Pharmacology Flashcards
Define pharmocokinetics
What the body does to the drug
Define pharmoacodynamics
What the drug does to the body
What are different methods of drug transfer across membranes
Aqueous diffusion Passive lipid diffusion Facilitated diffusion Pinocytosis (budding of membrane to ingest into cell) Active transport
What factors affect rate of membrane transport according to ficks law?
Diffusion coefficient Surface area Membrane thickness Partition coefficient (how drug distributes in liquid vs oil) Concentration gradient
What are the methods of drug disposition?
Absorption
Distribution
Metabolism
Excretion
Define bioavailability
Fraction of dose reaching systemic circulation after administration compared to same dose given intravenously
What factors affect drug absorption?
Route of administration
Formulation
How does ionisation affect absorption of drugs?
Drugs are weak acids or bases, with ionisation affected by their pKa and surrounding pH
pH changes with infection etc
Non-ionised drugs- cross by passive diffusion
Ionised drugs- cross by transport mechanisms, facilitated diffusion or pinocytosis
List routes of drug administration and how it affects drug absorbtion
Intravenous- rapid absorption as directly into systemic circulation
Intramuscular- speed dependent on local blood flow and diffusion of muscle
Subcutaneous- slower and less predictable, depends on site, temperature, hydration etc.
Oral- mainly absorbed in small intestine, effected by GI motility, splanchnic blood flow, drug size etc., will undergo first pass metabolism
Inhalational- causes local effect or absorbed into circulation
Epidural, transmucosal, transepithelial- effects at site of admin, can be taken up systemically
What is meant by first pass metabolism?
Concentration of drug given orally is reduced before entering systemic circulation
What determines volume of drug distribution?
Amount administered and concentration of the drug in plasma
How does protein and tissue binding of a drug affect its distribution?
Albumin binds weak acids
Alpha-1-acid glycoprotein binds weak bases
Only unbound drugs can interact and cause effect on the body
(Tissue binding can be specific or non-specific)
How does organ blood flow, membrane permeability and drug solubility effect drug distribution?
Drugs initially go to tissues with high blood flow
Highly lipid soluble drugs will accumulate in fat
Define clearance
Volume of plasma from which drug is completely removed per unit of time
Define half-life
Time taken for plasma concentration to fall 50% of original level
What factors affect drug metabolism and excretion?
Clearance and half life
Define biotransformation
Alteration of substance within the body
Name the stages of drug metabolism
Biotransformation
Excretion
Why do most drugs need to undergo biotransformation before they can be excreted by the kidneys?
Lipophilic and highly bound
Kidneys excrete polar water soluble compounds most easily
What is the main organ of metabolism and how does it work?
Liver
Phase one- convert drug to polar metabolites allowing renal excretion
Phase two- conjugation/combining with substrates
What can be the effects when drugs are activated by metabolism?
Become active drug
Produces active metabolites causing further effects
Produces toxic metabolites
What is the most common excretion of drugs and how does it work?
Renal
Active- tubular secretion
Passive- glomerular filtration
What other methods of drug excretion are there other than renal?
Biliary system
Exhalation
GI system
What is meant by enterohepatic circulation?
Pathway drugs take until plasma concentration drops
Describe the pathway taken by drugs in enterohepatic circulation
Drug metabolised by liver Biliary excretion Deglucorinidation/reverse metabolism by gut microflora Reabsorption in gut Drug metabolised by liver
List the stages a drug takes when causing an effect on the body
Drug site of action
Pharmacological effect
Clinical response- therapeutic effect and toxicity
Define clinical response
What is seen due to drug
Define therapeutic effect
Desired effect of a drug
Define toxicity
Side effects of a drug
List non-cellular mechanisms of effect of drugs
Physical
Chemical
Physiochemical
Modification of body fluid composition
List cellular mechanisms of effects of drugs
Alter physicochemical mechanisms of the body
Cell membrane structure and function modification
Enzyme inhibition
Receptor mediation
Define therapeutic index
Maximum non-toxic/minimum effective dose of a drug based off 50% of animals
Why is using therapeutic index for drugs flawed?
