College of Dentistry

AL- Kitab University

Third Grade -----Pharmacology
Lecture- 2-
Dr. Sabah Nuri Mizel
Board (Ph D ) Oral Maxillofacial
Medicine
 PHARMACOTHERAPEUTICS
Pharmacotherapeutic :principles relate to the use of drugs in the diagnosis, prevention, and treatment of disease.
The dosing regimen, which takes into account the route, amount, and frequency of drug administration, influences
the onset and duration of drug action. If the desired full effect of a drug must be achieved promptly, a loading dose,
which is larger than the maintenance dose, must be employed.
Following the administration of maintenance doses, a drug’s concentration in plasma is characterized by the time
course of accumulation, the maximal amount accumulated, and the fluctuations associated with the dose interval and
the half-life of the drug.
Dosage intervals are predicated on the fluctuation in drug concentration that can be tolerated without toxicity
or loss of efficacy;
however, different patients show significant variations in response to the same dosage regimen. Optimal
pharmacotherapy depends on the clinician’s awareness of the sources of such variations, which include both
disease-related and patient-related factors
 Pharmacogenetic Factors
Genetic determinants may affect both pharmacokinetic and pharmacodynamic factors and contribute to the normal
variability of drug effects.
The dose of a drug required to produce a specific response in an individual is referred to as the individual effective dose

If a drug produces its usual effect on a patient at an unexpectedly high dose, the patient is said to be hyporeactive

A patient is said to be hyperreactive when a drug produces its effect at an unexpectedly low dose.

Decreased response to a drug as a result of prior exposure to the drug is described as tolerance. When this occurs, cross-
tolerance may develop to the effects of other, structurally related drugs. In the case of tolerance, drug dosage must be
increased to maintain an acceptable therapeutic response.

When tolerance develops rapidly, subsequent to the administration of only a few doses of a drug, the response is described
as tachyphylaxis .‫ﺿﺎ ﺣﺎًدا وﻣﻔﺎﺟًﺋﺎ ﻓﻲ اﻻﺳﺗﺟﺎﺑﺔ ﻟﻠدواء ﺑﻌد ﺗﻧﺎوﻟﮫ؛ أي ﺑداﯾﺔ ﺳرﯾﻌﺔ وﻗﺻﯾرة اﻟﻣدى ﻟﺗﺣﻣل اﻟدواء‬
ً ‫ﺗّﺳرع اﻟﻣﻧﺎﻋﺔ ھو ﻣﺻطﻠﺢ طﺑﻲ ﯾﺻف اﻧﺧﻔﺎ‬
‫ ﻗد ﺗﻛون زﯾﺎدة ﺟرﻋﺔ اﻟدواء ﻗﺎدرة ﻋﻠﻰ اﺳﺗرﺟﺎع اﻻﺳﺗﺟﺎﺑﺔ اﻷﺻﻠﯾﺔ‬.‫وﯾﻣﻛن ﻟﮭذا أن ﯾﺣدث ﺑﻌد ﺟرﻋﺔ أوﻟﯾﺔ أو ﺑﻌد ﺳﻠﺳﻠﺔ ﻣن اﻟﺟرﻋﺎت اﻟﺻﻐﯾرة‬
An unusual reaction of any intensity, irrespective of drug dosage observed in a small percentage of the patients is referred
to as idiosyncrasy or an idiosyncratic reaction
 Weight of the Patient
Optimum therapeutic doses intended to produce a specific effect are generally determined in terms of the amount of
drug per kilogram of body weight of the patient. Although there are many rules and formulae to calculate dosages,
doses based on manufacturer recommendations or the prescriber’s experience provide the most reasonable approach to
dosing.
 The Pregnant Patient
Fetal abnormalities occur in 3% to 6% of pregnancies in the United States and drugs are considered to be responsible
for 1% to 5% of these malformations.
Each drug has a threshold concentration above which fetal abnormalities can occur and below which no effects are
discernible.
Most drugs in the maternal bloodstream cross the placenta by passive diffusion along the concentration gradient.
During early pregnancy the placental membrane is relatively thick, which tends to reduce permeability. The thickness
decreases and the surface area of the placenta increases in the later trimesters, increasing the passage of drugs.
Human teratogenicity is not predictable. Major malformations are usually the result of exposure to drugs during the
critical period of organogenesis (first trimester).
Exposure during the second and third trimesters primarily affects organ function.
Any drug in the fetal system at the time of birth must rely on the infant’s own metabolic and excretory capabilities,
which have not yet fully developed.
Consequently, drugs given near term, especially those with long half-lives, may have a prolonged effect on the
newborn. Finally, drugs that cause maternal addiction are also known to cause fetal addiction and the fetus
can undergo withdrawal following delivery. To assist practitioners in prescribing drugs for the pregnant patient, the U.S.
Food and Drug Administration (FDA) has established a code for categorizing drugs according to their potential to
cause fetal injury
 The Nursing Patient
With the increasing recognition of the advantages of breastfeeding, clinicians must often weigh the risks versus benefits of
drug therapy in lactating women. The rate of passage of a drug from plasma to milk depends on the characteristics of the
drug, such as the drug’s molecular weight, lipid solubility, pKa (a measure of the acidity or basicity of a drug molecule. It
is the negative logarithm of the acid dissociation constant (Ka) of a compound. The pKa value indicates the propensity of
a drug molecule to donate or accept a proton (H+), and degree of plasma protein binding .The pKa of weak electrolytes is
an important determinant of drug concentration in milk because the pH of milk is
generally lower (more acidic) than that of plasma and milk can act as an ‘‘ion
trap’’ for weak bases. At equilibrium, basic drugs may become more concentrated in milk. Conversely, acidic drugs are
limited in their ability to enter milk
 Because the concentration of the nonionized free form in milk is higher than it is in plasma, causing a net transfer
of the drug from milk to plasma.
The ratio of drug concentration in breast milk to drug concentration in maternal plasma is called the milk-to-plasma
drug-concentration ratio.
Factors that determine the advisability of using a particular drug in a nursing mother include the potential for
acute or long-term dose-related and non–dose-related toxicity, dosage and duration of therapy, age of the infant,
quantity of milk consumed by the infant, and the drug’s effect on lactation.
To minimize the infant’s exposure to medications in milk, clinicians should consider the following strategies:
1-withhold drug therapy; 2- delay drug therapy temporarily;
3--choose a drug that passes poorly into milk; 4---use alternative routes of drug administration (i.e., topical,
inhalation); 5---advise the mother to avoid nursing at peak plasma concentrations of the drug;
6--administer the drug to the mother before the infant’s longest sleep period;
7---and/or withhold breastfeeding temporarily
 Prescription for pediatric patient

