Psychopharmacological therapy Flashcards
(92 cards)
1
Q
Agonist natural catecholamies
A
- Epinephrine
- Norepinephrine
- Dopamine
2
Q
Agonist Synthetic catecholamies
A
- Isoproterenol
- Dobutamine
3
Q
Alpha receptors
A
receptors that respond with the following order of potency NE>E>ISO
-theres alpha 1 and 2
4
Q
Beta receptors
A
receptors that respond with the following order of potency: ISO>E>NE
5
Q
Alpha 1
A
Postsynaptic
- Vasculature, heart, glands, and gut
- activation causes vasoCONstriction and relaxation of GI tract
6
Q
Alpha 2
A
PREsynaptic
–peripheral vascular smooth muscle, coronaries, brain
–activation causes inhibition of NE release and inhibition of sympathetic outflow leading of decrease BP/HR, inhibition of CNA activity
POSTsynaptic
–Coronaries, CNS
–Activation causes constriction and sedation and analgesia
7
Q
Beta 1
A
Found: Myocardium, SA node, ventricular conduction system, coronaries, kidney.
**Activation causes: Increase in inotropy, chronotropy, myocardial conduction velocity, coronary relaxation, and renin release
8
Q
Beta 2
A
Found: Vascular, brochial, and uterine smooth muscle, smooth muscle in the skin, myocardium, coronaries, kidneys, gi tract.
**Activation causes: vasodilation, brochodilation, uterine relaxation, gluconeogenesis, insulin release, potassium uptake by the cells
9
Q
Dopamine receptor
A
receptor that interacts only with dopamine
D-1
*Postsynaptic. Found on: renal mesenteric, splenic, and coronary vessels. Renal tubules
-Activation causes: vasodilation.
D-2
*Presynaptic.
-Activation causes: inhibition of norepi release.
*Postsynaptic: May promote constriction
10
Q
Serotonin
A
5-Hydroxytryptamine (5-HT)
-Neurotransmitter and local hormone
Highest concentration in 3 areas: -Wall of intestine -Blood -CNS
11
Q
Antidepressants
A
Selective Serotonin Reuptake Inhibitors (SSRIs)
Tricyclic
Monoamine Oxidase Inhibitors
12
Q
SSRI use
A
-mild to moderate depression
-panic disorder
-OCD
-PTSD
-social phobia
“POPS”
13
Q
SSRI MOA
A
- block repute of serotonin, NE, and/or dopamine
- some produce alpha 2 receptor blockade
14
Q
SSRI drugs 5
A
*serotonin Fluoxetine (prozac) Sertraline (zoloft) Paroxatine (paxil) Fluvoxamine (Luvox) Escitalopram (Lexapro)
15
Q
SSRI atypical 5
A
*Serotonin and NE Bupropion (wellbutrin) Trazadone (desyrel) Nefazodone (serzone) Venlafaxine (effexor) Duloxetine (cymbalta)
16
Q
SSRI side effects
A
-different side effect profiles, higher index of safety that other classes of antidepres
*minimal effects of BP, Cardiac conduction, and changes in SZ threshold
Side effects:
-Insomnia/fatigue
-Agitation
-Orthostatic hypotension
-Headache
-Nausea/vomiting
-Sexual dysfunction
-Increased appetite
17
Q
SSRI Anesthetic Consideration (AC)
A
- INHIBITION of CP450 enzyme
- -may increase plasma [ ] of certain drugs
- Antiplatelet activity: increased risk of bleeding
- Serotonin syndrome-medication induced:
- –Confusion, fever, shivering, ataxia, diaphoresis, hyperreflexia, muscle rigidity
18
Q
Tricyclics use
A
depression
- chronic pain syndrom in lower doses
- -chemical structure similar to LA and phenothiazines
- -inhibits overactive inflamm responce system
- can take 2-3 weeks to have clinical effects
19
Q
Tricyclics MOA
A
blocks repute of serotonin and/or NE at PREsynaptic terminals
- *Tertiary amines-inhibit serotonin and NE reuptake
- *Secondary amines-inhibit NE reuptake
20
Q
Tertiary amines
A
Tricyclics
- Amytriptyline (elavil),
- imipramine (tofranil)
- clomipramine (anafranil)
21
Q
Secondary amines
A
Tricyclics
- Desipramine (norpramin)
- nortriptyline (pamelor)
22
Q
Tricyclics Pharmacokinetics
A
- highly lipid soluble
- strongly protein bound
- long elimination 1/2 time–10-80hrs
- metabolized in liver
- *have ACTIVE metabolites
- elderly can take about 1 week to clear
23
Q
Tricyclics side effects
