Pharmacology for MRT

students
By

Anteneh Kassahun (MD, MSC)

FEB, 2022

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 Course outline
• Chapter I: General Principles
✓Pharmacokinetics(PK)
✓Pharmacodynamics (PD)

• Chapter II: Autonomic Pharmacology

✓The Autonomic Nervous System (ANS)
✓Cholinergic Pharmacology
✓Adrenergic Pharmacology

• Chapter Ill: Cardiac and Renal Pharmacology

✓Introduction
✓Diuretics
✓Antihypertensive Drugs
✓Drugs for Heart Failure
✓Antianginal Drugs
✓Antiarrhythmic Drugs
✓Antihyperlipidemics

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 Course outline…
• Chapter IV: GIT Pharmacology
✓laxatives/purgatives
✓Anti-diarrhoeas
✓Anti-emetics
✓Drugs for peptic ulcer disease (PUD)
• Chapter V: Respiratory Pharmacology
✓Anti-tussive agents
✓Expectorant agents
✓Mucolytics
✓Antiasthmatic drugs
• Chapter VI: CNS Pharmacology
✓Sedative-Hypnotic-Anxiolytic Drugs
✓Anticonvulsants
✓Anesthetic Agents ( general and local)
✓Opioid Analgesics
✓Antidepressant Agents
✓Anti-Psychotics
✓Drugs for the treatment of Parkinson’s Disease

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 Course outline…
• Chapter VII: Endocrine Pharmacology
✓Drugs Used in Diabetes
✓Steroid Hormones
✓Antithyroid Agents
✓Drugs Related to Hypothalamic and Pituitary Hormones
✓Drugs Used for Bone and Mineral Disorders

• Chapter VIII: Chemotherapeutic drugs

✓Antibacterial Agents
✓Antifungal Agents
✓Antiviral Agents
✓Antiprotozoal Agents
✓Antihelminthic Agents
✓Cancer chemotherapy (anticancer Drugs)

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 Course outline…

• Chapter IX : Drugs for Inflammatory and Related Disorders

✓Autacoids-Histamine and Antihistamines
✓Eicosanoid Pharmacology( Nonopioid analgesics)
✓Drugs Used for Treatment of Rheumatoid Arthritis
✓Drugs Used for Treatment of Gout

• Chapter X: Drugs Used in Blood Disorders

✓Drugs for anemia
✓Anticoagulants
✓Thrombolytics
✓Antiplatelet Drugs

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References;

• Basic and clinical pharmacology Katzung, 12th edition

• Goodman & Gilman's: The Pharmacological Basis of
Therapeutics, 13 ED
• Rang & Dales Pharmacology 7th Ed
• Lippincott Illustrated Reviews, Pharmacology sixth
edition

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Assessment strategy

• 1. Class activity….5
• 2. Quiz…………….15
• 3. Mid exam………30
• 4. Final exam …….50

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 Chapter 1

General Pharmacology

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 General Principles of Pharmacology

Objectives
• Introduction
• Define pharmacology
• Define drug and Naming of drugs
• Sources of drugs
• Dosage forms
• Drug regulation and development
• Describe pharmacokinetics
• Describe pharmacodynamics
• Drug interactions

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 Pharmacology: Too interdisciplinary

• Full understanding of pharmacology demands

knowledge of
• Physiology
• Biochemistry
• Genetics
• Pathology
• Microbiology and Parasitology
• Clinical medicine
• Pharmaceutical sciences
• Epidemiology, Health economics & Biostatistics

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 Introduction
Pharmacology = pharmakon + logos
• Is the study of chemicals/ substances that
interact with living systems through chemical
process, especially by binding to regulatory
molecules & activating or inhibiting normal
body process
• Prehistoric people happened to have concepts of
“toxin” and “Medicine”…1500 BC in China
• Born as a science around the mid-19th century
following advances in biology and chemistry,
then, physiology and biochemistry.

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 Drug
• Any substance that brings about a change in biologic
function through its interaction with organ, tissues and/or
cells
• Administered deliberately for
• Diagnosis
• Treatment
• Prevention ….of disease(s)
• Poisons are chemicals with almost exclusively harmful
effects.
• Are drugs poisons?
➢“All substances are poisons; there is none that is not a poison.
The right dose differentiates a poison and a remedy” -
Paracelsus (1493-1541).

