Upload
jon-paulo-bautista
View
495
Download
0
Embed Size (px)
Citation preview
INTRODUCTION TO INTRODUCTION TO PHARMACOLOGYPHARMACOLOGY
Renato I. Dalmacio, RPh
Pharmacology 325
College of Pharmacy
1
PharmacologyPharmacology
study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes.
studies the effects of drugs and how they exert their effects.
2
History of PharmacologyHistory of Pharmacology
Pan TsaoAyurvedaEber’s PapyrusHippocratesTheophrastusGalenParacelsusDioscorides
3
DrugDrugis any substance which is used for the
following purposes: Prevention of the disease Diagnosis of the disease Mitigation of the disease Treatment or palliation (relief of
symptoms) of disease Maintenance of optimal health
4
Sources & Nature of DrugsSources & Nature of DrugsNatural sourcesAnimal sourcesMicrobiological sourcesMineral sourcesSemi-synthetic sourcesSynthetic sourcesBiosynthetic sources
5
Classification of Drugs Classification of Drugs According to General UseAccording to General Use
1. Functional Modifiers alters the normal physiologic
functions. Examples:
Analgesics Antipyretics Anti-Inflammatories
6
Classification of Drugs Classification of Drugs According to General UseAccording to General Use
2. Replenishers Supplement endogenous substances
that are lacking or deficient. Examples:
Insulin Water Electrolyte
7
Classification of Drugs Classification of Drugs According to General UseAccording to General Use
3. Diagnostic Agents Agents used to determine the
presence or absence of a condition or disease.
Examples: Edrophonium Histamine Technetium 99m
8
Classification of Drugs Classification of Drugs According to General UseAccording to General Use
4. Chemotherapeutic Agents Agents used to kill or inhibit growth of
cells or nucleic acid considered as foreign to the body.
Examples: Anti-infectives Antineoplastics
9
Branches of PharmacologyBranches of Pharmacology
1.Pharmacokinetics
2.Pharmacodynamics
10
PharmacokineticsPharmacokinetics
study of how the drugs move into, through and out of the body including delivery to their target sites.
deals with LADMER System.
11
PharmacodynamicsPharmacodynamics
study of biochemical and physiological effects of drugs and the mechanism by which they produce such effects.
deals with Mechanism of Action (MOA).
12
Pharmacokinetic PrinciplesPharmacokinetic Principles
1. Permeation
2. Ionization
3. Ionization Increases Renal Clearance of drugs
4. Order of Reactions
13
Fate of Drug In-VivoFate of Drug In-Vivo
1. L-iberation
2. A-bsorption
3. D-istribution
4. M-etabolism
5. E-xcretion
6. R-eabsorption
7. (T)-oxicity
14
1.1. LiberationLiberation• release of the active ingredient (drug) from its
dosage form
Pharmacotechnical Factors Affecting Liberation:
1.Pharmaceutic Factors
• Tablet disintegration
• Inert ingredient / Solvent effects
• Solubility
• Drug pH
• Concentration15
2. Patient Factors
• Absorbing surface
• Blood flow
• Environmental pH
• Disease states
• Interactions with food, other drugs
Rate Limiting Factors in Drug Liberation:
1. Disintegration
2. Dissolution
16
2.2. AbsorptionAbsorption The drug’s uptake from the site of administration
to the systemic circulation.
Factors Affecting Drug Absorption:Dose size administeredpH of absorbing environmentArea of absorbing surfaceDegree of perfusionGastric emptying timeDosage FormDrug SolubilityFirst Pass EffectEnterohepatic Recycling
17
Factors that Increase Gastric Emptying Time:
1.Stress
2.Heavy Exercise
3.Gastric Ulcers
4.Hot Food (Protein Rich, Lipid-Rich Foods)
5.Lying on the left side
6.Drugs that inhibit gastric motility
18
Factors that Decrease Gastric Emptying Time:
1.Mild Exercise
2.Gastrectomy
3.Cold Foods/Drinks
4.Lying on the right side
5.Use of motility enhancing drugs
19
Modes of Drug TransportModes of Drug Transportmeans of movement of drug molecule across
cell membrane.
Examples of Transport Mechanism
1.Passive Transport
2.Carrier-Mediated Transport
3.Convective Transport
4.Vesicular Transport
5.Ion-Pair Transport
20
1.1. Passive TransportPassive Transport higher concentration to lower concentration. movement of small lipophilic molecule along a
concentration gradient. non energy requiring
• only nonionized molecules can pass through cell membranes
• weakly acidic drugs can only be absorbed through the stomach which is acidic.
• Weakly alkaline drugs can be absorbed through the intestine, which is alkaline.
21
2.2. Carrier Mediated TransportCarrier Mediated Transport A process that accounts for passage through the
membrane of large, lipid-insoluble molecules and ions.
All use carrier systems, i.e., special carrier molecules are required to be present in the membrane to help in the movement of the transported molecules.
These carrier systems all show three properties: specificity, saturation and competition.
