Pharmacogenetic Considerations for Psychiatric Drugs Flashcards

Question

clomipramine (Anafranil) Biomaker

Answer 1

PMs: normal metabolizers (NMs) may resemble PMs since certain drugs inhibit CYP2D6. Caution with concomitant SSRIs or when switching from one class to the other. Sufficient time (at least 5wks) must elapse before initiating TCAs in patients being withdrawn from fluoxetine. Concomitant CYP2D6 inhibitors: may need to adjust dose of either drug; if withdrawn, may need to increase TCA dose (monitor).

Answer 2

Brand Clozaril, FazaClo

Answer 3

PMs: may need to reduce dose. Increased clozapine levels possible since it’s completely metabolized and then excreted.

Answer 4

Brand Norpramin

Answer 5

PMs: normal metabolizers (NMs) may resemble PMs since certain drugs inhibit CYP2D6. Caution with concomitant SSRIs or when switching from one class to the other. Sufficient time (at least 5wks) must elapse before initiating TCAs in patients being withdrawn from fluoxetine. Concomitant CYP2D6 inhibitors: may need to adjust dose of either drug; if withdrawn, may need to increase TCA dose (monitor).

Answer 6

Brand Nuedexta

Answer 7

PMs: quinidine component does not contribute to the effectiveness of Nuedexta in PMs but a possible risk of significant toxicity is present. Consider genotyping to determine PM status prior to initiation.

Answer 8

Brand Silenor

Answer 9

CYP2D6, CYP2C19

Answer 10

PMs: may have higher doxepin plasma levels than NMs

Answer 11

Brand Prozac

Answer 12

Concomitant drugs metabolized by CYP2D6 or narrow therapeutic index: NMs may resemble PMs since fluoxetine is a CYP2D6 inhibitor. Initiate lowest effective dose if receiv- ing fluoxetine or have taken it in previous 5wks. If already taking drugs metabolized by CYP2D6 and fluoxetine is added afterwards, consider decreasing dose of original drug.

Answer 13

Brand Symbyax

Answer 14

Concomitant drugs metabolized by CYP2D6 or narrow therapeutic index: NMs may resemble PMs since fluoxetine is a CYP2D6 inhibitor. Initiate lowest effective dose if receiv- ing fluoxetine or have taken it in previous 5wks. If already taking drugs metabolized by CYP2D6 and fluoxetine is added afterwards, consider decreasing dose of original drug.

Answer 15

PMs: caution with fluvoxamine and other concomitant drugs known to inhibit CYP2D6.

Answer 16

Brand Razadyne

Answer 17

PMs: similar pharmacokinetics parameters com- pared to EMs. No dosage adjustment needed in PMs since the dose is individually titrated to tolerability.

Answer 18

Brand Fanapt

Answer 19

PMs: higher exposure to iloperidone vs. EMs. Reduce dose by ½. Lab tests are available to identify CYP2D6 PMs.

Answer 20

Brand Tofranil

Answer 21

PMs: normal metabolizers (NMs) may resemble PMs since certain drugs inhibit CYP2D6. Caution with concomitant SSRIs or when switching from one class to the other. Sufficient time (at least 5wks) must elapse before initiating TCAs in patients being withdrawn from fluoxetine. Concomitant CYP2D6 inhibitors: may need to adjust dose of either drug; if withdrawn, may need to increase TCA dose (monitor).

Answer 22

Brand Provigil

Answer 23

PMs: metabolism by CYP2C19 may be substantially increased. Provigil may cause elevation in tricyclic levels; may need to reduce dose of tricyclics.

Answer 24

Brand Pamelor

Answer 25

PMs: normal metabolizers (NMs) may resemble PMs since certain drugs inhibit CYP2D6. Caution with concomitant SSRIs or when switching from one class to the other. Sufficient time (at least 5wks) must elapse before initiating TCAs in patients being withdrawn from fluoxetine. Concomitant CYP2D6 inhibitors: may need to adjust dose of either drug; if withdrawn, may need to increase TCA dose (monitor).

