Opioid Receptor Agonists

Are a structurally diverse group of compounds that are used for pain management. These drugs
are also called narcotics. Commonly used opioid agonists for pain relief include morphine,
hydromorphone, codeine, meperidine, oxycodone buprenorphine, hydrocodone, tramadol,
and fentanyl

Pharmacologic Actions - Opioid agonists bind to G-protein coupled receptors to cause cellular

hyperpolarization. Most clinically relevant opioid analgesics bind to MOP receptors in the
central and peripheral nervous system in an agonist manner to elicit analgesia.

Drug Interactions - Opioid receptor agonists can potentiate the CNS-depressant effects of
alcohol, barbiturates, benzodiazepines, other opioids, low-potency dopamine receptor
antagonists, tricyclic and tetracyclic drugs, and MAOIs.

Adverse Reactions - The most common adverse effects of opioid receptor agonists are
lightheadedness, dizziness, sedation, nausea, constipation, vomiting, perspiration, weight gain,
decreased libido, inhibition of orgasm, and insomnia or sleep irregularities.
 Opioid Receptor Antagonists: Naltrexone, Nalmefene, and Naloxone
They bind to opioid receptors without causing their activation. Because these drugs induce
opioid withdrawal effects in people using full opioid agonists, these drugs are classified as opioid
antagonists.

Pharmacologic Actions - Opioid receptor antagonists block one or more of the opioid receptors
in the central or peripheral nervous system. Opioid receptors are specific transmembrane
neurotransmitter receptors that couple G-proteins, which upon stimulation by endogenous or
exogenous opioids, lead to the intracellular process of signal transduction.

Drug Interactions - Opioid receptor antagonists have been reported to potentiate the sedation
associated with use ofthioridazine (Mellaril), an interaction that probably applies equally to all
lowpotency dopamine receptor antagonists.

Adverse Reactions - Common adverse effects includes, nausea, vomiting, sweating, tachycardia,
increased blood pressure, tremors
 Phosphodiesterase-5 Inhibitors
Phosphodiesterase (PDE)-5 inhibitors, such as sildenafil (Viagra), which was developed in 1998,
revolutionized the treatment of the major sexual dysfunction affecting men erectile disorder.
Two congeners have since come on the market ,vardenafil (Levitra) and tadalafil (Cialis).

Pharmacologic Actions - The mechanism of action involves active inhibition of the PDE-5
enzyme and resulting increase in cyclic guanosine monophosphate (cGMP) and smooth muscle
relaxation in the penis. Sildenafil citrate (Viagra) is a potent and selective PDE-5 inhibitor, which
is the first drug in this class to be approved for treatment of ED.

Drug Interactions - The major route of PDE-5 metabolism is through CYP3A4, and the minor
route is through CYP2C9.

Adverse Reactions - The most common adverse effects are headache, flushing, and stomach
pain. Other less common adverse effects include nasal congestion, urinary tract infection,
abnormal vision (colored tinge [usually blue] , increased sensitivity to light, or blurred vision),
diarrhea, dizziness, and rash. A major potential adverse effect associated with use of these drugs
is myocardial infarction.
 Selective Serotonin Norepinephrine Reuptake Inhibitors
Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class of medications that
are effective in treating depression. SNRIs are also sometimes used to treat other conditions,
such as anxiety disorders and long-term (chronic) pain, especially nerve pain. Common drugs that
are used are Venlaxafine, Desvenlaxafine Succinate, Duloxetine and Levomilnacipran. Venlafaxine
is approved for treatment of four disorders: major depressive disorder, generalized anxiety
disorder, social anxiety disorder, and panic disorder.

Pharmacologic Actions - SNRIs inhibit both SERT (serotonin transporter) and NET
(norepinephrine transporter), the initial inhibition of SERT induces activation of 5-HT1a and 5-
HT1d autoreceptors. This action decreases serotonergic neurotransmission by a negative
feedback mechanism until these serotonergic autoreceptors are desentisized. Then the enhanced
serotonin concentration in the synapse can interact with the postsynaptic 5-HT receptors

Drug Interactions - Venlafaxine is metabolized in the liver primarily by the CYP2D6 isoenzyme.
Because the parent drug and principal metabolite are essentially equipotent, medications that
inhibit this isoenzyme usually do not adversely affect therapy.

Adverse Reactions - Nausea is the most frequently reported treatment-emergent adverse effect
associated with venlafaxine, Other common side effects include headache, insomnia,
somnolence, dry mouth, dizziness, constipation, asthenia, sweating, and nervousness.
 Selective Serotonin Reuptake Inhibitors
Selective serotonin reuptake inhibitors (SSRIs) are a widely used type of antidepressant. They're
mainly prescribed to treat depression, particularly persistent or severe cases, and are often used
in combination with a talking therapy such as cognitive behavioural therapy (CBT).

