The nervous system and how it works MOA Decrease Increase Increase Decrease Increase Psychotropic drug Anti

psychotic Anti parkinsonian Antidepressant s Mood stabilizers Cholinesterase inhibitors NTM Dopa Dopa Serotonin, norepi Serotonin, norepi acetylcholine NTM imb Increase Decrease Decrease Increase Decrease Mental disorder Shizo Parkinsns Depression Mania Alzheimers

Brain: -cerebrum -cerebellum -brain stem -limbic system

Cerebrum: -left hemisphere- logic and reasoning -analytic function: reading, writing, mathematical tasks -right hemisphere- creative thinking, intuition, artistic abilities

-frontal-organization of thoughts(schiz) -body movements (shiz(catatonic) & parkinsons) -memories (alzheimers, amnesia) -emotions (depression-superego, mania-id/immediate gratification) -moral behaviour -helps regulate arousal (depression, mania) -focus attention (schiz, ADHD) -allow problem solving and decision making to occur (borderline personality disorder, dependent personality disorder>>> battered spuoses)

- schizophrenia, ADHD, mania

Catatonic schiz: Extreme: -catatonic neutism (negativism) -catatonic excitement-involuntary movements Psychosis: be visual, -hallucination-misperception in the absence of an actual stimulus; may auditory, tactile, gustatory, olfactory -delusion (false, fixed belief) Theme: grandiose, somatic, erotomanic -illusions- misconception in the presence of stimulus Amnesia -anterograde- recent past (early Alzheimers) -retrograde- distant past (later stage of Alzheimers) -parietal- interpreting sensations of taste and touch -assisting in spatial orientation (alzheimers) N!- lighting, arrangement

-temporal- hearing (alzheimers) -memory (alzheimers) -expressions of emotions (depression, mania)

-occipital-coordianting language generation (aphasia: receptive, expressive) -visual interpretation (schiz) derealisation-strange feelings about the environment -depth perception (2 dimension- without depth)

Anhedonia- decreased pleasure

CEREELLUM: -center for coordination and postural adjustments (parkinsons and catatonic shiz) -inhibited transmission of DOPA= lack of smooth, coordinated movements

BRAINSTEM: -midbrain (reticular activity system(motor activity, sleep, consciousness and awareness) and EPS- relays info about movement and coordination) -pons (primary motor pathway) -medulla (centers for respi and CV function)

LIMBIC SYSTEM: -thalamus- activity, sensation, emotion -hypothalamus- temp regulation, appetite ctrl, endo fx, sexual drive, impulse behaviour assoc w/ feelings of anger, rage, excitement -hippocampus and amygdale- emotional arousal, memory

-disorders: dementia, psychotic, manic behaviour

NTM -sending electrochemical messages through neuorons Axon- away from cell body Dendrite- towards cell body Synapse- motor end plate -after NTM are released from the synapse and relay the message to the receptor cells, they either: A. transported back from synapse to the axon to be stored for later use (reuptake) B. metabolized and inactivated by enzymes primarily MAO

Major types of NTM

Type Dopa Norepinephrine Epinephrine Serotonin Histamine ACTH-sleep and wakefulness; muscle alerts Neuropeptides Glutamate GABA

MOA excitatory Excitatory excitatory Inhibitory Neouromodulator Excitatory/ inhibitory Neuromodulator Excitatory inhibitory

DOPAMINE - from tyrosine -implicated in schiz and psychoses -as well as movement disorder parkinsons -antipsych meds

NOREPI -inc: anxiety disorder -dec: memory loss, social withdrawal, depression

SEROTONIN -from tryptophan (milk, oatmeal) -delusions, hallucinations, withdrawn behaviour

HISTAMINE -some psychotropic drugs block histamine, resulting in wt gain, sedation and hypotension

ACETYLCHOLINE -sources: red meat, vegetable-choline

GABA -benzodiazepine for anxiety and induce sleep

GLUTAMATE -neurotonic: -brain damaged caused by: stroke, hypogly, sustained hypoxia or ischemia, some degenerative diseases such as alzheimers

