Introduction to the course Clinical Pharmacy

Clinical Pharmacy - a Definition It is a health specialty, which describes the activities and

services of the clinical pharmacist to develop and promote the rational and appropriate use of medicinal products and devices.

Clinical Pharmacy includes all the services performed by pharmacists practising in hospitals, community pharmacies, nursing homes, home-based care services, clinics and any other setting where medicines are prescribed and used.

The term "clinical" does not necessarily imply an activity implemented in a hospital setting. It describes that the type of activity is related to the health of the patient(s). This implies that community pharmacists and hospital pharmacists both can perform clinical pharmacy activities.

How does clinical pharmacy differ from pharmacy?

the discipline of pharmacy embraces the knowledge on synthesis, chemistry and preparation of drugs

clinical pharmacy is more oriented to the analysis of population needs with regards to medicines, ways of administration, patterns of use and drugs effects on the patients.

The focus of attention moves from the drug to the single patient or population receiving drugs.

Clinical Pharmacy - Overall GoalThe overall goal of clinical pharmacy activities is

to promote the correct and appropriate use of medicinal products and devices. These activities aim at:

maximising the clinical effect of medicines, i.e., using the most effective treatment for each type of patient

minimising the risk of treatment-induced adverse events, i.e., monitoring the therapy course and the patient's compliance with therapy

minimising the expenditures for pharmacological treatments born by the national health systems and by the patients, i.e., trying to provide the best treatment alternative for the greatest number of patients.

Clinical pharmacy activities may influence the correct use of medicines at three different levels: before, during and after the prescription is written.

1. Before the prescription Clinical trials Formularies Drug information Clinical pharmacists have the potential to implement and

influence drug-related policies, i.e., making decisions on which drugs deserve to be marketed, which drugs should be included in national and local formularies, which prescribing policies and treatment guidelines should be implemented.

Clinical pharmacists are also actively involved in clinical trials at different levels: participating in ethical committees; study monitoring; dispensation and preparation of investigational drugs.

2. During the prescription Counselling activity Clinical pharmacists can influence the

attitudes and priorities of prescribers in their choice of correct treatments.

The clinical pharmacist monitors, detects and prevents harmful drug interaction, adverse reactions ad medication errors through evaluation of prescriptions' profiles.

The clinical pharmacist pays special attention to the dosage of drugs which need therapeutic monitoring.

Community pharmacists can also make prescription decisions directly, when over the counter drugs are counselled.

3. After the prescription Counselling Preparation of personalised formulation Drug use evaluation Outcome research Pharmacoeconomic studies After the prescription is written, clinical pharmacists play

a key role in communicating and counselling patients. Pharmacists can improve patients' awareness of their

treatments, monitor treatment response, check and improve patients' compliance with their medications.

As members of a multidisciplinary team, clinical pharmacists also provide integrated care from 'hospital to community' and vice versa, assuring a continuity of information on risks and benefits of drug therapy.

Pharmacology is the study of drugs (chemicals) that alterfunctions of living organisms.

CLINICAL PHARMACOLOGY is the use of drugs to prevent, diagnose, or

treat signs, symptoms, and disease processes. When prevention

or cure is not a reasonable goal, relief of symptoms cangreatly improve quality of life and ability to function in

activitiesof daily living.

Drugs given for therapeutic purposes

are usually called medications.

Medications may be given for various reasons. In manyinstances, the goal of drug therapy is to lessen diseaseprocesses rather than cure them. To meet this goal, drugsmay be given for local or systemic effects.

Drugs with local effects, such as sunscreen lotions and local anesthetics, act mainly at the site of application. Those with systemic effects are taken into the body, circulated through the bloodstreamto their sites of action in various body tissues, and eventuallyeliminated from the body. Most drugs are given for their systemic effects. Drugs may also be given for relatively immediate effects (eg, in acute problems such as pain or infection) or long-term effects (eg, to relieve signs and symptoms of chronic disorders). Many drugs are given for their long-term effects.

DRUG NAMES

Individual drugs may have several different names, but thetwo most commonly used are the generic name and the trade

name (also called the brand or proprietary name). The genericname (eg, amoxicillin) is related to the chemical or official

name and is independent of the manufacturer. The genericname often indicates the drug group (eg, drugs with

genericnames ending in “cillin” are penicillins). The trade

name isdesignated and patented by the manufacturer. For example,

amoxicillin is manufactured by several pharmaceutical companies,some of which assign a specific trade name (eg,

Amoxil, Trimox) and several of which use only the genericname. In drug literature, trade names are capitalized and

generic names are lowercase unless in a list or at the beginningof a sentence. Drugs may be prescribed and dispensed by

generic or trade name.

