Chapter 54 covers the topic of renal impairment. Through a short answer question format with topical MCQs for consolidation of learning, readers are brought through the management of psychiatric disorders in patients with renal impairment as a medical co-morbidity. Topics covered include the general principles of prescribing in patients with renal impairment, use of antipsychotics in renal impairment, use of antidepressants in renal impairment, use of mood stabilisers in renal impairment, use of sedatives in renal impairments, how haemodialysis affects the clearance of some psychotropics.

Chapter 53 covers the topic of hepatic impairment. Through a short answer question format with topical MCQs for consolidation of learning, readers are brought through the management of psychiatric disorders in patients with liver impairment as a medical co-morbidity. Topics covered include the general principles of prescribing in patients with liver impairment, use of antipsychotics in liver impairment, use of antidepressants in liver impairment, use of mood stabilisers in liver impairment, and use of sedatives in liver impairment.

This chapter covers the complex topics of pharmacokinetic and pharmacodynamics, core topics for anaesthetic exams and for practising anaesthetists. This includes route of drug administration, bioavailability, metabolism and elimination. We discuss one, two and three-compartment modelling for total intravenous anaesthesia including target-controlled infusion models. Pharmacodynamics covers drug-receptor interactions and their mechanism of action. This extends to drug isomerism, agonism and antagonism, and pharmacogenetics.

The addiction syndrome is quite similar across different addictive drug types, reflecting a shared pathway of pathological changes within motivational circuits that increasingly prioritize drug acquisition and use. This neurobiology, and drug addiction symptomatology, overlaps considerably with behavioral addictions (e.g., gambling disorder). However, addiction is distinct from symptoms and mechanisms underpinning intoxication and withdrawal, which are diverse and unique to each drug class. The intoxication phase is followed by some degree of withdrawal, manifesting clinically as opposite to intoxication, reflecting a homeostatic response to it. Withdrawal has a quality, duration, and dangerousness that depends on the individual, the drug type, and drug use history. Heavy/chronic patterns of use in addiction can produce longer, more severe withdrawal phases, but addiction and withdrawal can exist separately. How a drug acts upon different receptors and other downstream brain systems (pharmacodynamics) impacts the strength of its psychoactive (intoxicating) and motivational (addictive effects). Meanwhile, the route and rate of drug intake and its breakdown and elimination (pharmacokinetics) can also impact intoxication, withdrawal, and addiction risk. With addiction, the patient becomes tolerant (insensitive) to the intoxicating profiles of drugs they like, whereas their motivation, craving, and wanting to use the drug sensitizes (grows pathologically).

One of the core principles essential to an anesthesiologist’s fund of knowledge is that of general pharmacology. The aim of this chapter is to provide a foundation of key pharmacology principles necessary for the clinical application of anesthesia. The understanding of pharmacokinetics and pharmacodynamics is fundamental to maintaining anesthesia in a safe manner. This chapter will present basic pharmacological principles that govern anesthetic drug behavior, such as absorption, volume of distribution, clearance, metabolism, context sensitive half-time, extrahepatic modes of metabolism, and the impact of liver and renal dysfunction on anesthetic pharmacology.

Paediatric patients differ significantly from adults in the way that drugs affect them, for a number of reasons, including differences in their size, physiology and comorbidities. Developmental changes affecting the absorption, distribution, metabolism and excretion of many anaesthetic drugs, particularly during the first few months of life, profoundly affect both their pharmacokinetics and pharmacodynamics. Drugs discussed are the intravenous induction agents propofol, thiopental and ketamine; the sedatives dexmetetomidine and midazolam; and the opioids morphine, fentanyl and remifentanil, as well as muscle relaxants such as suxamethonium and non-depolarising relaxants. Inhalational anaesthetics are assessed for their usefulness in paediatric practice. Appropriate drug dosages are included and important differences from adult values emphasised.

The life expectancy for people with intellectual disability is increasing due to advances in medical treatment and social care. However, significant discrepancies in life expectancy between people with intellectual disability and the general population remain, and there continues to be scope to close the inequality gap. This was confirmed in the recent 2021 Learning Disability Mortality Review (LeDeR) report. The standardised mortality ratio for people with intellectual disability ranges from 2–5, which draws a comparison against the general population. Those with additional comorbidities such as epilepsy, genetic syndromes, and functional impairments have a lower age of death. The leading causes of death in older adults (at or over 65 years of age) between 2018 and 2021 were reviewed in the 2021 LeDeR report. In comparison to the general population, a higher proportion of deaths in older intellectual disability adults were due to COVID-19 (coronavirus disease), cancers, and influenza or pneumonia. Unsurprisingly, dementia (in particular Alzheimer’s disease), cerebrovascular disease, chronic lower respiratory tract infections, and diseases of the urinary system were more common causes of death in older intellectual disability compared to that reported in their younger counterparts. This chapter explores the various issues associated with medicating older people.

