Flashcards in Psych Meds Deck (75):
What is the order of potency between norepi, epi, and isoproterenol for alpha and beta receptors?
Note: a1/b1/dop1 are found post-synaptically, a2/b2/dop2 are found pre- and post-synaptically
Where is alpha-1 found and what are the effects?
Found in vasculature, heart, glands, gut
Activation causes vasoconstriction and relaxation of the GI tract
Where is alpha-2 found and what are the effects?
Presynaptic found in peripheral vascular smooth muscle, coronaries, brain, CNS. Activation presynaptically causes inhibition of norepi release and inhibition of sympathetic outflow leading to decreased BP and decreased HR, inhibition of CNS activity
Postsynaptic found in coronaries, CNS. Activation causes constriction and sedation and analgesia
Where is beta-1 found and what are the effects?
(post synaptic??) Myocardium, SA node, ventricular conduction system, coronaries, kidney. Activation causes increase in inotropy, chronotropy, myocardial conduction velocity, coronary relaxation, and renin release
What are the beta-2 effects and where are they found?
(pre and post synaptic??) Found in vascular, bronchial, skin, and uterine smooth muscle, coronaries, kidneys, GI tract. Activation causes vasodilation, bronchodilation, uterine relaxation, gluconeogenesis, insulin release, potassium uptake by the cells
What catecholamines do dopamine receptors interact with?
Dopamine ONLY (no other catecholamines)
Where does dopaminergic-1 work and what are the effects?
Postsynaptic, found on renal mesenteric, splenic, and coronary vessels and renal tubules, causes vasodilation (increases urine output)
Where does dopaminergic-2 work and what effects?
Presynaptic causes inhibition of norepi release
Postsynaptic may promote constriction
What is serotonin and where is it concentrated?
Serotonin is 5-HT (hydroxytryptamine), a neurotransmitter and local hormone
Highest concentration in wall of intestine, blood, and CNS
Mild- moderate depression, panic disorder, OCD, PTSD, social phobia, bipolar
SSRI mechanism of action?
Block reuptake of serotonin
New SSRI's act on serotonin, norepinephrine, and/or dopamine
Some produce alpha-2 receptor blockade
Which SSRI's work only on serotonin?
Fluoxetine (prozac), sertraline (zoloft), paroxatine (paxil), fluvoxamine (luvox), escitalopram (lexapro)
Note: Prozac has the longest half-life
Which Atypical SSRIs work on serotonin and norepi?
Bupropion (wellbutrin), trazadone (desyrel), nefazodone (serzone), venlafaxine (effexor), duloxetine (cymbalta)
SSRI side effects?
Insomnia, fatigue, agitation, orthostatic hypotension, headache, N/V, sexual dysfunction, increased appetite
Note: SSRIs have a higher index of safety than other antidepressants (minimal BP effects, cardiac conduction, changes in seizure threshold)
Anesthetic Considerations: What do SSRIs do to CP-450 and platelet activity?
INHIBITS CP-450 enzymes which may increase plasma concentration of certain drugs
Antiplatelet activity, increased risk of bleeding
What is serotonin syndrome?
It can be medication induced for patients taking SSRIs
s/s: confusion, fever, shivering, ataxia, diaphoresis, hyperreflexia, muscle rigidity
What are uses and mechanism of action of TCAs (tricyclic antidepressants)?
Uses: depression and chronic pain in lower doses (TCAs have a similar chemical structure to LAs, inhibit overactive inflammatory response)
MOA: blocks reuptake of serotonin and/or NE at presynaptic terminals
What is the MOA of tertiary amines vs secondary amines and name specific drugs?
Tertiary amines- inhibit serotonin and NE reuptake. Amytriptyline (elavil), imipramine (tofranil), and clomipramine (anafranil)
Secondary amines- inhibit NE reuptake. Desipramine (norpramin), nortriptyline (pamelor)
TCA pharmacokinetics? (lipid/water soluble, protein bound or not, E1/2t, metabolize)
Highly lipid soluble, strongly protein bound
LONG e1/2t (10-80 hours).. especially elderly population
Metabolized in liver and has ACTIVE metabolites
TCA side effects?
