Intro to drug kinetics and drug toxicity Flashcards
What is pharmacology?
Study of the effects of drugs on living systems (in relation to therapeutics and toxicology).
Pharmacodynamics
Deals with the study of the biochemical and physiological effects of drugs and their mechanism of action. Effect of the drug on the body.
Pharmacokinetics
absorption, distribution, biotransformation and excretion of drugs. Effect of the body on the drug.
Toxicology:
adverse effects of drugs and chemicals.
Pharmacotherapeutics
use of drugs in the prevention and treatment of disease.
What do drugs do?
Modify physiological processes
Do NOT create new processes or effects
Drug effects are expressed in terms of alteration of a known function or process
Returns a function to normal operation
Changes a function away from the normal condition
Why are drugs used?
Prevent, diagnose and/or treat disease
Modify actions of other drugs
Analyse mechanisms or functions of an organism
What is a drug?
A chemical substance of known structure which, when given to a living organism, produces a biological effect.
What are the effects of drugs?
- Specificity: Drug produces only one effect.
- Selectivity: One effect predominates over a particular dose range – this is called the “therapeutic window” – within this range, the drug may be termed “selective”.
- Toxicity: Normally occurs beyond the therapeutic dose range. Some drugs may show toxicity at the higher end of the therapeutic doses (i.e.; adverse effects).
What is the goal of therapeutics?
Achieve “specificity”.
Name the mechanisms of drug activity
Deficiency, excess action and physiochemical environment
Drug activity mechanism - what is deficiency?
Replacement therapy for conditions such as iron, vitamin or hormone deficiency
Drug activity mechanism - what is excess action?
Chemical antagonists can reduce or block the effects of excess activity of normal process.
Antagonists can also block excess effects of exogenous substances (e.g.; reversal of overdose).
Drug activity mechanism - what is physiochemical environment?
Drugs can alter the environment or characteristics of a cell or tissue, changing its activity - “nonspecific effects”.
Define dose or concentration
Drug quantity in weight (mg) or volume (ml).
Define drug response or effect (types of effects)
The change occurring after drug administration. Effects include:
- Therapeutic effect: The desired or anticipated effect
- Side effect: Other than therapeutic effects occurring at therapeutic doses
- Toxic or adverse effect: Deleterious (harmful) effects usually occurring at higher doses
- Lethal effect: Death caused by very high drug dose
Define acceptor
Substances drugs bind to without causing any effect (e.g.; plasma proteins)
Define receptor
Cell component directly involved in reaction of some drugs and initiate the chain events leading to the drug’s observed effect.
What does a ligand do?
Bind to a receptor
What does an agonist do?
Initiates a response - many endogenous agonists (e.g NT/hormones)
What do antagonists do?
Does not initiate a response
Prevents agonist binding
What can receptors do?
Can: activate (agonist) or block (antagonist)
Converts the drug molecule signal (3D shape) to a biochemical signal (transduction) via effectors
Give examples of receptors
Membrane, enzymes, DNA, cytosolic proteins, ion channels
7-TMS receptors; 650 genes, activated by 70 ligands - target for half of all prescription drugs
Where are receptors located?
Cell membrane (transmitters/peptides)
Cytoplasm (steroids)
Nucleus (thyrosin/insulin sensitivity)
Name the biological targets of drugs
Receptors - agonist binds to it and activates it, antagonists block it
Ion channels - some drugs block it and some modulate it (open it)
Enzymes
Transporters
Classes of cell surface receptors?
Ion channel linked receptor
G-protein linked receptor
Enzyme linked receptor
Receptor subtypes?
Adrenoreceptors
Beta-adrenoceptors
Beta-adrenoceptors - what occurs with tolerance and withdrawal?
Tolerance - B agonist down regulate Beta-adrenoceptor
Withdrawal - B antagonist upregulate Beta-adrenoceptor
Drug/receptor interaction - define EC50
Drug that produces 50% of the maximal effect
Drug/receptor interaction - define potency
How much drug is required to produce a particular effect. Depend on both affinity and efficacy
Drug/receptor interaction - define efficacy
Relationship between receptor occupancy and ability to initiate a response at molecular, tissue or cellular level.
Drug/receptor interaction - define affinity
Ability to bind a receptor
How is adrenaline similar and different to propanol ?
Similar affinity
Different efficay
Receptor activation; full agonist or partial agonist?
based on the maximal pharmacological response that occurs when all the receptor are occupied.
Receptor activation - antagonist action?
Binds but does not activate and used to prevent agonist from binding
Name the intracellular receptors; steroids?
Hydrocortisone
Betamethasone
Beclomethasone
What do steroids do?
Block prostaglandin pathway = anti-inflammatory action
Functions of glucocorticoids?
Vascular events - reduce vasodilation, decrease fluid exudation
Inflam and immune mediators;
- Reduces generation of eicosanoids and PAF
- Lipocortin inhibits phospholipase A2
- Reduces production and action of cytokines - IL-2, IL-6, TNFalpha
Cellular population - Reduces clonal expansion of T and B cells
Decreases action of cytokine-secreting T cells
Benzodiazepines/barbiturates function? Examples?
Binds to GABA receptors at different allosteric sites = barbiturates increase duration and benzodiazepines increase frequency of opening of Cl channels = depression of CNS
Diazepam
tamezepam
How do proton pump inhibitors work? When are they used? Eg?
Act by irreversibly blocking the H/K ion ATPase (gastric proton pump)
Used for prolonged and long lasting inhibition of gastric acid
Omeprazole, lansoprazole
What does successful antibiotic therapy depend on?
The host defence mechanisms, location of infection, pharmokinetics and dynamic properties of the antibacterial
Give examples of anti-infective agents
Acylovir
Amoxicillin
Metronidazole
Tetracyclin
Antifungal;
- Fluconazole, miconazole (inhibit CYP3A lanosine 14A)
- Metronidazole (inhibit DNA synthesis)
- Nystatin (cell membrane pores increases K efflux)
Anti-viral = inhibit DNA polymerase
- Acyclovir
- Penciclovir
Averse effects of anti-infective agents?
Diarrhoea, fever, allergy
What do beta-lactam antibiotics do?
Disrupt the synthesis of the peptidoglycan layer of bacterial cell walls
Examples of beta-lactam antibiotics?
Cephalosporine
- Cefalaxin, cefradine
Penicillins
- Amoxicillin, co-moxiclav, phenoxynethylpenicillin
