Neuropharmacology Flashcards
(94 cards)
How many neurotransmitters exist in they body?
21
What are some reasons why we don’t know why or how drugs work?
- We have an incoplete understanding of CNS physio
- mech of human/behavior/thought proceses/ consciousness - hard to determine in animals
- We usually have limited understanding of the patho phys
- Research presents many ethical/technical challenges
What is the amine hypothesis around depression?
- Involves major brain amines:” NE, 5HT, Dopa
- hypothesis: functional decrease in amine dependent synaptic transmission–> results in depression
Common treatments for depression?
- Psychotherapy
- ECT
- Pharmacology: all current antidepressants primarily act on either NE or serotonin (Except ketamine) by affecting:
- metabolism
- reuptake
- selective receptor antagonism
Ketamine treatment for depression?
- found to be almost similar to ECT
- Blocks NMDA receptor
MOA SSRI?
- Selectively inhibit the reuptake of serotonin into the presynaptic neuro
- higher index of safety than other classes of antidepressants
- takes several weeks to work; not only relying on decreased reuptake of 5-HT, may have other process involved
- Each agent has different side effect profiles
- examples:
- Fluoxetine (prozac)
- Sertraline (Zoloft)
- Paroxetine (Paxil)
- Citalopram (Celexa)
- Escitalopram (lexapro)
- fluvoxamine (lexiva)
- While efficacy is the same for each drug (Between all classes), one drug has a safety profiel to work best for one pt vs another. some patients also don’t respond to one drug in class but may respond to another
Adverse effects SSRIs?
- CNS excitation (agitation/insomnia/EPS (rare)/sleepiness, lightheadedness
- sexual dysfunction
- GI distress (nausea)
- Suppression of PLT aggregation (GI bleeding 3Xrisk)
- will often keep pt on antidepressants because long half-life, long time to restart, with potential risk of suicide
- Bruxism - griding of teeth
- Rash
- short term weight loss/long term weight gain
- hyponatremia (especially older adults and pts on diuretics)
- prolonged QT- only citalopram
- orthostatic hypotension
- withdrawal if stopped abrupty
- black box warning- suicide
- pregnancy category C
- late pregnancy use small risk: infant withdrawl symptoms and pulm hypotension
- Serotonin syndrome
What is SSRI pregnancy category?
C
late pregnancy has small risk: found infant witdrawal symptoms and infant pulmonary hypertension
What is serotonin syndrome?
Symptoms? precaution in ssri?
- Symptoms
- Hyperthermia
- diaphoresis
- muscle rigidity
- rapid fluctuations in VS
- rapid fluctuations in mental status (confusion, agitation, anxiety, hallucinations)
-
rare with SSRI but can be fatal
- never combine SSRI with MAOI’s or any other drug that affects serotonin levels, causes bad outcomes
Drug interactions SSRIs?
Contraindications?
- Use in caution in pt taking drug that impair PLTs or coags
- inhibits multiple p450 enzymes (especially 2D6)–> potential for drug interactions
- fluoxetine- most potent inhibitor of CYP450
- Will increase levels of warfarin, TCAs, and lithium
-
Contraindications:
- MAOI are ABSOLUTELY contraindicated
- other drugs that work via serotonin system (TCA, St John’s wort, etc)
MOA SNRIs?
- Block reuptake of serotonin and NE (weak blockade of dopamine reuptake)
- Agents
- prototype: venlafaxine (effecor)
- duloxetine (cymbalta)
- desvenlafaxine (prestiq)
Drug interactions/adverse effects SNRIs?
- Not many drug interactions, however, MAOIs contraindicated
- Adverse effects (similar to SSRIs)
- GI distress, sexual dysfunction, insomnia, diastolic BP elevation 5-7%
- pupil dilation (caution in glaucoma/increase IOP)
- Withdrawl symptoms (do not discontinue abruptly)
- neonatal withdrawal
What is buproprion MOA? Class?
- Class: atypical antidepressant
- Primarily an inhibitor of Dopa and NE reuptake
- also used to prevent seasonsal affective disorder, smoking cessation aid
- off label: neuropathi pain and ADHD
- Coontraindicated with MAOI, dopamine agents
- Avoid drugs that inhibit CYP2D6 such as SSRIs (increase seizure risk)d
Adverse effects of buproprion?
