W1 Pathophysiology, pharmacology, pharmacodynamics, Pharmacokinetics Flashcards
Explain the term pathophysiology
Is the study of changes in physiology that occur as a result of a disease or disorder.
Explain: Homeostasis of cell function, by disruption of internal/external. Cell compensates to try and (repair) to reach new state = functioning at a subprime state.
Disruption of homeostasis → Aetiological agent (initial insult) → defective tissue/organ function → defective organ system → related systemic effects
↓ Manifests as signs and symptoms → diagnosis → therapy → prognosis
Define aetiology
Aetiology is the cause of disease, Biological eg. bacteria, viruses Chemical: e.g poisons Nutritional: e.g excess or deficit in diet Physical: e.g trauma, burns UV Genetic
Define nosocomial
Cause of disease that arise specifically because of exposure to a hospital or clinical care environment. The source must have been acquired while in clinical care
Define iatrogenic
Induced inadvertently by clinical practitioners
Define idiopathic
Cause of disease are unknown and disease appears to rise spontaneously .
Explain the term pathogenesis.
The progression of diseases even so when it does not cause abnormal physiology by themselves but is required for disease progression . All stages from initial exposure to the cause of disease to complete recovery (or not).
Describe the types of clinical
manifestations Signs and manifestations
Signs: changes that can be MEASURED by an observer eg swelling, temp, BP
Symptoms: OBSERVATION changes reported by a sufferer eg. pain, dizziness
Define diagnosis
A conclusion reached after assessing the signs and symptoms and interpreting the results of diagnostic tests
Define morphology
Structure of cells and tissues; alterations may occur as a result of disease. The cell structure is known as histology.
Define histology
Cell structure
Define epidemiology
The study of diease within population - occurrence, determinants, distributions, and control of disease within a population
Define sporadic
Disease that occurs occasionally at irregular intervals
Define endemic
Disease that is always present at low frequency within a population
Define hyperendemic
an increase level of endemic disease
Define epidemic
a sudden increase in a disease above an expected level
Define pandemic diseases
a sudden increase in a disease above expected levels over a very wide region or larger population (global)
Define outbreak
A sudden and unexpected occurrence of a disease (specific location)
Define index case
The first case in a epidemic
Define prevalence
Total number of cases, new and existing
Define morbidity
Number of ill people in a population per unit of population
Define mortality
death rate per units of population
Define drugs and the 3 ways of naming them
Drug: substances or products that are used or intended to b used to modify or explore physiological systems. ANy substances that brings about a change in biological function through chemical actions.
Pharmacology - study of interaction between drugs and living organisms.
Theerapeautics - drugs used to diagnosee, prevent and treeat disease or prevent pregnancy
Generic or Non-Propietary, Chemical name, Proprietary or brand/trade name
Explain how drugs are grouped and exemplify
Uses: medicinal or recreational effect: on the body Source: synthetic or plant) Legal status (legal/illegal) Risk status (dangerous/safe)
HOT TIP:
azoles - antifungals
statins - anticholstrol drugs
mycin - antibacteria
Progression of pathogensis examples, small poxs + melanoma
Small pox:
Source → pathway of entry → transmission + retransmission (replication) → moves into organs → Incubation → widespread through organs → toxemic phase →death
Melanoma:
Exposure to UV light → Genetic damage to skin cells → damaged skin cellls, divide rapidly → growth of an abnormal cell mass → local tissue damage → movement of abnormal cells via vasculature → secondary melanoma → loss of organ function = death
Define Syndrome
Syndrome: a collection of signs and symptoms that occur together
Define complications
Complications: extention of disease or the result of treatment for a disease
Define sequelae
Sequelae: lesion or impairments that remain after a disease has been resolved
Outline and describe the phases of a disease’s clinical course (acute)
sudden onset but short term
Outline and describe the phases of a disease’s clinical course (chronic)
more slowly developing and longer lasting disease often relapsing/remitting
Outline and describe the phases of a disease’s clinical course (pre-clinical or prodromal period)
Disease present but not yet developed specific symptoms. Vague symptoms
Outline and describe the phases of a disease’s clinical course (subclinical)
Disease present but displays no symptoms
Outline and describe the phases of a disease’s clinical course (Convalescent)
In process of recovering
Describe Incidence
Number of new cases of a disease diagnosed within a particular period
Define the process of drug absorption,
correlating with routes of administration
[absorption]1. Oral: drug absorption is the movement of a drug into the blood stream after administration. Sublingual via vascular bed under the tongue Stomach - not an important site Small intestine - major site for absorption Rectal suppository - absorption via vascular bed. 2. Topical place on the skin 3. Inhaled into the lungs 4. Parenteral (needle) - subcutaneous Intramuscular Intravenous Intrathecal Epidural 5. Others Intra-articular Intra-osseous Intra-peritoneal Intrapleural
Describe ways a drug can cross biological
membranes.
