HARAR COLLEGE OF HEALTH SCIENCE

DEPARTMENT OF ANESTHESIA

Pharmacology introduction

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 Objective
• Explain words of pharmacology
• Identify the difference between
pharmacodynamics and pharmacokinetics
• Practical explanation of basic drug calculation

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 pharmacology
• Is the sciences of drugs.
• It deals with history, source, physical and
chemical properties of drugs, mechanism of
action, absorption, distribution,
biotransformation, excretion, and the use of
drugs.
• Drug-it is a single chemical agent used in the
prevention, diagnosis and treatment of
disease.

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 Cont..
• Pharmacy - it is the art and science of
compounding and dispending drugs.
• Clinical pharmacology - it is the scientific
study of drugs in man.
• Chemotherapy - treatment of systemic
infection/any disease with specific drugs that
have selective toxicity for the infecting/
malignant cell with no or minimal effect to the
host cells.

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 Cont…
• Toxicology- is the science of poisons and
poisoning
• Teratogenicity - administration of certain
drugs in the first trimester of pregnancy i.e
period of organogenesis which result in fetal
deformity

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 Principles of drug action
The basic types of drug action can be grouped
as follows
• Depression: it is a selective depression of the
targeted cells. Example barbiturates
• Stimulation: selective enhancement of the
activity of specialized cells. Example
adrenaline stimulates the heart

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 Cont…
• Irritation: these are non selective, often
noxious effect. Strong irritation often results
in inflammation and tissue narcosis and
morphological damage.
• Replacement: it is replacement of hormones
in deficiency states. Example- insulin for
diabetes mellitus, levodopa for parkinsonism
• Cytotoxic : selective cytotoxic action for
invading parasites or cancer cell to attenuate
them without harming the host cell

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 Mechanism of drug action
• Physical action-it is simply by physical
interaction of the drug to our body- by
osmotic activity
• Chemical action-the drug reacts extra
cellular according to simple chemical
equation. eg. acid - base neutralization
• Enzymes – can be induction or
inhibition

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 Mechanism…
• Through receptors-Terms in relation to drug receptor
are;
 Affinity – the ability to combine with the receptor
 Efficacy/ intrinsic activity – the a ability to produce a
response
 Agonist – is an agent that produces both affinity and
efficacy.
Eg : adrenaline is agonist of adrenergic receptors
 Anatagonist – an agent that has only affinity but no
have intrinsic activity.
Eg. Naloxon is a pure anatagonist of opoid receptor

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 The difference between pharmacokinetics and
pharmacodynamics?

• Pharmacokinetic involves the medication

body interaction includes, absorption,
distribution, metabolism, and elimination.
 deals with what the body does to the drug
• Pharmacodynamics Describes the effect of
drugs on the body
 deals with what the drug does to the body

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 Drug interactions
 Pharmacokinetic interaction;
– Out side the body-precipitation of thiopental with
sux. Mixture
– At the site of absorption; e.g. effect of opioids
and metoclopramide on gastric empting
– use of vasoconstrictors to delay local anesthetic
drug absorption, second gas effect
– Affecting metabolism-enzyme induction/inhibition
e.g.. Cimetidine(inhibition) or
barbiturates(induction)

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 Cont…
 pharmacodynamics;
• summation-net effect equals sum of individual
drug effect
• synergism-net effect exceeds the sum of
individual drug effects
• Potentiation-one drug increases the effect of
another

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 Description of drug action
• Desensitization; decrease in cellular sensitivity
or response due to repeated exposure to
agonists
• Tolerance :-the requirement of higher dose to
produce similar response

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 Pharmacokinetics
• What the body does to drug
• Study of how drugs enter the body, reach their
site of action and are eliminated from the
body
Absorption
Distribution
Metabolism
excretion

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 Absorption
• It is transfer of drugs from site of
administration to blood stream
• Rate and efficiency depends on rout of
administration

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 Physical factors influencing absorption
• Blood flow to the absorption site
• Total surface area available for absorption
• Contact time at the absorption surface
 Bioavailability
it is fraction of administered drug that
reaches the systemic circulation

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 Factors that influence bioavailability
• First-pass hepatic metabolism
• Solubility of drug
• Nature of the drug formulation

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 Distribution
• Distribution plays a key role in anesthetic
pharmacology because it is a major
determinant of end-organ drug concentration.
• A drug’s distribution depends primarily on
- Organ perfusion
- Protein binding and
- Lipid solubility

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 Cont…
• After absorption, a drug is distributed by the
bloodstream throughout the body.
• Highly perfused organs(the vessel-rich group)
take up a disproportionately large amount of
drug compared with less perfused organs(the
muscle, fat, and vessel-poor group).
• As long as a drug is bound to a plasma protein,
it is unavailable for uptake by an organ
regardless of the extent of perfusion to that
organ.
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 Cont…
• After, the highly perfused organs are saturated
during initial distribution, the greater mass of
the less perfused organs continue to take up
drug from the bloodstream
• As plasma concentration falls, some drug
leaves the highly perfused organs to maintain
equilibrium.
• This redistribution from the vessel-rich group
is responsible for termination of effect of
many anesthetic drugs
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 Metabolism