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Drugs

• Drugs mostly interact with a specific molecule in a biologic system

that plays a regulatory role [receptor]

• To interact chemically with its receptor, a drug molecule must

have the appropriate :
• Size, electrical charge, shape & atomic composition

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Source of drugs

• Plants: morphine,
▪ Digoxin from Digitalis (Foxglove)
▪ Atropine from Atropa Belladona (Nightshade)
• Animals: Insulin and heparin from pig’s pancreas,
• Microorganism: Penicillin from the fungus penicillium
• Mineral: liquid paraffin, iron
• Synthetic: aspirin (ASA)
• Genetic engineering: human insulin

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 Drug nomenclature/Naming of drugs
• A drug can have several names throughout its
development , production and use, drugs can be
named as the following…

• Chemical names-unique for a drug, but too complex

for common use

• Proprietary/trademark/trade or brand name- Coined

by the sole manufacturer and can’t be used by
others

• Nonproprietary/generic name- used in all countries

by all manufacturers
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 Dosage forms

• Drugs are not usually administered as pure

chemical substances
• Dosage forms are formulations into which
the drug is made for administration
• Drugs are formulated into dosage forms
• A single drug can be prepared in several
dosage forms

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 Types of dosage forms
Based on physical property
➢Solid dosage forms
• Tablets
• Capsules (powder filled)
• Powders
• Pessaries (vaginal tabs)

➢Semi-solid dosage forms

• Creams
• Lotions
• Suppositories

➢Liquid dosage forms

• Suspensions
• Solutions

➢Gaseous dosage forms

➢Inhalations

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 Types of dosage forms
Based on site of application
• Dosage forms for systemic use
• Injections
• Tablets
• Solutions
• Suspensions
• inhalations
• Dosage forms for topical use
• Creams
• Lotions
• Shampoos
• Soaps
• Sprays
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 Basic areas of pharmacology:
➢Pharmacokinetics
➢Pharmacodynamics

• After administration of a drug, the drug passes

through 2 phases

• Pharmacokinetics: deals with absorption,

distribution, biotransformation & excretion of
drugs
• Pharmacodynamics: study of biochemical &
physiological effects of drugs & their
mechanisms of action
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 • Toxicology: branch of pharmacology which deals with
the undesirable effects of chemicals on living systems

• Chemotherapy: effect of drugs upon microorganisms,

parasites and neoplastic cells living & multiplying in
living organism

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• Pharmacokinetics:
• Pharmaco: drug
• Kinetics: motion
• Action of body on drug/ what the body does to drug

• Pharmacokinetics:
“A D M E”

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 Absorption
• the processes of entry of a drug into the systemic
circulation from the site of its administration.
• Route and site of administration affect
• Rate
• Extent of absorption
• There are 4 mechanisms by which drug molecules cross
the cell membrane/absorption/
➢Passive diffusion
➢Facilitated diffusion
➢Active transport
➢Bulk transport mechanisms

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Routes of administration

• Enteral
• Oral, rectal, sublingual, buccal
• Parenteral
• Intramuscular(IM), subcutaneous, intravenous(IV), intrathecal
• Inhalation
• Topical

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Factors affecting GI absorption

• Absorbing surface area

• pH of media & pKa of the drug
• Particle size of the drug
• Formulation
• Gut motility
• Vascularity and Splanchnic blood flow
• Drug interaction

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Bioavailability

• fraction of administered drug that reaches the systemic

circulation
• Amount of drug available in the circulation
• Bioavailability is expressed in percentage
• IV route=100%, others less than 100%

Factors affecting bioavailability of oral route

• Extent of absorption
• First pass effect

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 • With oral administration, drugs are
absorbed into the portal circulation and
initially distributed to the liver. For some
drugs, their rapid hepatic metabolism
decreases bioavailability-the "first-pass"
effect
• E.g. Lidocaine (IV vs. PO)

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 First pass effect/FPE
• Also called first pass metabolism

• Refers to the metabolism of the drug before it reaches

the systemic circulation

• For oral doses, FPE occurs mainly in the liver

• Some drug will face major first pass effect in the GIT

• FPE decreases the bioavailability of a drug

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 Drug distribution
• Process by which a drug reversibly leaves the
blood stream & enters the interstitium and/or cells
of the tissues
• After entering the blood stream, drugs exist in two
forms [plasma protein bound & unbound form]

Factors affecting drug distribution

1. Plasma protein binding

• Albumin[acidic drugs]
• -glycoprotein [basic drugs]
• Plasma protein binding is not selective
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 Drug distribution cont’d
2. Tissue uptake of drugs (tissue-affinity of drugs )
-Some drugs have strong affinity to a particular body tissue
✓ adipose tissue [DDT]
✓ bone & teeth [TTC]
✓ liver & eyes [chloroquine]
✓ thyroid gland [iodine]
3. Barriers
✓Blood brain barrier & Placental barrier
4. Rate of blood flow
✓brain, kidney , liver & lung- highly perfused
✓Nails, Hair, Skin, Fat tissue - Poorly perfused

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 Volume of distribution (Vd)

• Is the apparent volume of body fluids to which a

drugs seems to be distributed.
• Relates the amount of drug in the body to the
concentration of drug in blood or plasma
• Shows the partition of drugs between the plasma
and the rest of the body

• Vd = [D]/[C]
• [D] = total concentration of the drug in the body
• [C] = concentration of the drug in the plasma

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 • Exercise
➢ 25mg of a drug is administered. After complete absorption
the plasma concentration was determined to be
0.001mg/ml. Calculate the apparent volume of distribution
[Vd] of the drug?

