Pharmacology Basics

Fundamental Principles of Pharmacology

• Pharmacology studies the properties of drugs and their effects on the body.

Term Definitions

• Drug: Any chemical substance that interacts with a living organism to produce a response.
• Medication: A chemical substance used in the diagnosis, treatment, or prevention of diseases, symptoms, or pathological signs.
• Drug (Droga): A substance usually of plant origin obtained directly from nature or through simple manipulations.
• Human Use Medicine: A substance with properties for the treatment or prevention of diseases in humans, aimed at restoring, correcting, or modifying physiological functions.

Pharmacokinetics

• Pharmacokinetics studies the processes a drug undergoes as it passes through the organism.

Pharmacodynamics

• Pharmacodynamics describes the effects of drugs on the body.

Processes Affecting Drugs

• Main processes: absorption, distribution, metabolism, and excretion.

Factors Determining Drug Concentration in the Biophase

• Factor: The drug must first be released from its pharmaceutical formulation.

Drug Absorption

• Drug absorption refers to the entry of drugs into the body from the site of administration.

How Drugs Cross Cell Membranes

• Drugs cross cell membranes through the composition and structure of biological membranes.

Usual Mechanism for Drugs Crossing Cell Membranes

• The usual mechanism involves dissolution in the lipid component of the membrane.

Factors Affecting Drug Passage Through Membranes

• Factors: concentration gradients, solubility, hydrostatic pressure, gas pressure, and osmotic pressure.

Facilitated Diffusion vs. Active Transport

• Facilitated diffusion is a process where transport occurs along the electrochemical gradient and does not require energy.
• Active transport is when the passage occurs against the gradient, requiring energy input.

Mechanisms for Drugs Traversing Membranes

• Mechanisms: passive diffusion, specialized transport, and other transport systems.

Bioavailability

• Principals of active quantity and the speed in which it accesses the body and disappears are conditioned by various factors

Factors Influencing Drug Bioavailability

• Bioavailability depends on absorption, distribution, and elimination; it reflects differences in absorption when distribution and elimination are constant, expressing the quantity and speed of active

Routes of Administration

• Immediate (direct) routes: oral, respiratory
• Mediate (indirect) routes: otic, sublingual, conjunctival, transdermal.

First-Pass Hepatic Metabolism

• Drug is absorbed in the gastrointestinal tract (mainly the small intestine) and passes through the portal vein to the liver
• In the liver, it undergoes metabolization, where substances are transformed into inactive or less active metabolites before entering systemic circulation, and what remains enters general circulation to exert its effect.

Drug Transport Within the Body

• Drugs are transported through the body via distribution.

Importance of Drug Binding to Plasma Proteins

• Drugs are transported within the body through the bloodstream compartment and then penetrate into tissues.

Biological Barriers Affecting Drug Distribution

• Albumin is the most abundant protein and has a large surface area and binding capacity.

Drug Metabolism

• Drug metabolism is the set of chemical reactions carried out by the body on endogenous substances, environmental contaminants, and drugs.
• It primarily occurs in the liver.

Main Routes of Drug Excretion

• The most important routes of excretion are renal and biliary.

Renal vs. Biliary Excretion

• Renal excretion: involves glomerular filtration, tubular secretion, and tubular reabsorption.
• Biliary excretion: eliminates basic, acidic, and neutral substances via bile through enterohepatic circulation.

Pharmacodynamics Definition

• Pharmacodynamics refers to the integration of molecular interactions by which pharmacological agents exert their effects and how they affect the entire organism.

Drug-Receptor Interaction

• The drug-receptor interaction occurs when responses in many cells can be observed at the organ level or even in the patient.

Types of Drug Receptors

• Types: Primary Structure, Secondary Structure, Tertiary Structure, and Quaternary Structure.

Influence of Molecular Structure on Receptor Interaction

• The molecular structure of a drug dictates the physical and chemical properties that contribute to its specific binding with the receptor, including hydrophilicity, ionization state, conformation, and stereochemistry of the molecule.

