Clinical Pharmacy and Pharmaceutical Care

Clinical pharmacy is the branch of pharmacy that integrates knowledge of medicines, disease processes, and patient-specific factors to optimise drug therapy and achieve definite outcomes that improve patients’ quality of life. Pharmaceutical care is the responsible provision of drug therapy for the purpose of achieving definite outcomes that improve patients’ quality of life. Together, these disciplines represent the shift of pharmacy from a product-centred to a patient-centred profession — a transition that is central to modern pharmacy practice in South Africa and worldwide.

The SAPC examination tests candidates on pharmaceutical care principles, drug therapy problem identification and resolution, therapeutic drug monitoring, clinical pharmacokinetics, and the pharmacist’s role in the multidisciplinary healthcare team. This topic builds directly on pharmacokinetics (pharma-003 through pharma-007) and pharmacodynamics (pharma-006), and connects to drug interactions (pharma-008) and adverse drug reactions (pharma-009).

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Pharmaceutical Care: The Hepler and Strand Model

The concept of pharmaceutical care was formalised by Hepler and Strand in 1990. It represents the philosophy that pharmacists have a responsibility to patients for resolving or preventing drug-related problems (DRPs) and achieving therapeutic goals.

Drug-Related Problems (DRPs)

DRPs are events or circumstances involving drug therapy that actually or potentially interfere with desired health outcomes. Categories of DRPs:

1. Indication without drug therapy — patient has a medical condition requiring drug therapy but is not receiving it
2. Inappropriate drug selection — wrong drug for condition, contraindicated, or not optimal for this patient
3. Suboptimal dose — dose too low or too high; incorrect dosing interval
4. Drug interactions — actual or potential interaction that may reduce efficacy or cause toxicity
5. Adverse drug reactions — actual or potential ADRs
6. Compliance/adherence problems — patient does not take drug as prescribed
7. Drug use without adequate indication — unnecessary drug therapy
8. Duplication therapy — multiple drugs from same class without added benefit
9. Laboratory monitoring needed — TDM or other monitoring required but not performed
10. Needs lifestyle modification — non-pharmacological measures required alongside drug therapy

The Pharmaceutical Care Process

The pharmaceutical care process consists of three main steps:

Step 1: Assessment

Gather patient information:

• Demographic data (age, weight, gender, race)
• Medical history (current and past diagnoses)
• Current medications (prescribed, OTC, traditional, herbal)
• Allergies and adverse drug reactions
• Social history (alcohol, tobacco, recreational drugs)
• Laboratory data (renal function, liver function, haematology)
• Clinical findings (BP, HR, temperature, oxygen saturation)
• Immunisation status
• Pregnancy/lactation status

Conduct a comprehensive medication review:

• Identify all actual and potential DRPs
• Assess the rationale for each medication
• Evaluate the therapeutic plan
• Identify gaps in therapy (undertreated conditions)

Step 2: Care Plan

Develop a plan for each DRP:

• For indication without drug therapy: recommend appropriate drug initiation
• For suboptimal dose: recommend dose adjustment
• For adverse reactions: suggest alternative therapy, dose reduction, or additional therapy to manage the ADR
• For interactions: suggest alternative therapy, dose adjustment, or enhanced monitoring
• For adherence problems: address barriers (cost, side effects, complexity, understanding); consider simplification strategies
• For compliance: patient education, reminder systems, blister packs

Set therapeutic goals:

• Specific, measurable, achievable, relevant, time-bound (SMART) goals
• Example: “Reduce BP to <140/90 mmHg within 3 months” rather than just “treat hypertension”

Step 3: Follow-up and Evaluation

Monitor outcomes:

• Clinical endpoints (BP reduction, pain score, HbA1c)
• Laboratory parameters (LFTs, renal function, drug levels)
• Patient-reported outcomes (symptom improvement, quality of life)
• Adverse effects

Document and communicate:

• Document interventions in patient record
• Communicate recommendations to prescriber where appropriate
• Arrange follow-up appointments
• Ensure continuity of care across transitions (hospital admission/discharge, clinic visits)

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Clinical Pharmacokinetics

Clinical pharmacokinetics is the application of pharmacokinetic principles to individualise drug dosing for specific patient populations. The SAPC examination frequently tests calculation-based pharmacokinetics.

