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General Principles of Pharmacology
General Principles of Pharmacology
PHARMACOLOGY
Psychotropic Medication
any drug prescribed to stabilize or improve mood, mental status, or
behavior
includes medications typically classified as antidepressants, antianxiety,
etc.
includes other medications not typically classified as psychotropic when
such medication is prescribed to improve or stabilize mood, mental
status or behavior (e.g., carbamazepine is usually an antiepileptic
medication but can be prescribed for affective disorders)
includes herbal or nutritional substances when such substances are used
to stabilize or improve mood, mental status, or behavior
Classification of Psychoactive Drugs
Generic name
written with lowercase initial letter and the name is derived from
the chemical structure of the drug
Pharmacokinetics
The time course and effects of drugs and their
metabolites on the body (what the drug does to
the body)
absorption
distribution
biotransformation
half-life
steady-state concentration
excretion
Pharmacokinetics
Absorption
the process whereby drug molecules enter the bloodstream
affected by the route of administration and the particulars of
manufacture, such as the thickness of pill coating, type of filler
substance, hardness of tablet
Distribution
the movement of drug molecules through the bloodstream to the site
of action
protein-binding affects distribution. The ratio of protein-bound to
unbound remains constant, so as unbound molecules pass out of the
bloodstream other molecules become unbound
Pharmacokinetics
Biotransformation
the changes in the structure of drug molecules characteristically
produced by enzymatic action in the liver
most drugs are converted into inactive metabolites, but some are
changed to an active form.
some drugs are not metabolized and pass from the body
unchanged
Half-life
determined by measuring the amount of time required for a given
blood level to decline by 50%
Pharmacokinetics
Steady State Concentration
the concentration of the drug when the amount administered is
equal to the amount eliminated per unit time
Excretion
the process responsible for the removal of drug molecules and
metabolites from the body, usually in the urine.
some variables that influence the rate of elimination include
genotype, age, drug history, and liver or kidney disease
Drug Effects
when a drug is used therapeutically, the desired action is
termed the therapeutic effect
Hepatic effects
changes in liver functions
Side Effects
Reproductive and Adverse Sexual Effects
changes in libido
priapism
impotence
ejaculatory and orgasmic disturbances
Convulsive effects
Side Effects
Neuromuscular Effects
myoclonus
nocturnal myoclonus
action (inaction) tremor of upper extremities
acute extrapyramidal symptoms (including dystonia,
neuroleptic-induced parkinsonism, bradykinesia, akinesia,
tremor, and rigidity)
akathisia
tardive symptoms
neuroleptic malignant syndrome
Side Effects
Monitoring Adverse Effects
Rating scales
general purpose
side effect-specific scales
Considerations include:
indications effects on behavior
side effects effects on learning
dosing guidelines
Stimulants - Indications
Attention Deficit Hyperactivity Disorder
ADHD with comorbid disorders (including
mental retardation, Fragile X Syndrome,
Tourette Disorder)
Hyperactivity in developmental disorders
narcolepsy
adjunctive treatment in refractory depression
Stimulant Medications
• Stimulant medications are the most studied,
most commonly used first-line agents for
ADHD treatment
• Stimulant medications improve:
• core symptoms: inattention, impulsivity, hyperactivity
• associated symptoms: cognition, on-task behavior, academic
performance, social function, defiance, and aggression
Metadate® CD 60 mg (3 x 20 mg)
15 Ritalin® LA 40 mg
10
0
0 5 10 15
Time (h)
Gonzalez MA, et al. Int J Clin Pharmacol Ther. 2002;40:175-184.
Data on file, Novartis Pharmaceuticals.
Selective Norepinephrine
Reuptake Inhibitor
Atomoxetine (Strattera)
Highly selective blockade of the presynaptic
norepinephrine transporter (relatively more
plentiful in the prefrontal cortex than the striatum)
• Increased concentration of norepinephrine in the anterior
and posterior brain attentional systems
• Downstream increase in dopamine in the prefrontal cortex
• Does NOT increase the concentration of dopamine in the
nucleus accumbens (abuse potential) or striatum (tics)
Selective Norepinephrine
Reuptake Inhibitor
Atomoxetine (Strattera)
Safety data
• diastolic BP and heart rate increase in a statistically but not
clinically significant manner
• 20% with decreased appetite - weight decreased in first 9-
12 weeks of treatment, then begins to catch up and parallel
growth curve
• no significant lab or EKG changes
• no exacerbation of tics or anxiety
• insomnia not a significant side effect
*** need to watch for abnormal liver function
*** black box warning – may increase suicidal thoughts
Selective Norepinephrine
Reuptake Inhibitor
Atomoxetine (Strattera)
• Several studies showed that once daily dosing strategy
similar to twice-daily dosing
• Atomoxetine associated with improved evening and early
morning parent ratings – single daily dose
• Non-controlled substance
• First non-stimulant, FDA approved medication for
treatment of ADHD in children, adolescents and adults
(November, 2002)
• May take up to 2-4 weeks to see optimal benefit
Antidepressants - Indications
major depressive disorder
enuresis
ADHD
anxiety disorders (e.g., school phobia, separation
anxiety, panic disorder, and obsessive-compulsive
disorder)
sleep disorders (night terrors)
some cases of self-injury in individuals with
developmental disabilities
Classes of Antidepressants
Tricyclics
amitriptyline (Elavil) desipramine (Norpramin)
imipramine (Tofranil) nortriptyline (Pamelor)
Monoamine Oxidase Inhibitors (MAOIs)
phenelzine (Nardil) tranylcypromine (Parnate)
Selective Serotonin Reuptake Inhibitors (SSRIs)
fluoxetine (Prozac) fluvoxamine (Luvox)
paroxetine (Paxil) sertraline (Zoloft)
citalopram (Celexa) escitalopram (Lexapro)
Others
bupropion (Wellburtin) trazodone (Desyrel)
venlafaxine (Effexor) nefazodone (Serzone)
Mirtazapine (Remeron)
Tricyclic Antidepressants
Side Effects
Common: dry mouth, constipation, blurred vision, weight
gain, sedation, mild liver and blood count changes
Rare: arrhythmias or tachycardia, induction of psychosis or
mania
** SLOWING OF CARDIAC CONDUCTION
(baseline and maintenance EKG monitoring is required)
Contraindicated in patients with cardiac conduction
disturbances
Sudden discontinuation of the medication may result in flu-like
symptoms, an increase in behavioral problems or insomnia
Antidepressants - Side Effects
MAOIs: changes in blood pressure, weight gain, need to
follow dietary restrictions
SSRIs: irritability, headaches, insomnia, nervousness,
drowsiness or fatigue, anorexia, nausea, or diarrhea
(safer side effect profile, especially reduced risks of
cardiotoxicity and lethality of overdose, compared to
tricyclics)
bupropion: irritability, insomnia, drug induced seizures
(with high doses)
trazodone: changes in blood pressure, sexual dysfunction
Traditional antipsychotics
dystonia anticholinergic effects
akasthesia tardive dyskinesia
sedation endocrine disturbances
confusion malignant neuroleptic syndrome
Atypical antipsychotics
Clozapine: risk of agranulocytosis
Antipsychotics - Side Effects
Extrapyramidal Sedation Weight Anticholinergic Risk for
Gain Diabetes