i want 30 multiple choice questions with their model answer below each question that covers different aspects of all of the followig: Introduction
“Medical pharmacology, is often defined as the science of substances used to prevent, diagnose, and treat disease.” [Definitions from Katzung BG, ed, McGraw-Hill]
Drugs: are chemical substances that stimulate or inhibit an existing cell function. They are used for treatment, prevention and diagnosis of diseases or modify a physiological process. * In order to study pharmacology, you may have to know
1- Pharmacokinetics: It describes what the body does to the drug, which includes Absorption, Distribution, Metabolism & Excretion [ADME].
2- Pharmacodynamics: It describes what the drug does to the body, which includes the study of the pharmacological actions of drugs and their possible mechanisms of action.
3- Pharmacotherapeutics: It is the study of the selection and use of drugs for diagnosis, prevention and treatment of disease.
N.B.: The main goal of a physician is to give to the patient adequate drug doses so that therapeutic levels are obtained to produce the desired response with the minimal adverse effects.
Passage of drugs across cell membranes
The cellmembrane is a lipid sheet interrupted by protein macromolecules in the form of ion channels, carriers and receptors, and contains water filled channels.
Passage of drugs across cell membranes occurs mainly by: 1. Simple diffusion 2. Carrier mediated transport1) Simple diffusion: The chief process involved in absorption & distribution of drugs.
Simple diffusion depends on:
1)
Concentration gradient: drugs pass from one side of the cell membrane to the
other along concentration gradient
2)
3)
Molecular size: the smaller the molecular size the better is the absorption.
Lipid solubility and lipid/water partition coefficient, the more, the better the
absorption.
N.B.: Lipid/water partition coefficient is the ratio of drug concentration in lipid
medium to its concentration in the water medium when it is put in lipid water
system.
4)
5)
No energy& no carriers are needed.
Degree of ionization:
- The more the ionization, the less the lipid solubility.
- Degree of ionization depends on:
* pKa of the drug = ionization constant of the drug.
* pH of the medium.
¢
pKa (ionization constant of a drug).
It is the pH at which 50% of the drug is ionized and 50% non-ionized e.g. pKa of aspirin 3.5.
So in a medium with a pH of 3.5 aspirin will be 50% ionized and 50% non-ionized.
opH of the medium.
1. Most drugs are either weak acids or weak bases.
2. Weak acids are better absorbed in acidic media where it is less ionized and
so more lipid soluble.
3. Weak bases are better absorbed in alkaline media where it is less ionized so
more lipid soluble.
The degree of ionization is determined by: Henderson Hasselbalch equation
unionized
Weak acids: pKa = pH + log
Sonized
Weak bases: pKa = pH + log u%fi%i—]%%
- Acidic drugs as aspirin will be less ionized in the acidic medium of the stomach leading to
better absorption in the stomach. When filtered by the glomeruli, a big percentage of aspirin
can be reabsorbed from the renal tubules since urine is usually acidic. Making urine less
acidic, or more alkaline would enhance excretion of aspirin because less aspirin will be
reabsorbed.
- Weak base drugs such as amphetamine will be better absorbed from the intestine and
acidic urine will enhance their excretion.L
2) Carrier mediated transport: of 2 types:
a) Facilitated diffusion
b) Active transport:
Drugs are transferred across cell
membranes:
-
Along their concentration gradient.
-
-
Carrier for substances which are
too large or lipid insoluble to diffuse
passively
No energy is required.
e.g. glucose uptake by cells.
Cell Membrane
L]
° [
o0
Pharmacokinetics [ADME]
1) Absorption
Absorption is the transfer of a drug from its site of administration to the systemic blood
stream.
Factors affecting drug absorption:
A) Factors Related to the Drug:
1- Water and lipid solubility:
- Drugs MUST be Water soluble as well as Lipid soluble.
- Drugs must be completely dissolved in water to be absorbed.
(Drugs
insoluble in water e.g. Barium chloride (BaClz) are NOT absorbed).
- More lipid solubility — a higher Lipid/Water partition coefficient —» better absorption.
2- lonization:
- Non-ionized —» More lipid soluble — Better absorption
- Depends on pKa of the drug & pH of the medium.
- Quaternary ammonium compounds “Neostigmine” - lonized — Poor absorption
- Tertiary amines “Physostigmine” — Non-ionized — Better absorption.