Effective dose will vary depending on what is being treated
Wont account for idiosyncratic drug reactions (reactions unrelated to dose)
Define affinity
How well a drug binds to its receptor
Define intrinsic activity/efficiacy
Magnitude of effect once bound, measured 0-1
Define agonist and state an example
Generate maximal response when bound to a receptor, have high affinity and intrinsic activity/efficacy
Morphine
Define partial agonist and state an example
Intrinsic activity less than 1 so cant generate maximal response even with full receptor occupancy
Buprenorphine
Define inverse agonist and state an example
Drug binding exerts opposite effect compared to endogenous agonist
Antihistamines
Define antagonist and state and example
Exhibits affinity without intrinsic activity
Atipamezole
Define potency
How much of the drug is needed to cause wanted response
List the molecular targets for drugs
Receptors Enzymes Transporters Ion channels Nucleic acid
Define ligand
Substance that forms complex with boimolecule
Define receptors
Protein interacting with extracellular physiological signals, converting them to intracellular effects
Name an example of a receptor for drugs
Mu opioid receptor
What is the difference in effect of agonists and antagonists on receptors?
Agonists- cause direct effects (ion channel opening/closing) or transduction mechanisms (enzyme activation or inhibition, ion channel modulation, DNA transcription) to cause effect
Antagonists- no effect caused or prevent agonist binding preventing or reversing effect of agonist
List the 4 main types of receptor
Ligand gated ion channels (ionotropic- membrane bound)
G-protein coupled receptors (metabotropic- initiates metabolic processes to modulate cell activity)
Kinase linked receptors
Nuclear receptors
What are the characteristics of ligand gated ion channel receptors? (Speed of action, how they cause effect, example)
Act in milliseconds
Hyperpolarise or depolarise
Nicotinic ACh receptor in neuromuscular junction post synaptic membrane
What are the characteristics of G-protein coupled receptors? (Speed of action, how they cause effect, example)
Act in seconds
Change membrane excitability or second messengers cause effect leading to cellular effects
Muscarinic ACh receptor in smooth muscle of blood vessels
What are the characteristics of kinase linked receptors? (Speed of action, how they cause effect, example)
Act in hours
Protein phosphorylation leading to protein synthesis and cellular effects
Cytokine recpetors
What are the characteristics of nuclear receptors? (Speed of action, how they cause effect, example)
Act in hours
Gene transcription and protein synthesis causing cellular effects
Oestrogen receptor
How do enzymes act as drug target and what is an example?
Become activated by agonists and inhibited by antagonists
Cyclooxygenase enzyme
What effect do enzymes have on prodrugs?
Converts to active drug undergoing reaction to produce more effect on the body
Define prodrug
Molecules converted into active drug
How do transporters work as drug target and what is an example?
Agonists bind and move into cell
Antagonists bind and block transporter
Insulin
How do ion channels work as drug targets and what is an example?
Agonists increase or decrease probability of opening
Antagonists block channel
Local anaesthetics on nerves channels
How do nucleic acids work as drug targets and what is an example?
Alter gene transcription
Chemotherapy drugs
How are antimicrobial agents classified?
Type of organisms effective against
Either bacteriostatic or bactericidal
Define bacteriostatic
Prevent bacterial multiplication to remove infection by immune system
Define bactericidal
Kill bacteria
What are antibiotic dependent on to be effective?
Concentration- outcome related to peak antibiotic concentration at site of infection compared to minimum inhibitory concentration
Time- concentration needs to be above minimum for enough time between doses
What are the mechanisms of action of antibiotics?
Cell wall- ruptures
Cytoplasmic membrane- altered structure
Nucleic acid metabolism- interfere with DNA replication or repair
Explain the process of antibiotic therapy
Make diagnosis
Remove barriers which prevent antibiotics working
Decide if therapy is needed
Select best drug
Administer drug at best frequency and route
Test if drug has worked