Pharmacogenomics is the study of genetic factors that influence drug response. Pharmacogenomics combines pharmacology and genomics to identify genetic predictors of variability in drug response that can be used to maximize drug efficacy while minimizing drug toxicity in order to tailor drug therapy for patients, thus improving patient care and reducing healthcare costs. In this chapter we review the field of pharmacogenomics in its current state and clinical practice. Recent research, methods, and resources for pharmacogenomics are reviewed in detail. We discuss the advantages and challenges in pharmacogenomic studies. We elaborate on the barriers to clinical translation of pharmacogenetic discoveries and the efforts of various institutions and consortia to mitigate these barriers. We also discuss applications and clinical translation of pharmacogenomic research moving forward, along with social, ethical, and economic issues that require attention. We conclude by previewing the use of big data, multi-omics data, advanced computing technology, and statistical methods by scientists across disciplinary boundaries along with the efforts of government organizations, clinicians, and patients that could lead to successful and clinically translatable pharmacogenomic discoveries, ushering in an era of precision medicine.

Cannabis produces its characteristic intoxicating effect through its actions with specific receptors in the brain. This chapter will explore what we know how about cannabis produces these effects. Since cannabis produces its effects by interacting with the endocannabinoid system, we will start with a brief consideration of the endocannabinoid system relevant to cannabis’ actions. This will be followed by a discussion of the primary psychoactive components of cannabis, their routes of administration, and pharmacokinetics. The next section will focus on how tetrahydrocannabinol interacts with CB1 cannabinoid receptors and how these interactions differ from endocannabinoid interactions with CB1 receptors. Finally, these results will be synthesized in a potential explanation on how cannabis works in the brain.

Safe and effective medication use in the elderly requires heightened awareness in comparison to other patient populations. The issues of increased sensitivity to drug effects, use of many medications to treat comorbidities, and a high incidence of medication nonadherence increase the need for due diligence in prescribing and monitoring drug therapy in this population. The employment of an interprofessional approach to patient care as well as the use of known methods for improving medication adherence are key to long-term success in the medical management of the elderly patient.

Phase 1 clinical trials are the entrance to the further clinical development of new compounds. The chapter describes the regulatory background and highlights most important issues about selection of the maximum recommended starting dose, dose escalation steps, and definition of maximum tolerated dose, or maximum applied dose in a study considering actual guidelines. There is an overview about selection of subject populations and frequently used trial designs. The principles of single-ascending-dose and multiple-ascending-dose tolerance studies are described with a few examples of studies in Alzheimer’s disease (AD). The safety assessment is important in clinical practice, as AD drugs will be used over many years, so excellent tolerability is a must! In Phase 1, a careful assessment of pharmacokinetic (PK) properties of a new compound forms the basis for dose selection in Phase 2 and 3 studies and supports the decision on the treatment regimen. The importance of inclusion of different biomarkers in these studies to allow assessment of pharmacodynamic and PK relationship and to potentially identify first signals in human studies indicating therapeutic usefulness in the indication.

There is a tremendous need for disease-modifying treatments for Alzheimer’s disease (AD). The pharmaceutical sector has expended considerable resources on AD drug discovery, yet to date have obtained regulatory approval for only one agent that slows AD progression. This has led to increased interest in identifying new AD drug targets and disease mechanisms. Academic laboratories can play a meaningful role in the validation of AD drug targets and the identification of molecular probes that modulate these targets. We discuss here how academic researchers can contribute to the AD drug discovery process. This includes examples of assays that have been used for AD small molecule screens within academic laboratories, and discussions on assay optimization for compound screening, the selection of molecular libraries, and the iterative process of compound optimization to identify molecules suitable for advancement to in vivo pharmacokinetic, safety, and efficacy testing. Finally, we outline how academic researchers might work with pharmaceutical partners in AD drug discovery, and note the pros and cons of such collaborations.

There are many challenges of proper drug dosing with nanodelivery systems. The first part of this discussion concerns how experts think about drug dosing with conventional drugs. In the second part, we need to consider the differences between nanodevices and traditional drug delivery, and pharmacokinetics using nanodrug delivery. Drug dosing uses scale-up methods from animal model data before testing on humans. New organ-on-a-chip and human-on-a-chip technologies may someday replace animal data.