residences. Such trials are desperately needed to determine the long-term safety and

efficacy of medications to be used in frail and older persons (Tolson et al. 2011).

15.13 Discussion

There are three groups of populations who are most sensitive to ADRs: the pregnant

mothers, the children, and the elderly. In this review, we have concentrated on drug

dose adjustment in the geriatric population group in which susceptibility to drugs

does not depend only on the age but also on comorbidities and concomitant

medications as well as the socioeconomic conditions. As highlighted in Fig. 15.1,

physiological age-dependent changes occur in GFR and other body organs such as

liver and GI tract. Elderly subjects, in comparison with their younger counterparts,

are more susceptible to drug-mediated changes due to reduction in CYP450

isozymes activity. Drug-induced side-effects and ADRs are mostly related to chronic

illnesses and polypharmacy.

We have described several examples in this review to illustrate changes in ADME

as well as in the PK and PD parameters in frail and older persons. Detailed

description has been given in the field of antidepressant drugs and the precautions

to be taken while prescribing antipsychotic therapy and monitoring of adverse events

in

elderly

and

frail

patients.

It

should

be

mentioned

that

individual’s

pharmacogenetics make-up sometimes overrides the framework based on general

population of elderly patients. For instance, the prevalence of CYP 2D6 polymor-

phism is different in ethnic populations: “fast and slow metabolizer” genotype in

Europe is around 5–10%, whereas in South-East Asians it may reach as high as 20%.

Consequently, this pharmacogenetics factor can potentially influence the metabo-

lism of CYP2D6 substrates. Further, the polymorphism of ABCB1 transporters

indicating allele variations (e.g., in C1236T: 34–42% in Caucasians; and 60–72%

in Asians) make pharmacokinetics variations in the metabolic disposition of certain

groups of xenobiotics or endogenous compounds (Lam and Scott 2019).

Pharmacogenetics can strongly influence the predisposition fate of several antide-

pressant drugs and alter the PK and PD values these drugs. In order to minimize any

adverse events, the dosing schedule of antidepressants should be individualized,

Table 15.3 (continued)

Reference

Drug combination

Potential consequences

PK/PD and mechanistic interactions

van der Lee et al.

(2007)

Antiretrovirals (ritonavir,

fosamprenavir) + paroxetine

Antiretroviral compounds reduce

total paroxetine exposure by 55%

due to the inhibition of CYP2D6

isoenzyme

Gärtner et al. (2010)

SSRI + acetylsalicylic acid,

clopidogrel

SSRIs increase the risk of post-

operative bleeding due to the

action on platelets’ cell membrane

serotonin transporters

262

M. Bhaskar et al.