Amoxicillin

Metronidazole

Ranitidin

Testing and Clinical TrialsThe testing process begins with animal studies to determine

potential uses and effects. The next step involves FDA reviewof the data obtained in the animal studies. The drug then

undergoes clinical trials in humans. Most clinical trials use arandomized, controlled experimental design that involves

selectionof subjects according to established criteria, randomassignment of subjects to experimental groups, and

administrationof the test drug to one group and a control substance

to another group.

PHARMACOKINETICS

Pharmacokinetics involves drug movement through the body

(ie, “what the body does to the drug”) to reach sites of action,

metabolism, and excretion. Specific processes are absorption, distribution, metabolism (biotransformation), and

excretion.Overall, these processes largely determine serum drug levels,

onset, peak and duration of drug actions, drug half-life, therapeuticand adverse drug effects, and other important aspects

of drug therapy.

PHARMACODYNAMICS

Pharmacodynamics involves drug actions on target cells and

the resulting alterations in cellular biochemical reactions and

functions (ie, “what the drug does to the body”). As previously

stated, all drug actions occur at the cellular level.

. ENTRY AND MOVEMENT OF DRUG MOLECULES

THROUGH THE BODYTO SITES OF ACTION, METABOLISM, AND

EXCRETION

ABSORPTION is the process that occurs from the time a drug entersthe body to the time it enters the bloodstream to be circulated.Onset of drug action is largely determined by the rateof absorption; intensity is determined by the extent of absorption.

Numerous factors affect the rate and extent of drugabsorption, including -dosage form, -route of administration,-blood flow to the site of administration, -GI function,

-the presence of food or other drugs, and other variables. Dosage form

is a major determinant of a drug’s bioavailability (the portionof a dose that reaches the systemic circulation and is availableto act on body cells). An intravenous drug is virtually100% bioavailable; an oral drug is virtually always less than100% bioavailable because some is not absorbed from the GItract and some goes to the liver and is partially metabolizedbefore reaching the systemic circulation.

Most oral drugs must be swallowed, dissolved in gastric

fluid, and delivered to the small intestine (which has a large

surface area for absorption of nutrients and drugs) before they

are absorbed. Liquid medications are absorbed faster than

tablets or capsules because they need not be dissolved.

Drugs injected into subcutaneous (SC) or intramuscular

IM) tissues are usually absorbed more rapidly than oral

drugs because they move directly from the injection site to

the bloodstream. Absorption is rapid from IM sites because

muscle tissue has an abundant blood supply. Drugs injected

intravenously (IV) do not need to be absorbed because they

are placed directly into the bloodstream.

Oral drugs

Some patients have difficulty swallowing tablets or capsules; some dislike the taste. In these cases, crushing of medication for powdered delivery (to be mixed with food or beverages) should be considered. But not all medications are suitable for crushing. Generally, meds that should not be crushed fall into one of these categories:

Drugs that should not be crushed

Sustained-release tablets, which can be composed of multiple layers for different drug release times, as can beads within capsules. Some of the more common prefixes or suffixes for sustained-release, controlled-release, controlled-delivery, extended-release, prolonged-release, slow-release products include: 12-hour, 24-hour, CC, CD, CR, ER, LA, Retard, SA, Slo-, SR, XL, XR, or XT.

Enteric-coated tablets, which are formulated because certain drugs can be irritating to the stomach or are degraded by stomach acid. By enteric-coating tablets or capsule beads, the drug’s release can be delayed until it reaches the small intestine. Prefixes include EN- and EC-.

Sustained-release tablets Advantages

Extended-release products offer 3 potential benefits:

sustained blood levelsattenuation of adverse effectsimproved patient compliance.

Sustained blood levels

The size and frequency of dosing is determined by the pharmacodynamic and pharmacokinetic properties of the drug. The slower the rate of absorption, the less the blood concentrations fluctuate within a dosing interval. This enables higher doses to be given less frequently. For drugs with relatively short half-lives, the use of extended-release products may maintain therapeutic concentrations over prolonged periods

Attenuation of adverse effects

With conventional dosage forms, high peak blood concentrations may be reached soon after administration with possible adverse effects related to the transiently high concentration. An example is hypotension in patients taking rapid-release nifedipine products. The use of an extended-release product avoids the high initial blood concentrations which cause the sudden reduction in blood pressure and other significant haemodynamic changes such as reflex tachycardia.1,2 Another example is the transient nausea at sub-toxic concentrations which results from the local irritation caused by high intestinal concentrations of some conventional-release products such as theophylline.