➢ VD=[D]/[C]= 25/0.001=25,000ml= 25L

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 Drug metabolism/biotransformation

Drug metabolism
• Is a chemical change to the drug due to reactions in
the body/Alteration of drug structure
• Helps facilitate the excretion of drug out of the body
• Usually changes lipophilic drugs to hydrophilic ones
that can easily be excreted
• Drugs can be metabolized at different sites of the
body [ liver, kidney, lungs, GIT, plasma etc…]
• Liver is the major organ for metabolism of drugs
…..why?

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 Liver: the major drug metabolizing organ

• Liver has the largest accumulation of

metabolizing enzymes

• The liver is the major organ where most

chemicals (food and DRUGS) are detoxified and
metabolized

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 PRO-DRUGS are drugs that are administered
in INACTIVE forms to be activated by
metabolism

➢The main purpose of biotransformation is to

make the drug ready for excretion by making it
more polar and water soluble
➢For a drug to be excreted from the body, it
should be converted into polar derivatives.

The liver metabolizes drugs in 2 phases of

reactions

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 Reactions of biotransformation
There are two phases of reactions

1. Phase I
• Also called functionalizing reaction due to the addition and/or
formation of new functional groups on to the parent drug
• Result in more Reactive and hydrophilic metabolites
• Include
• Oxidation
• Reduction
• Hydrolysis
• Most (not all) phase I reactions are catalyzed by a family of
microsomal enzymes called CYP 450 which are found in the
liver.

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 2. Phase II reactions
➢ Consist of conjugation reactions ( addition of polar
macromolecules to the drug molecule)
➢ Usually Follow the phase I reaction (not always
true)
➢ Make the products of phase reaction more polar
and water soluble so that they can easily be
excreted
➢ Most phase II products are pharmacologically
inactive

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 Types of phase II reaction

• Glucuronide conjugation (Glucuronidation)

• Acetyl conjugation (Acetylation)

• Sulphate conjugation (Sulfation)

• Methyl conjugation (Methylation)

• Glutathione conjugation

• Others…

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 • Conjugation = addition of endogenous
macromolecules to drug molecules( substrates)

• Some drugs may undergo phase II reaction

before undergoing phase I reaction
•Isoniazide is first acetylated (phase II) and then is
hydrolyzed to isonicotinic acid (phase I)

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 P450 ENYMES

• Enzyme induction
• Phenobarbitone
• Rifampin
• DDT

• Enzyme inhibition
• Cimetidine
• Ketoconazole
• Erythromycin
• Chloramphenicol
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 Effect of genetic makeup (polymorphism)
Fast metabolizers Vs Slow metabolizers
• Enzymes like acetyl transferase show genetic
polymorphism

• Fast acetylators metabolize isoniazid more rapidly

than slow acetylators

• Results in difference in drug efficacy and toxicity

among individuals of differing genetic make-up

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 Drug
Excretion
 • Most drugs leave the body with urine either
unchanged or as polar metabolites
• Some drugs are secreted into the bile and
excreted with feces (e.g. Rifampicin)
• Small amounts of some drugs are also excreted
in secretions such as milk or sweat but amounts
are negligible…(that is why most drugs are
avoided in breast feeding).

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 • The lungs play important role in the excretion of
gaseous and volatile drug (E.g. general anesthetics)

• Lipophilic drugs are not efficiently excreted by the

kidneys due to reabsorption

• Drugs excreted via urine are naturally water

soluble and polar or made so by biotransformation

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 Renal excretion
• The fundamental processes that account for renal
drug excretion include:
• Glomerular filtration
• Active tubular secretion
• Passive diffusion across tubular epithelium
Glomerular filtration
• Most drugs cross the barrier freely
• Macromolecules like heparin and drugs bound to
plasma proteins can’t cross the glomerulus
• Only 20% of the drugs delivered to the kidney are
filtered via the glomerulus

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 The nephron …drug excretion

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 Terminology
Dose
• Is the appropriate amount of a drug required to produce
desired response in an individual
Dosing interval
• Time gap between each dose
Loading Dose:-
• Higher dose that may be given at the onset of therapy to
achieve the target concentration rapidly
Maintenance Dose:-
• The dose which is repeated at regular intervals to
maintain a steady state concentration of the drug in
plasma and thus to maintain the effect

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 • Median Toxic Dose (TD50) = the dose of drug that causes a
toxic response in 50% of the population

• Median Effective Dose (ED50 )- the dose which produces a

desired response in 50% of the test population.

• Therapeutic Index- gives a rough idea about the potential

effectiveness and safety of the drug in humans. It is also
called as therapeutic window or safety.
TD 50
Therapeutic Index (TI) = ______
ED50
N.B- a safer drug has a higher therapeutic index

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 r
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dose

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 The five rights in drug administration

➢Right patient
➢Right drug
➢Right dose
➢Right route
➢Right time

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