2. References
n Davidson’s Principle and Practice of Medicine 3rd
edition 2018
n Clinical Pharmacology and Therapeutics Fifth edition
edited by Roger Walker and Cate Whittlesea
n Cecil’s Essentials Of Medicine . 10th edition 2022
n Current Medical Diagnosis and Treatment 61th
edition2022
n Applied Therapeutics the clinical use of drugs 9th ed .
3. Drug use process (DUP)
indicators
n Indication for drug therapy
n Select drug consider most appropriate drug
based on the ability to reach therapeutic goals ,
consideration of patient variable and cost
n Regimen used
n Adminstration
n Moniter Drug therapy
n Evaluate effectiveness
4. Case presentation
n Mr Ahmed, a 67-year-old retired person, has recently moved to
your area and has come to the pharmacy to collect his first
prescription. He has a PMH of coronary heart disease (CHD) and
has recently had a coronary artery stent inserted. He has a long
history of asthma which is well controlled with inhaled medicines.
Mr Ahmed gives a complete medication history that indicates he
takes his medicines as prescribed, he has no medication-related
allergies,but does suffer from dyspepsia associated with acute use
of NSAIDs . H e has a summary of his stent procedure from the
hospital that indicates normal blood chemistry and liver function
tests.
n Consider drug use process?
5. What drug–patient, drug–disease and drug–
drug interactions can be anticipated ?
Drug–drug interactions
Drug–Disease interactions
Drug–patient
interactions
Medicines
Combination of
antiplatelet agents
increases risk of
bleeding
Aspirin should be
used with caution in
asthma
Previous history of
dyspepsia
Aspirin
Previous history of
dyspepsia
Clopidogrel
Possible increased risk
of myopathy if
simvastatin given with
diltiazem
Statins
Combination of
different agents to
control angina may
lead to hypotension
β-Blocker
contraindicated in
asthma
B blockers
Steroid inhalers
6. What drug–patient, drug–disease and drug–
drug interactions can be anticipated ?
Drug – drug interaction
Drugs – Disease
interaction
Drugs – Patient
interaction
Medicines
Reduces metabolism of
simvastatin thereby
increasing the risk of side
effects
Diltiazem
Previous history of side
effects (e.g.headache,
flushing) may result in
patient not using spray
when required
Nitrates (GTN
spray)
Patient's ability to use
inhaler deviceseffectively
β2-Agonist inhalers
Antimuscarinics may reduce
effect of S/L nitrate tablets
(failure to dissolve under tongue
owing to dry mouth)
Antimuscarinic agents
can cause tachycardia
and atrial fibrillation
Antimuscarinic
inhalers
7. The case of Mr Ahmed : monitoring
criteria and patient advice
Ask patient about any symptoms of dyspepsia or worsening asthma
Aspirin
Ask patient about any symptoms of dyspepsia
Clopidogrel
If PPIs don't resolve symptoms, primary care doctor should be
consulted
Lansoprazole
Liver function tests 3 months after any change in dose, or annually
Creatine kinase only if presenting with symptoms of unexplained
muscle pain Cholesterol levels 3 months after any change in dose,
or annually if at target
Simvastatin
Frequency of use to be noted. I ncreasing frequency that results in
a resolution of chest pain should be reported to primary care
doctor and anti-anginal therapy may be increased ANY use that
does not result in resolution of chest pain requires urgent medical
attention
Nitrates (GTN
spray)
Blood pressure and pulse monitored regularly
Diltiazem
8. The case of Mr Ahmed : monitoring
criteria and patient advice Contin.
Renal function and blood pressure monitored
within 2 weeks of any dose change, or annually
Ramipril
Drugs that may have been prescribed for asthma
Salbutamol use should be monitored as any
increase in requirements may require increase in
steroid dose
Salbutamol
inhaler
Monitor for oral candidiasis
Beclometasone
inhalers
9. The case of Mr Ahmed : possible
therapeutic regimen
Rational
Recommendation
Medicine
Benefit outweighs risk if used with PPI
75 mg daily orally o.d. after
food
Aspirin
Benefit outweighs risk if used with PPI
Length of course should be established in
relation to previous stent
75 mg daily orally o.d. after
food
Clopidogrel
Decreases risk of GI bleeds with
combination antiplatelets Concerns
about some PPIs reducing the
effectiveness of clopidogrel makes
selection of specific PPI important
15 mg daily orally
Lansoprazole
Low dose selected due to diltiazem
reducing the metabolism of simvastatin
and increasing the risk of side effect
20 mg daily orally
Simvastatin
2 puffs sprayed under the
tongue when required for
chest pain
Nitrates
10. The case of Mr Ahmed : possible
therapeutic regimen—cont'd
Rational
Recommendation
Medicine
Used for rate control as β-blockers
contraindicated in asthma
90 mg m/r twice a day
Diltiazem
To reduce the progression of CHD
and heart failure
10 mg daily
Ramipril
Patient should follow asthma
treatment plan if peak
flow decreases
puffs (200 μcg) to be
inhaled when required t
Salbutamol inhaler
Asthma treatment plan which may
include increasing the dose of
inhaled steroids if peak flow
decreases
2 puffs (400 μcg) twice
a
day
Beclometasone inhalers
CHD, coronary heart disease; PPI, proton pump inhibitor;
GI, gastro-intestinal; m/r, modified release.