Oral: drug absorption is the movement of a dug into the blood stream after administration, primarily in the small intestine. They cross the cell membranes of epithelial cells in the gastrointestinal tract,
Define mechanism of action and mode of action of drugs
Mechanism of action (MOA) : biochemical interaction through which a drug substance produces it pharmacological affect.
- drugs molecular target
- the ways drugs interact with that molecular target when bound to it.
Define the mode of action of drugs
Mode of action (MoA): describes the functional or anatomical changes, at the cellular level resulting from the exposure of a living organism to a drug
Outline the 4 typical molecular targets, explaining their cellular functions
The molecular target of a drug: molecule in the body usually a regulatory protein associated with a particular disease process. Regulatory proteins respond to endogenous substance: a chemical produced by the body, such as hormones and neurotransmitters → producing a therapeutic effect
- Transporter
- Enzyme
- Ion channel
- Receptor
Exemplify drugs that do not interact with the typical protein targets.
Physiochemical action eg. some inhalant anaesthetics
Physical action: osmotic laxatives, activates charcoal
Some cancer chemotherapeutic and antimicrobial: e.g drugs bind to DNA
others: e.g sunscreens, spermacides
Explain the concepts of drug specificity
Specificty: how successful a drug is in interacting with only one molecular target having one effect
Outline molecular target RECEPTOR explaining their cellular functions
Receptors are proteins that bind specific molecules (lock and key) activating a repsonse within a cell. They are translators of molecular signals from inside or outside a cell. Intracellular → cascade of protein activation or deactivation. Extracellular receptors ↓ a. Protein G coupled receptor b. Enzymes-linked receptor c. Ligand-gated receptor
Intracellular receptors ↓: directly regulate gene expression.
a. steriod hormone receptors
Outline molecular target ION CHANNELS explaining their cellular functions
Regulate flow of ions (Na+, K+, Ca+) through the plasma membrane. Channel blocker drugs “close the gate” to ions
Outline molecular target TRANSPORTER/CARRIER explaining their cellular functions
Uses ATP energy (active transport) to move molecules that cannot cross the cell membranes by diffusion
Outline molecular target ENZYMES explaining their cellular functions
Are biological catalysts that control biochemical reactions therefore physiological responses.
Drugs can interact with enzymes in a number of ways
Explain the concepts of drug specificity
Specificty: how successful a drug is in interacting with only one molecular target having one effect
Outline molecular target ENZYMES explaining their cellular functions
Are biological catalysts that control biochemical reactions therefore physiological responses.
Drugs can interact with enzymes in a number of ways
Explain the concepts of drug selectivity
Drugs favor and bind to one receptor over another
Describe ways a drug can interact with molecular targets (possible effects).
Agonists: drugs that occupy receptors and activates them → produces a biological responses in the same way that endogenous agonist (naturally made by body). Mimics the natural receptor to bind ‘lock and key’ .
Effects:
Antagonists: Drugs that occupy receptors but do not activate them. Antagonists block receptor activation by agonists → bind by produce no functional response.
Effects: Agonist / Orthostetic agonist - occupies that same binding site as the endogenous agonists. → Produces a response.
Allosteric agonist: Occupies a distinct binding site as the endogenous agonists. ↑ the response in the presence of the endogenous agonist.
Competitive reversible antagonist: compete for binding site. Binds with low affinity so it can bounce off the receptor. Effect can be overcome by ↑ concentration of the receptor agonist.
Competitive irrevrsible antagonist: receptor becomes permanently blocked, The affinity between antagonist and binding site is hight.
Non-competitive antagonist: share the binding site with the agonist. ↓ response.
Allosteric modulator: occupies a different binding site (not the agonists binding site). Modulates (regulates) response (m may ↑or↓)
Explain the drug concentration-response relationship, contrasting potency and efficacy.
Relationship between the concentration of a drug at a receptor site and the magnitude of the response. EC50 effective concentration is the concentration at which the drug produces 50% of the maximal response.
Maximal efficacy Emax when all the receptors are occupied by the drug.
