The time course and intensity of a drug and is effects are referred to as its pharmacodynamics. Major pharmacodynamics considerations include receptor mechanisms; the dose-response curve; the therapeutic index; and the development of tolerance, dependence, and withdrawal phenomena. Drugs’ mechanisms of action are subsumed under pharmacodynamics. The clinical response to a drug, including adverse reactions, results from an interaction between that drug and a patient’s susceptibility to those actions.

Pharmacokinetics refers to the way in which the body processes a drug. Pharmacokinetics are divided into drug absorption, distribution, metabolism, and excretion. The field of pharmacogenetic grew out of observations of significant ethnic differences in response to drugs, in differential development, and in adverse effect profiles, leading to the discovery of defects or deficiencies in the genetically controlled activity of enzyme systems responsible for the metabolism of psychotropic medications and toxins such as alcohol. Pharmacogenetic studies are beginning to identify genetic polymorphisms linked to individual differences in treatment response and sensitivity to side effects.

The placebo effect is when a person exhibits a clinically significant response to a pill containing a therapeutically inert substance or a treatment without specific effect on the person’s condition. Placebo effects are not limited to subjective reports; physiologic functions may be objectively influenced. Idiosyncratic reaction is an unpredictable, non-dosage-related drug response. For example, diazepam (Valium) administered as a sedative paradoxically causes agitation in some persons.

In general, the newer psychotropic agents cause less frequent and less severe movement disorders than their first-generation counterparts. In sensitive individuals, however, these syndromes can still occur with second-generation antipsychotics. Furthermore, the general reduction in the incidence and severity of these syndromes may delay recognition when they are present. Included in these categories are parkinsonism, neuroleptic malignant syndrome, acute dystonia, acute akathisia, tardive dyskinesia, postural tremor, and medication-induced movement disorder not otherwise specified.

Clinically, clonidine (Catapres) has been useful and effective in a series of medical and psychiatric conditions. Among them are Tourette’s disorder, other tic disorders, opiate withdrawal, nicotine withdrawal, autism spectrum disorders, posttraumatic stress disorder (PTSD), and other anxiety disorders. Clonidine was synthesized in the early 1960s and was found to produce vasoconstriction mediated by α-receptors. Clonidine is well absorbed after oral administration, and its bioavailability is nearly 100 percent.

Indications for β-adrenergic receptor antagonists are lithium tremor, major depressive disorders, substance use disorders, performance anxiety, and neuroleptic-induced akathisia. The five β-adrenergic receptor antagonists most frequently studied for psychiatric applications are propranolol, metoprolol, atenolol, and pindolol. Propranolol is the most commonly used β-adrenergic receptor antagonist and is not known to exert a teratogenic effect in humans; however, some infant born to mothers taking propranolol during pregnancy have exhibited hypoglycemia or bradycardia.

Anticholinergic medications can lead to impairment in cognitive functions, particularly in elderly individuals. These agents have also been implicated in worsening (not improving) positive symptoms of psychoses. These agents also impair (not improve) storage of new information into long-term memory. Significant improvement has also been demonstrated in the cognitive total score, as well as in the ideational apraxia and orientation subscales.

The newer anticonvulsants such as gabapentin, levetiracetam, pregabalin, tiagabine, topiramate, and zonisamide have a variety of structures and mechanisms; among them, the enhancement of neuronal inhibition by increasing γ-amino butyric acid (GABA)ergic function, and decrease of neuronal excitation by decreasing glutaminergic function; they also increase the risk of suicidality and have analgesic effects. The risk for suicidality was higher among patients with epilepsy compared with patients with psychiatric disorders.

The use of H₂ receptor antagonists in psychiatric practice has primarily been for weight loss in overweight individuals and persons experiencing antipsychotic-associated weight gain. Initial studies indicated that the H₂ receptor antagonist nizatidine (Axid) was efficacious as a secondary prevention strategy for weight gain associated with the use of olanzapine (Zyprexa).

