Pharmacology Antidepressants / Antipsychotics and epilepsy drugs I

what is the main difference between clinical depression and just being “down in the dumps”?

the sad or empty mood doesn't go away after a couple of weeks, and everyday activities like sleeping, socializing or working can be affected

what are some symptoms of depression

• Feelings of worthlessness, hopelessness, guilt

• Significant change in weight or appetite

• Fatigue, loss of energy

• Agitation, restlessness, irritability

• Difficulty concentrating and making decisions

• Thoughts of death or suicide

what is the amine hypothesis of mood?

Depression arises from a functional decrease in the activity of neurotransmitters in neural pathways that function in the expression of mood states

what is the neurotransmitter receptor hypothesis?

Long-term antidepressants act to alter the number and/or sensitivity of both pre and post synaptic receptors to restore the normal balance between receptors and transmitter. This change correlates better timewise with clinical improvement

what are the theoretical chemical basis of depression?

• amine hypothesis of mood

• neurotransmitter receptor hypothesis

what is a flaw of the amine hypothesis of mood?

Amine hypothesis does not explain time lag to clinical improvement

what are some examples of antidepressants?

CAs, MAOIs, SSRIs, SNRIs

drugs that are classed as antidepressants can also be used for:

• anxiety,

• Obsessive compulsive disorder

• Eating disorders

• chronic skin disorders and/or itching,

• panic disorders, posttraumatic stress disorder (PTSD),

• sleep disorders,

• To stop the cravings of smoking,

• to decrease bed wetting

• chronic neuropathic pain

tricyclics are used as treatment of…?

• endogenous depression (now relegated to second choice drugs for depression unless cost of SSRIs is a limiting factor)

• non-depression use = bed-wetting, bulimia, panic disorders, phobias, chronic pain, and neuralgias

what are some dental uses for tricyclics?

treatment of chronic orofacial pain, bruxism (often caused by SSRIs)

t/f: tricyclics are not effective on an “as needed” basis because improvement takes several weeks of chronic drug administration

true

Imipramine, Amitriptylene, Desipramine,, Nortriptylene are prototypes for

tricyclics

what are some side effects of tricyclics?

• potent anticholinergic effects such as dry mouth, urinary retention, et.c

• orthostatic hypotension from alpha 1 receptor blockade

• sedation from antihistamine effects

• cardiotoxic

in pts taking tricyclics, avoid the use of __________ in local anesthetic preparations.

epinephrine

epi containing retraction cords are also contradindicated

what are monoamine oxidase inhibitors used for?

3rd line drugs due to frequency of adverse side effects

monoamine oxidase inhibitors: therapy

similar to TCAs (clinical improvement requires weeks)

is epinephrine contradindicated in monoamine oxidase inhibitors?

no but although many references will advise caution

what is wine and cheese syndrome?

hypertensive crisis from interaction between monoamine oxidase inhibitors and tyramine in food not being metabolized – it is sympathomimetic

severe interaction between monoamine oxidase inhibitors and meperidine can lead to…?

hyperpyrexia, hypertensive crisis

Fluoxetine (Prozac), Sertraline (Zoloft), Paroxetine (Paxil) Citalopram (Celexa), and Escitalopram (Lexapro) are examples of…?

SSRIs

Venlafaxine (Effexor), Duloxetine (Cymbalta) are examples of

SNRI

what are SSRIs and SNRIs used for?

replace TCAs and MAOI as first choice drugs (2nd gen/atypical antidepressants)

what are advantages of 2nd gen/atypical antidepressants like SSRIs?

• epinephrine use NOT contraindicated with SSRIs

• more selective = fewer side effects

• less anticholinergic side effects

• doesn’t cause weight gain (unlike TCAs)

t/f: SSRIs are not contraindicated with epinephrine whereas SNRIs, MAOIs, and tricyclics are contraindicated.

true

what are some adverse side effects of SSRIs?

• increased suicide risk in children/teens

• bruxism → tooth fracture (pts advised/offered a night guard)

• risk of serotonin syndrome

• reduced sexual function

what is Zyban (bupropion) used for? MoA?

smoking cessation

primarily weak inhibitor of DA uptake

Zyban (bupropion) is associated with a higher incidence of ________

seizures

Since Dentists often advise on smoking cessation treatments, don’t use Zyban in what patients…?

