Chapter 18
Chapter 18
Lecture 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
Anticonvulsants
Hydantoins
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
Anticonvulsants
Phenytoin (Dilantin)
Side effects - Gingival Hyperplasia = overgrowth of the gums - good oral hygiene a must!
* Long term use may elevate blood sugars
Drug Interactions - Lots!!
Anticonvulsants
Barbiturates
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
Anticonvulsants
Miscellaneous 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
Anticonvulsants
Miscellaneous 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
Antipsychotics
Phenothiazines
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
Antipaychotics
Phenothiazines
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
Antipsychotics
Nonphenothiazines
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
Antipsychotics
Atypical
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 or
Antianxiety 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
Anxiolytics
Benzodiazepines
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
Anxiolytics
Benzodiazepines
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 Agents
Tricyclic 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 Agents
Selective 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)
Antidepressants
SSRI’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
Antidepressants
Monoamine 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
Antidepressants
MAOI’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 disorder
Lithium
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
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