HPU1202 Human processes

What is Pharmacokinetics?

The way the body acts on the drug once it is administered.

Define Pharmacodynamics

How the drug acts on the body

What is Pharmacogenetics?

Genetic influences on medication response and focuses on inherited genetic differences such as single gene defects.

What is Pharmacognosy?

The study of medications derived from herbal and other natural sources. (complementary medicine.)

What are the six uses of medication?

• Symptom control

• Curative

• Contraception

• Diagnostics

• Prevention

• Health Maintenance

Oral Dosage Form

• Tablets

• Capsules

• Lozenges

• wafers

• sprays

• solutions

• suspension

• Emulsion

Suppositories/ Pessaries

Are administered via the rectum, vagina and Urethra.

Rapid uptake of drugs .

Topical Medications

• Semisolids

• Solution

• Transdermal Patches

• Implants

Parenteral Dosage forms

• Subcutaneous injection (SC) insulin, vaccines

• Intradermal (ID) TB tests

• Intramuscular (IM) Sustained release

• Intravenous (IV) Immediate absorption

• Intr-Arterial (IA) Rapid distribution to targets, contrast testing

• Intraosseous (IO) Into bone marrow, when IV not possible

• Intraperitoneal (IP) Experimental

• Intrathecal (IT) or Epidural Spinal cord/ Durmata

• Intraventricular (IVT) straight into the ventricles

• Intracameral - Anterior chamber of the eye

The four stages of Pharmacokinetics

• Absorption

• Distribution

• Metabolism

• Excretion

What is absorption?

Absorption is the process where medication passes from one site of administration to the blood stream to the tissues. To do so, the medication may need to cross one or more cell membranes. Passive transportation.

Factors affecting absorption

• Routes of administration

• Bioavailability

• Rate of absorption

• First Pass effect

• Bioequivalence

• Drug Formulation

• PH and Solubility

Define Distribution.

Distribution is the process by which a medication is carried from the site of absorption to the site of action.

5 points of distribution

• Blood flow

• Capillary Permeability

• Protein Binding

• Solubility

• Volume of distribution

Metabolism - Biotransformation

Changes an active medication into a less active metabolite. Changes a lipid soluble medication into a more water-soluble metabolite. Changes inactive prodrugs to an active form.

Metabolism - Biotransformation phase 1

• Occurs in the liver.

• Drugs are chemically modified through oxidation in hydrolyses

• enabled by CYP enzymes (Cytochrome P450)

• Makes medication more hydrophilic for easy excretion

• Can unmask functional groups to enable conjunction for phase 2

• These reactions can be active or toxic

Metabolism - Biotransformation - Phase 2

• Involves conjunction of medications with endogenous molecules

• The drug metabolites are chemically modified by the addition of a water-soluble group, such as glucuronic acid, sulfate methyl or amino acid

• These new larger molecules struggle to re- enter systemic circulation, so are excreted.

• This phase prevents the buildup of toxic or harmful compounds.

Define Polar

2 atoms do not share electrons evenly I.e. H2O

Define nonpolar

When the charge is distributed evenly involving two identical nonmetals i.e. O2, H2, N2

Define Hydrophobic

Resistant to water

Define Hydrophilic

Means Water loving

Define Lipophilic

Means Lipid loving

Define lipophobic

Resistant to lipids

Define ligand

A ligand is a molecule that binds to a receptor, to exert a biological or chemical effect. They can be anions, cations, neutral molecules and proteins ( hormones, insulin and neurotransmitters)

Define Pharmacodynamics

Pharmacodynamics is how the drug acts on the body

Drug receptor interactions

• Drugs act on the cell membrane by physical and chemical reactions

• This is usually through specific drug receptor sites known to be located on the membrane.

• Receptors are specific proteins, enzymes or molecules with which drugs interact

• Drug- receptor interactions determine the specificity and selectivity of a drug

• They dictate whether a drug activates or inhibits a cellular response

Types of receptors - G- PROTEIN - COUPLED RECEPTORS (GPCRs)

Mediate most cellular responses to hormones and neurotransmitters (Ligands)

Types of receptors - LIGATED ION CHANNEL RECEPTORS

Are integral membrane proteins that contain a pore which allows the regulated flow of selected ions across the plasma membrane.

Types of receptors - ENZYME - LINKED RECEPTORS

are a group of transmembrane proteins that contain intrinsic enzyme activity on their intracellular domain or a intracellular enzyme.

Types of receptors - INTRACELLULAR RECEPTORS

Are receptor proteins found on the inside of the cell, normally in the cytoplasm or nucleus

G Protein Coupled Receptors (GPCRs)

• These are seven transmembrane receptors, that transmit signals from the extracellular environment to the inside of the cell.

