Intro to drug kinetics and drug toxicity

Question 1

What is pharmacology?

Answer 1

Study of the effects of drugs on living systems (in relation to therapeutics and toxicology).

Question 2

Pharmacodynamics

Answer 2

Deals with the study of the biochemical and physiological effects of drugs and their mechanism of action. Effect of the drug on the body.

Question 3

Pharmacokinetics

Answer 3

absorption, distribution, biotransformation and excretion of drugs. Effect of the body on the drug.

Question 4

Toxicology:

Answer 4

adverse effects of drugs and chemicals.

Question 5

Pharmacotherapeutics

Answer 5

use of drugs in the prevention and treatment of disease.

Question 6

What do drugs do?

Answer 6

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

Question 7

Why are drugs used?

Answer 7

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

Question 8

What is a drug?

Answer 8

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

Question 9

What are the effects of drugs?

Answer 9

• 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).

Question 10

What is the goal of therapeutics?

Answer 10

Achieve “specificity”.

Question 11

Name the mechanisms of drug activity

Answer 11

Deficiency, excess action and physiochemical environment

Question 12

Drug activity mechanism - what is deficiency?

Answer 12

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

Question 13

Drug activity mechanism - what is excess action?

Answer 13

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).

Question 14

Drug activity mechanism - what is physiochemical environment?

Answer 14

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

Question 15

Define dose or concentration

Answer 15

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

Question 16

Define drug response or effect (types of effects)

Answer 16

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

Question 17

Define acceptor

Answer 17

Substances drugs bind to without causing any effect (e.g.; plasma proteins)

Question 18

Define receptor

Answer 18

Cell component directly involved in reaction of some drugs and initiate the chain events leading to the drug’s observed effect.

Question 19

What does a ligand do?

Answer 19

Bind to a receptor

Question 20

What does an agonist do?

Answer 20

Initiates a response - many endogenous agonists (e.g NT/hormones)

Question 21

What do antagonists do?

Answer 21

Does not initiate a response

Prevents agonist binding

Question 22

What can receptors do?

Answer 22

Can: activate (agonist) or block (antagonist)

Converts the drug molecule signal (3D shape) to a biochemical signal (transduction) via effectors

Question 23

Give examples of receptors

Answer 23

Membrane, enzymes, DNA, cytosolic proteins, ion channels

7-TMS receptors; 650 genes, activated by 70 ligands - target for half of all prescription drugs

Question 24

Where are receptors located?

Answer 24

Cell membrane (transmitters/peptides)
Cytoplasm (steroids)
Nucleus (thyrosin/insulin sensitivity)

Question 25

Name the biological targets of drugs

Answer 25

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

Question 26

Classes of cell surface receptors?

Answer 26

Ion channel linked receptor
G-protein linked receptor
Enzyme linked receptor

Question 27

Receptor subtypes?

Answer 27

Adrenoreceptors

Beta-adrenoceptors

Question 28

Beta-adrenoceptors - what occurs with tolerance and withdrawal?

Answer 28

Tolerance - B agonist down regulate Beta-adrenoceptor

Withdrawal - B antagonist upregulate Beta-adrenoceptor

Question 29

Drug/receptor interaction - define EC50

Answer 29

Drug that produces 50% of the maximal effect

Question 30

Drug/receptor interaction - define potency

Answer 30

How much drug is required to produce a particular effect. Depend on both affinity and efficacy

Question 31

Drug/receptor interaction - define efficacy

Answer 31

Relationship between receptor occupancy and ability to initiate a response at molecular, tissue or cellular level.

Question 32

Drug/receptor interaction - define affinity

Answer 32

Ability to bind a receptor

Question 33

How is adrenaline similar and different to propanol ?

Answer 33

Similar affinity

Different efficay

Question 34

Receptor activation; full agonist or partial agonist?

Answer 34

based on the maximal pharmacological response that occurs when all the receptor are occupied.

Question 35

Receptor activation - antagonist action?

Answer 35

Binds but does not activate and used to prevent agonist from binding

Question 36

Name the intracellular receptors; steroids?

Answer 36

Hydrocortisone
Betamethasone
Beclomethasone

Question 37

What do steroids do?

Answer 37

Block prostaglandin pathway = anti-inflammatory action

Question 38

Functions of glucocorticoids?

Answer 38

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

Question 39

Benzodiazepines/barbiturates function? Examples?

Answer 39

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

Question 40

How do proton pump inhibitors work? When are they used? Eg?

Answer 40

Act by irreversibly blocking the H/K ion ATPase (gastric proton pump)
Used for prolonged and long lasting inhibition of gastric acid
Omeprazole, lansoprazole

Question 41

What does successful antibiotic therapy depend on?

Answer 41

The host defence mechanisms, location of infection, pharmokinetics and dynamic properties of the antibacterial

Question 42

Give examples of anti-infective agents

Answer 42

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

Question 43

Averse effects of anti-infective agents?

Answer 43

Diarrhoea, fever, allergy

Question 44

What do beta-lactam antibiotics do?

Answer 44

Disrupt the synthesis of the peptidoglycan layer of bacterial cell walls

Question 45

Examples of beta-lactam antibiotics?

Answer 45

Cephalosporine
- Cefalaxin, cefradine
Penicillins
- Amoxicillin, co-moxiclav, phenoxynethylpenicillin