DRUG KINETICS & TOXICITY 1

what is pharmacology

• study of the effects of drugs on living systems (in relation to therapeutics and toxicology)

• study of drugs, their source, chemical properties, biological effects and therapeutic uses

what is pharmacodynamics

pharmacodynamics: the study of the biochemical and physiological effects of drugs and their mechanism of action

• effect of the drug on the body

what is pharmacokinetics

pharmacokinetics: absorption, distribution, biotransformation and excretion of drugs

• effect of the body on the drug

how can a drug be sourced

• natural

• synthetic biotechnology

what are the types of actions that drugs can produce

• agonist

• antagonist

• partial agonist

• inverse agonist

what are special branches of pharmacology

• clinical pharmacology - safe and effective use

• toxicology - study of harmful effects

what do drugs do VS not do

drugs modify physiological processes

drugs do not create new processes of effects

how are the effects of drugs expressed

what is a drug

drug: a chemical substance of known structure which, when given to a living organism, produces a biological effect

what is specificity in pharmacology

the capacity of a drug to manifest a kind of action

are the majority of drugs specific

no, very few drugs are completely specific, virtually all drugs produce more than one effect

give an example of a specific drug

• local anaesthetic

define selectivity

selectivity: the preferred site of action

most drugs are _________ rather than ________

most drugs are selective rather than specific

what is the ‘therapeutic window’

one safe (and effective) effect predominates over a particular dose range that does not cause toxic effects

• within this range, the drug may be termed ‘selective’

give an example of a selective drug

ibuprofen

when does toxicity occur

normally at concentrations beyond the therapeutic window

what is the therapeutic goal

maximise selectivity while minimising toxicity

what are drugs used for (3)

• prevent, diagnose and/ or treat disease

• modify actions of other drugs

• analyse mechanisms or functions of an organism

general mechanisms of drug activity

• deficiency

• excess action

• physiochemical environment

outline deficiency

replacement therapy for conditions such as iron, vitamin or hormone deficiency

outline excess action

chemical antagonists can reduce or block the effects of excess activity of a normal process

• antagonists can also block excess effects of exogenous substances e.g. reversal of overdose

outline physiochemical environment

drugs can alter the environment or characteristics of a cell or tissue, changing its activity - ‘non-specific effects’

define dose/ concentration

drug quantity in weight (mg) or volume (ml)

define response/ effect and outline what effects can occur

define acceptor

substances drugs bind to without causing any effect e.g. plasma proteins

define receptor

cell component on or within cells that directly interacts with a drug and initiates the chain events leading to the drug’s observed effect

• drugs either activate (agonist) or block receptors (antagonist)

what is a ligand

any molecule that binds to a receptor - can be endogenous e.g. neurotransmitters or exogenous e.g. medication

• many endogenous agonists e.g. NT and hormones

what are the effects of ligands/ how do they function

• agonist: binds to the receptor and initiates a response

• antagonist: binds to the receptor but does not activate it/ initiate a response, prevents agonist binding

what type of receptor is a target for ≈ half of all prescription drugs

7-transmembrane (7-TMS) G-protein couples receptors (GPCRs)

• there are around 800-1000 GPCRs

how do receptors work to produce an effect

receptors convert the drug’s 3D structure into a biochemical signal via signal transduction pathways involving effectors

diagram 1 showing biological drug targets

diagram 2 showing biological drug targets

where can receptors be located

diagram showing classes of cell-surface receptors (3)

state the adrenoreceptor subtypes

• beta1 - heart

• beta2 - lung

• beta3 - bladder

(mediates blood vessel size)

why can patients develop a tolerance to beta agonists

because beta agonists down regulate beta adrenoreceptors

why can patients develop withdrawl to beta antagonists

because beta antagonists upregulate beta adrenoreceptors

what type of molecule commonly binds to intracellular receptors

steroids

give examples of steroids

• hydrocortisone

• betamethasone

• beclomethasone

(all are corticosteroids and therefore anti-inflammatory)

what aspects of the body do glucocorticoids influence

• vascular events

• inflammatory and immune mediators

• cellular population

glucocorticoids: effect on vascular events

• reduce vasodilation

• decrease fluid exudation

glucocorticoids: effect on inflammatory and immune mediators

• reduces generation of eicosanoids and platelet activating factor (PAF)

• reduces production and action of cytokines (IL-2, IL-6, TNF-alpha)

glucocorticoids: effect on cellular population

• reduces clonal expansion of T and B cells

• decreases action of cytokine-secreting T cells

give examples of NSAIDs

• aspirin

• diclofenac

• ibuprofen

what do NSAIDs do

inhibit enzymatic activity

what are examples of benzodiazepines

• diazepam

• temazepam

benzodiazepine mechanism of action

treats insomnia, seizures, spasms

give examples of proton pump inhibitors

• omeprazole

• lansoprazole

what do PPIs do

• irreversibly blocking the gastric proton pump (H⁺/ K⁺ ATPase)

• used for prolonged inhibition of the gastric (stomach) acid

monoclonal antibody nomenclature

successful antibiotic therapy depends on what (4)

• host defence mechanisms

• location of infection

• pharmacokinetics

• dynamic properties of antibacterial

list of anti-infective agents and their adverse effects

diagram showing protein synthesis inhibitors (4)

what do beta-lactam antibiotics do

disrupt the synthesis of the peptidoglycan layer of bacterial cell walls

give examples of beta lactam antibiotics

• cephalosporin

  • cefalexin

  • cefradine

• penicillins

  • amoxicillin

  • co-amoxiclav

  • phenoxymethylpenicillin

state anti-fungal anti-infective agents

• fluconazole

• miconazole

• metronidazole

• nystatin

state anti-viral anti-infective agents

• acyclovir

• penciclovir

both inhibit DNA polymerase

define efficacy VS affinity

efficacy: relationship between receptor occupancy and ability to initiate a response at a molecular, tissue or cellular level

affinity: ability to bind a receptor

define potency

potency: how much drug is required to produce a particular effect

• depends on efficacy and affinity

receptor activation in the presence of a full agonist/ partial agonist

what does an antagonist do

binds but does not activate and are used to prevent agonists from binding

define therapeutic index

therapeutic index: margin between the therapeutic dose and the toxic dose

what is the relationship between the therapeutic index and drug safety

the higher the therapeutic index is the safer the drug is