- Nervousness, HA, insomnia, N/V/constipation, dry mouth, tremor, weight loss, small risk fo psychotic symptoms
- Increased risk of sz (0.4%)
- useful in pt not tolerating other antidepressants (ie weight gain SSRI)
- Used in hypoactive sexual desire disorder
- good for when pt having issue with decreased energy levels as symptoms of depression
What is mirtazapine (Remeron) MOA?
- Presynaptic alpha antagonist
- blocks negative feedback= increased release of NE and serotonin
- 5HT2 5HT3 serotonin antagonist
- fewer GI effects, more pronounced effect on co morbid anxiety (will decrease anxiety more)
- E1/2 life= 20-40 hours
S/E mirtazapine (remeron)
- Sedation (>50%)
- constipation
- increased appetitie
- weight gain
- increased cholesterol
- less sexual S/E
- less GI s/e
Drug interactions Remeron?
MAOI contraindicated
CNS depressants- go slow with anesthetics
TCAs MOA?
- Blocks reuptake of serotonin and/or NE at presynaptic terminals
-
tertiary amines- inhibit serotonin and NE reuptake
- amytriptyline (elavil)
- imipramine (tofranil)
- clomipramine (anafranil)
-
secondary amines- inhibit NE reuptake
- despiramine (norpramin)
- notriptyline (pametlor)
-
tertiary amines- inhibit serotonin and NE reuptake
- Severeal other receptors are antagonized by TCA
- Alpha adrenergic- orthostatic hypotensiob
- Histamine- sedative
- cholinergic- tachycardia, dry mouth, constipation
- cardiac conduction system affected (QT prolongation)
Use of TCAs?
- Treatment of depression and bipolar d/o (during depressive epidodes)
- chronic pain syndroms in lower doses
- chemical structure similar to LA and phenothizines
- inhibits overactive inflammatory response systmes
- potentiation of endogenous opioids
Adverse effects TCA?
Narrow therapeutic index
- anticholinergic effects
- sedation, dry mouth, tachycardia, urinary retention, ileus, slow gastric emptying
- weakness and fatigue
- orthostatic hypotension
- modest increase in heart rate
- cardiotoxicity
- arrhythmias via vagal and bundle of his cell conduction inhibition
- lowers seizures threshold
- hypomania
- overdose often fatal (CNS depression, anticholinergic and direct cardiac toxicity
- suicide risk (1 week supply at time)
What are some pharmacokinetics of TCA?
- Highly protein bound
- acidsosi may increase unbound drug–> more dysrhythmia
- metabolized in liver- all have active metabolites (worry clearing in liver dx)
- tricyclics should be weaned to prevent withdraw syndrome
- high lipid solubility–> easily crosses BBB
- Metabolized by CYP 450 enzymes–> prone to drug interactions
Drug interactions with TCAs?
- MAO- contrindicated (can lead to severe HTN (NE) and serotonin syndrome
- direct and indirect acting sympathomimetic drugs
- anticholinergic drugs
- sedating drugs
- ETOH, barb, antihistamines, opioid, inhaled agents, IV induction agents
Anesthetic considerations for TCA?
- Volatile anesthetic agents- may need higher MAC
- Opioid and barbiturates- decrease dose
-
Anticholinergics- more likely to have postop delirium and confusion (central anticholinergic syndrome)
- S/S central anticholinergic syndrome- flushing, dry mouth, myrdiasis
- pysostigmine for anticholinergic psychosis
- if you MUST give anticholinesterase, give glycopyrrolate- doesn’t cross BBB
-
Sympathomimetics
- unpredictable
- indirect acting- exaggerated responses d/t larger amounts of NE available to stimulate post synaptic adrenergic receptors (because we’re increasing NE reuptake with TCA)
- go with direct instead!!
- acute vs chronic txmt with tricyclics
- acute: use lower dosages of sympathomimetics
-
chornic: may need potent direct acting drug
- receptor desensitization
- depleted catechol stores
What is MAOI MOA?
- MAOI form a stable irreversible complex with MAO–> nicreasing availability of these neurotransmitters in CNS and peripheral ANS
- dopamine
- serotonin
- epinephrine
- norepinephrine