Children, and particularly neonates, differ from adults in their response to drugs. Special care is needed in the neonatal
period (first 28 days of life) and doses should always be calculated with care. At this age, the risk of toxicity is increased
by reduced drug clearance and differing target organ sensitivity. Whenever possible, intramuscular injections should
be avoided in children because they are painful . The identification and reporting of adverse reactions to
drugs in children is particularly important because:
1-the action of the drug and its pharmacokinetics in children (especially in the very young) may be different from that
in adults;
2-. drugs are not extensively tested in children;
3-. many drugs are not specifically licensed for use in children and are used ‘off-label’;
4-. suitable formulations may not be available to allow precise dosing in children;
5-. the nature and course of illnesses and adverse drug reactions may differ between adults and children
 It is particularly important to state the strengths of capsules or tablets. Although liquid preparations are
particularly suitable for children, they may contain sugar which encourages dental decay. Sugar-free medicines are
preferred for long-term treatment.
Many children are able to swallow tablets or capsules and may prefer a solid dose form; involving the child and
parents in choosing the formulation is helpful.
When a prescription for a liquid oral preparation is written and the dose ordered is smaller than 5 mL an oral syringe
will be supplied

Parents should be advised not to add any medicines to the infant’s feed, since the drug may interact with the milk or
other liquid in it; moreover the ingested dosage may be reduced if the child does not drink all the contents.
Parents must be warned to keep all medicines out of reach of children
 Dose calculation for Children
Many children’s doses are standardized by weight (and therefore require multiplying by the body-weight in
kilograms to determine the child’s dose); occasionally, the doses have been standardized by body surface area (in m2 ).
These methods should be used rather than attempting to calculate a child’s dose on the basis of doses used in adults.
For most drugs the adult maximum dose should not be exceeded. For example if the dose is stated as 8 mg/kg (max.
300 mg), a child weighing 10 kg should receive 80 mg but a child weighing 40 kg should receive 300 mg (rather than 320
mg).
Young children may require a higher dose per kilogram than adults because of their higher metabolic rates. Other
problems need to be considered. For example, calculation by body-weight in the overweight child may result in much
higher doses being administered than necessary; in such cases, dose should be calculated from an ideal weight, related to
height and age .Body surface area (BSA) estimates are sometimes preferable to body-weight for calculation of pediatric
doses since many physiological phenomena correlate better with body surface area. Body surface area can be estimated
from weigh. Dose frequency Antibacterials are generally given at regular intervals throughout the day. Some flexibility
should be allowed in children to avoid waking them during the night. For example, the night-time dose may
be given at the child’s bedtime
 Prescribing in hepatic impairment
Liver disease may alter the response to drugs in several ways as indicated below, and drug prescribing should be
kept to a minimum in all patients with severe liver disease. The main problems occur in patients with jaundice, ascites,
or evidence of encephalopathy.
Impaired drug metabolism
Metabolism by the liver is the main route of elimination for many drugs but hepatic reserve is large and liver disease has
to be severe before important changes in drug metabolism occur. Routine liver-function tests are a poor guide to
the capacity of the liver to metabolize drugs, and in the individual patient it is not possible to predict the extent
to which the metabolism of a particular drug may be impaired.
A few drugs, e.g. rifampicin and fusidic acid, are excreted in the bile unchanged and can accumulate in patients with
intrahepatic or extrahepatic obstructive jaundice.
Hypoproteinaemia The hypoalbuminaemia in severe liver disease is associated with reduced protein binding and
increased toxicity of some highly protein bound drugs such as phenytoin and prednisolone.
Reduced clotting Reduced hepatic synthesis of blood-clotting factors, indicated by a prolonged prothrombin time,
increases the sensitivity to oral anticoagulants such as warfarin and phenindione.
 Hepatic encephalopathy
In severe liver disease many drugs can further impair cerebral function and may precipitate hepatic
encephalopathy. These include all sedative drugs, opioid analgesics, those diuretics that produce hypokalaemia, and
drugs that cause constipation.
Fluid overload Oedema and ascites in chronic liver disease can be exacerbated by drugs that give rise to
fluid retention, e.g. NSAIDs and corticosteroids. Hepatotoxic drugs Hepatotoxicity is either dose related or
unpredictable (idiosyncratic).
Drugs that cause dose-related toxicity may do so at lower doses in the presence of hepatic impairment than in
individuals with normal liver function, and some drugs that produce reactions of the idiosyncratic kind do so more