A
Anticholinergic
–Dry mouth, tachy, urinary retention, ileum, slow gastric emptying
Cardiovascular
–Orthostatic hypotension, mild increased HR, depressed conduction through the atria and ventricles
CNS
–lower sz threshold (easier for sz), weakness, fatigue
These can be fatal with overdose
24
Q
Tricyclics drug interaction
A
- Monoamine oxidase inhibitors (MAOI): can cause CNS toxicity with tricyclics–hyperthermia, sz, coma
- Sympathomimetics
- Inhaled anesthetics
- Anticholinergics
- Antihypertensives
- Opioids
25
Tricyclics AC sympathomimetics
Sympathomimetics
- unpredictable
- indirect acting--exaggerated responses due to larger ant of NE available to stimulate postsynaptic adrenergic receptors
- Acute vs chronic (receptor becomes desensitized, with chronic) tx with tricyclics
- -use lower dosages of sympathomimetics
- Or may need potent direct acting drug
* *basically do not use indirect acting!! ex ephedrine, USE phenylephrine, start slow on dose
26
Tricyclics AC
volatile anesthetic agents--may need higher mac
- exogenous epinephrine
- opioids--decreased dose
- Barbs--decreased dose
- Anticholinergics-more likely to have post op delirium and confusion
- Anticholinergic Toxicity or Central Anticholinergic syndrome: flushing, dry mouth and skin, mydriasis
* *atropine cross BBB
* *glycopryate does not cross BBB
27
Tricyclics overdose
life threatening-intractable myocardial depression or ventricular dysrhythmias usual cause of death
-presenting features: agitation, excitement, delirium, sz, progresses to coma, resp depression and dysrhythmias and sudden death, hypotensive, anticholinergic effects
28
Tricyclic tx for overdose
vent support
manage CNS and cardiac toxicity
physostigmine for anticholinergic psychosis
acidosis may increased unbound drug---more dysrhythmias
**should be weaned to prevent withdraw syndrome
29
MAO enzyme system
found in outer mitochondrial membrane
function to inactivate the monoamines: do, serotonin, epi, NE
**this enzyme metabolizes the neurotransmitters
30
MAOI MOA
- Block the enzyme that metabolizes biogenic amines--increasing availability of these neurotransmitters in the CNS and peripheral autonomic nervous system
- Forms a stable irreversible complex with MAO enzyme
31
MAOI risk
Not often used- side effects, lethal in overdose, difficult dosing, tyramine free diet
32
MAOI drugs
Phenelzine (nardil)
- Tranylcypromine (parnate)
- Isocarboxazid (marplan)
- Selegiline (eldepryl)
33
MAO A
serotonin
NE
Epi
dop
34
MAO B
Phenylethylamine
| dop
35
MAOI side effect
most common is orthostatic hypotension: especially prominent in elderly
- anticholinergic like effects
- impotences/anorgasmy
- weight gain
- sedation or mild stimulant effects
* *NO cardiac dysrhythmias and doesn't change sz threshold
36
MAOI diet
MAO enzyme present in liver GI tact, kidneys, lungs
**MAO A in GI and liver: metabolizes tyramine
So eat tyramine: massive release of endogenous catecholamines--hypertensive crisis, hyperpyrexia, CVA
**Dietary Restrictions:
-cheese -fava beans -wine -avocado -liver -cured meat
37
MAOI symptoms to report
serious HA
Vomiting
Chest pain
38
MAOI drug interactions (which drugs)
```
DRUG Caution:
Tricyclic antidepress
-Opioids
-NO Meperidine
-Cold/allergy drugs
-Sympathomimetics
-Nasal decongestants
-SSRIs
Demerol
```
*HTN, CNA excitation, delirium, sz, death
39
MAOIs interaction with Demerol
* type1 excitatory responce
- agitation
- Skeletal muscle rigidity
- hyperpyrexia
* type 2 depressive response
- Hypotension
- resp depression
- coma
40
MAOIs interaction with sympathomimetics
may get exaggerated response from indirect acting drugs **NO EPHEDRINE
* *use direct acting agents
- decrease does by 1/3 and titrate to effect
41
MAOI AC
Minimize possibility of sympathetic nervous stimulation or drug induced hypotension.