Psychopharma

Efficacy- max the effect; desired effect

Potency- amount of drug that needed to achieve the max effect -low potency=high dosage -high potemcy=low dosage

Half life- amount of time it takes for half of the drug to be removed from the bloodstream Short half life- 3-4x a day Long half life- once a day -amount of time needed for a drug to leave the body completely aftec it has been d/c= 5x half life

*psychotropic drugs must be given in adequate dosages for a period of time before their full effect is realized TCA- may require 4-6 weeks to provide optimal thx benefit High dosages- stabiliza

Low dosages-maintain, for geria patients Observe tapering due to: rebound (temp return of sx), withdrawal (new sx resulting from d/c of drug)

What to know: -MOA -S/E -CI -interactions -nsx considerations

ANTIPSYCHOTIC DRUGS (neuroleptics/ major tranquilizers/ high potency) -treat sx of psychosis: delusions and hallucinations (hallmark sign schiz) -bloks dopa receptors

TYPICAL: Chlorpromazine (thorazine)- paranoid delusions Perphenazine (Trilafon) Fluphenazine (Prolixin) Thioridazine (Mellaril)-have difficulty handling extremes of temp Mesoridazine (Serentil) Trifluoperazine (Stelazine) Thiothixene (Navane) Haloperidol(Haldol)- DOC for hallucinations Loxapine (Loxitane) Meliridone (Moban)

*phenothiazine- calming effect, can easily be aroused

ATYPICAL: Clozapine (Clozari) Risperidone (Resperdol) Olanzapine (Zyprexa) Quetiapine (Seroquel)

MOA -major action: block dopa -typical-high potency -potent antagonist (blockers) of dopa receptors d2, d3, d4- makes them effective in treating target sx but also produces EPS side effects -atypical-low potency -weak blockers of d2= low incidence of EPS side effects -inhibit (antipsy) reuptake of serotonin, which makes them more effective in treating the depressive aspects

S/E: -EPS (APAT)- serious neurologic symtoms taht are major S/E -acute dystonia -pseudoparkinsonsm -akathisia -tardive dyskinesia-irreversible, long term course -blockade of d2 receptors in the midbrain- responsible for development of EPS -therapies for neuro S/E of acute dystonia, pseudoparkinsonis and akathisia are similar and include: 1. decrease doseage of antipsych drugs 2. changing to a different antipsych 3. administering anicholinergic meds/ anti EPS meds

Drugs to treat EPS side effects: Amantadine (Symmetrel)-dopa antagonist Benztropine (congentin)- anticholinergic Beperiden(Akinelon)- anticholinergic Diazepam (Valium)- benzodiazepine Diphenhydramine (Benadryl) antihistamine Lorazepam (Ativan)- benzodiazepine Procyclidine (Kemadrin) Propanolol (Inderal)- tremors, beta blockers Trihexaphenidyl (Artane)- anticholinergic

Acute dystonia -spasms of diff muscle groups -torticollis- twist head and neck -opisthotonus- entire body, head back and arched neck -oculogyric crisis- eyes rolled back in a locked position

Pseudoparkinsonism -drug incude sx: -stiff syooped posture -mask like face -dec arm swing -shuffling FESTINATING gate (small steps) -cogwheel rigidity (vatchet like movements) -drooling -tremor -bradycardia -coarse, pill rolling movement while at rest

Akathisia -intense need to move about -px: restless, anxious and agitated, rigid posture or gait and a lack of spontaneous gestures -often leads client to d/c antipsych meds

Tardive dyskinesia -permanent, involuntary movement of tongue, facial, and neck muscles, upper and lower ex ad truncal musculature

Sx: tongue thrusting and protrusion, lip smacking, blinking, grimacing and other excessive unnecessary facial movements

Drugs: atypical>>> low incidence

Other S/E Neuroleptic Malignant syndrome -potentially fatal -idiosyncratic reaction to an antipsych drug w/ sx: high fever, unstable BP, rigidity, autonomic instability -high risk: DHN, poor nutrition