frequently in patients with liver disease. These drugs should be avoided or used very carefully in patients with
liver disease
 Prescribing in renal impairment
The use of drugs in patients with reduced renal function can give rise to problems for several reasons:
. reduced renal excretion of a drug or its metabolites
may cause toxicity;
. sensitivity to some drugs is increased even if elimination is unimpaired;
. many side-effects are tolerated poorly by patients
with renal impairment;
. some drugs are not effective when renal function is
reduced.
Many of these problems can be avoided by reducing the dose or by using alternative drugs
 Writing the Medical Prescriptions
1 should be written legibly in ink or otherwise so as to be indelible
2-should be dated, should state the name and address of the patient, the address of the prescriber, an indication of the type
of prescriber, and should be signed in ink by the prescriber
3-The age and the date of birth of the patient should preferably be stated, and it is a legal requirement in the case of
prescription-only medicines to state the age for children under 12 years.
The following should be noted:
(a) The strength or quantity to be contained in capsules, lozenges, tablets etc. should be stated by the
prescriber. In particular, strength of liquid preparations should be clearly stated (e.g. 125 mg/5 mL).
(b) The unnecessary use of decimal points should be avoided, e.g. 3 mg, not 3.0 mg. Quantities of 1 gram or more should be
written as 1 g etc. Quantities less than 1 gram should be written in milligrams, e.g. 500 mg, not 0.5 g.
Quantities less than 1 mg should be written in micrograms, e.g. 100 micrograms, not 0.1 mg.
When decimals are unavoidable a zero should be written in front of the decimal point where there is
no other figure, e.g. 0.5 mL, not .5 mL. Use of the decimal point is acceptable to express a
range, e.g. 0.5 to 1 g.
(c) ‘Micrograms’ and ‘nanograms’ should not be abbreviated. Similarly ‘units’ should not be abbreviated.
(d) The term ‘millilitre’ (ml or mL)4 is used in medicine and pharmacy, and cubic centimetre, c.c., or cm3
should not be used.
(e) Dose and dose frequency should be stated; in the case of preparations to be taken ‘as required’ a
minimum dose interval should be specified
.
(g) The names of drugs and preparations should be
written clearly and not abbreviated, using approved
titles only
(h) The quantity to be supplied may be stated by
indicating the number of days of treatment required
. In most cases the exact amount will be supplied. This
does not apply to items directed to be used as required—
if the dose and frequency are not given then the
quantity to be supplied needs to be stated.
When several items are ordered on one form the
box can be marked with the number of days of
treatment provided the quantity is added for any
item for which the amount cannot be calculated.
(i) Although directions should preferably be in English
without abbreviation, it is recognized that some
Latin abbreviations are used
Computer-issued prescriptions
1. The computer must print out the date, the patient’s
surname, one forename, other initials, and address,
and may also print out the patient’s title and date of
birth. The age of children under 12 years and of
adults over 60 years must be printed in the box
available; the age of children under 5 years should
be printed in years and months. A facility may also
exist to print out the age of patients between 12 and
60 years.
2. The doctor’s name must be printed at the bottom of
the prescription form; this will be the name of the
doctor responsible for the prescription (who will
normally sign it). The doctor’s surgery address,
reference number, and Primary Care Trust (In addition,
the surgery telephone number should be printed.
3. When prescriptions are to be signed by general
practitioner registrars, assistants, locums, or deputising
doctors, the name of the doctor printed at the
bottom of the form must still be that of the responsible
principal
.
4. Names of medicines must come from a dictionary
held in the computer memory, to provide a check
on the spelling and to ensure that the name is
written in full. The computer can be programmed
to recognize both the non-proprietary and the proprietary name of a
particular drug and to print out
the preferred choice, but must not print out both
names. For medicines not in the dictionary, separate checks are required
—the user must be warned
that no check was possible and the entire prescription must be
entered in the lexicon.
5. The dictionary may contain information on the
usual doses, formulations, and pack sizes to produce standard
predetermined prescriptions for common preparations,
and to provide a check on the validity of an individual
prescription on entry.
6. The prescription must be printed in English without
abbreviation; information may be entered or stored
in abbreviated form. The dose must be in numbers,
the frequency in words, and the quantity in numbers
in brackets, thus: 40 mg four times daily
 Analgesics
Divided into three groups
1-nonopioids 2-opioids 3- adjuvants.
(Adjuvants are drugs that have been approved for use for conditions other than pain; anticonvulsants
are an example.)
Benzodiazepines they may be helpful for relief of muscle pain due to tension or spasm
But are not analgesic and are not recommended for long-term chronic pain management.