• The chemical modification of drugs with

the overall goal of getting rid of the drug

• Enzymes are typically involved in Metabolism

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 Consequences of Metabolism
• Drug Metabolism = Drug Inactivation
• The metabolite may have:
 Equal activity of the drug
 No or reduced activity of the drug
 Increase activity (Pro drug)
 Toxic properties, not seen with the parent
drug

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 Metabolic reactions
• There are two main patterns of drug metabolism.
These are:
1) phase l
2) phase ll
phase i:it includes;
a. Oxidation
b. Reduction
c. hydrolysis

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 Phase I
Oxidation:
• is the addition of oxygen and/or the removal
of hydrogen. Most oxidation steps occur in the
endoplasmic reticulum. The most important
enzyme: microsomal P-450

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 Phase l cont…
Reduction:
• Add a hydrogen or remove oxygenazo (-N=N-)
or nitro groups (-NO2) -----> amines (-NH2) for
example nitrazepam
Hydrolysis
• Addition of water with breakdown of molecule
In blood plasma (esterases) and liver

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 Phase II
• Also known as conjugation reaction
– it involves the addition of molecules naturally
present in the body to the drug molecule.The drug
may have undergone a phase I reaction
a.Glucuronidation: main conjugation reaction in the
body. This occurs in the liver.
– Natural substrates are; bilirubin and thyroxin
• b. Acylation. Acylation, especially acetylation
with the acetyl group, e.g. sulfonamides

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 Phase ll cont…
c. Glycine: Glycine addition (NH2CH2COOH) for
example; nicotinic acid
d. Sulfate: Sulfate (-SO4) for example morphine,
paracetamol

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 Elimination
• Elimination Half Time - time for plasma
concentration to decline by 50%

• Elimination Half Life - time for 50% of a drug

to be eliminated from the body

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 Elimination
• Elimination - all the various processes that
terminate the presence of a drug in the body.
• Processes:
- renal excretion
- hepato-biliary excretion
- pulmonary excretion (inhaled anesthetics)
- other: saliva, sweat, breast milk, tears

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 Renal Excretion
• Both metabolically changed and unchanged
drugs
• LMW substances: filtered from blood through
the Bowman membrane of the capsule
• Some: actively secreted
• Reabsorption in the tubule: depending on the
lipid solubility, degree of ionization, molecular
shape, carrier mechanism (for some)

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 Renal Excretion cont…
• Weak acid: best reabsorbed from an acidic
urine.

• Important to know if the drug is dependent

on renal function or excretion.

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 Hepatobiliary Excretion
• Drugs metabolites – excreted in the intestinal
tract with the bile.
• Majority: reabsorbed into the blood and
excreted through urine. (enterohepatic cycle).

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 Pulmonary Excretion
• Volatile anesthetics and anesthetic gases: in
large part eliminated unchanged through the
lung

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 Rules of drug administration-
6R’S
• The right drug
• The right dose
• The right patient
• The right route
• The right time
• The right documentation

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 ROUTES OF ADMINISTRATION
• Orally
• Rectally
• Inhalation
• Topical
• Parenteral:
– Intravenous
– Intramuscular
– Subcutaneous

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 Routes of Administration cont..

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 Basic principles of drug calculation

• Drugs in anaesthesia are commonly expressed in

grams, milligrams or micrograms which refer to their
mass.
Example: 500mg thiopentone, 600mcg atropine. The
words milli-, micro- and nano- which appear in front of
“gram” refer to how many multiples of 10 are present

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 Percent weight in volume
• This is expressed as % w/v which is to mean the
number of gram of a solute dissolved in 100ml of a
solvent
• When using drugs prepared in this way it is necessary
to calculate the number of mg in ml of solution.
• This is easiest done by multiplying the percentage of
the solution by 10.
• E.g. 2.5% of any drug means there is 25 mg/ml of
that specific drug.

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 Basic drug calculation cont….

• Drug mass units

 1 gram = 1000mg = 1,000,000 microgram

 1L = 1000 ml
 1ml = 15-20 drops in a normal iv infusion

1mg = 1000 mcg

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 Calculation of infusion rates
•The flow rate of intravenous of fluid and/or drugs
may be expressed interms of ml/hr or drop/min.
• Fluid/drug in ml/hr or drop/min =
total fluid to be run in ml x drop factor
total time in minute
Where drop factor is 15-20
E.g .1000 ml in 4 hrs is 83 drops/min,(drop factor 20
gtt)

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 Question
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• Questions ?

Thanks.
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