• More than half of all drugs target CPCRs and either activate or inactive them.

• Binding of specific ligands, such as hormones, neurotransmitters, chemokines, lipids and glycoproteins activates GPCRs by inducing or stabalising a new shape in the receptor

Ligated ions Channel receptors -

• Allows the movement of ions (Ligands) such as Na+ and C+ in and out of the cell.

• When the ligand or agonist drug binds it opens the channel

• The response of these channels is rapid

• This is a passive activity driven by an electrochemical for the semipermeable ions.

Enzyme- Linked Receptors

• Upon ligand binding enzymes are activated, initiating signaling cascades.

• An Extracellular signal is sent to the nucleus which alters the gene expression of the cell.

• All these receptors share the below features;

  Ligand - binding domain

  Transmembrane domain

  Cytosolic enzyme domain

• There are six types

  1) Receptor tyrosine kinases

  2) Receptor serine/ threonine kinases

  3) Receptor guanylyl cyclase’s

  4)Receptor tyrosine phosphatases

  5) Receptor histidine kinases

  6) Receptor-linked tyrosine phosphatases

Intracellular Receptors

• Are activated by hydrophobic (Lipophilic) ligand molecules that can pass through the plasma membrane

• Cell - surface receptors bind to an external ligand molecule and convert an extracellular signal into an intracellular signal

• These receptors play a crucial role in endocrinology and the development of drugs that modulate gene expression

Types of drug reactions to receptors - AGONIST

Are molecules that activate receptors, they simply bind to receptors and mimic the actions of the body’s own regulatory molecules.

Types of drug receptors - ANTAGONIST

Produce their effects by preventing receptor activation by endogenous regulatory molecules and drugs.

Types of drug reactions to receptors - PARTIAL AGONISTS

Are interesting in that they can act as antagonists as well as agonists for this reason they are sometimes referred to as agonists-antagonists

Drug action

• The effect of a drug is a product of the concentration of the drug at the binding site, this is called the dose response relationship.

• This is measured using a drug response curve

• This effect can be influenced by age, weight, gender and race.

• The three drug actions below impact on the dose-response relationship.

  Affinity, potency, efficacy.

Drug action - Affinity

Refers to the strength of the binding interaction between a drug ( or ligand) and its target receptor.

Drug action - Potency

Refers to the concentration or dose of a drug required to produce a specific side effect or response.

Drug action - Efficacy

Refers to the maximum biological response that a drug can produce when it fully activates its target receptor.

The seven R’s of medication Administration ddd prn max

• Right medication

• Right dose

• Right route

• Right Patient

• Right time

• Right documentation

• Right reason

• Right Date

List the Four types of Receptors in Pharmacodynamics

• G-Protein coupled receptors

• Ligand- gated ion channels

• Intracellular receptors

• Tyrosine kinase coupled receptors

Pediatric Implications Synaptic Formulation

• Childhood is characterized by a process of synaptogenesis, involving the formation of synaptic connections between neurons.

• As childhood progresses, synapsis pruning occurs, where unnecessary synapses are removed.

Pediatric Implications Myelination

• Myelination, the formation of myelin sheaths around nerve fibers, continues during childhood.

• The maturation of myelin contributes to the refinement motor and sensory functions.

Pediatric Implications Plasticity

• Childhood is characterized by heightened neuroplasticity, allowing the nervous system to adapt in response to experiences

• Including experience- dependent changes in synaptic strength, receptor sensitivity, and even structural modifications in the brain’s architecture.

Pediatric Implications Limbic System

_ Childhood experiences significantly influence emotional and social development, impacting the limbic system, which is involved in emotions and social behaviors.

Pediatric Implications Neurotransmitters

• Childhood experiences shape neurotransmitter systems, positively influencing the balanced release of serotonin, dopamine and glutamate. This contributes to optimal neural development in children.

Pediatric Implications Sensory and Motor development

• Childhood experiences influence the refinement of sensory processing, leading to the specialization of neural circuits dedicated to visual, auditory and tactile information.

• The maturation of the motor cortex during childhood contributes to the development and refinement of motor skills.

Pediatric Implications Hormonal changes

• Childhood is marked by a dynamic change in the levels of hormones such as cortisol, which is released in response to stress.

• Chronic stress during childhood can dysregulate the hypothalamic- pituitary - adrenal axis, influencing the stress response system.

Definition of Volume of distribution (VD)

Theoretical Volume of Fluid into which the total drug administered would have to be diluted to produce the same concentration in plasma

What is the equation for volume of distribution?