Improved patient compliance

Drugs with short half-lives often need to be given at frequent intervals to maintain blood concentrations within the therapeutic range. There is an inverse correlation between the frequency of dosing and patient compliance. A reduction in the number of daily doses offered by extended-release products has the potential to improve compliance.3 However, this advantage probably only occurs when conventional formulations need to be given 3 or more times a day.

Sustained-release tablets Disadvantages

For many controlled-release products, the release rate can be altered by various factors including food and the rate of transit through the gut. There may be some differences in the release rate from one dose to another, but these have been minimised by modern formulations.

Extended-release products contain a higher drug load and thus any loss of integrity of the release characteristics of the dosage form has potential problems. While some extended-release products can be divided to provide half-doses, others should only be taken whole. Modified-release products should never be crushed or chewed as the slow-release characteristics may be lost and toxicity may result. This is particularly important in patients unable to swallow whole tablets, a problem commonly affecting the elderly. The larger size of extended-release products may cause difficulties in ingestion or transit through the gut. These problems may result in some drugs, e.g. Slow-K, causing local tissue damage in patients who have a pathological or drug-induced reduction in gut motility.

Oral drugs

Other medications have objectionable tastes and are sugar-coated to improve tolerability. If this type of medication is crushed, the patient would be subject to its unpleasant taste, which could significantly impair medication adherence. Additionally, both sublingual and effervescent medications should not be crushed because it will decrease the medication’s effectiveness.

Drug transport pathways. Drug molecules cross cellmembranes to move into and out of body cells by directly

penetratingthe lipid layer, diffusing through open or gated channels,

or attaching to carrier proteins.

Plasma proteins, mainly albumin (A), act as carriers for

drug molecules (D). Bound drug (A–D) stays in bloodstream and is

pharmacologically inactive. Free drug (D) can leave the bloodstreamand act on body cells.

THE LIVER IS THE PRINCIPAL ORGAN OF DRUG

METABOLISM. Other tissues that display considerable activity include the gastrointestinal tract, the lungs, the skin, and the kidneys. Following oral administration, many drugs (eg, isoproterenol, meperidine, pentazocine, morphine) are absorbed intact from the small intestine and transported first via the portal system to the liver, where they undergo extensive metabolism. This process has been called a first-pass effect. Some orally administered drugs (eg, clonazepam, chlorpromazine) are more extensively metabolized in the intestine than in the liver. Thus, intestinal metabolism may contribute to the overall first-pass effect. First-pass effects may so greatly limit the

bioavailability of orally administered drugs that alternative routes of administration must be used to achieve therapeutically effective blood levels.

Pharmacodynamic Variables Maximum Effect (аll pharmacologic responses must have a

maximum effect (Emax). No matter how high the drug concentration goes, a point will be reached beyond which no further increment in response is achieved.

Sensitivity (the sensitivity of the target organ to drug concentration is reflected by the concentration required to produce 50% of maximum effect, the EC50. Failure of response due to diminished sensitivity to the drug can be detected by measuring—in a patient who is not getting better—drug concentrations that are usually associated with therapeutic response. This may be a result of abnormal physiology—eg, hyperkalemia diminishes responsiveness to digoxin—or drug antagonism—eg, calcium channel blockers impair the inotropic response to digoxin.

Pharmacodynamic Variables (cont’d)

Clearance is the single most important factor determining drug concentrations.

Clearance is readily estimated from the dosing rate and mean steady-state concentration. Blood samples should be appropriately timed to estimate steady-state concentration.

SERUM HALF-LIFE

Serum half-life, also called elimination half-life, is the time

required for the serum concentration of a drug to decrease by

50%. It is determined primarily by the drug’s rates of metabolism

and excretion. A drug with a short half-life requiresmore frequent administration than one with a long half-life.When a drug is given at a stable dose, four or five halflives

are required to achieve steady-state concentrations and

develop equilibrium between tissue and serum concentrations. Because maximal therapeutic effects do not occur until

equilibrium is established, some drugs are not fully effective for

days or weeks. To maintain steady-state conditions, the amount

of drug given must equal the amount eliminated from the body.

When a drug dose is changed, an additional four to five halflives

are required to re-establish equilibrium; when a drug is discontinued,

it is eliminated gradually over several half-lives.