Nonopioid Analgesics This group consists primarily of acetaminophen and the large group of nonsteroidal
anti-inflammatory drugs (NSAIDs).
 Non OPIODS Analgesics
1-–Acetaminophen
Acetaminophen is dispensed over the counter and is also available in controlled formulations in combination with codeine
and other opioids (Norgesic or Myogesic ).
Advantage :fewer adverse effects when compared with NSAIDs. It does not affect platelet function, rarely causes
gastrointestinal (gI) disturbances, and can be given to patients who are allergic to aspirin or other NSAIDs. Caffeine has
been
shown to enhance the effectiveness of nonopioid drugs and is often added to the analgesic.
The mechanism of action
of acetaminophen is different from that of the NSAIDs but
remains unknown; there is some evidence that suggests a central action.
Indications mild pain of all types and is also combined with opioids for an additive analgesic effect or to reduce the
amount of opioid required. Has a Ceiling analgesic effect.
Side effects Due to its potential to cause liver damage, it may pose a danger to patients with liver disease, patients who
regularly consume moderate to large amounts of alcohol, and patients who are fasting
Dose Acetaminophen has an analgesic “ceiling,” and the
recommended maximum dose in a 24-hour period is 4 g.
 Non OPIODS Analgesics
2-Non Steroidal anti inflammatory Drugs (aspirin, ibuprofen, ketoprofen, and
naproxen)
and Diclofena Sodium (Voltarin , Cataflam)
Mode of action :
Inhibit Synthesis of Prostaglandins in body tissues by inhibiting at least 2
cyclooxygenase isoenzymes (COX) , COX-1 and COX-2.
The enzyme cyclooxygenase (COX), which is
required for the synthesis of prostaglandins (PGs), substances
that sensitize peripheral sensory nerves and contribute to the
experience of pain.
 May inhibit chemotaxis , alter lymphocyte activity, decrease pro
inflammatory cytokine activity and inhibit neutrophils
aggregation. These effects may contribute to the anti inflammatory
activity.