Pharmacologic Actions - Balance levels of neurotransmitters to boost mood. SSRIs act on

serotonin transporter they block the reuptake of serotonin in pre-synaptic neuron thus more
serotonin persist in the synaptic cleft causing more post-synaptic neuronal activities. The
balancing of serotonin help brain cells send and receive chemical messages, which in turns
boosts mood.

Drug Interactions - The SSRis do not interfere with most other drugs. A serotonin syndrome can
develop with concurrent administration of MAO Is, L-tryptophan, lithium, or other
antidepressants that inhibit reuptake of serotonin. Fluoxetine, sertraline, and paroxetine can
raise plasma concentrations of TC As, which can cause clinical toxicity.

Adverse Reactions - Nausea, headache, weight gain, anxiety, insomnia, acne. Anticholinergic
effects such as dry mouth and constipation
 Serotonin Dopamine Antagonists and Similarly Acting Drugs
The serotonin-dopamine antagonists (SDAs ), also known as second-generation or atypical
antipsychotic drugs, are a group of pharmacologically diverse drugs that have largely supplanted
the older dopamine receptor antagonists (DRAs).

Pharmacologic Actions - The presumed antipsychotic effects of the SDAs are blockade of D2
dopamine receptors. Where the SDAs differ from older antipsychotic drugs is their higher ratio
interactions with serotonin receptor subtypes, most notably the 5-HT2A subtype, as well as with
other neurotransmitter systems. It is hypothesized that these properties account for the distinct
tolerability profiles associated with each of the SDAs .

Drug Interactions - Fluvoxamine (Luvox) and cimetidine (Tagamet) increase, whereas

carbamazepine and phenytoin decrease serum concentrations of olanzapine. Ethanol increases
olanzapine absorption by more than 25 percent, leading to increased sedation. Olanzapine has
little effect on the metabolism of other drugs.

Adverse Reactions - The most common drug-related adverse effects are sedation, dizziness,
syncope, tachycardia, hypotension, electrocardiography (ECG) changes, nausea, and vomiting.
Other common adverse effects include fatigue, weight gain, various GI symptoms (most
commonly constipation), anticholinergic effects, and subjective muscle weakness.
 Stimulant Drugs and Atomoxetine
Currently these drugs are most commonly used to treat symptoms of poor concentration and
hyperactivity in children and adults with attention-deficit/hyperactivity disorder (ADHD).
Paradoxically, many patients with ADHD find that these drugs can have a calming effect.
Sympathomimetics are also approved for use in increasing alertness in narcolepsy.

Pharmacologic Actions - All of these drugs are well absorbed from the gastrointestinal tract.
Amphetamine (Adderall) and dextroamphetamine (Dexedrine, Dextrostat) reach peak plasma
concentrations in 2 to 3 hours and have a half-life of about 6 hours, thereby necessitating once-
or twice-daily dosing.

Drug Interactions - The coadministration of sympathomimetics and tricyclic or tetracyclic

antidepressants, warfarin (Coumadin), primidone (Mysoline ), phenobarbital (Luminal),
phenytoin (Dilantin), or phenylbutazone (Butazolidin) decreases the metabolism of these
compounds, resulting in increased plasma levels. The sympathomimetics should be used with
extreme caution with monoamine oxidase inhibitors (MAOis).

Adverse Reactions - The most common adverse effects are stomach pain, anxiety, irritability,
insomnia, tachycardia, cardiac arrhythmias, and dysphoria. Sympathomimetics cause a
decreased appetite, although tolerance usually develops for this effect
 Thyroid Hormones
Thyroid hormones-levothyroxine (Synthroid, Levothroid, Levoxine) and liothyronine (Cytomel)
are used in psychiatry either alone or as augmentation to treat persons with depression or
rapid-cycling bipolar I disorder. They can convert an antidepressant-nonresponsive person into
an antidepressant-responsive person.

Pharmacologic Actions - Thyroxine (T 4) crosses the blood-brain barrier and diffuses into
neurons, where it is converted into T3, which is the physiologically active form. The half-life of T4
is 6 to 7 days, and that of T3 is 1 to 2 days.

Drug Interactions - Thyroid hormones can potentiate the effects of warfarin (Coumadin) and
other anticoagulants by increasing the catabolism of clotting factors. They may increase the
insulin requirement for diabetic persons and the digitalis requirement for persons with cardiac
disease. Thyroid hormones should not be coadministered with sympathomimetics, ketamine
(Ketalar), or maprotiline (Ludiomil) because of the risk of cardiac decompensation.