Managemet: d/c, rehydration, hypothermia measures Med management: musle relaxants: dantrolene (Dantrium) Centrally acting dopaminergic: bromocriptine (parlodel)

Anticholinergic S/E Less than 3-4 weeks but do not entirely ___

Management: -nutrintional -OTC remedies -sugar free fluids and eat sugar free hard candy>>> dry mouth -avoid calorie laden beverages>>>to avoid dental caries and weight gain -constipation: inc OFI, inc bulk forming foods, exercise, stool softeners but avoid laxatives (docusate salt) -photophobia: sunscreen to prevent burning, wear protective covering -orthostatic hypotension- rising slowly... -monitor amount of sleepiness -if you forget a dose take it if the dose is only 3-4 hours late, use chart or pillbox -hypotension-major anticholinergic effect of antipsych -blcking apha 1(constrict blood vessels) -occurs most often in older adults -sudden changes in position CNIII- occulomotor blockade- mydriasis (ciliated pupils); impaired accommodation; blurred vision CNVII- facial nerve blockade- dry mouth, decreased tearing, dry nasal passages CN IX- glossopharyngeal nerve blockade- dry mouth, dry nasal passages CN X- vagu nerve blockade- tachycardia, constipation, urinary hesitation, bronchodilation

GI -wt gain -new agents -blockade of 5HT2 (serotonin) and other receptors ENDO -traditional: elevate dprolactin by blocking dopa receptors; dopa inhibits prolactin F: -amennorhea

-loss of libido -galactorrhea -osteoporosis -chanes in mens cycle

M: -impotence -loss of libido -gynecomastia - dec sperm count -feminization (?)

METABOLIC SYNDROME: -insulin resistance syndrome -dec metab of glucose and resistance to insulin by insulin receptor on cells

*central obesity- inc BP, inc trigly, dec HDL, insulin resistance

3 or more: -abdominal girth- M:35 -inc trigly -dec HDL -inc BP - inc fasting glucose

Ultimate antipsychotic agent 1. Might block dopamine receptors in the mesolimbic area or III (dec hallucinations and delusions)

2. Liberate dopamine in the mesocortical area or tract IV (negative and cognitive symptoms) 3. While neither obstructing the fx of the nigrostriatal tract or tract I (hence, not causing EPS) 4. Nor blocking receptors in the tuberoinfundibular tract or II (therefore, not elevating prolactin levels) *atypical antipsychotics and do all these

Dripripazole (abilify) -represents what has been called 3rd generation antipsychotics -referred to as dopamine synthesis stabilizer (DSS) -balance dopamine synthesis by: -decreasing dopamine -____ + symptoms

ANTIDEPRESSANT drugs -used in tx of: major depressive illness- panic disorders, etc -interact with: serotonin and norepi (help regulate arousal, vigilance, attention, mood)

Class: -tricyclic -ssri -MAOis Others (venlafaxin, bupropion, trazodone, nafozodone)

MOA: (cyclic and venlafaxine) -block the reuptake of norepi primarily and serotonin to some degree -rapidly inactivates monoamines: dopamine, morepinephrine, serotonin

-located in: liver, intestinal wall, CNS (terminals, synapses of neurons containing monoamines)

MAO system Forms: 1. MAO-A: -inactivates norepinephrine and serotonin 2. MAO-B: -inactivates dopamine

MAOI-interfere with enzyme metab SSRI- block serotonin reuptake

1. Cyclic (traditional, typical) -1950s- DOC for depression N! -overdose- lethal -prescription and refills in limited amounts to dec risk

Imipramine (tofranil)- bed wetting/ enuresis Despiramine (Nopramin) Amitryptiline (Elavil) Nortrytiline (Pamelor) Doxepin (Simuequan) Trimipramine (Surmontil) Protriptylline (Vivactil) Maprotiline (Ludiomil) Amoxapine (Ascendin)

Clomipramine (Anafranil)

S/E -block cholinergic receptor -anicholinergic effects -sexual dysfunction is frequently reported by clients taking TCA

