Introduction to

pharmacology part II

Clinical pharmacist
Dr. Fatima Bani Salama
 Half-life
 The time it takes for one half of the original amount of
a drug to be removed from the body

 A measure of the rate at which a drug is removed from

the body

 Most drugs considered to be effectively removed after

about five half-lives

 Steady state
• The speed of elimination is the main factor in
deciding the duration of action of the drug & is
referred plasma half-life (t½) of the drug

T½: The time required to change the plasma

concentration of the drug by one half
• The blood level & therapeutic effectiveness
depend on:
the dose, distribution within the body & speed
of elimination.

• Rapidly excreted drugs with short t½ will

require frequent administration to maintain a
fairly constant concentration in the body
where as those that are eliminated slowly can
be given once or twice
• With repeated dosing, concentration in plasma
climbs until more or less steady state (SS) is
obtained.

At steady-state the rate of drug

administration equals the rate of elimination
• To hasten achievement of SS & full therapeutic
effect with more slowly excreted drugs

===== a large loading dose is given followed by

smaller maintenance doses
 – Single dose
7 Loading dose

6
Therapeutic
Plasma Concentration
5
level
4

2 Repeated doses –
Maintenance dose
1

0
0 1.9 3.9 5.9 7.9 9.9 11.9 13.9 15.9 17.9 19.9 21.9 23.9

Time
 Dose Response Relationships
• Loading dose
– Bolus of drug given initially to rapidly reach therapeutic levels

• Maintenance dose
– Lower dose of drug given continuously or at regular intervals to
maintain therapeutic levels
 Onset, Peak, and Duration
Onset
• The time it takes for the drug to elicit a
therapeutic response

Peak
• The time it takes for a drug to reach its maximum
therapeutic response

Duration
• The time a drug concentration is sufficient to elicit a
therapeutic response
 Therapeutic Drug Monitoring

Peak level
• Highest blood level

Trough level
• Lowest blood level
 If the peak is too high == toxicity
 If the trough is too low== not be at
therapeutic levels.

 In therapeutic drug monitoring

Therapeutic Index
The ratio of the dose that produce toxicity to that
produce clinical response

Therapeutic index TD50/ED50

• TD50: The dose that cause toxicity in 50% of
individuals
• ED50: The dose that produce an effect in 50% of
individuals

The ratio must be large in order to be a safe drug

 Pharmacodynamics:
Mechanisms of Action
 The action of the drug on the body

 Receptor interactions

 Enzyme interactions Drugs may either inhibit (most common) or enhances

the action of specific enzyme.

 Nonselective interactions nonspecific mechanisms of action do not

interact with receptors or enzymes. cell membranes and various cellular processes such as
metabolic activities
• A receptor : reactive site on the surface or
inside of a cell.

• binding gives pharmacologic response .

• The degree to which a drug attaches to and

binds with a receptor is called its affinity
• The drug interacts with a receptor:
• D+R D – R complex  effect

• This reaction is reversible & in order to occur,

an affinity between the drug & receptor
Receptor interactions
 Receptor interactions

• The drug with the best “fit” and

strongest affinity for the receptor will
elicit the greatest response from the cell
or tissue
Types of drugs:

 Agonist: a drug that interact with a receptor

followed by effect

 Antagonist: a drug that interact with a

receptor but with no effect

 Partial Agonist: a drug that bind to a receptor

followed by weak effect
 PARTIAL AGONISTS - EFFICACY
Even though drugs may occupy the same # of receptors, the magnitude of their
.effects may differ

Full Agonist
1.0

Maximal Effect % 0.8

0.6 Partial agonist

0.4

0.2

0.0
0.01 0.10 1.00 10.00 100.00 1000.00

]D[ )concentration units(

 The 7 traditional rights of medication
administration
 right drug
 right dose
 right patient
 right route
 right time
 right reason
 right documentation

 now include : right education, right evaluation, and right to

refuse the medication.
 Contraindications
• Any characteristic of the patient, especially a disease state, that
makes the use of a given medication dangerous for the patient

• It is important to assess for contraindications!

 Monitoring
• The effectiveness of the drug therapy must be evaluated

• One must be familiar with the drug’s:

– Intended therapeutic action (beneficial)
– Unintended but potential adverse effects (predictable, adverse
reactions)
 Monitoring (cont’d)
 Therapeutic index ,,Drug concentration

 Patient’s condition

 Interactions

 Adverse drug effects

 Monitoring (cont’d)
Interactions may occur with other drugs or food

• A drug interaction is the alteration of a drug’s action by:

– Other prescribed drugs
– Over-the-counter medications
– Herbal therapies
 Monitoring (cont’d)
• Drug interactions
– Additive effect
– Synergistic effect
– Antagonistic effect
– Incompatibility
Adverse drug events: is a broad term for any
undesirable occurrence involving medications.

 A medication error is a preventable situation. (during the prescribing,

dispensing, administering, or monitoring of drug therapy).

 An adverse drug reaction is any reaction to a drug that is unexpected and

undesirable and occurs at therapeutic drug dosages.
- may or may not be preventable, depending on the situation.
-range from mild to more severe drug reactions that can be life-threatening,
or fatal
 Monitoring (cont’d)
Adverse drug reactions

• Pharmacologic reactions, including adverse effects

• Hypersensitivity (allergic) reaction
• Idiosyncratic reaction
 Other Drug-Related Effects
 Teratogenic (structural defects in the fetus)

 Mutagenic (permanent changes in the genetic composition of living organisms )

 Carcinogenic (cancer-causing effects of drugs)

 Life Span Considerations
• Pregnancy
• Breast-feeding
• Neonatal and pediatric
• Elderly
Pregnancy :
 Drug properties
 Fetal gestational age
 Maternal factors
 Breast-feeding
• Breast-fed infants are at risk for exposure to drugs consumed
by the mother

== (fat solubility, low molecular weight, nonionization, and high concentration)

• Consider risk-to-benefit ratio

 Factors Affecting Pediatric
Drug Dosages
• Skin is thin and permeable

• Stomach lacks acid to kill bacteria

• Lungs have weaker mucus barriers

• Body temperatures less well regulated, and dehydration

occurs easily

• Liver and kidneys are immature, impairing drug

metabolism and excretion
 The Elderly
Elderly: older than age 65
 Use of OTC medications
 Increased incidence of chronic illnesses
 Polypharmacy

• Physiologic Changes in the Elderly Patient:

 Cardiovascular
 Gastrointestinal
 Hepatic
 Renal
 The Elderly:
Pharmacokinetics

• Absorption
– Gastric pH less acidic
– Gastric emptying slowed
– Movement through GI tract slowed
– Blood flow to GI tract reduced
– Use of laxatives may accelerate GI motility
 The Elderly:
Pharmacokinetics (cont’d)
• Distribution
– Lower total body water percentages
– Increased fat content
– Decreased production of proteins by the liver,
resulting in decreased protein binding of drugs
(and increased circulation of free drugs)
 The Elderly:
Pharmacokinetics (cont’d)

• Metabolism
– Aging liver produces fewer microsomal
enzymes, affecting drug metabolism
– Reduced blood flow to the liver
 The Elderly:
Pharmacokinetics (cont’d)

• Excretion
– Decreased glomerular filtration rate
– Decreased number of intact nephrons
The end