Potency: how strong the drug is
- Correlated with affinity of the drug for it’s target.
Efficacy: how well the drug does it’s job; the ability of the drug to elicit a response once bound to the receptor
Define toxic dose, effective dose, and therapeutic index.
Toxic does: Keep giving drug until 50% of people DIE, can damage an organisim
Effective dose: Persons whom have responded to does
Therapeutic index: is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity.
- Explain the relevance of knowing the therapeutic index of a drug.
Therapeutic index: is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity.
Compare adverse drug reaction, adverse drug event and adverse effects.
Adverse effects: unwanted effect that results from activation of a secondary molecular target. May or may not be dose related.
Adverse drug reaction: any response to a drug that is noxious, unintended, and occurs at doses normally and appropriately used in man for prophylaxis, diagnosis, therapy of a disease.
Adverse drug event: Inury resulting from medical intervention related to a drug. Occurs while taking the drug but may not be directly due to the drug, eg operator
Explain and contrast drug tolerance from tachyphylaxis.
Drug tolerance: When the repeated use of a drug leads to a ↓ in drug effect for same does. May be due to an ↓ in drug metabolism or receptor downre gulation.
Tachyphylaxis (short term, acute, sudden): ↑ doses are ineffective! Sudden irresponsiveness
Define drug dependence and withdrawal.
The need to use a drug to function normally. may exist when the body has a deficienxy and a drug is needed for survival.. May develop fron continual exposure, leading to body adaptation.
Drung withdrawal: Group of symptoms that occur upon the abrupt discontinuation of ↓ in intake of medications or recreational drugs to which the body was dependent.
Explain the concepts of drug affinity.
Strength of the bond between a drug and its molecular target. Bonds well to it’s binding site.
Eg. ionic, covalent, or hydron bonding, hydrophobic interactions
Explain the concepts of drug affinity.
Strength of the bond between a drug and its molecular target. Bonds well to it’s binding site.
Eg. ionic, covalent, or hydron bonding, hydrophobic interactions
Outline the 4 processes described by pharmacokinetics.
Is the branch of pharmacology concerned with how the body affects a specific drug after administration. Movement of drugs inside the body and the physiological process that acts on the drug once it enters the body
Absorption: how the drug enters the blood
Distribution: where the drug goes in the body
Metabolisim: how the body processes the drug
Excretion: eventually the body gets rid of the drug
Describe ways a drug can cross biological membranes.
Transporter proteins and channels
move charged or polar molecules
across membranes through pores
lined with hydrophilic domains
Discuss factors that may impact drug absorption.
- Surface for absorption – area of the GIT wall
- Blood flow – increased blood supply improves absorption
- Formulation – e.g. the type of drug coating
- Molecule size – most drugs are small. It’s harder to absorb larger
molecules such as peptides (like hormones). - Drug concentration gradient – the larger the dose, quicker is
absorption - Solubility of the drug – non-polar molecules move across
membranes more rapidly than polar ones. - Ionisation – unionised molecules can cross membranes
– ionised drugs use transport systems to move drugs from gut to
blood and from blood to urine
Define drug metabolism, explaining roles of phase I and phase II metabolic reactions.
Drug metabolism is the term used to describe the biotransformation of
pharmaceutical substances in the body so that they can be more easily
eliminated
• Occurs predominantly in the liver.
Phase I – catabolic reactions
• Tends to make more chemically reactive products
• Uses cytochrome (CYP) P450 family of enzymes
Phase II – anabolic (synthetic) reactions
• Conjugation reactions that tend to result in inactive products.
1. makes the drug more water soluble to increase renal excretion – pentobarbital → hydroxypentobarbital 2. Inactivates the drug – procaine → PABA 3. Increase or change the action – codeine → morphine 4. Activate a prodrug – Levodopa → dopamine 5. Alter toxicity – paracetamol → hepatotoxic compound
PHASE 1 Functionalisation Enzymes make drug more polar, adding a functional group PHASE 2 Conjugation Different enzymes bind that functional group to a polar molecule
Explain the role of the P450 enzyme group in drug metabolism.
Phase I: functional group added, oxygen, hydrogen, water. ↑ water solubility
Involves; cytochrome (CYP) p450 enzyme family. Main role is to generate a reactive site. Eg, asprin, heroin .
ConjugationL joins modified compind to a polar moleecule. Increases water solubility even more enhancing renal excretion
Define bioavailability and hepatic first-pass effect, discussing their relationship.