2. MAOI (traditional/typical) -1950s- low incidence of sedation -anticholinergic effects -to treat: sleep problems, nightmares, intrusive daytime thoughts>>> post traumatic stress disorders N! -overdose-lethal -prescriptions, refill limited

Phenelzine (Nardil) Tranylcypromine (Parnate) Isocarbox acid (Marplan)

s/e -daytime sedation -insomnia -wt gain -dry mouth -ortho hypotension -sexual dysfunction *sedation and insomnia are difficult to treat and may necessitate a change in meds

*potential-life threatening hypertensive crisis if the client ingests foods containing tyramine such as: Alcohols: beer, ale, chianti wine, sherry wine, alcohol free beer Dairy products: cheddar, bleu, brie, mozzarella, sour cream, yogurt Fruits and vegetables: avocado, banana, fava beans, canned figs Meats: bologna, salami, chicken liver, dried fish, liver, meat tenderizer, ___, sausage, sauerkraut, soy sauce, yeast

Sx: -severe hypertension -hyperpyrexia -tachycardia -diaphoresis -cardiac arrhythmias

N! fatal drug interaction: -other MAOI -SSRI -certain cyclic compounds -Meperidine (Demerol) -Buspirone (buspar) -Dextromethorphan -General Anesthetic

*2 weeks washout period

3. SSRI -1987: fluoxetine (Prozac)

-replaced cyclic in treating depression -equal efficacy -fewer troublesome effects -DOC for acute depression -not potentiated by alcohol * SSRI and clomipramine- effective in treating OCD as well -eventually, nawawala yung insomnia -days=effective

Fluxetine (Prozac) Fluvoxamine (Luvox) Paroxetine (Paxil) Seraline (Zoloft) Nefazadone HCL (Sertone) Esctalopram Exalate (Lexapro) Dulonetine HCL (Cymbalta)

s/e: -enhanced serotonin transmission -anxiety -agitation -akathisia/ motor restlessness Tx: beta blocker -nausea Tx: food -insomnia (if taken every morning) Tx: sedative hypnotics, dec dosage trazadone -sexual dysfunction

Less common s/e: -sedation -sweating -diarrhea -hand tremor -headahces * uncommon but potentially serious drug interaction (MAOI + SSRI) -serotonin/ serotonergic syndrome- occur if taken too close to end N!- 2 weeks washout period

Sx: -agitation -sweating -fever Tachycardia -hypotension -rigidity -hyperreflexia/ exaggeration of reflexes -coma and death

4. Other antidepressant drugs Buprorion (Weelbutrin) Venlafaxine (Effexor) Trazodom (Desyrel) Nefazodone (Serzone) Mirtazapine (Remeron)

s/e -same Ach effects -others: sexual dysfx, priapism- necessitates immediate tx and d/c of drug

Client teaching and management: -take food to dec nausea -morning -OTC- tx diarrhea and headache -blanced diet to avoid wt gain -inc OFI, bulkforming, stool softeners -do not drink alcohol!

CLASSIFICATION (based on MOA) 1. Non selective inhibition of norepinephrine and serotonin-TCA 2. Inhibition of enzymes: MAOI (only antidep that inhibit NTM breakdown) MAOIs -MAO-A and MAO-B inhibitors (nonselective MAOIS) Phenelzine (Nardil) Tranylcypromine (Parmate) -selective MAOIs (inhibit either norepinephrine/serotonin) Moclobemide (Manerix)- MAO-A >>> increase norepinephrine/ serotonin Selegline (Emsam)- MAO-B >>>increase dopamine *tyramine rich foods should be avoided

3. SSRI-block serotonin reuptake Citalopram (Celexa) Escitalopram )Lexapro) *not potentiated by alcohol

S/E: -relatively few anticholinergic, antihistamine/ adrenergic effects -dry mouth, blurred vision, sedation, CV sx not as common -do not cause same intensity of TCAs -GI sx: nausea, diarrhea, loose stools, wt gain, wt loss *common -due to activation of 5HT3 receptors by elevated levels of serotonin>>> GI symptoms -CNS effect: headache, dizziness, tremors, anxiety, insomnia, dec libido, impotence, ejaculatory delay, dec orgasm (related to 5HT2 receptor activation)