In general, the brief duration of electroconvulsive therapy (ECT) requires shorter acting agents. Methohexital (Brevital) is usually the first-line agent for anesthesia during ECT. The rapid onset and offset of action of etomidate make it an appropriate choice. Thiopental (Pentothal) is longer acting, and its anticonvulsant properties can interfere with induction of therapeutic seizures. Propofol (Diprivan) may also shorten seizure duration. The proconvulsant action of ketamine makes it useful when seizures are different to induce, and ketamine may have acute antidepressant effects, but it can cause psychosis and may also have cardiovascular side effects. A randomized comparison of etomidate, propofol, and thiopental found all of them to be relatively free of important cardiovascular effects in otherwise healthy patients undergoing ECT. Etomidate raises the seizure threshold less than propofol, and its use is associated with a requirement for a lower stimulant dose to produce adequate seizures.

All benzodiazepines except clorazepate (Tranxene) are completely absorbed after oral administration and reach peak serum levels within 30 minutes to 2 hours. Metabolism of clorazepate in the stomach converts it to desmethyldiazepam, which is then completely absorbed. Intra muscular absorption of benzodiazepines other than lorazepam is slower than oral absorption. The onset of action is nearly immediate with IV administration of high-potency benzodiazepines, such as midazolam.

Bupropion (Wellbutrin) is the only antidepressant to receive Food and Drug Administration (FDA) approval for the preventive treatment of seasonal affective disorder. Bupropion was originally introduced in the 1980s and has become one of the more commonly prescribed antidepressants in the United States. As a result of a unique pharmacology, bupropion is often used as an alternative to SSRIs and serotonin–norepinephrine reuptake inhibitors (SNRIs). In addition to its FDA approval in the treatment of depression, bupropion is also approved for smoking cessation (Zyban). Additionally, bupropion is used for numerous off-label indications, including the treatment of patients with attention-deficit/hyperactivity disorder, sexual dysfunction, obesity, and fatigue related to nonpsychiatric medical conditions. Currently, all formulations of bupropion are generically available, and the major metabolite of bupropion, hydroxybupropion, is being investigated as a potential antidepressant.

Buspirone (Buspar) has not demonstrated any clear efficacy in the treatment of psychosis. In the context of schizophrenia, efficacy has not been observed in the treatment of either positive or negative symptoms. Some studies have shown improvement of cognitive functions among patients with schizophrenia taking buspirone but no significant improvement in psychotic symptomatology.

Carbamazepine (Tegretol) inhibits calcium channels on a comparable basis to verapamil (Calan, Isoptin). Lamotrigine (Lamictal) also has calcium channel blocking properties, as also do valproate (Depakene), gabapentin (Neurontin), pregabalin (Lyrica), and lithium (Eskalith). All of these medications are useful to the treatment of patients with bipolar disorders.

Carbamazepine is an iminostilbene drug possessing some structural similarity to the tricyclic antidepressant imipramine. Carbamazepine was approved for use in the United States for the treatment of trigeminal neuralgia in 1968 and for temporal lobe epilepsy (complex partial seizures) in 1974. It is now recognized in most guidelines as a second-line mood stabilizer useful in the treatment and prevention of both phases of bipolar affective disorder.

Dementia commonly occurs in patients with Parkinson’s disease in an average prevalence of about 40 percent in cross-sectional studies. The cholinesterase inhibitors and memantine (Namenda) are currently the only types of medications approved by the FDA to treat Alzheimer’s disease and other dementias. Recently, the efficacy of the cholinesterase inhibitors has expanded to include severely ill patients with Alzheimer’s disease, patients with Lewy body disease, and patients with dementia associated with Parkinson’s disease.

Risperidone (Risperdal) is a second-generation antipsychotic. Other second-generation antipsychotics include clozapine (Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), and aripiprazole (Abilify). Second-generation antipsychotics have gradually replaced the first-generation antipsychotics as the most widely prescribed agents for schizophrenia and other psychotic disorders in the United States; however, the first-generation antipsychotics still remain the most commonly prescribed antipsychotics in many parts of the world. The first-generation antipsychotics represent the first group of effective agents for schizophrenia and other psychotic illness. They include all of the antipsychotics in the following groups: phenothiazines (i.e., chlorpromazine [Thorazine], thioridazine [Mellaril], and perphenazine), butyrophenones (i.e., haloperidol [Haldol]

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