Depression pharmacodynamics

Serrette A, Artioli P, Quartesan R (2005). Pharmacogenetics in the treatment of depression pharmacodynamic studies. Pharmacogenet. Genomics. 15 61-67. 

Geriatric factors a variety of factors, both pharmacokinetic and pharmacodynamic, that contribute to variable dmg responses in the elderly. These responses are not seen for every class of dmg. Thus, the depressant effects of the glycosides also appear to increase with aging (116,117). 

Medications that have been used as treatment for anxiety and depression in the postwithdrawal state include antidepressants, benzodia2epines and other anxiolytics, antipsychotics, and lithium. In general, the indications for use of these medications in alcoholic patients are similar to those for use in nonalcoholic patients with psychiatric illness. However, following careful differential diagnosis, the choice of medications should take into account the increased potential for adverse effects when the medications are prescribed to alcoholic patients. For example, adverse effects can result from pharmacodynamic interactions with medical disorders commonly present in alcoholic patients, as well as from pharmacokinetic interactions with medications prescribed to treat these disorders (Sullivan and O Connor 2004). 

Drug interactions with the BZs are generally pharmacodynamic or pharmacokinetic (Table 68-11). The combination of BZs with alcohol or other CNS depressants may be fatal. 

The l.d. of a typical fluoroacetate varies considerably from species to species moreover, the pharmacodynamic action of the material is very varied. The main point of attack may be the central nervous system or the heart or sometimes both. Death can result from (i) respiratory arrest after convulsions, (ii) cardiac failure or ventricular fibrillation, or (iii) gradual depression... 

Pharmacodynamic Interactions. Sometimes medications interact pharmacody-namically. If two medications produce similar side effects, then those effects can be additive. This can be advantageous. For examples, coadministering two antidepressants that relieve depression in different ways can be more effective than either medication alone. However, added effects can be problematic. If two medications that each produce drowsiness are coadministered, then the combination may produce intolerable daytime sedation. 

There are some clinically important pharmacodynamic drug-drug interactions to be mentioned. Antipsychotics will potentiate the central depressant effects of sedatives and of alcohol. They will also increase the risk of respiratory-depressant effects of opiates. Inducers of drug metabolic enzymes like for example rifampicin and several antiepileptics, may increase the elimination rate of antipsychotic agents and thus decrease their efficacy. 

In normal subjects the tricyclics only show anticholinergic and sedative activity but have no mood elevating action. In depressed subjects their mood elevating effect has a delay of 2-3 weeks. The reasons for this delay are unknown and could be both pharmacokinetic or pharmacodynamic in natme. 

Murdoch D. and D. McTavish (1992). Sertraline A review of its pharmacodynamic properties and therapeutic potential in depression and obsessive compulsive disorder. Drugs 44 604-624. 

Less effective compared to morphine, but less respiratory depression and opposite cardiovascular pharmacodynamics increases pulmonary, arterial, and central venous pressure... 

Asberg M Treatment of depression with tricyclic drugs— pharmacokinetic and pharmacodynamic aspects. Pharmakopsychiatrie Neuro-Psychopharmakologie 9[l) 18-26, 1976... 

Benca RM, Obermeyer WH, Thisted RA, et al Sleep and psychiatric disorders a metaanalysis. Arch Gen Psychiatry 49 651-668, 1992 Benfield P, Ward A Fluvoxamine a review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in depressive illness. Drugs 32 313-334, 1986... 

In pharmacodynamic interactions, the pharmacological effect of a drug is changed by the action of a second drug at a common receptor or bioactive site. For example, low-potency antipsychotics and tertiary amine TCAs have anticholinergic, antihistaminic, a-adrenergic antagonist, and quinidine-Kke effects. Therefore, concurrent administration of chlorpromazine and imipramine results in additive sedation, constipation, postural hypotension, and depression of cardiac conduction. 

Research on drug interactions with zolpidem and zaleplon is limited, but any drug with CNS depressant effects could potentially enhance the CNS depressant effects of zolpidem and zaleplon through pharmacodynamic interactions. In addition, zolpidem is primarily metabolized by CYP 3A3/4, and zaleplon is partially metabolized by CYP 3A3/4. Thus, inhibitors of these enzymes may increase blood levels and the toxicity of zolpidem. 

Charles HC, Lazeyras, AQ Krishnan KRR, et al. Brain choline in depression in vivo detection of potential pharmacodynamic effects of antidepressant therapy using hydrogen localized spectroscopy. Prog Neuropsychopharmacol Biol Psychiatry 1994 18 1121 -1127. 

The recovering patient who remains depressed after appropriate treatment of the abstinence syndrome should be given an antidepressant trial. Treatment planning should take into account the patient s physical status, especially because it may affect the pharmacokinetics and pharmacodynamics of the agent selected (see Chapter 3). 

MAOIs have the most serious pharmacodynamic interactions of any antidepressant class. As discussed earlier, they can cause a hypertensive crisis and the serotonin syndrome. They potentiate the hypertensive effects of most sympathomimetic amines, as well as tyramine, which is the reason for the avoidance of over-the-counter preparations containing such agents, in addition to the tyramine-free diet ( 508, 509). The serotonin syndrome occurs most often when MAOIs are used in combination with SSRIs and venlafaxine but it can also occur when MAOIs are used with tryptophan, 5-hydroxytryptophan, and some narcotic analgesics. In addition, MAOIs can also significantly potentiate the sedative and respiratory depressant effects of narcotic analgesics. 

The similar pharmacological profile of selective serotonin reuptake inhibitors and St. John s wort would suggest the potential of a pharmacodynamic interaction due to an additive effect. A case of concurrent use of sertraline and St. John s wort, resulting in mania, was reported for a patient with a history of depression who was prescribed sertraline and who also took St. John s wort against medical advice (58). A similar potentiation of serotonergic effect was reported by Gordon (49). 

Pharmacodynamic interactions are also of great clinical significance. The additive CNS depression that occurs when alcohol is combined with other CNS depressants, particularly sedative-hypnotics, is most important. Alcohol also potentiates the pharmacologic effects of many nonsedative drugs, including vasodilators and oral hypoglycemic agents. 

Pharmacodynamics considers the sites, modes, and mechanisms of action of drugs. For example, if a patient with multiple fractures receives a subcutaneous injection of 10 to 15 mg of morphine sulfate (Papaver somniferum, Chapter 47), analgesia, sedation, respiratory depression, emesis, miosis, suppression of the gastrointestinal tract, and oliguria may ensue. These diversified effects occur at multiple peripheral and central sites through the action of numerous modes and mechanisms. 

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