11. Principle of clinical Pharmacy &
Therapeutics :
n Pharmacodynemic : what the drug does to the
body .
n Pharmacokinetic : what the body does to the
drug .
12. Pharmacodynamics
* Drug targets and mechanisms of action :
1 . Affinity : describes the propensity for a drug to bind to
a receptor
2 . Selectivity describes the propensity for a drug to bind to
one target rather than another .
3 . Agonists bind to a receptor to produce a
conformational change that is coupled to a biological
response
4 . Antagonists bind to a receptor but do not produce the
conformational change that initiates an intracellular
signal.
13. * The dose–response relationship varies between patients
because of variations in the many determinants of
pharmacokinetics and pharmacodynamics.
n Efficacy describes the extent to which a drug can
produce a target-specific response when all
available receptors or binding sites are occupied
n Potency describes the amount of drug required
for a given response.
* Therapeutic Index :The ratio of the ED50 for
therapeutic efficacy and for a major adverse
effect is known as the ‘therapeutic index’.
14. * Desensitization and withdrawal effects
n Desensitisation refers to the common situation in which the
biological response to a drug diminishes when it is given
continuously or repeatedly. It may be possible to restore the
response by increasing the dose of the drug but, in some cases, the
tissues may become completely refractory to its effect : examples
Tachyphylaxis , Tolerance , Drug resistance
n When drugs induce chemical, hormonal and physiological
changes that offset their actions, discontinuation may allow
these changes to cause ‘rebound’ withdrawal
effects ( alcohol, Barbiturates , Glucocorticoids ,
Opioids , SSRUI )
15. Pharmacokinetic : what the body does to the
drug .
n Drug absorption and routes of administration:
Enteral { Oral , Buccal , Intranasal , Sublingual (organic
Nitrates , Opiates and triptans for migrain ) , Rectal
PR .}
Parentral ( IV , IM , Subcutaneous SC , Transdermal
e .g . Oestrogens , Nitrates , nicotine )
Others ( Topical application: skin , eye , ear .
INHALED : airway
16. Pharmacokinetic : what the body
does to the drug .
n Drug distribution depends on molecular size , lipid solubility ,
plasma proteins binding and it’s susceptibility to transporters on
cell surface .
n VD = The size of the “compartment” into which a drug is distributed
following absorption and is determined by the equation:
Vd = Dose (mg) drug administered/Initial plasma concentration (mg/L)
Vd = D / Co ( Drugs that are highly bound to plasma proteins may
have Vd below 10 e.g. Warfarin and aspirin
17. Drug Elimination via
metabolism
phase I
Oxidation, reduction ,or hydrolysis , Oxidation
mainly by hepatic Cytochrome P 450 enzyme .
Phase II
glucuronidation , sulphonation , Acetylation ,
Methylation and conjugation with glutathione .)
Via Renal or Faecal excretion What is the EHC ?
What is t ½ , What is Zero Order kinetics ?
.
18. Zero-order kinetics& TI
n ZOK It is less common and means that the rate of
elimination is constant and does not depend on the
plasma drug concentration. This may be a
consequence of a circumstance such as saturation of
liver enzymes or saturation of the kidney transport
mechanisms.
n Therapeutic index (TI): Defined as the TD 50
/ED 50 (the ratio of the dose that produces a toxic
effect in half the population to the dose that produces
the desired effect in half the population).
19. Patient- Specific factors that infleunce
Pharmacokinetics
n Age & sex
n Weight
n Live function , Renal function , GIT function
n Food
n Smoking alcohol other drugs
20. Pharmacogenetic variation that affect
drug response
n Pharmacokinetic :
Aldehyde dehydrogenase 2 deficiency – Alcohol .
Slow acetylation in INH therapy . HLA –B
1502 Carbamazepine increased risk of skin reaction
SJS .
Pseudocholine esterase deficiency ( succinylcholine )
n Pharmacodynemic ( Porphyria , G6PD deficiency )
21. Questions
( 1 ) A drug M is injected IV into a laboratory subject. It is noted to have high serum
protein binding. Which of the following is most likely to be increased as a result?