Biochemical and Physiological Changes from Drug-Receptor Binding

• For receptors with enzymatic activity, drugs can bind to the active or inactive site.

Types of Drug Receptors

• Transmembrane ion channels have diverse functions, including neurotransmission, cardiac conduction, muscle contraction, and secretion.
• Transmembrane receptors coupled to intracellular G proteins are involved in processes such as vision, olfaction, and neurotransmission.
• Transmembrane receptors with linked enzymatic domains act in physiological processes like cell metabolism, growth, and differentiation.
• Intracellular receptors bind to small, lipophilic drugs capable of crossing the membrane by diffusion, including intracellular enzymes, signal transduction molecules, transcription factors, structural proteins and nucleic acids.

Dose-Response Relationship

• The pharmacodynamics of a drug can be quantified by the relationship between its dose and the body's response.

Graded vs. Quantal Dose-Response

• Graded dose-response: Effect of various doses of a drug in an individual.
• Quantal dose-response: Effect of various doses of a drug in a population of individuals.

Agonist

• An agonist is a molecule that binds to a receptor and stabilizes it in a particular conformation, typically the active conformation.

Partial Agonist

• A partial agonist binds to a receptor at its active site but produces only a partial response, even when all receptors are occupied.

Adverse Agonist

• An agonist that suppresses the receptor's intrinsic activity when the receptor is free.

Inverse Agonist

• An agonist that inactivates a constitutively active receptor.

Antagonist

• A molecule that inhibits the action of an agonist but has no effect in the absence of the agonist.

Competitive Antagonist

• An antagonist that competes with the ligand to bind to the agonist site.

Non-Competitive Antagonist

• An antagonist that binds covalently or with very high affinity to the agonist site.

Allosteric Non-Competitive Antagonist

• An antagonist binds reversibly or irreversibly to a site distinct from the receptor's active site, preventing the conformational change required.

Antimicrobial Pharmacology

Antibiotic Defined

• Antibiotic: A chemical compound used to destroy or inhibit the growth of microorganisms.

Discovery of Penicillin

• Alexander Fleming discovered penicillin in 1929.

First Human Use of Penicillin

• Howard Florey and Ernest Chain pioneered the use of penicillin in humans in 1940.

Distinctions Between Antimicrobials

• Antibiotic: A chemical substance produced by a microorganism used to eliminate or inhibit the growth of other microorganisms.
• Chemotherapeutic: A compound obtained through chemical synthesis with antimicrobial activity.
• Anti-infective: Any effective medication in the treatment of infectious processes.
• Antimicrobial agent: A substance produced by a microorganism or synthesized chemically that, in low concentrations, inhibits or destroys microorganisms.

Antimicrobial Agent

• A substance produced by microorganisms or chemically synthesized to inhibit or destroy microorganisms at low concentrations without adverse effects on the host.

Bacteria Sensitivity and Resistance

• Sensitive: The antibiotic can destroy or inhibit its growth.
• Resistant: Can only be destroyed with concentrations higher than what the drug achieves at the site of infection.

Characteristics of an Antibiotic

• Characteristics: specificity (spectrum of action), high biological potency (minimum inhibitory concentration – MIC), and selective toxicity (non-toxic to the host).

Antibiogram

• An antibiogram defines the in vitro activity of an antibiotic against a specific organism and reflects its ability to inhibit a bacterial population.

Methods of Dilution

• Broth or Agar: Microdilution in broth, disk-plate technique (Kirby and Bauer), and Epsilon test.

Kirby-Bauer Method

• Measures the diameter of the zone of inhibition of bacterial growth to determine the minimum inhibitory concentration (MIC).

Factors for Choosing an Antimicrobial

• Considerations: antibiogram results, pharmacokinetic and pharmacodynamic parameters, patient's clinical condition, and resistance patterns.

