Pharmacology Chapter 5 Quiz

Introduction to Pharmacology: Pharmacodynamics

• Goal of pharmacology is to prevent, cure, or control disease
• Anesthesia aims to manage physiologic changes
• This includes sedation, general anesthesia, amnesia, pain treatment, relaxation, and prevention of complications
• Safety is a key concern in pharmacology

Pharmacodynamics

• Study of what the body does to a drug
• Examines the relationship between effect site concentration and clinical effects
  • A specific effect site (biophase) is where the drug interacts with a receptor.

Pharmacology (General)

• Pharmacodynamics

  • The effect a drug has on the body.

• Pharmacobiophasics

  • The specific area of effect or site, where drugs interact with receptors.

• Pharmacokinetics

  • What the body does to the drug.
  • How the body absorbs, distributes, metabolizes, and eliminates a drug.

Physiology Review

• Cell membrane structure
  • Bi-layer
  • Mostly impermeable to ions and glucose
  • Contains channels, receptors, and enzymes.
• Mechanism for oxygen and carbon dioxide movement across cell membranes
• Sodium-potassium ATPase
  • Function: moves sodium and potassium ions across the membrane.
  • Number of Na+ ions moved (out).
  • Number of K+ ions moved (in).
• Endoplasmic reticulum and its role in protein, lipids, and carbohydrate metabolism.
• Sarcoplasmic reticulum role in muscle cell function.

The Action Potential

• Action potential graph

  • Motor neuron, skeletal muscle, cardiac ventricle
  • Time scales (2ms, 5ms, and 200ms)

• Resting membrane potential

  • Slightly polarized at -70 mV
  • ICF is relatively negative compared to ECF

Neuronal Action Potential

• Stimulus (e.g., change in nearby membrane potential) initiates the process.
• Threshold at -55 mV when Na+ voltage-gated channels open
• Membrane potential reaches +30 mV, Na+ channels close= inactivation
• K+ voltage-gated channels open as a delayed response
• Action potentials from three cell types are shown.

Action Potential Abnormalities

• Hypocalcemia
  • Prevents Na+ channels from closing between APs
  • Can cause sustained repetitive firing.
• Hypercalcemia
  • Decreases cell membrane permeability to Na
  • Results in decreased excitability of the membrane
• Hypokalemia
  • Negative effect on membrane excitability
• Sodium
  • Channel blockade affects AP generation.
  • Results in decreased contractility and altered cardiac conduction.

The Synapse

• Transmission from pre-synaptic membrane to post-synaptic membrane
• Neurotransmitter vesicles release neurotransmitters across a cleft
• Reuptake pumps and voltage-gated Ca channels are involved
• Receives afferent action potential

Synapse: Modulation and Fatigue

• Changes in synaptic function
• Synaptic signaling involves membrane potentials influencing depolarization and stimulus response.
• Interval is 0.3–0.5 ms for neurotransmitter release, diffusion, binding, ion flow.
• Fatigue occurs in excitatory synapses during repetitive stimulation.
• Reduced post-synaptic response occurs, possibly due to neurotransmitter depletion.

Neuronal Responsiveness

• Changes in pH
  • Alkalosis increases excitability
  • Acidosis decreases excitability
• Changes in PaO2
  • Hypoxia decreases excitability
• Other factors such as changes in pH and PO2 affect neuronal excitability.

Receptor Pharmacology

• Receptors bind endogenous chemical or drug
• Properties: sensitivity, selectivity, specificity, and locations
• Receptors are located in the membrane or inside the cell

The Receptor

• Administration leads to onset of effect
• Molecular orientation and receptor attachment rely on hydrophobic bonding.
• Conformational changes lead to cellular activity or tissue responses.
• Acceptors (e.g., albumin, alpha1 acid glycoprotein, beta-globulin) bind drugs, potentially reducing free drug concentration.

Chemistry Applications

• Dipole-dipole interactions are important for several biological processes.
• Hydrogen bonds play a crucial role in receptor pharmacology.
• Other specific chemical mechanisms are relevant.