- Caution with sympathomimetics
- Caution with opioids - NO demerol
- May need higher MAC with volatile agents
42
MAOIs overdose
```
excessive sympathetic discharge *think increased fight/flight
-tachy
-hyperthermia
-mydriasis
-Sz-coma
Tx: supportive
```
43
Antidepressant discontinuation
All should be tapered
- Can get dizziness
- Myalgias
- Parasthesia
- Irritability
- Insomnia
- Visual disturbances
- Tremors
- Lethargy
- N/V/D
44
Anxiolytics
- Benzodiazepines: for anxiety and insomnia
| - Buspirone: non-benzo, used form anxiety but not panic disorder (no effect on GABA)
45
Benzo MOA
Facilitates the action of GABA
(increases GABAs potencyX3
Causes greater frequency of channels to open:
-Increases chloride influx
-Hyperpolarization
-Decreased neuronal excitability)
-GABA- Major inhibitory neurotransmitter in the CNS
46
Benzo 5 effects
- Anxiolysis
- Sedation
- Anterograde Amnesia
- Anticonvulsant Actions
- Muscle Relaxation (Spinal Level)
47
Benzo pharmacokinetics
- highly protein bound
- high lipid solubility
- hepatic metabolism by CP450
- eliminated via kidneys
48
Benzo pharmacodynamics
| CNS effects
Decreases CBF and CMRO2
- Does NOT produce isoelectric EEG
- Preserves cerebrovascular response to CO2
- Does not attenuate ICP response to laryngoscopy
- Potent anticonvulsant and amnestic
- Paradoxical Excitement- RARE
49
Benzo resp effects
```
Dose dependent decrease in ventilation
-Hypoxemia and hypoventilation
enhanced in presence of opioid
-Depress (swallowing) reflex deglutition
-CO2 Response curve flattens- does not shift
```
50
Benzo cardiovascular effects
Decreases SVR at induction dosage
- BP consequently decreases
- C.O. unchanged
51
Benzos
Midazolam/Versed
| Diazapam/Valium
52
Midazolam
Water soluble preparation
- Imidazole ring
- 2-3* x potency of Diazepam
- 90-98% Protein bound
- Rapid redistribution → short duration
53
Midazolam uses and dosages
Premedication/Pediatrics: 0.5 mg/kg po.
-IV sedation/Adults 1- 2.5 mg IV can give
as high as 5mg, as needed.
-Induction: 0.1 – 0.2 mg/kg over 30-60 sec
-Maintenance: Incremental or Infusion
**?? 1/2 life 2-3hrs?
54
Diazepam
Highly lipid soluble with prolonged duration of action
- Commercially prepared in organic solvents including propylene glycol and benzyl alcohol
- Viscous, pH 6.6 - 6.9
- PAINFUL IV and IM injection (z-tract)
- Rapidly absorbed from GI tract
- Highly protein bound
55
Diazepam T 1/2 elimination
21 - 37 hours in healthy volunteers, increases with age
| to active metabolite: Desmethyldiazepam: 48 – 96 hours
56
Diazepam uses and doses
Premedication/Oral: 10-15 mg
- Premedication/IV: 0.2 mg/kg (reduces MAC)
- Induction: 0.5 – 1.0 mg/kg IV
- Anticonvulsant: 0.1 mg/kg IV
57
Antipsychotics (neuroleptic) drugs
- Phenothiazines
- Thioxanthenes
- Butyrophenones
58
Phenothiazines
| and Thioxanthenes
- Chlorpromazine (thorazine)
- Thioridazine (Mellaril)
- Pherphenazine (trilafon)
- Trifluoperazine (Stelazine)
- Thiothizene (naval)
59
Phenothiazines
| and Thioxanthenes
Blockade of dopamine receptors in the basal ganglia and limbic portions of the forebrain
- -Interference with dopamine leads to extrapyramidal side effects
- Blockade of dopamine receptors in chemorecptor trigger zone of medulla: antiemetic effects
60
Phenothiazines
| and Thioxanthenes pharmacokinetics
- Erratic patterns of absorption after po administration
- Highly lipid soluble
- Highly protein bound
61
Phenothiazines
| and Thioxanthenes metabolism
- Oxidation in liver with conjugation
- Most have inactive metabolites
- T1/2 10-20 hours
- Prolonged in the elderly or those with decreased capacity to metabolize drugs
62
Phenothiazines
| and Thioxanthenes side effects
- Due to blockade of dopamine receptors in forebrain
| - Large margin of safety and overdoses rarely fatal