Key Parameters for Individualised Dosing

Half-Life (t½)

The time required for the plasma concentration to decrease by 50%. For a drug following first-order kinetics:

t½ = 0.693 / Ke

Where Ke is the elimination rate constant.

Clinical utility:

• After 4–5 half-lives, steady state is essentially achieved (>90%)
• After 4–5 half-lives, drug is >90% eliminated after cessation of therapy
• Half-life determines dosing frequency

Factors affecting half-life:

Parameter	Effect on Half-life
↑ Clearance (Cl)	↓ Half-life
↑ Volume of distribution (Vd)	↑ Half-life
Zero-order elimination	Half-life is dose-dependent
Non-linear kinetics	Half-life changes with concentration

Volume of Distribution (Vd)

Apparent volume in which the drug distributes. Not a real volume — it is a proportionality constant relating the amount of drug in the body to the plasma concentration:

Vd = Amount of drug in body / Plasma concentration

Clinical interpretation of Vd:

• Vd > total body water (~42 L in 70 kg adult): drug extensively tissue-bound
• Vd close to plasma volume (~3 L): drug remains primarily in plasma
• Vd of 5–10 L: drug distributes in extracellular fluid
• Vd of 40–60 L: drug distributes in total body water
• Vd > 100 L: extensive tissue binding (e.g., amiodarone Vd ~5000 L)

Examples:

Drug	Vd (approx.)	Interpretation
Warfarin	10 L	Highly protein-bound; remains in plasma
Gentamicin	15–20 L	Extracellular fluid distribution
Diazepam	70–100 L	Highly lipophilic; tissue distribution
Amiodarone	5000 L	Extreme tissue binding
Digoxin	500–700 L	Binds to Na⁺/K⁺-ATPase; high tissue binding

Clearance (Cl)

Volume of blood cleared of drug per unit time (mL/min or L/h):

Cl = Ke × Vd

Total body clearance = renal clearance + hepatic clearance + other clearance

For dosing adjustments:

• Renal impairment: Adjust doses of drugs with predominant renal elimination (e.g., aminoglycosides, vancomycin, digoxin, many β-lactams)
• Hepatic impairment: Adjust doses of drugs with predominant hepatic elimination (e.g., midazolam, morphine, warfarin, statins)

Loading Dose

A loading dose rapidly achieves therapeutic plasma concentrations:

Loading Dose = Vd × Target Concentration / Bioavailability (F)

When to use loading doses:

• Drug with long half-life (e.g., amiodarone t½ ~50 days; loading achieves effect faster)
• Need for immediate effect (e.g., digoxin loading in atrial fibrillation)
• Drug where maintenance dosing alone would take too long to reach steady state

Example: Warfarin loading (4–5 mg) achieves anticoagulation faster than 3–5 mg maintenance alone.

Maintenance Dose

Maintenance Dose = Clearance × Target Concentration / Bioavailability (F)

Or expressed per dosing interval: Maintenance Dose = (Cl × Cssavg × τ) / F

Where τ = dosing interval.

Drugs Requiring Individualised Dosing

Aminoglycosides (Gentamicin, Amikacin)

Why narrow therapeutic index: Toxicity (nephrotoxicity, ototoxicity) closely related to peak and trough levels.

Traditional dosing (multiple daily dosing):

• Peak level: ~5–10 mg/L for gentamicin (drawn 30 min after IM/IV infusion end)
• Trough level: <2 mg/L (drawn immediately before next dose)
• Target peak/MIC ratio >8–10 for Gram-negative infections

Once-daily dosing (extended interval):

• 5–7 mg/kg gentamicin IV daily (actual body weight or adjusted body weight for obese patients)
• Draw level 6–14 hours after dose; use Hartford nomogram or Makinnon formula to calculate dosing interval

Dosing in renal impairment:

• Reduce dose or extend interval
• Monitor serum creatinine and drug levels

SAHPRA note: Gentamicin and amikacin are registered in South Africa; availability in public sector may be limited; amikacin reserved for serious Gram-negative infections resistant to gentamicin.