Answer 26

Brand Dilantin

Answer 27

HLA-B*1502

Answer 28

Chinese ancestry: limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN. Consider avoiding phenytoin as an alternative for carbamazepine if HLA-B*1502-positive. Use of HLA-B*1502 genotyping has important limitations and must never substitute for appropriate clinical vigilance and patient management.

Answer 29

PMs: metabolize perphenazine slower and have higher concentrations vs. NMs or extensive metabolizers (EMs).

Answer 30

Elderly: PMs have higher plasma concentra- tions of antipsychotics at usual doses, which may correlate with the emergence of side effects. Prospective phenotyping prior to initiation may identify those at risk for adverse events.

Answer 31

Brand Orap

Answer 32

Children (>0.05mg/kg/day): perform CYP2D6 genotyping. PMs: max 0.05mg/kg/day; should not increase dose earlier than 14 days.

Answer 33

Adults (doses >4mg/day): perform CYP2D6 genotyping. PMs: max 4mg/day; should not increase dose earlier than 14 days

Answer 34

Brand Vivactil

Answer 35

PMs: normal metabolizers (NMs) may resemble PMs since certain drugs inhibit CYP2D6. Caution with concomitant SSRIs or when switching from one class to the other. Sufficient time (at least 5wks) must elapse before initiating TCAs in patients being withdrawn from fluoxetine. Concomitant CYP2D6 inhibitors: may need to adjust dose of either drug; if withdrawn, may need to increase TCA dose (monitor).

Answer 36

Brand Risperdal

Answer 37

EMs and PMs have similar pharmacokinet- ics even though EMs convert risperidone to 9-hydroxyrisperidone quicker than PMs. Risperidone EMs half-life: 3hrs. Risperidone PMs half-life: 20hrs. Overall mean half-life: 20hrs.

Answer 38

Brand Xenazine

Answer 39

>50mg/day: perform CYP2D6 genotyping to determine PM or EM status prior to initiation. Individualize dose based on PM or EM status. EMs or intermediate metabolizers (IMs): max 37.5mg/dose or 100mg/day. PMs: max 25mg/dose or 50mg/day.

Answer 40

PMs: normal metabolizers (NMs) may resemble PMs since certain drugs inhibit CYP2D6. Caution with concomitant SSRIs or when switching from one class to the other. Sufficient time (at least 5wks) must elapse before initiating TCAs in patients being withdrawn from fluoxetine. Concomitant CYP2D6 inhibitors: may need to adjust dose of either drug; if withdrawn, may need to increase TCA dose (monitor).

Answer 41

how drugs interact with specific target sites in the nervous system to induce changes in mood, thinking, or behavior are interested in a wide variety of drug classes that produce psychological side effects, such as antidepressants, stimulants, antipsychotics, hallucinogens, benzodiazepines, opiates, and hypnotics.

Answer 42

Potency is an index of the concentration required for a given effect - usually the EC50. It is not the same as effect. Drugs that are highly potent require only small doses (concentrations) to achieve their effects. High potency is often considered desirable because less drug (in molar terms) is available to cause adverse effects.

Answer 43

Efficacy is the desired effect (e.g. analgesia). Some drugs (e.g. morphine) have greater analgesic effect than others (e.g. paracetamol).

Answer 44

The therapeutic index represents the relationship between concentrations causing adverse effects and concentrations causing desired effects. Drugs with a high or large therapeutic index are desirable in practice

Answer 45

Step 1: Define the patient's problem. Step 2: Specify the therapeutic objective. Step 3: Choose the treatment. Step 4: Start the treatment. Step 5: Educate the patient. Step 6: Monitor effectiveness.

