Side Effect Mitigation- Dr. Campbell

Question 1

Side effect

Answer 1

• Secondary undesired effect from a medication
• Known/ expected to occur
• Usually mild in nature

Question 2

Adverse effect

Answer 2

• Undesired and unexpected

- Often due to an unrecognized drug-drug interaction

Question 3

Pleotropic effect

Answer 3

• A side effect usually viewed as beneficial

- Often previously undescribed or unexpected

Question 4

Nausea & Vomiting Mechanism

Answer 4

• Altered GI transition time
• Often due to increased serotonergic tone
• Decreased dopaminergic/ cholinergic tone

Question 5

Nausea & Vomiting worst offenders

Answer 5

• SSRIs
• SNRIs
• MAOIs
• Cariprazone
• Aripiprazole

Question 6

Nausea & Vomiting solution

Answer 6

• Split into smaller doses
• Take with food
• Change agent if unrelenting

Question 7

Diarrhea mechanism of action

Answer 7

-Increased GI serotonin

Question 8

Diarrhea worst offenders

Answer 8

• Sertraline
• SSRIs
• SNRIs
• Lithium

Question 9

Diarrhea solution

Answer 9

• Usually self limiting

- Increase dietary fiber

Question 10

Constipation mechanism

Answer 10

-Anticholinergic effect

Question 11

Constipation worst offenders

Answer 11

• TCAs
• Dozapine
• Paroxetine
• Stimulants

Question 12

Constipation Solution

Answer 12

• Increase fluid intake
• Increase physical activity
• Stimulant + Osmotic laxative
  ex. Osmotic= PEG
  ex. Stimulants= senna, bisacodyl

Question 13

Anticholinergic side effects

Answer 13

Can’t

• See
• Pee
• Spit
• Shit

Question 14

Two mechanisms of Anticholinergic side effects

Answer 14

1) Inhibition of the PNS (more common)
ex. TCAs, Paroxetine
2) Activation of SNS (less common)
ex. SNRIs, stimulants

Question 15

Sedation: Histamine antagonism

Answer 15

• Associated with rapid tolerance
• Usually does not require any specific treatment
• Wait it out

Question 16

Sedation: Anticholinergic

Answer 16

• Highly variable

- Try bed time dosing

Question 17

Sedation: 5HT2A antagonism

Answer 17

• Effect seems to be related to peak concentration

- Try bed time dosing

Question 18

Sedation: Enhancement of GABA

Answer 18

• Sedation is the desired effect
• Treatment is unnecessary
• Try using a shorter acting agent to avoid “Hang over” effect
• Temazepam > Zolpidem

Question 19

4 mechanisms that can lead to sedation

Answer 19

• H1 antagonism
• 5HT2A
• Anticholinergics
• GABA upregulation

Question 20

What is the mechanism behind orthostatic hypotension

Answer 20

• Alpha 1 antagonism
• 20mmHg drop in systolic
• 10mmHg drop in diastolic

Question 21

Biggest offenders for orthostatic hypotension

Answer 21

• Clozapine
• Quetiapine
• Prazosin
• TCAs

Question 22

QT interval prolongation

Answer 22

• MONITOR ECG
• taper off offending agent
• If TdP developes immediately defibrillate

Question 23

Loss of libido or Anorgasmia

Answer 23

• Change to agent with lower potential
• Mirtazapine
• Nefazodone
• Bupropion

Question 24

Erectile dysfunction

Answer 24

• PDE5is are prefered agent

- Use same dose as used for ED

Question 25

Withdrawal effects: Serotonergic agents

Answer 25

• Flu like symptoms
• Agitation
• Anxiety
• Insomnia
• Paresthesia
• ETC
• Diarrhea

Question 26

Withdrawal effects: Benzos & Barbiturates

Answer 26

• Anxiety
• Imparied concentration
• Hallucinations
• Psychosis
• Seizures

Question 27

Withdrawal effects: Stimulants

Answer 27

• Depressed mood
• Anxiety
• Hypersomnolence
• Hyperphagia

Question 28

Serotonin Syndrome

Answer 28

• Rare outside of overdose situation
• Due to overactivation of serotonin synaptic transmission
• Altered mental status
• Neuromuscular hyperactivity
• Autonomic hyperactivity

Question 29

Treatment of serotonin syndrome

Answer 29

• Stop causative agent
• Supportive therapy
• Benzos
• Avoid physical restraints
• Cyproheptadine
• Atypical antipsychotics??

Question 30

Neuroleptic Malignant Syndrome (NMS)

Answer 30

• Similar presentation as serotonin syndrome
• Hyporeflexia (lead pipe) Rigidity
• Most commonly due to high potency FGAs

Question 31

Neuroleptic Malignant Syndrome (NMS) treatment

Answer 31

• Bromocriptine: dopamine agonist
• Dantrolene: muscle relaxer
• Sodium bicarbonate and IV hydration
• Benzos: to minimize agitation

Question 32

Antidepressants and suicidality

Answer 32

• slight increase in suicidal thoughts
• Do NOT increase rates of suicide
• Benefits of therapy out weigh the risks

Question 33

Death related to antipsychotic use

Answer 33

• Increase in death in elderly with dementia
• Due to increased MI and stroke risk
• More common with FGAs than SGAs
• Campbell likes VALPROIC ACID best
• Aripiprazole, quetiapine, and olanzapine are lower risk too

Question 34

Priapism

Answer 34

• Trazodone is the biggest offender

- Requires emergency phenylephrine

Question 35

Ways to treat tremor

Answer 35

-Primidone may be an option

Question 36

Side effects found with Lithium

Answer 36

• Polyurea/polydyspia
• Tremor
• Diarrhea
• Thyroid abnormalities
• Nephrotoxicity

Question 37

Side effects found with Valproic acid

Answer 37

• Fatigue
• Dizziness
• Tremor
• N/V
• Thrombocytopenia
• Weight gain
• Pancreatitis
• Hepatitis

Question 38

Side effects found with Antipsychotics

Answer 38

• Pseurdoparkinsonism
• Akathisia
• Hyperprolactinemia
• Cardiometabolic
• Sedation
• Constipation

Question 39

Tardive Dyskinesia

Answer 39

• Can occur after weeks or even years of antipsychotic therapy
• Jerky, rigid, uncontrollable movements
• Due to chronic D2 and D3 antagonism
• Slowly withdrawal the offending antipsychotic agent = best treatment

Question 40

VMAT 2 inhibitors

Answer 40

• FDA approved for Tardive Dyskinesia
• Sequesters dopamine in the presynaptic nerve ending
• Leads to depletion of dopamine
• Overall little benefit to TD and high risk of inducing depressive symptoms

Question 41

Examples of VMAT 2 inhibitors

Answer 41

• Dutertrabenazine (Austedo)

- Valbenazine (Ingrezza)