Vancomycin

Why narrow TI: Nephrotoxicity and ototoxicity; target trough levels for efficacy in serious Gram-positive infections.

Dosing (traditional):

• 15–20 mg/kg loading dose IV (actual body weight)
• Maintenance 15–20 mg/kg IV every 8–12 hours (adjusted for renal function)
• Target trough: 10–15 mg/L for serious infections (MRSA meningitis, endocarditis); 5–10 mg/L for less severe infections
• Peak levels rarely monitored now; trough is the key parameter

Monitoring: Serum vancomycin levels (trough immediately before next dose); serum creatinine (weekly or more frequently if renal function unstable)

Dosing in renal impairment: Significantly extended; use Cockcroft-Gault to estimate CrCl and adjust dose.

Phenytoin

Why narrow TI: Non-linear (Michaelis-Menten) pharmacokinetics at therapeutic concentrations.

Saturation kinetics: At therapeutic concentrations, the enzymes responsible for phenytoin metabolism become saturated. Small increases in dose produce disproportionate increases in serum concentration and risk of toxicity.

Michaelis-Menten kinetics:

• Vmax = maximum rate of metabolism (mg/day)
• Km = concentration at which metabolism is half-maximal (mg/L)
• At steady state:Css = Km × Cl / Vmax

Target range: 10–20 mg/L (total); free (unbound) phenytoin more accurate in hypoalbuminaemia (target 1–2 mg/L free)

Protein binding: Phenytoin is 90% protein-bound. In hypoalbuminaemia (elderly, liver disease, nephrotic syndrome), free phenytoin is elevated even if total phenytoin appears “therapeutic.” Monitor free phenytoin in these patients.

Dosing adjustments in renal failure: Not significantly altered, but protein binding is reduced; monitor free phenytoin.

Example phenytoin calculation for SAPC: A patient is on phenytoin 300 mg/day and has a serum level of 18 mg/L. The phenytoin is in the upper therapeutic range. The patient experiences drowsiness (a sign of toxicity). Km for phenytoin is approximately 4 mg/L. Calculate whether dose reduction is appropriate.

Using the Michaelis-Menten relationship for maintenance dosing: Dose at steady state is approximately proportional to Css within the therapeutic range when Css is near Km. If Css is above target (10–20 mg/L), a modest dose reduction would reduce Css substantially because the enzyme is nearly saturated.

Digoxin

Why narrow TI: Toxicity can occur at concentrations close to therapeutic range; toxicity is dose-related and exacerbated by hypokalaemia, renal impairment, drug interactions.

Target range: 0.5–2.0 ng/mL (0.9–2.6 nmol/L) for heart failure/atrial fibrillation

Dosing:

• Loading: 0.5–1.0 mg IV/PO in divided doses over 24 hours (digitalising dose)
• Maintenance: 0.0625–0.5 mg/day depending on renal function, lean body mass, and concurrent medications

Factors increasing digoxin levels:

• Renal impairment (digoxin cleared renally; half-life ~36 hours in normal renal function, up to 4–5 days in anuria)
• Amiodarone, quinidine (now withdrawn), verapamil, dronedarone — inhibit P-gp → ↑ digoxin levels
• Hypokalaemia, hypomagnesemia — predispose to digoxin toxicity
• Hypothyroidism — ↑ sensitivity to digoxin

Factors decreasing digoxin levels:

• Rifampicin, phenytoin, carbamazepine — induce P-gp → ↓ digoxin levels

Monitoring: Serum digoxin (trough, at least 6–8 hours post-dose); ECG (signs of toxicity: PAT, AV block, premature ventricular contractions); electrolytes (K⁺, Mg²⁺, Ca²⁺)

Creatinine Clearance Estimation

Creatinine clearance (CrCl) is used to estimate renal function for drug dosing adjustments. The Cockcroft-Gault equation is most commonly used:

Cockcroft-Gault Equation:

CrCl (mL/min) = [(140 − age in years) × weight (kg)] / [72 × serum creatinine (mg/dL)]

For females, multiply by 0.85.

