Pharmacology - drug kinetics and toxicity Flashcards
What is pharmacology?
a study of the effects of drugs on living systems (in relation to therapeutics and toxicology)
what is pharmacodynamics?
deals with the study of the biochemical and physiological effects of drugs and their mechanism of action. (the effect of the drug on the body)
what is toxicology?
the adverse effects of drugs and chemicals
what is pharmacotherapeutics?
use of drugs in the prevention and treatment of disease
what do drugs modify?
Drugs modify physiological processes. they DO NOT create new processes or effects Drug effects are expressed in terms of alteration of a known function or process. They either: • Returns a function to normal operation • Changes a function away from the normal condition
what is a drug?
A chemical substance of known structure which, when given to a living organism, produces a biological effect.
what is the difference between specificity and selectivity of a drug?
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”. There is not a single drug that is completely specific or selective.
when does drug toxicity occur?
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 ultimate goal of therapeutics?
to achieve specificity
what are drugs used to do?
• Prevent, diagnose and/or treat disease • Modify actions of other drugs • Analyze mechanisms or functions of an organism
how can we use drugs in deficiency?
Replacement therapy for conditions such as iron, vitamin or hormone deficiency
how can we use drugs to alter the physiochemical environment?
Drugs can alter the environment or characteristics of a cell or tissue, changing its activity - nonspecific effects.
what is the dose / concentration?
Drug quantity in weight (mg) or volume (ml).
what is the response and effect of drug activity?
The change occurring after drug administration.
Give 4 different types of effects from drugs?
Therapeutic effect: The desired or anticipated effect Side effect: Other than therapeutic effects occurring at therapeutic doses Toxic or adverse effect: Deleterious effects usually occurring at higher doses Lethal effect: Death caused by very high drug dose
how can we use drugs when there is an excess action?
Chemical antagonists can reduce or block the effects of excess activity of normal process. So we can use antagonists can also block excess effects of exogenous substances (e.g. reversal of overdose). - e.g. atenolol
what is an acceptor and receptor in terms of drug activity?
acceptor: substance the drug binds to without causing any effect (e.g. plasma proteins) receptor: cell component directly involved in the reaction of some drugs
what are receptors?
the component of a cell or organism that interacts with a drug and initiate the chain events leading to the drug’s observed effect.
what are ligands? what are the two types of ligand?
Ligands - bind to a receptor • Agonist - initiates a response. There are many endogenous agonists (e.g. neurotransmitters and hormones) • Antagonist - does not initiate a response, these prevent agonist binding
what are the importance of receptors in terms of drugs?
Receptors are the molecules on or in the cell that the drug molecule first interacts with and activates (agonist) or blocks (antagonist) Receptors convert the drug molecule signal (3D shape) to a biochemical signal (transduction) via effectors The effect is hard-wired: drugs modify ongoing physiological processes
what are the different types of receptors?
membrane receptors, enzymes, DNA, cytosolic proteins, ion channel 7-TMS receptors (800-1000); 650 genes, activated by 70 ligands. These are the target for half of all prescription drugs.
Where can receptors be located on/in the cell? (3) Give examples of what these receptors at different locations are for?
CELL MEMBRANE - receptors for transmitters/peptides. NUCLEUS - receptors for thyrosin/insulin sensitivity CYTOPLASM - receptors for steroids.
What are the different biological targets of drugs and what happens when they get bound?
What are the classes of cell-surface receptors? (3)
- Ion channel-linked receptor
- G-protein-Linked receptor - these cross the membrane 7 times. They’re linked to a G protein. Once a ligand binds to a G protein it causes a cascade of events.
- Enzyme-Linked receptor
What are adrenoreceptors?
G-protein-linked receptors that are activated by adrenaline or noradrenaline.
mainly classifiied into alpha and beta receptors:
- Alpha receptors are mainly found in blood vessels.
- Beta receptors are found in:
B1 = heart
B2 = lung
B3 = bladder
Tolerance - Β agonist down regulate β-adrenoceptor = need to increase dose to achieve effects.
Withdrawal - if pt is exposed to β antagonist for a long period = our body compensates by upregulating β-adrenoceptor
EC50: [drug] that produces 50% of the maximal effect
Potency: how much drug is required to produce a particular effect. Depend on both affinity and efficacy
Efficacy: relationship between receptor occupancy and ability to initiate a response at molecular, tissue or cellular level.
Affinity: ability to bind a receptor.
Adrenaline is similar affinity than propanolol but very different efficacy
Describe the difference between agonists and antagonists?
Full agonist/Partial agonist: based on the maximal pharmacological response that occurs when all the receptor are occupied.
Antagonist: binds but does not activate and are used to prevent agonist from binding. We can shift a dose of an agonist by adding an antagonist (useful when managing side effects)
What do type of receptors to steroids bind to? Give 3 examples of steroids?
Intracellular receptors
Examples of steroids: hydrocortisone, betamethasone, beclomethasone
Describe the anti-inflammatory action of steroids?
What are the actions of glucocorticoids in terms of vascular events, inflammation and cell population?
Vascular events: Reduce vasodilation & decrease fluid exudation
Inflammatory and immune mediators
Reduces generation of eicosanoids and PAF Lipocortin inhibits phospholipase A2
Reduces production and action of cytokines -IL-2, IL-6, TNFα
Cellular population
Reduces clonal expansion of T and B cells Decreases action of cytokine-secreting T cells
What are the most common OTC drug? Give examples (4)
Explain what happens at ion channels for benzodiazepines/barbiturates? Compare benzodiazepenes to barbiturates.
Both act on the channel that lets chloride ion channels. They both have specific sites (GABA sites) at whcih
They facilitate GABA action and lets more chloride ions into the cell.
Main difference = barbiturates increase duration of the opening of the channel. modify the frequency of opening and closing of the channel.
they depress the action of the CNS by causing membrane hyperpolerisation (lots of negative charge)
Benzodiazepene are safer than barbiturates.
diazepam and temazepam
How do proton pump inhibitors (omeprazole/lansoprazole) work and when are they used?
Act by irreversibly blocking the H+/K+ ATPase (the gastric proton pump)
They are used for prolonged and long lasting inhibition of the gastric acid
What does successful antibiotic therapy depend on?
Successful antibiotic therapy depends on the host defense mechanisms, location of infection, pharmacokinetics and dynamic properties of the antibacterial
Give a list of anti-infective agents:
What are the common adverse effects of anti-infective drugs?
Diarrhoea
Fever
Allergy
What are some examples of anti-fungal agents and their actions?
What are 2 anti-viral drugs? What do they do?
Acyclovir and penciclovir
they inhibit DNA polymerase
How do the following protein synthesis inhibitors work?
chloramphenicol, streptomycin, tetracyclines, erythromycins?
How do B-lactam antibiotics work? Give examples of these B-Lactam antibiotics:
Disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. This is crucial for the bacteria in order to survive.
Cephalosporine: Cefalaxin. Cefradine
Penicillins: Amoxicillin. Co-moxiclav. Phenoxynethylpenicillin