A . Drug interaction
B. Distribution of the drug to tissue sites
C. Renal excretion
D. Liver metabolism
( 2 ) A 25-year-old medical student is given a prescription for asthma, which the physician
states has a very high therapeutic index. Which of the statements best characterizes the
drug as it relates to the therapeutic index?
A. The drug’s serum levels will likely need to be carefully monitored.
B. The drug is likely to cross the blood-brain barrier.
C. The drug is likely to have extensive drug-drug interactions.
D. The drug is unlikely to have any serious adverse effects.
22. First pass , Vd
Which of the following describes the first-pass effect?
A. Inactivation of a drug as a result of the gastric acids.
B. Absorption of a drug through the duodenum.
C. Drug given orally is metabolized by the liver before entering the circulation.
D. Drug given IV accumulates quickly in the central nervous system (CNS).
An agent is noted to have a very low calculated volume of distribution (V d )
Which of the following is the best explanation?
A. The agent is eliminated by the kidneys, and the patient has renal insufficiency.
B. The agent is extensively bound to plasma proteins.
C. The agent is extensively sequestered in tissue.
D. The agent is eliminated by zero-order kinetics.
24. The prescriber should have the following
5 aims:
n Maximise effectiveness
n Minimise risks
n Minimise costs
n Respect the patient's choices.
n Follow the principles of Biomedical Ethics
25. Another popular framework to support rational
prescribing decisions is known as STEPS
Steps model includes five criteria to
consider when deciding on the choice of
treatment:
n Safety
n Tolerability
n Effectiveness
n Price
n Simplicity.
26. Principles of Biomedical Ethics
n Beneficence,
n Non-maleficence,
n Justice
n Veracity (Veracity or ‘truth telling’ underpins both effective
communication and patient consent.)& Fidelity ( Trust )
n respect for Autonomy
27. Good prescribing is sometimes defined as the lack of
irrational prescribing.
Prescribing can be described as irrational for many
reasons:
n Poor choice of a medicine
n Polypharmacy or co-prescribing of interacting
medicine
n Prescribing for a self-limiting condition
n Continuing to prescribe for a longer period than
necessary
n Prescribing too low a dose of a medicine
n Prescribing without taking account of the patient's
wishes
28. Prescriptions
n In writing prescriptions, use English or the dominant language of
the patient.
n "Rx" is said to be an abbreviation for the Latin word recipere,
meaning "take" or "take thus," as a direction to a pharmacist,
preceding the physician's "recipe" for preparing a medication.
n The abbreviation "Sig" for the Latin Signatura, is used on the
prescription to mark the directions for administration of the
medication.
n The prescription must be accurately and legibly prepared to
identify the patient, the medication to be dispensed, and the mode
of drug administration. Avoid abbreviations and Include the
therapeutic purpose in the subscription (e.g., "for control of blood
pressure") to prevent errors in dispensing.(e.g. Losartan )
29. Prescription Paper ر
ا
ﺟ
ﯾ
ﺗ
ﺔ
n The superscription includes the date the prescription order is written;
the name, address, weight, and age of the patient; and the Rx (Take).
n The body of the prescription, or inscription, contains the name and
amount or strength of the drug to be dispensed, or the name and
strength of each ingredient to be compounded
n The subscription is the instruction to the pharmacist, usually
consisting of a short sentence such as: "dispense 30 tablets." The
signa or "Sig" is the instruction for the patient as to how to take the
prescription, interpreted and transposed onto the prescription label by
the pharmacist.
n Many physicians continue to use Latin abbreviations; e.g., "1 cap
tid pc," will be interpreted by the pharmacist as "take one after
meal .
31. A 65-year-old man with heart failure is admitted to hospital with a K
level of 7.1 mmol/L. Already stabilised on lisinopril 20 mg daily, he
had recently been started on spironolactone 25 mg
daily. He had a serum creatinine of 160 μmol/L.
Questions
n 1. What is the mechanism of any possible
adverse drug reaction?
n 2. How should future episodes of hyperkalaemia
be avoided?
32. Which of the following is the most likely
reason for pharmacokinetic tolerance?
(A) changes in absorption
(B) changes in distribution
(C) changes specific to that drug
(D) changes in metabolism
(E) renal adaptation
(D) The most common cause of pharmacokinetic tolerance is an increase in
the metabolism of the drug. Since these same enzymes can then metabolize
other drugs, this kind of tolerance is not necessarily specific to the drug that
induced it)
33. A72-year-old man is prescribed
hydrochlorothiazide for hypertension.
Which of the following is the most likely
symptomatic side effect?
(A) increased serum potassium
(B) metabolic acidosis
(C) sexual impotence
(D) respiratory alkalosis
(E) hypernatremia
34. A 69-year-old man develops renal failure.
Which of the following drugs requires a
major adjustment in dosage?
(A) levofloxacin
(B) ceftriaxone
(C) amphotericin B
(D) clindamycin
(E) ampicillin