Stereochemistry & Chirality

• Stereochemistry involves the 3D molecular structure.
• Chirality relates to 3D asymmetry in molecules.
• Enantiomers are mirror images that cannot be superimposed.

Receptor States

• Varying receptor conformations influence ligand binding and affect physiologic effects.

Receptor Actions

• Receptors receive and transduce signals following ligand binding.
• Signal transduction pathways involve signal amplification and integration.

Receptor Types

• G-protein-coupled receptors
• Ligand-gated ion channels
• Voltage-gated ion channels
• Kinase-linked receptors
• Nuclear receptors

G Protein-Coupled Receptor

• Comprises a receptor protein and G-proteins like α, β, and γ.
• Activation involves extracellular ligand binding, conformational change, GDP-GTP exchange, and interaction with effector proteins.
• Generates downstream events to affect response in cells.

Ion Channels

• Flow of ions driven by concentration gradients
• Different types include voltage-gated, ligand-gated, and mechanically gated channels.
• Na+, K+, Ca2+, and Cl− channels play crucial roles in cellular function.

Ligand-Gated Ion Channels

• Facilitate fast synaptic transmission between cells.
• Ligand-receptor binding causes conformational changes, opening or closing channels, affecting ion flow.
• Excitatory channels include acetylcholine, glutamate NMDA, AMPA, kainate, and serotonin receptors.
• Inhibitory channels include GABA and glycine receptors.

Voltage-Gated Ion Channels

• Channels change conformation in response to voltage changes across cell membranes.
• Involved in nerve impulse conduction and muscle contraction.

Cellular Response

• Cellular processes, enzymatic activities, and cell migration, are triggered by different signals and ligand binding.
  • Examples: increased/decreased activity, chain reactions, and more.

Cellular Response and Homeostasis

• Increased receptor number increases response to the agonist.
• Decreased receptor number and sensitivity reduces response to agonist.

Upregulation/Downregulation

• Upregulation increases receptor number; downregulation reduces.
• Chronic exposure to ligands can result in downregulation.
• Examples include drug exposure.

Drug Dose Response

• Dose recommendations are based on averages in normal, healthy populations; individualized treatment may be required
• Titration is typically needed until the desired therapeutic response
• Dose–response curves can be graded or quantal.

Potency vs Efficacy

• Potency refers to the drug concentration needed to produce a given effect
• Efficacy refers to the maximum effect a drug can produce (y-axis).

Receptor Pharmacology: Agonists, Antagonists

• Agonists mimic endogenous ligands.
• Antagonists block receptors.
• Partial agonists have only part of the maximal effect.
• Inverse agonists produce an effect opposite to that of an agonist.

Allosteric Modulator

• Binds to an allosteric site on the receptor
• Modifies the receptor's response to an agonist.
• Distinct from normal agonist binding site

Drug Interactions

• Additive effect: sum of effects due to combined use of drugs
• Antagonistic effect: one drug blocks the effect of another.
• Potentiation: effect of one drug is enhanced by another.

Tachyphylaxis

• Response to a given dose decreases with repeated administration
• Possible reasons include pharmacokinetic and pharmacodynamic mechanisms
• Examples include certain drugs that can cause tachyphylaxis

Quick Review/Trick Review

• Review of drug dose-response curve.
• Questions to help with understanding potency, safety margins and other related concepts.

Memory Master Knowledge Check

• Questions related to different concepts.

Pharmacogenetics and Population Variability

• Variations in genetic makeup can affect drug response.
• Pharmacogenomics helps identify optimal therapies.
• Drugs differ in their metabolic pathways.
  • Examples: CYP450 isoenzymes and more

Older Adult/Geriatric Considerations

• Changes in blood volume, body composition, and organ function affect drug response in older adults.
• These include factors affecting organ function.

Pediatric/Neonatal Considerations

• Factors like immature organs and rapidly maturing systems influence responses to drugs in children.
• Considerations of body composition, and metabolism affect drug action.

Obstetric Considerations

• Pregnant persons have physiological changes.
• Including considerations of increased blood volume, altered metabolism, and more.

Sex-Dependent Differences

• Hormonal differences and differences in organ function can influence drug responses in males vs females.