Anticholinergic- dry mouth, tachycardia, urinary retention, ileus
CV- orthostatic hypotension, tachycardia, depressed conduction
CNS- lower seizure threshold, weakness, fatigue
With overdose, cardiotoxicity, seizure, CNS depressant effects can be fatal
What can happen if someone is taking TCAs and MAOI's?
CNS toxicity: hyperthermia, seizure, coma
What are drug interactions/considerations for people taking TCAs? (list the class of drugs)
Sympathomimetics, inhaled anesthetics, anticholinergics, antihypertensives, opioids
What is the anesthetic consideration with a patient taking TCAs and giving sympathomimetics?
Unpredictable because it is indirect acting, there will be exaggerated responses due to longer amounts of NE available to receptors
Use low dosages of sympathomimetics (ephedrine) OR use a potent direct acting drug (phenlyephrine will directly effect the receptor to increase BP)
Note: Someone just started TCA will react stronger than someone who has been on TCAs for a long time
What is the anesthetic consideration for patients on TCAs using... volatile anesthetics agents? Opioids? Barbiturates?
Higher mac of volatile anesthetic agents
Decrease dose of opioids
Decrease dose of barbiturates
What is the anesthetic consideration for patients on TCAs using anticholinergics?
More likely to have post op delirium and confusion (central anticholinergic syndrome)
s/s of anticholinergic toxicity or central anticholinergic syndrome- flushing, dry mouth and skin, mydriasis
Note: Use glycopyrrolate instead of atropine because atropine crosses BBB
What are s/s of TCA overdose? What will they die from?
s/s- agitation, excitement/delirium, progresses to coma, respiratory depression, and cardiac dysrhythmias and sudden death, hypotensive, anticholinergic effects
With TCA will die from myocardial depression or ventricular dysrhythmias
What inactivates MAO enzyme system?
Dopamine, epinephrine, norepinephrine, and serotonin inactivate MAOs
Note: MAOs found in the outer mitochondrial membranes
MAOI (monoamine oxidase inhibitors) mechanism of action?
Blocks the enzyme that metabolizes biogenic amines, forms a stable irreversible complex with MAO enzyme (breaks down amine) which increases amount of neurotransmitter available in the brain/CNS and peripheral nervous system
Why aren't MAOIs used often?
Lethal in overdose
Tyramine free diet
Selegiline (eldepryl) - also used for parkinson's
What neurotransmitters do MAO A vs. MAO B work on?
MAO A: serotonin, norepinephrine, epinephrine (dopamine, tyramine too)
MAO B: phenylethylamine (also dopamine)
MAOI side effects?
Orthostatic hypotension (especially elderly)
Sedation or stimulant effects
What dietary restrictions are there for MAOIs? Why?
Tyramine! Cheese, fava beans, wine, avocado, liver, cured meats
Dietary tyramine can cause a massive release of endogenous catecholamines leading to hypertensive crisis, hyperpyrexia, CVA (symptoms of headache, vomiting, or chest pain must be reported)
Note: MAO enzyme is present in the liver, GI tract, kidneys, lungs (MAO A in GI and liver)
List of drug cautions with MAOIs
TCAs, opioid (NO meperidine!), cold/allergy drugs, sympathomimetics (NO ephedrine!), nasal decongestants, SSRIs
May need higher mac with volatile agents
What is the MAOI interaction with demerol (meperidine)- an opioid?
Excitatory response (type I) is agitation, skeletal muscle rigidity, hyperpyrexia
Depressive response (type II) is hypotension, respiratory depression, coma
What is the interaction between MAOIs and sympathomimetics?
May get exaggerated response from indirect acting drugs (DONT give ephedrine), use direct acting agents if indicated, decrease dose by 1/3 and titrate to effect
What are the s/s of MAOI overdose?
Excessive sympathetic discharge: tachycardia, hyperthermia, mydriasis, seizure to coma
Why should Antidepressants be tapered when discontinued?
Discontinuation syndromes: dizziness, myalgia, paresthesia, irritability, insomnia, visual disturbances, tremors, lethargy, N/V/D
Benzodiazepine mechanism of action?
