CEE 2. Pcol (Introdution)

Pharmacology

Pharmacology

Study of drugs: structure, physical properties, chemical characteristics relevant to its activity as therapeutic agent

exogenous

Pharmacology is the study of ___ substances

prevent, diagnose, treat

Pharmacology is the science of substances used to —, —, and — diseases

Drug

Substance that brings about change in biologic function through its chemical actions

enzymes

Drugs need to bind to ___

effector

___ translates drug-receptor interactions into specific biological responses or effects.

oral preparations

LADME is for ___

IV drugs

ADME is for ___

MPDC

DRUG DEFINITION mnemonics

mitigate, prevent, diagnose, and cure

Drug is any article used in the —, —, — and — of diseases in man and animals

Pharmacokinetics

Fate of the drug inside the body

body, drug

Pharmacokinetics is the action of the ___ on the ___,

Liberation

release of drug from its dosage form for it to be absorbed by the body

Absorption

when the drug enters the systemic circulation

Distribution

drug reaches the target site of action

Excretion

final loss of drugs from the body

• Formulation of salts for easy absorption

• Formulation of prodrug

Factors affecting liberation

hypertension

Enalapril is a drug for ____

Ethyl ester of enalaprilat

Enalapril is the ___ of ___

enalaprilat alone is very water soluble, hence lipophobic

EXPLAIN: Enalapril (Ethyl ester of enalaprilat)

ulcerative colitis

Olsalazine is a drug for ___

Dimer of mesalamine

Olsalazine is the ___ of ___

mesalamine alone is poorly absorbable so it won’t reach the small intestine

EXPLAIN: Olsalazine (Dimer of mesalamine)

chloramphenicol is very water soluble so add palmitate (salty w/ lots of carbon), making it effective for oral administration

EXPLAIN: Chloramphenicol palmitate

typhoid

Chloramphenicol is the old drug of choice for ___

Salmonella typhi

causative agent of typhoid fever

more

Factors affecting absorption: Chemical structure (NonPolar is ___ absorbable than Polar)

less

Factors affecting absorption:

• Chemical structure (Polar is ___ absorbable than NonPolar)

surface area

Factors affecting absorption:

• Variation in particle size & surface area ( ↑ ___ )

particle size

Factors affecting absorption:

• Variation in particle size & surface area ( ↓ ___ )

crystalline

Factors affecting absorption:

• Nature of crystalline form ( ___ slower absorption)

compact

crystalline is more ___

amorphous

Factors affecting absorption:

• Nature of crystalline form ( ___ - faster absorption)

tablet coating, matrix

Factors affecting absorption:

• Type of ___ and ___

minimally absorbed in the stomach and reach the small intestine

Bisacodyl (Brand name: Dulcolax) is designed to be ______ (absorption property)

heart, lungs, liver

Factors affecting distribution:

• Blood flow ( ↑ in ___, ___ and ___ )

liver

Factors affecting distribution:

• Capillary permeability ( ↑ ___ )

BBB

Factors affecting distribution:

• Capillary permeability ( ↓ ___ )

Protein

Factors affecting distribution:

• ___ binding

albumin

where acidic drugs bind

orosomucoid

where basic drugs bind

1. Albumin is a protein

2. Warfarin is an anticoagulant drug that is 95% bound to albumin

3. Phenylbutazone is an NSAID that when bound to albumin, will displace warfarin, thus increasing warfarin in the body until toxic

EXPLAIN: drug distribution in albumin-warfarin-phenylbutazone

Non-Polar

Factors affecting distribution:

• Affinity of drugs to tissue deposits ( ↑ ___ )

elimination

____ = metabolism + excretion

functionalization or asynthetic

Metabolism: Phase 1 is also known as “” or “”

conjugation or synthetic

Metabolism: Phase 2 is also known as “” or “”

P - 1

Phase __ introduces a polar functional group (-OH, -COOH, -SH, -NH2) to the xenobiotic molecule

P - 2

Phase __ attach a small, polar, ionizable endogenous compound to the functional handles of Phase 1

Oxidation, Reduction, Hydrolysis

Examples of Phase 1

Glucuronidation

Example of Phase 2 (most common)

Sulation

Example of Phase 2 (in neonates)

INDUCERS

• Increases the number of CYP

• increase in metabolism

decrease

INDUCERS →  ___ in pharmacologic action

INHIBITORS

• Decreases the number of CYP

• decrease in metabolism

increase

INHIBITORS → ___ in pharmacologic action

PPRCO

INDUCERS mnemonics

MEDICKAV

INHIBITORS mnemonics

• Phenytoin

• Phenobarbital

• Rifampicin

• Carbamazepine

• Omeprazole

What does PPRCO stand for?

• Metronidazole

• Erythromycin

• Disulfiram

• Isoniazid

• Cimetidine/Chloram

• Ketoconazole

• Amiodarone/Allopurinol

• Valproic acid

What does MEDICKAV stand for?

drug, body

Pharmacodynamics is the action of the ___ on the ___,

Pharmacodynamics

Effect of the drug on the body

Affinity

ability of a Ligand to bind to receptors

Intrinsic Activity

ability of the ligand to stimulate the receptors

Agonist

binds to regulatory receptors and mimic regulatory effects of the endogenous signaling compounds

• Full Agonist

• Partial Agonist

• Inverse Agonist

Types of Agonists

Full Agonist

• Affinity: 1

• Intrinsic Activity: 1

Partial Agonist

• Affinity: 1

• Intrinsic Activity: > 0 or < 1

Inverse Agonist

• Affinity: 1

• Intrinsic Activity: 0

Beta

Insulin: ___ cells

Anabolic

Insulin: ___ process

synthesis

Insulin: glucogen ___

Alpha

Glucagon: ___ cells

Catabolic

Glucagon: ___ process

lysis

Glucagon: glucogen ___

Antagonist

Drugs that block or reduce the effects of an Agonist

1. Functional

2. Receptor

3. Chemical

Antagonist: Based on MOA

Physiologic Antagonism

bind to different receptors and produce opposite effects

Pharmacologic Antagonism

bind to same receptors and produce opposite effects

Inactivation

directly interacts with agonist/ligand to deactivate it

1. Reversible

2. Irreversible

Antagonist: Based on Type of Interaction

reversible

Most drugs are (reversible/irreversible)

acetylcholinase

organophosphates inhibits ___

COX-1 and COX-2

aspirin inhibits

1. Competitive

2. Non-competitive

Antagonist: Based on Surmountability of Interaction

active site

Competitive Antagonism binds in the ___

allosteric site

Non-competitive Antagonism binds in the ___

Physiologic Antagonism

Functional Antagonism aka “___”

Pharmacologic Antagonism

Receptor Antagonism aka “___”

Inactivation

Chemical Antagonism aka “___”

Reversible

Temporary (less than 24 hours)

Irreversible

Permanent (more than 24 hours)

Competitive Antagonism

Surmountable

Non-competitive Antagonism

Non-surmountable

Haloenzymes

catalystically active enzymes

Apoenzymes + Coenzymes

Haloenzymes = ___ + ___

Cofactor

Coenzymes: loose, vitamins

Prosthetic

Coenzymes: tight, metals

B3

NAD belongs to the ___ vitamin group

B2

FAD belongs to the ___ vitamin group

ADEC

mnemonic used to remember the fat-soluble vitamins