63
Phenothiazines
and Thioxanthenes side effects:
extrapyramidal
**Extrapyramidal effects
-Tardive dyskinesia: Abnormal involuntary movements involving the tongue, facial/neck muscles, extremeties, and occasionally skeletal muscle groups used in breathing/swallowing
-Occurs in 20% of patients receiving therapy for > 1 year
-Elderly and women more susceptible
**Usually permanent—no treatment
ACUTE dystonic reaction
-Usually occur in first few weeks of therapy
-Acute skeletal muscle rigidity & cramping in neck, tongue, face or back
-Respiratory distress from laryngeal dyskinesia (laryngospasm)
-Responds well to diphenhydramine 25-50 mg. IV
64
Phenothiazines
and Thioxanthenes
Cardio side effects
Cardiovascular effects
- Decreases in B/P
- Due to depression of vasomotor reflexes/peripheral alpha adrenergic blockade
- Relaxant effects on vascular smooth muscle
- Direct cardiac depression
- No cardiac dysrhythmic effects
- Prolonged QT interval on ECG
65
Phenothiazines
and Thioxanthenes
CNS side effects
*Sedation
--Due to antagonism of alpha 1, muscarinic, and
histamine receptors
--Tolerance to sedation develops with chronic therapy
*Seizure threshold is decreased-similar EEG pattern as seen with seizure disorders, and sensory evoked potentials often decreased in amplitude
*Skeletal muscle relaxation: By CNS action not neuromuscular junction
66
Phenothiazines
and Thioxanthenes
yup more side effects
Antiemetic properties
-Interacts with dopaminergic receptors in
chemoreceptor trigger zone
-Effective in preventing opoid induced N/V
-No sedation or hypotensive effects and rarely cause extrapyramidal symptoms
*Neuroleptic malignant syndrome
-Develops over 24-72 hrs usually in young men
-Hyperthermia
-Hypertonicity of skeletal muscles
-Instability of autonomic N.S.
-Fluctuating LOC
67
Phenothiazines
| and Thioxanthenes drug interaction
Potentiation of opioids: Sedative effects, Ventilatory depression, Analgesic properties
68
Butyrophenones
- Droperidol (inapsine)
- Haloperidol (haldol)
* *Structurally resemble phenothiazines
- Side effects similar to phenothiazines
69
Butyrophenones: Droperidol Pharmacokinetics
- Clearance is perfusion dependent-Hepatic metabolism opposed to hepatic enzyme activity
- accumulation of drug with decreased hepatic blood flow
- max excretion of metabolites in first 24 hrs
70
Butyrophenones: Droperidol side effects
CNS: extrapyramidal reactions, cerebral vasoconstrictor (decreased CBF), dysphoria
CV
-Decrease in systemic BP from alpha
blockade-usually minimal
-Antidysrhythmic, protects against epinephrine induced dysrhythmia
-Large doses decrease conduction along accessory pathways responsible for tachy dysrhythmias WPW syndrome
-Prolonged QT
-Torsades: have occurred at low doses, pt with no risk factors, no precise cause, some fatal
71
Droperidol Black box warning
all pts get 12 lead prior to administration
- must be monitored prior to and continues for 2-3 hrs
- caution with pts at rick for developing QT syndrome
72
Droperidol uses
- neurolept analgesia: combines with fentanyl (innovate), prolonged action of fentanyl, intense analgesia
- antiemetic: simmilar to zofran
* does not help motion sickness
73
Mood stabilizer
Lithium
74
Lithium
- tx of bipolar
- Neurobiogenic effects not well understood how it works or which effects are necessary for mood stabilization
- Competes with Na+, Ca+, and Mg+ affecting cell membranes, H2O, and neurotransmitters
75
Lithium pharmacokinetics
- Distributed throughout total body H2O and excreted by the kidneys
- Filtered by glomerulus and reabsorbed by the proximal renal tubules
- Proximal reabsorption of lithium and Na+ is competitive (so low Na and more lithium is absorbed)
- Elimination 1⁄2 time is 24 hrs.