VD (L) Amount of drug in the body in mg

Over the amount of drug in the plasma in mg/ml

Parasympathetic Nervous system neurotransmitter

Acetylcholine

Enteric nervous system

• Myenteric

• Submucosal plexus

Define autocrine chemical communication

Released by cells and have a local effect on same cell type from which chemical signals released

Describe Paracrine chemical communication

Released by cells and affect other cell types locally without being transported in blood.

Describe what a neurotransmitter is.

Produced by neurons and secreted into extracellular spaces by presynaptic nerve terminals, travels short distances and influences post synaptic cells.

Describe endocrine chemical communication

Produced by cells of endocrine glands, enter circulatory system and affect distant cells.

Characteristics of the endocrine system include ?

• Body control system where regulation requires duration rather than speed

• Glands that secrete chemical messengers(hormones) into circulatory system (blood)

• Hormone characteristics:

  • produced in small quantities

  • Transported some distances in circulatory system

  • Acts on target tissues elsewhere in the body. -

  • Hormone secretion can be:

  • Acute - sudden release due to stimulus eg adrenaline in response to stress

  • Chronic - small variations over long periods, eg thyroid hormones

  • Episodic - estrogen and progesterone during menstrual cycle.

  • Target cells respond to a hormone because they have the correct receptor.

Functions of the endocrine system

• Metabolism

• Control of food intake and digestion

• Tissue maturation

• ion regulation

• water balance

• heart rate and blood pressure regulation

• control of blood glucose and other nutrients

• control of reproductive functions (gametogenesis and pregnancy)

• Uterine contractions and milk release

• Immune system regulation

Pineal gland -( in the head) main function

• sleep and wake cycle - circadian rhythm.

• Melatonin hormone

Hypothalamus CNS (Head)

Makes oxytocin and ADH, regulates the anterior pituitary gland

Pituitary gland - Anterior (Head) master gland

Tropic hormones

• Can make hormones -

• Stores hormones made from the hypothalamus

• Growth hormones - to promote growth

• Prolactin for milk production

• Thyroid stimulating hormones for the release of hormones from the thyroid gland

• Follicle stimulating hormones stimulates gonads to make gametes

• Luteinizing hormones stimulates the ovaries to produce estrogen and progesterone in females and stimulates the testes to produce testosterone for sperm production

• Adrenocorticotropic hormone (ACTH) stimulates the adrenal cortex to release hormones

Pituitary gland - Posterior (head) master gland

• Stores tropic hormones made from the hypothalamus

• Is completely regulated by the hypothalamus

• Oxytocin for childbirth (contractions)

• Antidiuretic hormone for stimulation of kidneys to reabsorb water

Parathyroid gland (neck, posterior )

• Parathyroid hormone - raises blood calcium level

• Bone metabolism

Thymus - (chest)

• immune system

• Pre puberty T cell maturity happens in the thymus

Thyroid Gland (neck, butterfly shape)

• T3 and T4 Stress and growth

• Calcitonin- lower the blood calcium levels

Adrenal glands cortex (Upper abdomen) Above the kidneys

• Glucocorticoids - Cortisol - increase blood glucose levels

• Mineralocorticoids - aldosterone - reabsorbs sodium in the nephrons

Adrenal glands medulla (upper abdomen) Above the kidneys

• Epinephrine - adrenaline, flight or fight, increased blood sugar levels. increased heart rate, increased contractility of the heart, relaxation of smooth muscle in the airways to improve breathing.

• Norepinephrine - Noradrenaline - increased blood sugar level, heart rate, increased contractility. Norepinephrine can also cause your blood vessels to narrow, which increases blood pressure.

Pancreas (left upper abdomen)

Sugar metabolism

• Glucagon

• Insulin

Gonads - ovaries and testes

• sperm

• - oocytes

• Hormones- testosterone, estrogen, progesterone

Similarities of Nervous vs Endocrine systems

• Both systems associated with the brain, endocrine - hypothalamus

• May use the same chemical messenger as neurotransmitter and hormone eg. epinephrine

• Two systems are cooperative eg. same parts of endocrine system innervated by nervous system (adrenal medulla)

Differences of nervous vs endocrine systems

• mode of transport - axon and blood

• speed of response

  • Nervous- instant / millisecond

  • Endocrine - delayed/seconds

    Duration of response

  • Nervous - milliseconds/seconds

  • Endocrine - minutes/days

Neuroglia of the CNS and PNS

• Astrocyte

• Oligodendrocyte

• Microglial cell

• Ependymal cell

• Schwann Cell

• Satellite Cell

Feedback loops

Homeostasis is regulated by feedback loops. feedback loops have three components.

1) a receptor which monitors the value of a variable by detecting stimuli.

2) A control center - Such as a part of the brain which determines the set point for the variable and receives input from the receptor about the variable.