Answer 46

Functions: – Consciousness (How we know what we are doing in our environment) – How we initiate activity in response to our environment – Judgments we make about what occurs in our daily activities – Controls our emotional response – Controls our expressive language – Assigns meaning to the words we choose – Involves word associations – Memory for habits and motor activities

Answer 47

Observed Problems: – Loss of simple movement of various body parts (Paralysis) – Inability to plan a sequence of complex movements needed to complete multi-stepped tasks, such as making coffee (Sequencing) – Loss of spontaneity in interacting with others. Loss of flexibility in thinking – Persistence of a single thought (Perseveration) – Inability to focus on task (Attending) – Mood changes (Emotionally Labile) – Changes in social behavior. Changes in personality – Difficulty with problem solving – Inability to express language (Broca's Aphasia)

Answer 48

Functions –Location for visual attention –Location for touch perception –Goal-directed voluntary movements –Manipulation of objects –Integration of different senses that allows for understanding a single concept

Answer 49

Observed Problems – Inability to attend to more than one object at a time – Inability to name an object (Anomia) – Inability to locate the words for writing (Agraphia) – Problems with reading (Alexia) – Difficulty with drawing objects – Difficulty in distinguishing left from right – Difficulty with doing mathematics (Dyscalculia) – Lack of awareness of certain body parts and/or surrounding space (Apraxia) that leads to difficulties in self-care. Inability to focus visual attention – Difficulties with eye and hand coordination

Answer 50

Observed Problems – Defects in vision (Visual Field Cuts) – Difficulty with locating objects in the environment – Difficulty with identifying colors (Color Agnosia) – Production of hallucinations Visual illusions - inaccurately seeing objects – Word blindness - inability to recognize words – Difficulty in recognizing drawn objects – Inability to recognize the movement of an object (Movement Agnosia) – Difficulties with reading and writing

Answer 51

Functions –Hearing ability –Memory acquisition –Some visual perceptions –Categorization of objects

Answer 52

Observed Problems – Difficulty in recognizing faces (Prosopagnosia) – Difficulty in understanding spoken words (Wernicke's Aphasia) – Disturbance with selective attention to what we see and hear – Difficulty with identification of, and verbalization about objects – Short-term memory loss. Interference with long-term memory Increased or decreased interest in sexual behavior – Inability to categorize objects (Categorization) – Right lobe damage can cause persistent talking – Increased aggressive behavior

Answer 53

Functions –Breathing Heart Rate Swallowing Reflexes to seeing and hearing (Startle Response) –Controls sweating, blood pressure, digestion, temperature (Autonomic Nervous System) –Affects level of alertness –Ability to sleep –Sense of balance (Vestibular Function)

Answer 54

Observed Problems –Decreased vital capacity in breathing, important for speech –Swallowing food and water (Dysphagia) –Difficulty with organization/perception of the environment –Problems with balance and movement –Dizziness and nausea (Vertigo) –Sleeping difficulties (Insomnia, sleep apnea)

Answer 55

Functions – Coordination of voluntary movement Balance and equilibrium – Some memory for reflex motor acts

Answer 56

Observed Problems – Loss of ability to coordinate fine movements – Loss of ability to walk – Inability to reach out and grab objects – Tremors. Dizziness (Vertigo) – Slurred Speech (Scanning Speech) – Inability to make rapid movements

Answer 57

– “central switching station” – relays incoming sensory information (except olfactory) to the brain

Answer 58

– controls the autonomic nervous system (maintains the body’s homeostasis)

Answer 59

– Emotional expression, particularly the emotional component of behavior, memory, and motivation

Answer 60

– Attaches emotional significance to information and mediates both defensive and aggressive behavior

Answer 61

– involved more in memory, and the transfer of information from short-term to long-term memory

Answer 62

– Glutamate is the major excitatory neurotransmitter in the brain. – It is required for learning and memory. – Low levels can lead to fatigue and poor brain activity. – Increased levels of glutamate can cause death to the neurons (nerve cells) in the brain. Dysfunction in glutamate levels are involved in many neurodegenerative diseases such as Alzheimer's disease, Parkinson's, Huntington's, and Tourette's. High levels also contribute to Depression, OCD, and Autism.

Pharmacogenetic Considerations for Psychiatric Drugs Flashcards

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