22
22 Types of Carrier Mediated TransportTypes of Carrier Mediated Transport
1. Facilitated Transport
• a passive process requiring no cellular energy
• drug moves along a concentration gradient
• saturable and structurally selective
2. Active Transport
• from lower concentration to higher concentration
• “pushing a rock uphill”
• requires cellular energy
23
3.3. Convective TransportConvective Transport• small drug molecules simply move along with
fluid through the pores in cell walls• mediated through “water-filled
pores/channels/aquaporins”.Characteristics:a. Pore size/Diameterb. Charge of pore liningc. Solvent Dragd. Movement is governed by electrochemical
gradient
24
4.4. Vesicular TransportVesicular Transport An active process in which materials move
into or out of the cell enclosed as vesicles. Vesicles are bubble-like structures
surrounded by a membrane. They can form at the cell membrane or can
fuse with the membrane. Vesicular transport is also known as bulk
transport because large quantities of materials can be transported in this way.
25
2 Basic Types of Vesicular Transport2 Basic Types of Vesicular Transport
1.Endocytosis- It is a process by which cells absorb molecules (such as proteins) by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane.
2.Exocytosis- It is a process in which an intracellular vesicle (membrane bounded sphere) moves to the plasma membrane and subsequent fusion of the vesicular membrane and plasma membrane ensues.
26
5.5. Ion-Pair TransportIon-Pair Transport Occurs when ionized drug is linked up
with an opposite charged ion, an ion pair is formed in which the overall charge of the pair is neutral.
Drugs like quaternary ammonium compounds and sulphonic acids, which ionise under all pH conditions, is ion-pair transport.
Ex. Propranolol - membrane neutral ion pair complex GI lumen.
27
3.3. DistributionDistribution
The extent to which the drug passes into different tissues and fluid compartments in the body.
Physiologic Factors Affecting DistributionCardiac OutputRegional Blood Flow
Parameters Volume of Distribution Protein Binding BBB and Placental Barrier
28
Volume of Distribution (VD)The hypothetical volume of body fluid
necessary to dissolve a given amount or dose of a drug to achieve a concentration equal to that of the drug plasma concentration.
High VD Low VD-basic drugs -acidic drugs-examples: -examples:
-atropine, chloroquine -chlorpropamide -Digoxin, B-Blockers -tolbutamide -warfarin -furosemide
29
Protein Binding It is the phenomenon that occurs when a drug
combines with plasma (particularly albumin) or tissue protein to form a reversible complex.
2 Types of Protein Binding
1.Reversible Drug-Protein Binding implies that the drug binds the protein with weaker chemical bonds such as hydrogen bonds or Van der Waals forces.
2. Irreversible Drug Protein Binding is usually a result of chemical activation of the drug, which then attaches strongly to the protein or macromolecule by covalent chemical bonding.
30
Protein Binding Site1. AlbuminMajor plasma protein componentReversible drug bindingBinds with acidic drugs2. Alpha-Acid GlycoproteinNonselectiveBinds with basic drugs3. GlobulinSpecific, and Responsible for transport of certain
endogenous substancesBinds with basic drugs
31
4. Lipoproteins Macromolecular complexes of lipids and
proteins Responsible for the transport of plasma lipids Responsible for binding if albumin is
saturated.5. Erythrocytes (RBC)• May bind to both exogenous and
endogenous compounds.• Penetration is dependent on the free
concentration of the drug.• Binding does not significantly affect
distribution.
32
Factors Affecting Protein Binding
1.The drug
2.The protein
3.Affinity between drug & protein
4.Drug Interaction
5.Physiologic Condition of the patient.
33
Special Barriers:Placental: most small molecular weight drugs
across the placental barrier, although fetal blood levels are usually lower than maternal.
Blood-Brain: permeable only to lipid-soluble drugs or those of very low molecular weight.
34
4.4. MetabolismMetabolism
a.k.a. “Biotransformation”the drug’s conversion to active
metabolites.
Phases of Drug Metabolism
1.Phase I Metabolism
2.Phase II Metabolism
35
Drug Biotransformation Reactions1.Active Drug to Polar Metabolite
2.Active Drug to Inactive Metabolite
3.Active Drug to Active Metabolite
4.Inactive Drug to Active Metabolite
5.Active Drug to Reactive Metabolite
36
1.1. Phase I MetabolismPhase I Metabolism a.k.a. “Functionalization”. Unmasking or addition of functional group.
Oxidation Reduction Hydrolysis
37
2. Phase II Metabolism a.k.a. “Conjugation”. these groups are relatively polar and make
the product less lipid-soluble than the original drug molecule.
Liver is the most important organ for drug metabolism.
Glucuronidation, Acetylation, Glutathione conjugation, Glycine conjugation, Sulfate conjugation, Methylation
38
5. Excretion the drug’s removal from the body. polar, water-soluble drug or metabolite.Route of Drug Excretion Kidney Biliary excretion Skin Tears Mammary gland Lungs Saliva Feces
39
Factors Affecting/Influencing Drug Effects
Weight Age Gender Pathological Factors Genetic Factors
40