Вioavailability is defined as the fraction of a given drug dose that reaches the circulation in unchanged form and becomes available for systemic distribution. The larger the

presystemic elimination, the smaller is the bioavailability of an orally administered

drug.

Сеll membrane contains receptors for physiologic substances

such as hormones (H) and neurotransmitters (NT). These substances

stimulate or inhibit cellular function. Drug molecules (Da and Db)

also interact with receptors to stimulate or inhibit cellular function

Drug-Related Variables Dosage Route of Administration Drug–Diet Interactions Drug–Drug Interactions:

Increased Drug Effects (Additive effects, Synergism or

potentiation, Interference by one drug with the metabolism or elimination of a second drug, Displacement of one drug from plasma protein-binding sites by a second drug increases the effects

of the displaced drug) Decreased Drug Effects - Interactions in which drug

effects are decreased are grouped under the term antagonism (Example: naloxone (a narcotic antagonist) + morphine (a narcotic or opioid analgesic) >relief of opioidinduced respiratory depression. Naloxone molecules displace morphine molecules from their receptor sites on nerve cells in the brain so that the morphine molecules cannot continue to exert their depressant effects.

Agonists are drugs that produce

effects similar to those produced by naturally occurring

hormones, neurotransmitters, and other substances. Agonists

may accelerate or slow normal cellular processes,

depending on the type of receptor activated. For example,

epinephrine-like drugs act on the heart to increase

the heart rate, and acetylcholine-like drugs act

on the heart to slow the heart rate; both are agonists.

Antagonists are drugs that inhibit cell function by occupying

receptor sites. This prevents natural body substancesor other drugs from occupying the receptor

sites and activating cell functions. Once drug action occurs,

drug molecules may detach from receptor molecules(ie, the chemical binding is reversible), return to

the bloodstream, and circulate to the liver for metabolismand the kidneys for excretion.

Client-Related VariablesAgeBody WeightGenetic and Ethnic CharacteristicsGender (еxcept during pregnancy and

lactation, gender has been considered a minor influence on drug action).

Pathologic ConditionsPsychological Considerations

TOLERANCE AND CROSS-TOLERANCEDrug tolerance occurs when the body becomes accustomed

to a particular drug over time so that larger doses must be

given to produce the same effects. Tolerance may be acquired

to the pharmacologic action of many drugs, especially opioid

analgesics, alcohol, and other CNS depressants. Tolerance to

pharmacologically related drugs is called cross-tolerance.

For example, a person who regularly drinks large amounts of

alcohol becomes able to ingest even larger amounts before

becoming intoxicated—this is tolerance to alcohol. If the person

is then given sedative-type drugs or a general anesthetic,

larger-than-usual doses are required to produce a pharmacologic

effect—this is cross-tolerance.

Tolerance and cross-tolerance are usually attributed to activation

of drug-metabolizing enzymes in the liver, which accelerates

drug metabolism and excretion. They also are attributed

to decreased sensitivity or numbers of receptor sites.

ADVERSE EFFECTS OF DRUGSТhe term adverse effects refers to any undesired responses to drug administration, as opposed to therapeutic effects, which are desired

responses.

Some adverse effects occur with usual therapeutic doses

of drugs (often called side effects); others are more likely to

occur and to be more severe with high doses. CNS effects may result from CNS stimulation (eg, agitation,confusion,

delirium, disorientation, hallucinations,psychosis, seizures) or CNS depression (dizziness, drowsiness, impaired level of consciousness,sedation, coma, impaired respiration and circulation).

Gastrointestinal effects (anorexia, nausea, vomiting, constipation, diarrhea)

Hematologic effects (blood coagulation disorders, bleeding disorders, bone marrow depression, anemias, leukopenia, agranulocytosis, thrombocytopenia)

ADVERSE EFFECTS OF DRUGS Hepatotoxicity (hepatitis, liver dysfunction or failure, biliary tract

inflammation or obstruction) Nephrotoxicity (nephritis, renal insufficiency or failure) Hypersensitivity or allergy Drug fever Idiosyncrasy refers to an unexpected reaction to a drug that occurs the

first time it is given. Drug dependence Carcinogenicity is the ability of a substance to cause cancer. Teratogenicity is the ability of a substance to cause abnormal fetal

development when taken by pregnant women.

Drug toxicity (also called poisoning, overdose, or intoxication)results from excessive amounts of a drug and may

cause reversible or irreversible damage to body tissues.