3) a effector- which generates the response that adjusts the value of a changed variable. A changed variable is a stimulus because it initiates a homeostatic mechanism.

Negative feedback

Negative feedback mechanisms are more commonly involved in maintained of homeostasis than are positive feedback mechanisms. In everyday terms the negative is used to mean bad or under usable. In the context of homeostasis mechanisms, negative means to decrease. The response by the effector is stopped once the variable returns to its set point.

Positive feedback loop

mechanisms occur when a response to the original stimulus results in the deviation from the set point becoming even greater. In other words, posture means to increase.

What are the three layers of skin?

• Epidermis

• Dermis

• Hypodermis (subcutaneous layer)

The Epidermis

• Thin outmost layer

• Is composed of stratified squamous epithelium

• Made up of 4 types of cells, Keratinocytes, melanocytes, Langerhans cells and Merkel cells

• There are five layers - Stratum corneum, Stratum lucidium, stratum granulosum, stratum spinosum and stratum Basale

Corneocyte (Cells of the Epidermis)

• Flattened non nucleated

• Makes skin hydrophobic

• Creates a physical barrier

• Trigger repair mechanisms

Keratinocytes (Cells of the Epidermis)

• Epidermis - most common cell

• Tough protective layer

• Synthesis and secretion of lipids

• Keratinocytes have cholesterol precursor molecules that are activated by UVB into vitamin D.

• Immune response

Langerhans cells (Cells of the Epidermis)

• Stratum Spinosum

• Innate immune system

• Role in skin homeostasis

Melanocyte cells (Cells of the Epidermis)

• Produce melanin

• Melanin offers protection from UV radiation.

• Melanin production controlled by the sun.

Basal cells (Cells of the Epidermis)

• Maintains and renews epidermis

• Primary source of new cells.

• Anchored to basement membrane

Merkel Cells (Cells of the Epidermis)

• Involved in sensory perception of touch

• Closely approximated to nerve endings

• Release neurotransmitters.

The Dermis

• 2nd layer of skin

• Located between Epidermis and hypodermis

• Provides support, nourishment, elasticity to the skin, mechanical support, regulates temperature and sweat production and contributes to sensory perception.

• Divided into two mail layers: - the papillary layer and the reticular layer.

• Hair follicles and glands

• Papillary layer - loose Ariola connective tissue - finger prints and grip

• reticular layer - dense irregular tissue - collagen, blood vessels, sebaceous glands

• Hyaluronic acid

• Fibroblasts

• Elastin

Fibroblasts (Cells of the hypodermis)

• Fibroblasts are the most abundant cells in the dermis

• Are responsible for synthesizing and secreting extracellular matrix components

Macrophages (Cells of the Dermis)

• Immune cells that defend against pathogens

• Involved in phagocytes

Mast cells (Cells of the Dermis)

• Involved in inflammatory Reponses

• Releases histamine and other inflammatory mediators

Adipocytes (Cells of the Dermis)

• Are energy storage reservoirs

• Contribute to insulation and padding of the skin

Epithelial cells (Cells of the Dermis)

• Line blood vessels and lymphatic vessels within the Dermis.

• Regulate blood flow, nutrient exchange and immune responses

Pericytes (Cells of the Dermis)

• Associated with blood vessels

• Regulate blood vessel stability and play a role in wound healing

Neurons (Cells of the Dermis)

• Transmit sensory information, including touch, temperature and pain

Myofibroblasts (Cells in the Dermis)

• Specialized fibroblasts with contractile properties

• Involved in wound healing and tissue repair by contracting the wound edges.

The Hypodermis (subcutaneous level)

• Is an integral part of the skin and contributes to its overall structure and function.

• Has 2 types of tissue - Areolar (Superficial) and Adipose (Deep) tissue

• Functions are insulation, energy storage, cushioning and protection, connection with the dermis, vascular and nervous network.

• Also anchors to the skin and underlying muscle.

Fibroblasts (Cells of the Hypodermis)

• Fibroblasts are connective tissue cells that produce the extracellular matrix, including collagen and elastin fibers.

• They contribute to the structural support and integrity of the hypodermis.

Macrophages (Cells of the hypodermis)

• Immune cells that defend against pathogens

• Involved in phagocytes

Adipocytes (Cells in the hypodermis layer)

• Are the most common cells in the hypodermis

• These cells store triglycerides (fat) in the form of lipid droplets.

• Can be used as an energy source during periods if increased demand.

Endothelial cells (Cells of the hypodermis)

• Endothelial cells line the blood vessels that pass through the hypodermis, facilitating blood flow and nutrient exchange.

Pericytes (Cells of the hypodermis)

• Play a role in blood vessel stability