cause aggranulocytosis dec. in body’s

defense mechanism & seizures - used for severely ill only• Risperdal, Zyprexa & Seroquel - Do not cause

aggranulocytosis, similar action to Clozaril

Anxiolytics orAntianxiety Drugs

• Primarily used for treating anxiety and insomnia• Major group = benzodiazepines - a minor tranquilizer

group• More effective than barbiturates - enhance action of

GABA within the CNS, have fewer side effects, less dangerous in overdosing - Wide therapeutic index

• Used when anxiety is excessive & could be disabling• These agents treat the symptoms - not the cause• Long term use discouraged - tolerance can occur• Nonpharmacologic measures should be tried first, before

giving anxiolytics

AnxiolyticsBenzodiazepines

• Multiple uses: anticonvulsants, antihypertensives, sedative-hypnotics, pre -op drugs & anxiolytics

• Used mainly for severe or prolonged anxiety, panic attacks, phobias, compulsions ( not day to day stress)

• 3 frequently used = diazepam (Valium), alprazolam (Xanax), & lorazepam (Ativan)

• Highly protein bound & could displace other highly protein bound drugs

• Controlled substances - class IV• Avoid ETOH an in CNS depression

AnxiolyticsBenzodiazepines

• Diazepam (Valium) -

- Action - acts on limbic & subcortical levels of CNS

- Use - control anxiety, pre-op, muscle relaxant, ETOH withdrawl, anticonvulsant

- SE - Drowsiness, orthostatic hypotension, confusion

- CI - Pregnancy - Potential to cause fetal birth defects

- Alert - Do not D/C abruptly = withdrawl symptoms• Buspirone hydrochloride (BuSpar) - newest anxiolytic

- Action - ?? - may inhibit neuronal firing, serotonin

- Use - short-term relief of anxiety. 1-2 weeks for relief

- SE - < benzodiazepines, but still monitor CNS

Antidepressants

• Depression is the most common psychiatric problem, about 10 - 20% of pop. affected

• Def. - mood changes & loss of interest in normal activities, occurs every day for at least 2 weeks, interferes with daily functioning. Symptoms: loss if interest in most activities, weight loss or gain, insomnia or hypersomnia, loss of energy, fatigue, feelings of dispair, suicidal thoughts.

• Cause - Genetic, social & environmental factors, change in neurotransmitter (NT) levels - norep. and/or serotonin in the brain

Antidepressants• Action - Antidepressants work to normalize NT balance• Classes of drugs include:

- Tricyclic antidepressants (TCAs) or tricyclics

- Selective serotonin reuptake inhibitors (SSRIs) & atypical antidepressants

- Monoamine oxidase (MAO)• Most drugs need to be taken for 2-4 weeks for full effect• Treatment should continue for 9 months after remission

of 1st episode; 5 yrs after 2nd; indefinitely after 3rd

Antidepressant AgentsTricyclic Antidepressants

• Amitriptyline (Elavil)

*Action - Serotonin & Norep. increased in nerve cells

*Use - Depression & anxiety

* SE - Sedation, drowsiness, anticholinergic effects (dry mouth, urinary retention, constipation), EPS, orthostatic hypotension

Antidepressant AgentsSelective serotonin Reuptake inhibitors (SSRI)

• Action - not well defined - blocks reuptake of serotonin into the nerve terminal of the CNS

• Do not block uptake of dopamine or norep.• Do not block cholinergic receptors• More commonly used to treat depression D/T fewer side

effects - but more costly• Use - major depressive disorders, anxiety disorders, panic

attacks, phobias, • 4 SSRI’s since 1988: fluoxetine (Prozac), fluvoxamine

(Luvox), sertraline (Zoloft), paroxetine (Paxil)

AntidepressantsSSRI’s

• Fluoxetine (Prozac) - most commonly prescribed

*Action - ?? - Thought to inhibit reuptake of seretonin

* Use - Depression, obsessive-compulsive disorders, bulimia

* SE - agitation, nervousness, insomnia, wt. loss

* DI - Lots!!1

* Onset of effect between 1 and 4 weeks

* Some clients experience sexual dysfuction

AntidepressantsMonoamine Oxidase Inhibitors

• Monoamine oxidase (MAO) - an enzyme - normally inactivates norep., dopamine, epi. & serotonin. By inhibiting = rise in these NT’s

• 2 forms of MAO - A & B

- MAO -A inactivates DA in the brain

- MAO -B inactivates norep. & serotonit

• MAOI’s are nonselective = inhibits both A & B

• Inhibition is thought to relieve symptoms of depression

AntidepressantsMAOI’s

• 3 MAOI’s currently prescribed: tranylcypromine sulfate (Parnate), phenelzine sulfate (Nardil), isocarboxazid (Marplan)

• As effective as TCA’s for treating depression, but D/T side effect of hypertensive crisis resulting from food & drug interactions, only 1% of clients use - tyramine rich foods & CNS stimulants can cause the crisis

Bipolar disorderLithium

• Used mostly for the manic phase of manic-depressive illness - has a calming effect without impairing intellectual activity

• Increases receptor sensitivity to serotonin• Has a narrow therapeutic index - monitor biweekly until

theraputic level reached then monitor monthly

- monitor sodium levels since lithium tends to dec. Na • SE - dry mouth, thirst, increase urination, weight gain• May have teratogenic effects on fetus• Depakote is now being used to treat bipolar disorder