• someone who is being treated for seizures

• someone currently or previously diagnosed with an eating disorder such as bulimia (higher incidence of seizures)

how do SNRIs work?

inhibit reuptake of serotonin, norepinephrine, and to a lesser extent, dopamine

what is Effexor (SNRI) used for? what are some side effects?

treatment of general anxiety disorder (GAD)

what are some side effects of SNRIs?

nausea, headache, insomnia, sweating, and sexual dysfunction

what is Cymbalta (SNRI) used for?

relief of pain and tingling associated with diabetic neuropathy – also lower back pain

what is ketamine used for?

depression, bipolar disorder, and suicidal thoughts

how is it believed that ketamine works?

• some theories think depression is caused by damage to brain cells in key regions critical to controlling mood

• high stress hormones can cause overrelease of glutmate which damages cells in same areas

• antidepressants increase cell growth in these areas

• ketamine rapidly spurs growth of new synapses (reversal of atrophy caused by chronic stress)

what are symptoms of mania?

• Heightened mood, exaggerated optimism and self confidence

• Decreased need for sleep without experiencing fatigue

• Grandiose delusions, inflated sense of self- importance

• Excessive irritability, aggressive behavior

• Increased physical and mental activity

• Racing speech, flight of ideas, impulsiveness

• Poor judgment, easily distracted

• Reckless behavior such as spending sprees, rash business decisions, erratic driving, sexual indiscretions

• In the most severe cases, hallucinations

how does bipolar disorder progress?

• mean onset age of first manic episode = early 20s (adolescence to age 50)

• manic episodes typically begin suddenly with rapid escalation

• episodes occur following psychosocial stressors

• episodes last few weeks to several months (briefer and more abrupt than major depressive episodes)

what are different mood stabilizers in the management of bipolar disorder?

• lithium

• valproic acid

  • caution with antibiotics and NSAIDs

• atypical antipsychotics

  • effective in acute management of manic phase

characteristics of lithium as a mood stabilizer in the management of bipolar disorder?

• MOA: unknown

• narrow therapeutic index

• NSAIDs decrease renal clearance

  • discontinue prior to dental surgery due to disturbance of renal function

important interactions: TCAs and SNRIs with epinephrine?

potential hypertensive crisis

important interactions: MAOIs and tyramine?

wine and cheese syndrome

important interactions: Prozac, Paxil (SSRI antidepressants) and codeine?

inhibition of 2D6 mediated conversion of codeine to morphine, thus reduced analgesic efficacy

important interactions: SSRIs and NSAIDs?

additive effects on upper GI bleeding

important interactions: Lithium and NSAIDs?

lithium toxicity due to NSAIDs reducing renal clearance of lithium

important interactions: Any combination of drugs that elevate serotonin?

serotonin syndrome: Confusion, seizures, severe hypertension

Contrast the differences in MOA of TCAs, MAOIs, SSRIs, and SNRIs

• All act to increase NT levels

• TCAS → Block reuptake of NE, 5-HT, and Dopamine

• MAOIs → Block enzyme destruction of NTs after reuptake

• SSRIs → Block reuptake of 5-HT selectively

• SNRIs → Block reuptake of 5-HT and NE

Which type of antidepressant does not interact adversely with epinephrine?

SSRIs

What are the worst side effects of TCAs and SSRIs that are of concern to dentists?

a. Dry mouth

b. Bruxism leading to tooth fracture – patients need to be advised and probably offered a night guard

Which of the following is an SSRI and which is an SNRI: Prozac and Effexor? Which type, SSRI or SNRI, is approved for generalized anxiety and chronic neuropathic pain?

• Prozac → SSRI

• Effexor → SNRI

• SNRI:

  • Anxiety → Effexor

  • Pain → Duloxetine (cymbalta)

Name 3 types of drugs classed as “mono stabilizers” that are used to treat bipolar disorder? Which one is the historical standard?

• Lithium → the standard !

• Valproic acid → Benzodiazepine anticonvulsants

• Atypical antipsychotic (olanzapine)