Limitations:

• Less accurate at extremes of renal function (very low or high)
• Weight should be ideal body weight (IBW) for obese patients:
  • IBW (male) = 50 + 2.3 × (height in inches − 60)
  • IBW (female) = 45.5 + 2.3 × (height in inches − 60)
• For obese patients, use adjusted body weight (ABW) or calculated CrCl based on creatinine generation

CKD-EPI and MDRD equations are used for staging chronic kidney disease (CKD) by eGFR but are not ideal for drug dosing calculations (they normalise for body surface area).

Dosing adjustments by CrCl:

CrCl (mL/min)	Category	Drug Examples
>50	Normal	Most drugs at normal doses
30–50	Mild renal impairment	Reduce dose of some drugs
10–30	Moderate renal impairment	Significant dose reduction; avoid certain drugs
<10	Severe renal impairment (anauria)	Haemodialysis may be required for elimination
Haemodialysis	ESRD on dialysis	Dose after dialysis; consider drug removal by dialysis

Drugs requiring renal dose adjustment (examples):

• Aminoglycosides: dose reduction or extended interval
• Vancomycin: dose reduction; monitor trough
• Betalactams (many): dose reduction; some require extended interval
• Enoxaparin (LMWH): dose reduction in moderate renal impairment; avoid in severe
• Metformin: contraindicated in severe renal impairment (risk of lactic acidosis)
• Digoxin: dose reduction; monitor levels

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Therapeutic Drug Monitoring (TDM)

TDM is the clinical practice of measuring drug concentrations in biological fluids to optimise drug therapy. Not all drugs require TDM.

When TDM is Indicated

Narrow therapeutic index drugs:

• Phenytoin, carbamazepine, valproic acid (anticonvulsants)
• Digoxin, lidocaine, amiodarone (cardiovascular)
• Gentamicin, vancomycin, amikacin (antibiotics)
• Lithium (mood stabiliser)
• Warfarin (indirect INR monitoring; drug levels not routinely measured)

Non-linear pharmacokinetics:

• Phenytoin (saturation kinetics)
• Methotrexate (high-dose protocol)

Special populations:

• Neonates and infants (developmental pharmacokinetics differ)
• Elderly (altered Cl and Vd)
• Renal/hepatic impairment
• Obesity (altered Vd and Cl)
• Pregnancy (increased Vd and Cl; changing pharmacokinetics)

Difficult to monitor clinically:

• Drugs where clinical signs of toxicity are difficult to detect
• Drugs with long half-lives requiring loading doses
• Drugs with active metabolites contributing to effect

Interpreting Drug Levels

Scenario	Interpretation	Action
Subtherapeutic + poor response	Underdosing OR non-compliance OR increased metabolism	Increase dose; address compliance
Therapeutic + good response	Optimal therapy	Maintain; continue monitoring
Toxic + therapeutic	Narrow TI; individual sensitivity	Reduce dose; consider alternative
Toxic + supratherapeutic	Overdosing	Reduce dose immediately; supportive care

Note: TDM must always be interpreted in clinical context. The drug level is one piece of information among many.

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Drug Therapy Monitoring in Specific Conditions

Hypertension Management

Goal: BP control to <140/90 mmHg (general); <130/80 mmHg in high-risk patients (diabetes, CKD).