Facilitates GABA (the major inhibitory neurotransmitter of the CNS)
Binds to GABA receptors in the brain and potentiates GABA mediated neuronal inhibition by increasing chloride permeability, cellular hyperpolarization, and inhibition of neuronal firing
Benzodiazepine 5 pharmacological effects?
Muscle relaxation (at spinal level, NOT neuromuscular junction)
Benzodiazepine pharmacokinetics? (protein bound, lipid/water soluble, metabolism, elimination?)
Highly protein bound
High lipid solubility
Hepatic metabolism by CP-450 system
Eliminated by the kidneys
How do benzodiazepines effect the CNS?
Decrease CBF and CMRO2
Preserves cerebrovascular response to CO2
Does NOT attenuate ICP response to laryngoscopy
Paradoxical excitement is rare
What is the respiratory effect of benzodiazepines?
Dose dependent decrease in ventilation
Hypoxemia and hypoventilation enhanced in presence of opioid!!
Depress reflex deglutition (decreased esophageal motility)
CO2 response curve flattens (does not shift)
Benzodiazepine effect on CV?
Decreases SVR at induction dosage (rarely used for induction)
BP consequently decreases
How does Midazolam (versed) compare to diazepam (which is more potent, which has a longer duration of time)?
Versed is 2-3 x more potent than diazepam
Both are highly protein bound
Versed has a rapid redistribution and short duration of action, prepared in water soluble mix
Diazepam (valium) is highly lipid soluble with prolonged duration of action, prepared in propylene glycol/ benzyl alcohol, low pH (Painful IV/IM injection!!), rapidly absorbed form GI
What are the usages and dosages of versed?
(Pediatrics vs. adults vs. induction dosages)
Premedication/pediatrics: 0.5 mg/kg po
IV sedation/adults: 1-2.5 mg IV up to 5 mg as needed
Induction: 0.1-0.2 mg/kg over 30-60 sec
What is diazepam's E1/2t compared to desmethyldiazepam?
Diazepam: 21-37 hours
Desmethyldiazepam: 48-96 hours
**Desmethyldiazepam is diazepam's active metabolite. So this is unique to have the active metabolite last so much longer than the drug
What are uses and dosages of diazepam?
Premedication/oral: 10-15 mg
Premedication/IV: 0.2 mg/kg (reduces mac)
Induction: 0.5-1 mg/kg IV
Anticonvulsant: 0.1 mg/kg IV
What are the classes of antipsychotic/ neuroleptic drugs?
Phenothiazines, thioxantheses, butyrophenones
List phenothiazines and thioxanthenes
Phenothiazine and thioxanthene mechanism of action?
Blockade of dopamine receptors in the basal ganglia and limbic portions of the brain
Interfering with dopamine will cause extrapyramidal side effects
Blocking dopamine receptors in chemoreceptor trigger zone of the medulla will cause antiemetic effects
What is absorption and E1/2t of phenothiazines and thioxanthenes?
Although highly lipid soluble and protein bound, erratic patterns of absorption from po administration
E1/2t 10-20 hours
Side effects of phenothiazines and thioxanthenes?
Extrapyramidal effects: tardive dyskinesia (permanent, in the first year in 20% of patients)
Acute dystonic reactions (in the first few weeks of therapy), rigidity, respiratory distress (treat with diphenhydramine 25-50mg IV)
CV: decreases BP (depresses vasomotor alphas, relaxes smooth muscle), prolong QT
CNS: sedation (tolerance develops with chronic therapy) due to tolerance of alpha1/muscarinic/histamine receptors, seizure threshold is decreased, skeletal muscle relaxation of CNS
Antiemetic (effective against opioid N/V)
Neuroleptic malignant syndrome
Note: overdose is rarely fatal
What is neuroleptic malignant syndrome?
Side effect of phenothiazine and thioxanthenes
Develops over 24-72 hours usually in young men
Hyperthermia, hypertonicity of skeletal muscles, instability of autonomic NS, fluctuating LOC
What anesthetic considerations are there for phenothiazines and thioxanthenes?
