PHARMACOLOGY

NOTES

BY: ABOLMAGD

BE AWARE!
These are just the most important enumerate questions.
Don’t study it only.
 A) PHARMACOKINETICS

v DEFINE:

Ø FIRST PASS EFFECT:

§ Means metabolism of drug in gut wall or liver before reaching systemic

circulation.

Ø BIOAVAILABILITY:

§ The fraction of unchanged drugs reaching systemic circulation after any

route of administration, and its 100 % after IV administration and Variable

after oral administration.

Ø CLEARANCE OF DRUGS:

§ Process through which drug or its metabolites can be eliminated from the body.

Ø LOADING DOSE:

§ The initial dose of the drug which can raise its plasma level to the target

concentration. = Vd x desired concentration (Css)

Ø MAINTENANCE DOSE:

§ The dose needed to replace the drugs eliminated since the preceding

state (Css). = Cl x Css x Tm

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PHARMA ABOLMAGD

 Ø HME inducers (Hepatic Microsomal Enzymes):

§ Are drugs which stimulate the activity of hepatic microsomal enzymes.

§ EX: Oral anti-coagulants, Phenytoin and Carbamazepine.

§ EFFECT: They ↑ Metabolism of other drugs & ↑ in their own metabolism.

Ø HME inhibitor (Hepatic Microsomal Enzymes):

§ Are drugs which inhibit the activity of hepatic microsomal enzymes.

§ SPECIFIC:

• EX: Grapefruit juice, Cimetidine, Theophylline

• EFFECT: They↓ metabolism of other drugs & ↓ in their own metabolism.

§ GENERAL:

• EX: Hepato-toxic drugs, β-Blockers (Propranolol) & H2-Blockers (Cimetidine).

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v ENUMERATE:

Q1: Enumerate factors affecting oral absorption related to Drug:

A) 1- water & lipid soluble 2- ionization

3- valency 4- nature

5- pharmaceutical preparation

Q2: Enumerate factors affecting oral absorption related to Patient:

A) 1- surface area of absorbing surface

2- state or absorbing surface

3- Motility of the gut and rate of dissolution

4- PH within the gut 5- specific factors

6- gut contents (food & other drugs) 7- first pass effect

Q3: Enumerate types of metabolic reactions:

A)

Ø Phase 1:

§ Oxidation

§ Reduction

§ Hydrolysis

Ø Phase 2:

§ Glucuronic acid

§ Acetic acid

§ Methylation

§ Glycine

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PHARMA ABOLMAGD

Q4: Enumerate results of Phase 1:

A)

1- Inactivation (commonest): Active Drug —> Inactive Metabolite

2- Activation: Inactive Drug (Prodrug) →Active metabolite

3- Maintain Activation: Active Drug →Active Metabolite

4- Toxification: Drug → Toxic metabolite

Q5: Enumerate results of Phase 1:

A)

1) Alkalinization of urine (Na or K Acetate, Bicarbonate or Citrate)

→ ↑Renal excretion of weak Acid drugs

2) Acidification of Urine (NH4CI or Ascorbic acid “Vit C”)

→ ↑Renal excretion of weak Base drugs

Q6: Enumerate factors affecting DofD binding to plasma protein:

A)

- Drugs are carried in blood in 2 forms:

a) Free form: Pharmacologically active – diffusible – metabolized – excreted.

b) Bound form (act as a reservoir): inactive, non-diffusible, not metabolized,

not excreted.

- The amount of drug bound to plasma protein will change according to:

a) Affinity for binding sites

b) Hypoalbuminemia

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PHARMA ABOLMAGD

Q7: Write short note about ‘Plasma half-life’:

A)

1-Time needed body to decrease a certain plasma concentration of a drug to one half.

1- It is affected by clearance and volume of distribution (Vd).

2- Most of drugs disappears from the body within 4-5 t1/2 after stopping its intake.

3- t1/2 is useful to determine the frequency & route of drug administration.

Q8: Mention advantages & dis of ‘oral’ route of administration:

A)

a) Advantages:

1- Easy

2- Safe

3- Economic

4- Convenient

b) Disadvantages:

1- Not suitable for Emergency

2- Uncooperative patients

3- Not in vomiting or severe diarrhea.

4- Some drugs undergo extensive first pass metabolism:

- by digestive & hepatic microsomal enzymes.

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PHARMA ABOLMAGD

Q9: Mention advantages & characters of ‘sublingual’ administration:

A)

a) Advantages:

1- Easy

2- Rapid

3- Good bioavailability

4- Proper control of dose

b) Characters:

1- Small sized tablet

2- Good taste

3- Easily dissolved

Q10: Mention advantages & dis of ‘rectal’ route of administration:

A)

a) Advantages:

1- Rapid

2- Avoid hepatic first pass effect

3- Useful in large volume medications

4- Suitable in case of vomiting

b) Disadvantages:

1- Inconvenient to most patients.

2- Psychological trauma.

3- Unsuitable in cases of diarrhea.