- Steady state is 4-5 elimination 1⁄2 times
76
Lithium side effects
kidneys-evaluate renal function every 6 months
- Polydipsia and polyuria: > 3 liters/day
- Impaired renal concentrating ability
- Decrease in sensitivity to ADH
- EKG—T wave changes, flattening or inversion: No related clinical effects
- Hypothyroidism can develop– more common in females
- New onset psoriasis/acne
- Hand tremor
- Sedation
- Memory disturbances/cognitive slowing
77
Lithium Toxicity
*Mild: Sedation, nausea, skeletal muscle weakness, wide QRS complex, AV heart block, hypotension, dysrhythmia, seizure
**Significant toxicity
Medical emergency
Aggressive RX
Hemodialysis
Osmotic diuresis and IV bicarbonate
78
Lithium AC
- Pre operative labs and ECG
- Many drug interactions
- Anesthetic requirements may be decreased
- Action of neuromuscular blocking agents may be prolonged
79
epilepsy
Designates a group of chronic central nervous system disorders characterized by sudden onset of sensory, motor, autonomic, psychic disturbances
- usually transient and associated with rapid, synchronous uncontrolled spread of eletrical activity in the brain.
- May be associated with an identifiable neurologic/systemic disorder or may be idiopathic
80
Antiepileptics
Goal of therapy is to control seizures without medication related side effects
- 70% of patients can achieve this using a single anti epileptic drug
- Drug selected to treat is influenced by the type of seizure experienced
81
Antiepileptics MOA
Decrease neuronal excitability or enhance
inhibition of neurotransmission
-Achieve by altering intrinsic membrane ion currents (sodium, potassium, and calcium conductance)
-Enhancement of GABA action
82
Antiepileptics Pharmacokinetics
Slow absorption from GI tract
- Protein binding varies 0%->90%
- Most are metabolized by the liver and excreted by the kidneys
- Elimination 1⁄2 times range from hours to days
- Most all associated with drug interactions in which effects of concomitantly administered drugs may be altered
83
Antiepileptics lab testing
Routine monitoring of plasma concentration
guide dosing adjustments
-“Therapeutic ranges” often do not correspond to individual responses
-Titrate to clinical efficacy: Check plasma levels to determine compliance with RX and pharmacokinetic interactions
-Many antiepileptics associated with life threatening bone marrow suppression and hepatotoxicity: Liver function tests and Hematologic studies
84
Antiepileptics
```
Phenobarbital
Phenytoin (dilantin)
Fosphenytoin (cerebyx)
Primidone (mysoline)
Carbamazepine (tegretol)
Valproate (depakote)
Levetiracetam (Keppra)
```
85
Phenytoin MOA
-Effective for Rx of partial and generalized
seizures, can be given po or IV
-Regulates neuronal excitability and thereby the spread of seizure activity from a seizure focus by regulating Na+ and Ca++ ion transport across neuronal membranes
86
Phenytoin
| Pharmacokinetics
Pharmacokinetics
-pH of 12 and precipitates in solutions with pH
of < 7.8
-Not recommended for IM injection- precipitates at site and poorly absorbed
-Infusion no faster than 50 mg./min in adults; 1-3mg/kg/min in peds or 50mg/min whichever is slower.
-Poorly H2O soluable-variable absorption from GI tract
-Highly protein bound-90% to plasma albumin
87
Phenytoin metabolism
- By hepatic microsomal enzymes CP450
- Inactive metabolites
- Plasma concentration 10mcg/ml zero order kinetics
88
Phenytoin Side effects
```
CNS toxicity-nystagmus, ataxia, diplopia,
vertigo, peripheral neuropathy
-Acne
-Facial coarsening
-Allergic rash→Stevens Johnson Syndrome
-GI irritation
-Hepatotoxicity
-Induces hepatic enzyme system
```
89
Fosphenytoin
```
-Slightly safer than dilantin
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/treat seizures
-10-20 mg/kg IV loading dose
```
90
Phenobarbital
-Long acting barbiturate
-Cognitive and behavioral side effects limit
usefulness-2nd line drug
-Sedation in adults; hyperactivity in children
-Depression
-Confusion in elderly
91
Phenobarbital MOA
Mechanism of action
-Modulation of post synaptic actions of GABA
and glutamate
-Enhances cytochrome P450 system in liver
92
Benzodiazepines: as antiepileptics
Binds to GABA receptors in brain and potentiate GABA mediated neuronal inhibition by increasing chloride permeability, cellular hyperpolarization,and inhibition of neuronal firing