Potentiation of opioids: sedative effects, ventilatory depression, analgesic properties
List 2 butyrophenones
Droperidol (inapsine): used for neurolept analgesia with fentanyl, also used as antiemetic
Haloperidol (haldol): similar to structure and side effects of phenothiazines
Is Droperidol's clearance perfusion dependent?
Clearance is perfusion dependent, hepatic metabolism opposed to hepatic enzyme activity, so accumulation will occur with decreased hepatic flow
Droperidol side effects?
Note: Haldol's side effects are similar to phenothyazine side effects
CNS: extrapyramidal, cerebral vasoconstriction (decreased flow but not consumption), dysphoria
CV: decrease BP from alpha blockade (minimal), protects against epi-inducced dysrhythmias (large doses will decrease conduction for tachy-dysrhythmias/ WPW syndrome), prolonged QT, Torsades de pointes (Block Box Warning!)
Due to the black box warning on Droperidol, what is required?
12-lead EKG prior to administration, monitor 2-3 hours after administration
This is why it isn't used as a common antiemetic used for surgery anymore
What is lithium used for? How does it work?
Mood stabilizer, treatment of bipolar (gold standard),
Competes with Na, Ca, and Mg affecting cell membranes, H2O, and neurotransmitters (but not well enough understood to know exactly how it works)
What are lithium's pharmacokinetics?
A patient with low levels of ______ will absorb MORE lithium
Filtered by glomerulus and reabsorbed by proximal tubules
Proximal reabsorption of lithium and Na is competitive, so a pt with low sodium will absorb more lithium
E1/2t is 24 hours
Steady state is 4-5 E1/2t (blood draw is important to monitor)
Lithium side effects?
Kidneys- evaluate renal function every 6 months for polyuria/polydipsia
EKG- T wave changes, flattening or inversion
(for OR pt we need baseline EKG and electrolytes)
Other- hypothyroidism, psoriasis, acne, tremor, sedation, memory disturbances/cognitive slowing
What are s/s of lithium toxicity?
Mild- sedation, nausea, weakness, wide QRS, AV block, hypotension, dysrhythmia, seizure
Significant toxicity- emergency! hemodialysis, osmotic diuresis and IV bicarb
Lithium anesthetic considerations
Prolonged neuromuscular blocking agents, anesthetic requirements may be decreased
Get EKG and labs (electrolytes)
Antiepileptic mechanism of action?
Decrease neuronal excitability or enhance inhibition of neurotransmission by altering intrinsic membrane ion currents (sodium, potassium, and calcium) or enhancing GABA
Slow absorption from GI tract, protein binding varies
Most are metabolized by liver and excreted by kidneys
E1/t from hours to days
Monitor plasma concentration to determine compliance with drug and pharmacokinetic interactions
Dangerous side effects of antiepileptics?
Life threatening bone marrow suppression and hepatoxicity
This is why labs (liver function tests and hematologic studies) are done to monitor.
Phenobarbital, phenytoid (dilantin), fosphenytoin (cerebyx), primidone (mysoline), carbamazepine (tegretol), valproate (depakote), levetiracetam (keppra)
Phenytoin uses and mechanism of action?
Effective for partial and generalized seizures
MOA: regulates neuronal excitability and spread of seizure activity from a seizure focus by regulating Na and Ca transport across neuronal membranes
pH of 12, precipitates in solutions with pH 10 mcg/ml for zero order
Phenytoin side effects?
CNS toxicity- nystagmus, ataxia, diplopia, vertigo, peripheral neuropathy
Acne, facial coarsening
Allergic rash ( SJS)
Hepatotoxicity, induces hepatic enzyme system
Fosphenytoin: how does it work? Pharmakodynamics?
Acts on Na ion channel blockade
Highly protein bound, water soluble phenytoin pro drug
Used in hospitals for status epilepticus and in neurosurgery to prevent seizures
What is the dose of fosphenytoin when used for status epilepticus or in surgery to prevent seizures?
10-20 mg/kg IV loading dose
What is the mechanism of action of phenobarbital? Pharmacokinetics?
Modulates post synaptic actions of GABA and glutamate
Enhances CP450 (dilantin and phenobarbital both do this, meaning you need to give more doses)