3- Valency: Ferrous iron (Fe?*) is better absorbed than is Ferric Iron (Fe3*).
4- Nature:
Inorganic (small molecules) are
better absorbed than are Organic (Big
molecules).
5- Pharmaceutical Preparation:
- Dosage form: Solution > Suspension > Tablet.
- Shape & size of particles and rates of disintegration & dissolution of tables:
Rapid with paracetamol & propranolol BUT slow with digoxin.
- Excipient (Filler): CaCO3 & Ca Phosphate — Absorption of Tetracyclines.
4
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Afrier
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Drugs are transferred across cell
| membranes:
-
Against their concentration gradient
-
-
Transport requires energy
Transport requires a carrier
e.g. secretion of penicillin by renal tubules.
Cell Membrane
Carsier ... ®
+ Energy
.. ®B) Factors Related to the Patient: 1-Route of Administration: 1.V. and inhalation > |.M. > S.C. > Oral > Skin. 2-Absorbing Surface: - Vascularity: Alveoli > Skeletal muscle > Subcutaneous tissues. - Surface area: Alveoli > Intestine > Stomach (Intestines have 1000 times the surface area of the stomach.). - State of health of the absorbing surface: Diarrhea & mal-absorption -\ Oral absorption. 3-Systemic circulation: Shock & Heart failure —\ Absorption. 4-Specific factors: Intrinsic factor for Vit B-12. 5-Presence of other drugs: - Adrenaline S.C.
- V.C. -\ Absorption of Local anesthetics —» Longer duration of action
of local anesthetics. - Milk (Calcium) -\ Oral absorption of Tetracyclines (Antibiotic).
Factors affecting oral absorption: A) Factors related to the druq: See before B) Factors related to the patient: 1- Surface area of absorbing surface: The intestine has surface area 1000 times that of stomach (due to microvilli) and rich blood flow. Thus, absorption from intestine > stomach. 2- State of health of the absorbing surface: Gastritis, malabsorption syndrome Soral absorption 3- Motility of the gut and rate of dissolution: o
Prokinetic drugs increase the gut motility e.g. Metoclopramide ¢ gut motility — gastric emptying — @ absorption of rapidly disintegrated drugs (paracetamol) and & absorption of slowly disintegrated drugs (digoxin).
e
Atropine inhibits the gut motility —&8 gastric emptying. —& Absorption of rapidly disintegrated drugs and © absorption of slowly disintegrated ones.
4- pH within the gut: * Weak acids (aspirin) are better absorbed in an acidic media. So better absorbed in stomach.
* Weak bases (amphetamine, ephedrine) are better absorbed in the alkaline medium of the intestine.
5- Specific factors: Intrinsic factor from stomach is essential for Vit B12 absorption. 6- Gut contents: presence of food & other drugs: « Presence of food:
Bad — Food dilutes Drugs & may compete with them for absorption e.g. amino acids compete for the same carrier of L-DOPA.
Good — with IRRITANT drugs e.g. aspirin & iron. ¢
Tetracycline calcium and iron absorption by chelation. ¢ Cholestyramine & charcoal & absorption of many drugs by adsorption.o Grape fruit juice fabsorption of drugs by inhibiting P. glycoprotein (which cause reversed transport of drug from gut wall to lumen). Tea —J{ iron absorption by its content of tannic acid.
*
7- Eirst pass effect: Means metabolism of a drug in the gut wall or the liver before reaching the systemic circulation.
Gut first pass effect: o
Gastric acidity: destroys benzyl penicillin. s Digestive enzymes: destroy insulin ¢ Mucosal enzymes: destroy chlorpromazine.
Hepatic first pass effect: ¢
Drugs extensively metabolized: e.g. Nitroglycerine.
To avoid: change the route of administration: Nitroglycerine is administered sublingually.
» Drugs metabalized ta a large extent: 6.g. propranolol and nitroglycerine. To avoid: r the oral dose.
Bioavailability ¢ ¢
Bioavailability is the fraction of a drug that reaches the systemic circulation after administration by any route.
Bioavailability is 100 % after IV administration and Variable after oral administration. Oral bioavailability = (AUC-oral/AUC-IV) X 100
AUC= Area under the plasma —concentration time curve Conc Conc Time Time Eactors affecting oral bioavailability:
1. Amount of drug absorbed = Factors affecting GIT absorption. 2.
First pass metabolism.