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PHARMA ABOLMAGD

v COMPARE:
Ø Between: [First order kinetics & Zero order kinetics]

1ST ORDER KINETICS ZERO ORDER KINETICS

- Kinetics of drug (ADME) are - limited capacity of drug’s kinetics due to
PROPORTIONAL to its concentration. SATURATION of involved enzyme.
- Fixed FRACTION - Fixed AMOUNT
- LINEAR drug disappearance curve. - NON-LINEAR drug disappearance curve.
- t1⁄2 is fixed. - t1⁄2 increases with drug concentration.
- AUC is PROPORTIONAL - AUC is NOT PROPORTIONAL
- Repeated intake of the drug at regular - If rate of intake of drug > Rate of its
intervals→ Css within 4-5 t 1 ⁄2
elimination → Cumulation ↑ Css→ Toxicity.
- Examples: S.D. of Aspirin, Phenytoin - Examples: L.D. of ‘Same S.D.’ & Alcohol

Ø Between: [Microsomal Enzymes & NON-Microsomal Enzymes]

Microsomal Enzymes NON-Microsomal Enzymes

SITE - Smooth endoplasmic reticulum - Cytoplasm, Mitochondria
ORGANS - Mainly Hepatic - All Organs
PHASE- | - Oxidation / Reduction - Oxidation / Reduction &
(Cytochrome P450) Hydrolysis
PHASE- || - Glucuronidation ONLY - All Except Glucuronic acid
INDUCTION - Inducible - Not inducible
SUBSTRATES - Usually lipophilic - Lipophilic & hydrophilic

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PHARMA ABOLMAGD

 B) PHARMACODYNAMICS

v DEFINE:

Ø AFFINITY:

§ The ability of drug to fit onto the receptor to form drug-receptor (D-R) complex.

Ø Efficacy OR Intrinsic activity:

§ Ability of drug-receptor (D-R) complex to evoke a response.

Ø AGONISTS:

§ Drugs which have affinity, efficacy and rapid dissociation.

Ø ANTAGONISTS:

§ Drugs which block receptors. They have affinity, no efficacy and slow

dissociation.

Ø PARTIAL AGONISTS:

§ Stimulate then block receptors. They have affinity, weak efficacy and slow

moderate dissociation.

Ø UP REGULATION:

§ Long use of ANTAGONISTS or drugs that ↓ transmission and ↑ sensitivity

of receptors.

Ø DOWN REGULATION:

§ Long use of AGONISTS and ↓ sensitivity of receptors.

Ø HYPER SENSITIVITY (ALLERGY):

§ Unpredictable abnormal response to drugs due to immune reaction.

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PHARMA ABOLMAGD

 Ø SUPER SENSITIVITY:

§ An exaggerated pharmacological action of the drug in response to small

therapeutic dose of the drug in some individuals due to tissue hyper-

responsiveness (sensitivity).

Ø IDIOSYNCRASY:

§ Unpredictable abnormal response due to genetic abnormality, Occurs on

first exposure.

Ø TOLERANCE:

§ Lack of drug sensitivity that respond to higher dosage than the usual

therapeutic dose.

Ø ACQUIRED TOLERANCE: (AND TYPES)

§ Progressive decrease of drug sensitivity as a result of continued

administration.

• CROSS TOLERANCE

• TACHYPHYLAXIS

• BACTERIAL RESISTANCE

Ø TERATOGENICITY (Dysmorphogenetic):

§ Any agent that results in structural or functional abnormalities in the fetus,

or in the child after birth, as a consequence of maternal exposure during

pregnancy.

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PHARMA ABOLMAGD

 Ø RESULTS OF DRUG INTERACTION:

1- ADDITION (1+1=2)

• The resultant action = sum of individual drug actions.

2- SYNERGISM (1+1>2)

• The resultant action More than sum of individual drug actions.

3- POTENTAITION (1+0>1)

• One drug has no action (0), increases the effect of another drug (>1)

(‫ ﻟﻨﻮع واﺣﺪ ﺑﺲ وﻣﻤﻜﻦ ﻟﻠﺜﻼﺛﺔ‬DEF. ‫)ﻣﻤﻜﻦ ﯾﻄﻠﺐ‬

v ENUMERATE:

Q1: EXPLAIN ‘Mechanism of Acquired Tolerance’:

A)

1- Pharmacokinetic changes:

- Decreased absorption: long term alcohol → atrophic gastritis → ↓↓ alcohol absorption

- Increased metabolism: HME inducers like barbiturates → ↑ its own metabolism

2- Pharmacodynamic changes:

- Down-regulation of receptors: e.g. beta-2 & opioid

- Antibody formation: e.g. insulin

Q2: ENUMERATE ‘TYPES OF RECEPTORS’:

A)

1- Ligand-Gated Ion Channels 2- G Protein-Coupled Receptors

3- Enzyme-Linked Receptors 4- Intercellular Receptors

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PHARMA ABOLMAGD

v COMPARE:
Ø Between: [Competitive Antagonists & Non- Competitive]

COMPETITIVE NON- COMPETITIVE

- Antagonists bind REVERSIBLE - Antagonist is NOT DISPLACED
with the receptors. by agonist → NON-SURMOUNTABLE.
- Antagonists can be DISPLACED - NON-PARALLEL shift of curve
by excess agonists→ SURMOUNTABLE. to the Right = ↓ POTENCY.
- PARALLEL shift of the curve - Decrease maximum response
to the RIGHT → ↓ POTENCY. (Emax) = ↓ EFFICACY.
- NO effect on the maximum response
(E-max) = SAME EFFICACY.
- Examples: Propranolol, atropine & naloxone.

Ø Between: [Types of Non-Competitive Block]

REVERSIBLE IRREVERSIBLE
- The antagonist binds REVERSIBLY to - The antagonist binds COVALENTLY to
the receptor. the receptor.
- The block ends by the METABOLISM - The block ends by RESYNTHESIS OF
OF THE BLOCKER. NEW RECEPTORS.
- Usually of SHORT duration of action. - Usually of LONG DURATION of action.
- Examples: Nicotine LD & Succinylcholine. - Examples: Phenoxybenzamine &
organophosphorus compounds.

‫متت بحمد اهلل‬

‫اسألكم الدعاء‬

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PHARMA ABOLMAGD