Monitoring parameters:

• BP (home monitoring recommended)
• Serum electrolytes, renal function (especially with ACE-I, ARBs, diuretics)
• Lipid profile (statins if indicated)
• Glucose (metabolic syndrome screening)

Common drug-specific monitoring:

Drug Class	Monitor
ACE-I/ARB	K⁺, creatinine (↑ K⁺; check for renal impairment)
Thiazides	K⁺, Na⁺, glucose, uric acid
β-blockers	HR, fasting glucose (can mask hypoglycaemia)
Calcium channel blockers	Peripheral oedema, flushing
Spironolactone	K⁺, renal function

Diabetes Management

Goal: HbA1c <7% (individualised; <6.5% in young patients, <8% in elderly/multimorbid).

Monitoring parameters:

• Fasting and postprandial blood glucose
• HbA1c (every 3 months if unstable, 6-monthly if stable)
• Foot examination (annually for sensation; more frequently if neuropathy)
• Retinal examination (annually)
• Renal function: eGFR, urine albumin:creatinine ratio (ACR) annually
• Lipid profile, BP

Drug-specific monitoring:

Drug	Monitor
Metformin	Renal function (creatinine or eGFR); B12 (long-term use)
Sulfonylureas	Hypoglycaemia (especially with renal impairment)
Insulin	Blood glucose; site rotation; lipodystrophy
SGLT2 inhibitors	Genital mycotic infections, eGFR, ketoacidosis
GLP-1 agonists	GI side effects; pancreatitis history

Anticoagulation

Warfarin monitoring:

• INR (target 2–3 for most indications; 2.5–3.5 for mechanical heart valve)
• INR point-of-care testing available in many SA pharmacies
• Patient self-testing and self-management (with training) improves outcomes
• Vitamin K intake consistency (leafy green vegetables)
• Drug interactions (CYP2C9 inhibitors and inducers)
• Bleeding risk assessment (HAS-BLED score)
• Stroke risk assessment (CHA₂DS₂-VASc score)

Heparin/LMWH monitoring:

• aPTT for unfractionated heparin (target 1.5–2.5 × control)
• Anti-Xa levels for LMWH (in renal impairment, obesity, pregnancy)
• Platelet count for HIT surveillance (monitor every 2–3 days)

DOACs (direct oral anticoagulants):

• Apixaban, rivaroxaban, dabigatran, edoxaban
• Do not require routine monitoring in most patients
• Specific monitoring: renal function (all DOACs), hepatic function (Child-Pugh B/C for some), adherence
• In South Africa, DOACs are registered but not always available in public sector (warfarin remains first-line)

Asthma/COPD

Inhaler technique assessment:

• Essential at every dispensing visit
• Check technique for MDI (with and without spacer), DPI, nebuliser
• Common errors: failure to shake, inadequate exhalation before inhalation, breath-holding <10 seconds, wrong sequence (reliever before preventer)

Monitoring parameters:

• Peak expiratory flow (PEF) — patient home monitoring
• FEV1, FVC (spirometry annually or as clinically indicated)
• Exacerbation frequency (marker of control)
• Inhaler adherence
• Corticosteroid side effects: oral thrush (rinse mouth after inhalation), hoarseness; systemic effects with high-dose/long-term use

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Clinical Pharmacy Services in South Africa

Hospital Pharmacy Services

Ward-based clinical pharmacy:

• Medication reconciliation on admission and discharge
• Participating in ward rounds (multidisciplinary team)
• Drug therapy problem identification and resolution
• TDM service
• IV additive service
• Nutrition support service (TPN formulation)
• Antimicrobial stewardship programme (ASP)

Antimicrobial stewardship (ASP): A core component of hospital clinical pharmacy. Objectives:

• Optimise antimicrobial selection, dose, and duration
• Reduce antimicrobial resistance
• Improve patient outcomes
• Reduce costs

South African context: The South African Antibiotic Stewardship Programme (SAABSP) and individual hospital ASPs promote appropriate antibiotic use. Pharmacists review antibiotic prescriptions, monitor cultures and sensitivities, suggest de-escalation based on culture results, and monitor for drug interactions and ADRs.