Interactions Among Antimicrobials

• Types: indifference (no difference in combined activity), addition (combined effect equals the sum of individual effects), synergism (combination increases effectiveness), and antagonism (combination reduces effectiveness).

Classification Criteria for Antimicrobials

• Antimicrobials are classified by origin (biological, synthetic, semi-synthetic), chemical structure, spectrum of activity (broad, intermediate, narrow), antimicrobial effect (bactericidal or bacteriostatic), and mechanism of action.

Bactericidal vs. Bacteriostatic

• Bactericidal: Kills the bacteria (irreversible effect).
• Bacteriostatic: Inhibits its growth but does not kill it (reversible effect).

Mechanisms of Antibiotics

• Inhibition of cell wall synthesis (e.g., beta-lactams).
• Alteration of the cell membrane (e.g., polymyxins).
• Inhibition of protein synthesis (e.g., aminoglycosides, macrolides).
• Inhibition of nucleic acid synthesis (e.g., quinolines, rifampicin).
• Inhibition of the synthesis of essential metabolites (e.g., sulfonamides).

Murein Synthesis Inhibitors

• Murein synthesis inhibitors bind to the d-ala-d-ala end of the murein monomer unit, inhibiting peptidoglycan glycosyltransferase; addition of murein units to the growing polymer chain is prevented.

Types of Bacterial Resistance

• Types: natural resistance (present from origin) and acquired resistance (developed through genetic mutations or transfer).

Mechanisms of Bacterial Resistance

• Enzymatic inactivation of the antibiotic (e.g., beta-lactamases destroy beta-lactams).
• Modification of the bacterial target (mutations prevent the antibiotic from acting).
• Blockade of antibiotic-bacteria interaction (changes in the membrane or expulsion pumps).

Mechanisms of Bacterial Resistance Acquisition

• Bacteria acquire resistance through conjugation (exchange of genetic material), transduction (transfer of genes by bacteriophages), and transformation (acquisition of free DNA).

Pharmacology of the Peripheral and Somatic Nervous System

Neuron Composition

• A neuron comprises dendrites, a cell body, and an axon.

Function of Dendrites and Axon

• Dendrites receive information from other neurons; the axon transmits information to other neurons or tissues.

Classification of Nerve Axons and Characteristics

• Fibers A: Myelinated, larger diameter, rapid conduction velocity.
• Fibers B: Myelinated, intermediate diameter and conduction velocity.
• Fibers C: Unmyelinated, smaller diameter and slow conduction velocity.

Pain Transmitted by Ad Fibers

• Transmit primary pain, which is sharp and highly localized.

Pain Transmitted by C Fibers

• Transmit secondary pain, which is slow, of longer duration, poorly localized, and characterized as dull or burning.

Analgesia vs. Anesthesia

• Analgesia: Specific inhibition of pain sensitivity using drugs or procedures.
• Anesthesia: Complete blockade of nerve conduction, affecting sensitivity to pain and other stimuli.

Local Anesthetic Definition

• A non-specific inhibitor of sensory, motor, and autonomic nerve transmission in the peripheral nervous system.

Chemical Structure of Local Anesthetics

• Chemical Structure: A lipophilic portion, an intermediate chain, and a hydrophilic portion.

Effects of Histamine in the Body

• Changes in permeability, vasodilation of arterioles and gastric secretion

Absorption of Local Anesthetics

• Absorption depends on the site of administration, the dose and concentration used, the physiochemical characteristics of the anesthetic, and the addition of a vasoconstrictor.

Ways to Administer Local Anesthetics

• Ways: Topical anesthesia, infiltration anesthesia, peripheral nerve block, central nerve block (neuroaxial), and intravenous regional and systemic anesthesia.

Adverse Effects of Local Anesthetics on the Central Nervous System

• By traversing the blood-brain barrier, effects on the central nervous system correlate with administered dosage, physiochemical nature, and pharmacokinetic characteristics.