Users of NSAIDs do not exhibit tolerance or physical dependence, but

these drugs do have an analgesic ceiling.
Patients may vary in their response to NSAIDs, and if appropriate dosage
adjustment does not produce an analgesic effect after several days to 1
week, it is appropriate to switch to a different NSAID
 Non OPIODS Analgesics

2-Non Steroidal anti inflammatory Drugs

It is inadvisable to prescribe two different NSAIDs at the same time; rather, one
NSAID should be used and its dose and timing adjusted for maximum analgesic
effect.
Combinations of NSAIDs increase the risk of side effects.

Side Effects:
1- Bleeding Prevent platelets aggregation , hence increase bleeding
2-G.I.T Side effectsProstaglandins perform other functions in the body, and
this is maintaining the protective layer of gastric mucosa, and the loss of this
layer makes the mucosa more vulnerable to erosion. The longer NSAIDs are
administered, the greater the risk of GI bleeding. This effect is a systemic one
and is not avoided by administering the drug by other routes (eg, rectal
suppository). NSAIDs should be taken with food or at least with a full glass of
water.
 Non OPIODS
2-Non Steroidal Analgesics Drugs
anti inflammatory
Side Effects
2-G.I.T. Side effects

To prevent G.I.T. side effects , Proton pump inhibitors( Omeprazole 20 , 40 mg./Day )or (Lansoprazole
30 mg./Day ) have also been used concurrently to reduce the risk of gastric erosion. Although all NSAIDs
pose a risk of GI bleeding, ibuprofen and diclofenac sodium ( Voltarin )are considered to pose a lower
risk, and ketoprofen and piroxicam are considered to pose a higher risk.

Types of NSAIDs are available that selectively inhibit only one of the isoforms of COX, namely, COX-2.
The inhibition of COX-2 seems to be related to the anti-inflammatory and analgesic effects, whereas the
inhibition of COX-1 is thought to be responsible for many of the side effects.
The COX-2 inhibitors celecoxib and rofecoxib pose less risk of GI bleeding and do not inhibit platelet
aggregation.
Recent evidence indicates that patients treated with selective COX-2 inhibitors may be at increased risk of
cardiovascular problems. This had led to the removal of rofecoxib and valedocoxib from the market
 Analgesics
2-Opioids (morphine-like agonists)

Indications : moderate to severe acute pain and cancer pain and chronic
nonmalignant pain.

Mode of action :These drugs bind to m-opioid receptors, resulting in actions

that lead to the analgesic effects. Opioids exert a number of effects after
binding to receptor sites. Effects at the membrane level include opening
potassium channels and inhibiting voltage- gated calcium channels, leading to
a decrease in neuronal excitability.

Side effects Addiction and risk of additional disability and antisocial

behavior with long-term opioid use
 Analgesics
3-Adjuvant Drugs
Tricyclic Antidepressent Drugs(TCAs) Anticonvulsant drugs
(Amitriptyline )introduced at low doses are effective in the treatment of
and are gradually increased Neuralgias i.e. TN
to reduce the adverse effects, which can (carbamazepine)and diabetic
be intolerable even neuropathy and for migraine
at low doses. prophylaxis
Mode of action block the reuptake of Mode of action: suppress the excessive
rapid firing of neurons during
serotonin and norepinephrine ,
enhancing seizures.
the central inhibitory system in pain
processing Side effects sedation, dizziness, ataxia,
and mood changes) that can limit their usefulness.
Side effects such as dry mouth, increased New anticonvulsants (lamotrigine, and gabapentin) .
appetite Gabapentin commonly used in pain management
and weight gain, cardiac effects, because of its relatively few side effects. Dose: 300
sedation, and dysphoria ( ‫ خلل في النطق‬.( mg. 1x2 or 1x3 according to pain severity , increase
slowly .