Bioavaliablity: Amount % of the drug that is available to the body to produce a therapeutic effect. The amount of a drug reaching the systemic circulation is dependent on:
1. The amount of drug not actually absorbed.
2. The amount drug inactivated the first time it passed through the liver.
Hepatic first-pass effect: The amount of drug inactivated after passing through the liver for the first time after absorption. Eg loss of active drug molecules.
Discuss how chemical substances may interfere with metabolic enzymes
Enzyme induction: enzymes and transporters are proteins an ↑ in a proteins expression ↑ it activity. ↓ bioactivaliablity
Induction ↑ expression of enzyme.
Inhibition: result of competition for the active site of an enzyme. ↓ metabolisim of atleast. this affects bioavaliablity by ↑ it
Explain how genes influence drug metabolism.
Genetic differences between people can influence absorption time, hepatic drug metabolism, clearance and drug effects.
Describe how plasma protein binding of a drug affects drug distribution and action.
Distribution: Some drugs are carried around the body by plasma proteins. Only free (unbound) drug can exert a therapeutic effect,
- This may depend on drug/plasma protein affinity.
- The amount of free drug tends to be constant.
Explain the factors affecting drug distribution.
Factors that impact on binding:
- Number of binding sites
- Abnormal plasma protein
- drug concerntration
- Blood supply to tissue
- Lipid soluable drugs cross membranes
- Affinity for plasma protein binding
- Presence of drug transporters
DRUGS WILL NOT GO:
The brain (blood brianbarrier.
The placenta.
Only lipid soluable drugs will pass through thse tissues
Explain the factors affecting drug distribution.
Factors that impact on binding:
- Number of binding sites
- Abnormal plasma protein
- drug concerntration
- Blood supply to tissue
- Lipid soluable drugs cross membranes
- Affinity for plasma protein binding
- Presence of drug transporters
DRUGS WILL NOT GO:
The brain (blood brain barrier.
The placenta.
Only lipid soluable drugs will pass through these tissues
Define drug clearance and explain why it is it is clinically relevant.
Clearance: a measurement of how quickly a drug is eliminated by the body - useful to determine dosage regime
CL = CL hepatic + CL rental + Cl other
Define the half-life of a drug and explain why it is clinically relevant.
Half-life is the time rquired to reduce th plasma concerntration of the drug to 50% of the original value. Used to determin dosing requirements to reach a steady state. (steady state → the amount of drug administrated = amount od drug eliminated within one dosing interval resulting in a plateau or constant serum level
When a drug is ingested: plasma drug concentration will ↑ until the drug is fully absorbed then ↓ while it is eliminated.
( The area under the curve reflects the time body is exposed to drug aftere dose administration.
Drugs administered intravenously reach a peak concentration sooner. Drugs administered orally take longer to have an effect but stay longer in the system
Discuss how renal failure can impact on drug half-life and the risk for drug toxicity.
Renal failure results in not being able to eliminate the drug, Therefore remains in blood longer, thus increasing in the blood. The dose should be decreased
Discuss how age interferes with drug therapy.
Organ fucntion may be comprimised by
OLDER
age = ↑ risk of toxicity.
Absorption: slower gastric emptying.
Distribution: ↓ body water. ↓ increased body fat. ↓ reduced plasama protein. blood-brain barrier more permeable.
Metabolism: ↓ hepatic blood flow,’↓Reduced enzymatic activity.
Excretion: ↓ renal blood flow, ↓atrophic renal tissue.
NEONATES: less than one month old. - ↓ protective mechanisims ↓ skin is thin and permeable ↓ body fat ↓ stomach lacks acid ↓ renal excretion is less efficient ↓ regulate temp poorly ↓ becomes easily dehydrated ↓ delayed maturation of hepatic drug metabolsim enzymes which can lead to drug toxicity
Define drug distribution and describe interactions with different body tissues.
Distrubution through the blood stream → exits the blood stream through capillary walls. → enters ECF, diffuses to cells → binds to target on cell → (1) DRUG ACTION or enters cell → (2) drug action.
DRUGS WILL NOT GO:
The brain (blood brainbarrier.
The placenta.
Only lipid soluable drugs will pass through these tissues.
Drugs maybe stored in adipose tissue (fat). It has a ↑ affinity for lipid soluable drugs. Acts as a stable reservoir of the drug .
Bone affinity: tetracycline antibiotics absorbed by bone crystal matrix acting as a storage site for teeth: this causes discolouration.
- Bisphosphonates: uses to stablise bone matrix in osteoporosis