Cardiovascular Effects of Local Anesthetics

• Local anesthetics act as membrane stabilizers, antiarrhythmics, and cardioplegics for the cardiovascular system.

Effects on Autonomic Nervous System

• They block nicotinic, muscarinic, histaminergic, and serotonergic receptors, behaving like curare by preventing the release of acetylcholine.

Muscle Relaxants (Estrated)

• Drugs (or medications) which block the function of the skeletal muscle for paralysis or to reduce spasticity

Action Mechanisms of Neuromuscular Blockers

• Mechanisms: blockade of the physiological agonist (acetylcholine) and excess of depolarizing agonist (like acetylcholine).

Types of Muscle Relaxants

• Types: neuromuscular blocking agents, spasmolytics, and antispasmodics.

Clinical Applications of Neuromuscular Blocking Agents

• Applications: orthopedic procedures, esophagoscopy, and treatment of strabismus.

Effects of Histamine Release from Neuromuscular Blockers

• Effects: vasodilation, hypotension, bronchoconstriction, and gastric secretion.

Inhibitory Neurotransmitters in CNS

• GABA (gamma-aminobutyric acid) and glycine are inhibitory neurotransmitters.

Spasmolytic Agents

• Spasmolytic agents with a central action mechanism facilitate GABAergic transmission in the CNS, such as diazepam.

Acetylcholine

• Acetylcholine is a neurotransmitter synthesized from choline and acetyl coenzyme A by the enzyme choline acetyltransferase (ChAT).

Release of Acetylcholine in the Synaptic Cleft

• Action triggers the opening of Ca2+ channels, causing the fusion of the vesicle membrane with the nerve terminal and releasing acetylcholine.

Degradation of Acetylcholine

• Acetylcholine is degraded by cholinesterase enzymes: acetylcholinesterase and butyrylcholinesterase.

Types of Muscarinic Receptors and Functions

• M1: central nervous system, M2: heart, M3: Smooth muscle contraction and glandular secretion
• M4 and M5: Less defined Functions

Types of Nicotinic Receptors

• Receptors: N1 (Nm) at the neuromuscular junction and N2 (Nn) in autonomic ganglia and the CNS.

Autonomic Effects of Acetylcholine

• Effects: contraction of smooth muscle, increased glandular secretion, and a decrease in heart rate.

Pirenzepine

• Pirenzepine is an antiulcer drug that blocks the M1 receptors in the acetylcoli, reducing Gastric secretion

Clinical Use of Metacoline

• Diagnosis of bronchial hyperreactivity (asthma).

Synthetic Nicotinic Receptors

• Produce adverse effects: cardiac arrhythmia, cardiac arrest, hyperkalemia, anaphylaxis, respiratory depression.

Fisostigmina

• An antiolinesterasiqeu blocks the hydrolysis of the anetilcolina and prolongs the action

Clinical Applications of Acetilcolinesterasic Inhibitors

• Increase the transmition to the neuromusclar union and the intensity parasimtatico
• Can treat sintomas of EA

The Adverse Effects of Acetilcolinesterasic Inhibitors are:

• Nausea, vomits and anorexia

Principles of Pharmacology in the Central Nervous System

Primary Inhibitory Neurotransmitter

• GABAergic inhibits conductions/electrolytes

Dopamine

• Dopamine can be related to Parkinson’s decease and esfirofrenia (Verdadera)

Que farmaco presenta

• Benzodiacepina ( Respiratory depression, apnea, agitation, excessive somnolencu, cefalea and fatia

Que farms produce efectos adversos

• Barbicurios (Causes Stevon’s Johbson system, medular depression, sedition, ataxia and confusion)

Tiopentato sodico

• Produces Constant sedation and diminish the inhibitorio processes

Inducction Anestesia Pharmacu

• Estomidato (Induction for anesthesia)
• Has hypotentsion and vomit

Pharmaco utilizado induction en la anestesua

• Propofol (Cardiovascular and respiratoru depression)