Primary Healthcare Pharmacy Services

CCMDD (Central Chronic Medicine Dispensing and Distribution): In South Africa, stable patients on chronic medication (HIV, TB, hypertension, diabetes, epilepsy) can collect their repeat medicines from external pickup points (pharmacies, clinics, community agents) rather than queuing at hospitals. Pharmacists and pharmacy assistants at these sites:

• Dispense and distribute chronic medicines
• Provide adherence counselling
• Monitor for ADRs and interactions
• Refer patients requiring clinical review

STGs (Standard Treatment Guidelines) and EML (Essential Medicines List): South Africa’s National Department of Health publishes STGs and EML for primary healthcare:

• STGs define evidence-based treatment algorithms for common conditions
• EML lists essential medicines that should be available at all levels of care
• Pharmacists must know the relevant STGs/EML for their practice setting
• Public sector: prescribers should follow STGs; deviation requires motivation

Key STGs for the SAPC exam:

• PHC STGs (adult and paediatric)
• Hospital level STGs (adult and paediatric)
• EML for each level

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Medication Adherence

Definitions

Compliance (or adherence): The degree to which a patient’s medication-taking behaviour corresponds with the agreed recommendations of the healthcare provider.

Persistence: The continuation of treatment for the prescribed duration.

Causes of Non-Adherence

Unintentional:

• Forgetfulness
• Physical barriers (difficulty swallowing, opening containers)
• Cognitive impairment
• Cost/cannot afford
• Limited health literacy

Intentional:

• Beliefs about medicines (side effects worse than disease)
• Stigma (especially with HIV, mental health)
• Mistrust of healthcare system
• Cultural or religious beliefs
• Concerns about dependency/addiction

Strategies to Improve Adherence

Strategy	Example
Simplify regimen	Once-daily dosing; combination tablets; fewer medicines
Patient education	Explain mechanism, benefits, expected side effects
Reminder systems	Alarms, calendars, pill organisers, smartphone apps
Telecommunication	SMS reminders (used in SA HIV adherence programmes)
Behavioural	Habit formation; link to daily routine activity
Address cost	Generic substitution; social support; CCMDD for chronic meds
Address beliefs	Motivational interviewing; shared decision-making
Involve family	Family counselling for chronic disease management
Blister packs	Week-at-a-time or month-at-a-time blister packs improve adherence

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SAPC Examination Focus Areas

High-yield topics for the SAPC exam:

1. Pharmaceutical care process — assessment, care plan, follow-up; three steps and DRP categories
2. Aminoglycoside TDM — peak/trough targets, once-daily dosing, nomogram use
3. Vancomycin TDM — trough targets 10–15 mg/L for serious infections
4. Phenytoin non-linear kinetics — Michaelis-Menten; effect of saturation
5. Digoxin toxicity — narrow TI, hypokalaemia as risk factor, P-gp inhibitors (amiodarone)
6. Creatinine clearance (Cockcroft-Gault) — calculation, dosing adjustments
7. Loading dose and maintenance dose calculations — including applications to specific drugs
8. STGs and EML — when to use and how they guide therapy in SA public sector
9. Antimicrobial stewardship — pharmacist role, de-escalation based on cultures
10. Adherence strategies — especially for HIV, TB, hypertension, diabetes in SA context
11. Drug therapy problem identification — categorisation of DRPs
12. Hypertension and diabetes monitoring — parameters and targets

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Summary of Key Concepts

• Pharmaceutical care involves identifying and resolving drug-related problems through a systematic process of assessment, care planning, and follow-up
• Clinical pharmacokinetics allows individualisation of dosing based on patient parameters (weight, renal function, hepatic function)
• Narrow TI drugs require TDM; interpretation requires clinical context
• Renal function is estimated by CrCl (Cockcroft-Gault); hepatic function assessed by Child-Pugh or albumin/INR
• The CCMDD programme and STGs/EML are key frameworks for pharmaceutical care in the South African public sector
• Medication adherence requires addressing both intentional and unintentional barriers
• Clinical pharmacists are integral members of the multidisciplinary team in both hospital and primary healthcare settings
• Antimicrobial stewardship is a core clinical pharmacy service with national importance in SA (high HIV/TB burden)