Treatment strategies for SSRI sexual dysfunction: a. Wait and see if improvement in patient occurs naturally b. Dec dosage of SSRIs c. Time SSRI dose to maximize probability of sexual satisfaction d. Change antidepressants

Medical management of sexual dysfx associated to SSRIs Amantadine-dopaminergic that inhibits prolactin Amphetamines- inc dopamine Bupropion-inc dopamine Methylphenidate- stimulant Sildenatil (Viagra)- enhances erection

4. Norepinephrine and dopamine reuptake inhibitors(NDRIs)- bupropion: only drug in this category Bupropion:

TN: Wellbutrin Aplenzin Zyban *unique- does not affect serotonin system, only antidep w/ dopareuptake inhibitor -should not be given in combination w/ drugs that increase dopa levels -effective replacement for SSRI -increase intrasynaptic dopa >>> offsets -prescribed in low doses along w/ SSRI -contraindicated w/ individuals with seizure disorders 5. Selective serotonin- norepinephrine reuptake inhibitors Venlafaxine (effexor) Desvenlafaxine (Pristia) Duloxetine (Cymbalta) -at lower doses, causes serotonin to be enhanced by inhibiting serotonin reuptake -medium to high doses- inc dopa intrasynaptic levels -combine best qualities of TCAs and SSRI -do not bind to muscarinic, histaminergic/ adrenergic -Venlafaxine- causes inc BP at inc doses -low potential for drug interactions -does not exaggerate effects of alcohol -effective in tx: generalize anxiety disorder (GAD), social phobias, SSRI induced sexual dysfx. OCD, panic disorder -Desvenlafaxine (Pristiq) -active metabolite -same s/e- nausea is common -Duloxetine -tx of diabetic neuropathy pain

6. Alpha 2 antagonism w/ 5HT2 and 5HT3 antagonist- Mirtazapine belongs to this category-referred to as a non adrenergic-specific serotonergic agent (NaSSa) Mirtazapine (Remeron) -has faster onset of action than SSRI -used to dec sexual dysfx -selectively blocks alpha 2 autoreceptors >>> inc norepi and serotonin levels by presynaptic feedback system -antihistaminic effects: sedation, weight gain -unique characteristics: antagonism of 5HT2>>> dec sexual dysfx Antagonism of 5HT3>>> dec GI distress -available in an orally dissolvable form- Remcon Soltabs -dissolves 30 seconds

MOOD STABILIZING -to treat bipolar affective disorder by stabilizing clients mood -avoid or minimize highs and lows -acute phase of mania

Lithium carbonate- most establishes Anticonvulsant- carbamazepine (tegretol), valproic acid (Depakene, Depakote) Other: Gabapentin (Neurontin), Lamotriginr (Lamictal)- dangerous, may cause stevens johnsons and toxic epidermal necrolysis, Clonapin- acute mania

MOA Lithium- normalizes reuptake of certain NTM -serotonin -norepi -Ach -dopa -reduces release of norepo though competition w/ Ca -produces its effects intracellularly rather than w/n neuronal synapses

Valproic and carbamazepine -stabilize mood by inhibiting the kindling process (snowball like effect)

Dosage of lithium: -no parenteral form -900-3600 mg -serum lithinum: 10 meq/L -<0.5 mEq/L-rarely therapeutic -.1.2mEq/L-considered toxic *monitor every 2-3 days while therapeutic dosage is being determined, then weekly -if stable, once a month or less frequently

N! -bawal magpawis!

s/e (Ach) -mild nausea -anorexia -polydypsia

-polyuria -wt gain and acne

N! >3.o mEq/day- dialysis

Salt intake- 3g/day H20/fluid- 3L/day

Carbamazepine and valproic acid -alopecia -rashes