Fármaco receptores GABA B

• Baclofeno: sedation, depression, cardiaca

Sirve Para la Epilepsia

• Lomotrigina: Stabalisar el estado actica

FÁRMACOS NO DOPAMINÉRGICOS

• amantadina y anticolinergico

TIPICOS vs ATIPICOS

• Antisipticos

Fármaco Precursor Dopamina

• Pertanencen Los efectos adversos

Drogas Que te ayuden arejar fumar

• Antidespresivos atipico

farmacu que es util to polat disorders

• Altera los caones y los transportadores
• Lisio (Daño cardio vascular and deshidrataciones)

Parte de los frmacus inhibitarios de los cabales

• Benzodiacepina (inhibitors de la canales Gaba)

De inhibidir de canales de sodio que toene efectos

• Fenitoína Cabamazepina Lamotrigina= Hematopaias Ataquia Nitsmo (Sodium inhibitors)

tipo de dolor pde occurir despues

• Neuropatico- Alteracioner furracionales

farmaco 4-6 horas

• Tramadol convulsiones y serotinérgico

se utilizan tratamientos

• antidespresuvos- adjuvant in the manjo del dolor

manejanel dolor cirnico

• Antiepileplos- cronoic dolor

en su rol en la inducion

• antagonism del receptor NMDA.
• Ketanina and Dextromutafeno.

Que en el cuero dorsal

• agonistas adrenérgicos- ANTI Nociseptivo

farmacus utilizadas

• Triptanos: attacks a miocardio/ migranosas agudos- se tome al inicio de un episodio.

Pharmacology of Oral Rehydration and Endovenous Solutions

Forces Controlling Fluid Movement

• Starling forces control liquid displacement.

Measurement of Solute Concentration

• Osmolarity measures the concentration of solutes, expressed in milliosmoles per kilogram of water (290 mosm/kg +/- 10 mosm/kg).

Electrolyte Concentrations

• Intracellular: large amounts of K+, phosphates, Mg2+, and proteins.
• Extracellular: large amounts of Na+, Ca2+, Cl-, and HCO3-.

Parameters

Clinical Parameters Usadas

• valor de 7-35-7-45 and PacO3-Hco2

¿Cuáles SON LOSS perridas fisiologias?

• 70 kg de perdidas
• 90-1000 ml de aguay-

Physiological Factors

• Collabora

Following

• estimar el balance
• estudios de laboratorium
• evaluar al paciente

Symptons of Hipolovolemia

• Sed / vomiting/ diarrhea/loss of weight

symptomas de HIPERVOLEMIA

• dismena/ orthopnea/ night

¿hipovolemia quie por lo reqular si tranmiento?

• Hipovolemia leve

hipovolemia gue su tranmiento obiliga?

• Hipovolemia graves

Cual Es la Solucion Mas

• HIPONATREMICO AND hipotonicos

Que Terapias Estal Indicada prevent

• TRO Therapy- Deshitatacion

Que Proteina Transportadora

• SGLT-1 de el transport

Los factors fisiológicas

• Content de electrioltos y bases

Coma es la formacion Recomendada

• GLUCOSA 60-111 -mMOLi

El rango es to glosado o soluciónsde OSORALAD

• Los farmacos 65

Cual ES La SRO que deminuye eel volomen

• sro fortificadas son zinc

se utiliza en deshdratacios por diarrea?

• Hiposomolores- desnutricion sever

Ente 1000 and 20 mil

• Entre edadaes o retroaimatación debes

la correct de ellilibros

• fluidoterapia inttravenosa- electrolitos.

Clucosidad al 5%

Que Produce La Potasio Dilucion?

• Hiperpotsarmia

Cual el el traamiento innial

• Observa y tratar the trastomos.

hiponatrerma silinomica gie intervencion on la

• Infusion de surero salino hipernionico.

que tipp de solusiion se neeeeitoisa

• Suere salino insotonico- volume extraceluula

aPPoretdde agua?

• La nomoverdemia