Pharmacology - drug kinetics and toxicity

Question 1

What is pharmacology?

Answer 1

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

Question 2

what is pharmacodynamics?

Answer 2

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)

Question 3

what is toxicology?

Answer 3

the adverse effects of drugs and chemicals

Question 4

what is pharmacotherapeutics?

Answer 4

use of drugs in the prevention and treatment of disease

Question 5

what do drugs modify?

Answer 5

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

Question 6

what is a drug?

Answer 6

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

Question 7

what is the difference between specificity and selectivity of a drug?

Answer 7

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.

Question 8

when does drug toxicity occur?

Answer 8

Normally occurs beyond the therapeutic dose range. Some drugs may show toxicity at the higher end of the therapeutic doses (i.e. adverse effects).

Question 9

what is the ultimate goal of therapeutics?

Answer 9

to achieve specificity

Question 10

what are drugs used to do?

Answer 10

• Prevent, diagnose and/or treat disease • Modify actions of other drugs • Analyze mechanisms or functions of an organism

Question 11

how can we use drugs in deficiency?

Answer 11

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

Question 12

how can we use drugs to alter the physiochemical environment?

Answer 12

Drugs can alter the environment or characteristics of a cell or tissue, changing its activity - 􏰀nonspecific effects􏰁.

Question 13

what is the dose / concentration?

Answer 13

Drug quantity in weight (mg) or volume (ml).

Question 14

what is the response and effect of drug activity?

Answer 14

The change occurring after drug administration.

Question 15

Give 4 different types of effects from drugs?

Answer 15

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

Question 16

how can we use drugs when there is an excess action?

Answer 16

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

Question 17

what is an acceptor and receptor in terms of drug activity?

Answer 17

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

Question 18

what are receptors?

Answer 18

the component of a cell or organism that interacts with a drug and initiate the chain events leading to the drug’s observed effect.

Question 19

what are ligands? what are the two types of ligand?

Answer 19

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

Question 20

what are the importance of receptors in terms of drugs?

Answer 20

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

Question 21

what are the different types of receptors?

Answer 21

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.

Question 22

Where can receptors be located on/in the cell? (3) Give examples of what these receptors at different locations are for?

Answer 22

CELL MEMBRANE - receptors for transmitters/peptides. NUCLEUS - receptors for thyrosin/insulin sensitivity CYTOPLASM - receptors for steroids.

Question 23

What are the different biological targets of drugs and what happens when they get bound?

Answer 23

Question 25

What are the classes of cell-surface receptors? (3)

Answer 25

1. Ion channel-linked receptor
2. 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.
3. Enzyme-Linked receptor

Question 26

What are adrenoreceptors?

Answer 26

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

Answer 27

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

Answer 28

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

Question 29

Describe the difference between agonists and antagonists?

Answer 29

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)

Question 30

What do type of receptors to steroids bind to? Give 3 examples of steroids?

Answer 30

Intracellular receptors

Examples of steroids: hydrocortisone, betamethasone, beclomethasone

Question 31

Describe the anti-inflammatory action of steroids?

Answer 31

Question 32

What are the actions of glucocorticoids in terms of vascular events, inflammation and cell population?

Answer 32

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

Question 33

What are the most common OTC drug? Give examples (4)

Question 34

Explain what happens at ion channels for benzodiazepines/barbiturates? Compare benzodiazepenes to barbiturates.

Answer 34

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

Question 35

How do proton pump inhibitors (omeprazole/lansoprazole) work and when are they used?

Answer 35

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

Question 36

What does successful antibiotic therapy depend on?

Answer 36

Successful antibiotic therapy depends on the host defense mechanisms, location of infection, pharmacokinetics and dynamic properties of the antibacterial

Question 37

Give a list of anti-infective agents:

Question 38

What are the common adverse effects of anti-infective drugs?

Answer 38

Diarrhoea

Fever

Allergy

Question 39

What are some examples of anti-fungal agents and their actions?

Question 40

What are 2 anti-viral drugs? What do they do?

Answer 40

Acyclovir and penciclovir

they inhibit DNA polymerase

Question 41

How do the following protein synthesis inhibitors work?

chloramphenicol, streptomycin, tetracyclines, erythromycins?

Answer 41

Question 42

How do B-lactam antibiotics work? Give examples of these B-Lactam antibiotics:

Answer 42

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