Adverse Reactions - The most common adverse effects associated with thyroid hormones are
transient headache, weight loss, palpitations, nervousness, diarrhea, abdominal cramps,
sweating, tachycardia, increased blood pressure, tremors, and insomnia. Osteoporosis may also
occur with long-term treatment, but this has not been found in studies involving liothyronine
augmentation. Overdoses of thyroid hormones can lead to cardiac failure and death.
 Tricyclics and Tetracyclics
Tricyclic and tetracyclic antidepressants, also called cyclic antidepressants, are among the
earliest antidepressants developed. They're effective, but they've generally been replaced by
antidepressants that cause fewer side effects.

Pharmacologic Actions - Tricyclic antidepressants act on approximately five different

neurotransmitter pathways to achieve their effects. They block the reuptake of serotonin and
norepinephrine in presynaptic terminals, which leads to increased concentration of these
neurotransmitters in the synaptic cleft.

Drug Interactions - The TCAs should not be taken within 14 days of administration of an MAOI.
Birth control pills may decrease TCA plasma concentrations through the induction of hepatic
enzymes.

Adverse Reactions - Orthostatic hypotension is the most common cardiovascular autonomic

adverse effect and the most common reason TCAs are discontinued. It can result in falls and
injuries in affected persons. Other adverse effects are drowsiness, blurring of vision,
constipation, dry mouth.
 Valproate
Valproate (Depakene, Depakote ), or valproic acid, is approved for the treatment of manic
episodes associated with bipolar I disorder and is one of the most widely prescribed mood
stabilizers in psychiatry. It has a rapid onset of action and is well tolerated, and numerous studies
suggest that it reduces the frequency and intensity of recurrent manic episodes over extended
periods of time.

Pharmacologic Actions - Tricyclic antidepressants act on approximately five different

neurotransmitter pathways to achieve their effects. They block the reuptake of serotonin and
norepinephrine in presynaptic terminals, which leads to increased concentration of these
neurotransmitters in the synaptic cleft.

Drug Interactions - Valproate is commonly prescribed as part of a regimen involving other

psychotropic agents. The only consistent drug interaction with lithium, if both drugs are
maintained in their respective therapeutic ranges, is the exacerbation of drug-induced tremors,
which can usually be treated with β-receptor antagonists.

Adverse Reactions - Orthostatic hypotension is the most common cardiovascular autonomic

adverse effect and the most common reason TCAs are discontinued. It can result in falls and
injuries in affected persons. Other adverse effects are drowsiness, blurring of vision,
constipation, dry mouth.
 Nutritional Supplements and Medical Foods
In the United States, the term nutritional supplement is used interchangeably with the term
dietary supplement. The Dietary Supplement Health and Education Act (DHSEA) of 1994 defined
nutritional supplements as items taken by mouth that contain a "dietary ingredient" meant to
supplement the diet. These ingredients may include vitamins, minerals, herbs, botanicals, amino
acids, and substances such as enzymes, tissues, glandulars, and metabolites. By law such
products must be labeled as supplements and may not be marketed as conventional food.

Medical Foods - In recent years the FDA has introduced a new category of nutritional
supplement called medical foods. According to the FDA, medical food, as defined in the Orphan
Drug Act, is "a food which is formulated to be consumed or administered enterally under the
supervision of a physician and which is intended for the specific dietary management of a
disease or condition for which distinctive nutritional requirements, based on recognized
scientific principles, are established by medical evaluation."

Adverse Reactions - Adverse effects are possible, and toxic interactions with other drugs may
occur with all phytomedicinals, dietary supplements, and medicinal foods. Adulteration is
possible, especially with phytomedicinals.
 Weight Loss Drugs
Weight management is an important element of psychotropic drug treatment because obesity is
common among persons with mental disorders. Thus, medical conditions such as hypertension,
diabetes mellitus, and hyperlipidemia need to be taken into account when selecting medications.
With few exceptions, most psychotropic drugs used to manage mood disorders, anxiety disorders,
and psychosis are associated with significant risk of weight gain as a side effect.

All of the drugs approved by the FDA as weight loss agents are specifically indicated as an adjunct to
a reduced calorie diet and increased physical activity for chronic weight management in adult
patients

Phentermine - Phentermine hydrochloride (Adipex-P) is a sympathomimetic amine with

pharmacological activity similar to the amphetamines. It is indicated as a short-term adjunct in a
regimen of weight reduction, but in fact, many patients use the drug for extended periods. As with
all sympathomimetics, contraindications include advanced arteriosclerosis, cardiovascular disease,
moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to the
sympathomimetic amines, agitated states, and glaucoma

Phentermine/Topiramate Extended Release (Qsymia) - This drug is a combination of phentermine

and topiramate (Topamax). The phentermine/topiramate combination was approved by the FDA in
20 1 2 as an extended-release formulation. Both active agents in this formulation are associated
with weight loss through separate mechanisms