Introduction of pharmacology Flashcards
What is pharmacokinetics?
What the body does to the drug
Metabolism and absorption
What is pharmacodynamics?
What the drug does to the body
Binding, drug-receptor interaction
How drug works as therapeutic agen
define - drug
a chemical substance of known structure, which when administered to a living organism produces a biological effect
Can be used as part or wholly as a medicine
define - medicine
‘usually, but not necessarily, contains one or more drugs which is administered with the intention of producing a therapeutic effect.
• any substance or combination of substances presented as having properties of preventing or treating disease in human beings
• any substance or combination of substances that may be used by or administered to human beings with a view to restoring, correcting or modifying a physiological function by exerting a pharmacological, immunological or metabolic action, or making a medical diagnosis’
Define - therapeutics
use of drugs to diagnose, prevent and treat illness (and/or pregnancy) i.e., the medical use of drug
define - formulations
how the drug is ‘packaged’ e.g., different chemical substances, including the active drug, are combined to produce a medicine
define - excipients
Substances formulated along side drug
State the three different names of drugs
- chemical name (chemical structure described)
- Generic name (which molecule class of drug belongs)
Proprietary name (manufacturers came for drug – trade name)
What is a ligand?
Molecule that binds to receptor
Can be – drug, neurotransmitter or hormone
Act on different receptors
Synthetic vs natural
Exogenous (outside body) vs endogenous (within body)
What is a receptor?
molecular target for a drug
what is an agonist?
molecule that activated a receptor
what is an antagonist?
blocks or reduces agonist medicated responses
what an ideal drug would do?
- Describe pharmacological action
- Acceptable side effects or none
- Reach target in right concentration at the right time
- Remain at site of action for sufficient time in sufficient concentration
- Rapidly and completely removed from body when no longer needed
define affinity
- How well the ligand binds to receptor
Strong or weak?
What are the aspects of drug binding?
- Drugs usually interact in structurally specific way it targets
- Steric interaction – based on spatial 3D relationship
- Lock and key model
what properties affect drug receptor binding?
1.physico-chemical properties (electrostatic charges)
2/ steric properties (physical shape)
what are physical-chemical properties?
electrostatic charges
what are steric properties?
physical shape of binding
what is pharmacogenomics?
The way an individuals genetics attributes affect response to therapeutic drugs
Genetic variation can lead to differences in the way people respond to any given drug – most drugs are proteins so encodes in genome and have specific shape and receptor site
State the targets for drug action
RICE
- Receptors
- Ion channels
- Carrier molecules
- Enzymes
what are receptors?
Biological relevant molcular site with which a drug binds to produce a response
- Endogenous ligand activates exogenous agonist activated – antagonist (receptor)
how are G-protein linked trans-membrane receptors ?
-Ligand binds and alters rejector confomation and activation of intracellular second meddagers cascade (knock on effect)
- Diverse intracellular effects – cellular excitability
- modulation of other ion channels
- calcium ion channels -c ell excitability
- down regulation of G-protein linked receptors
what are ion channels?
Movement of ion across membranes (down electrochemical gradient)
- Complex membrane protein (actual physical pore)
- Molecular selectivity filter – specific substrates
what are carrier proteins?
-Facilitators for transport
Activ e transport or facilitated diffusion
- Circa. 400 characterised and uncharacterised transporter proteins
Inhibitor or false substrates are common drug types
WHat are enzymes?
-Normal reaction inhibited and blocked by drug (substrate analogues)
- enzyme inhibitor
- false substrate – abnormal metabolite produced
- Pro-drug – active drug produced
Eg. Aspirin – pain, inflammation and clotting – blocks pain signals
What are the families of drugs that interact with enzymes?
- Enzyme inhibitors
- False substrates
- Prodrugs
what is drug specificity?
Binding site specificity (no drug acts with complete specificity)
- More likelihood of non-specific interactions becoming significant with larger doses
- Side effects often related to non-specific interaction (less potent effect than drug
Pharmacokinetics – ADME
4 processes determine time and onset and duration of drug action in the body
- Absorption
- Distribution
- Metabolism
Excretion
WHat is absoprtion?
Th eprocess by which drug reaches the systemic circulation
Effected by – route of administration – and permeation (the absorption process)
WHat are the two types of routes of administration?
Enteral administration – via gut – oral, buccaneers and rectal
Parenteral administration – not via gut – injection and topical
What are the Pros and cons of enteral routes of administration ?
pros
- Oral ingestion – gut absorption
- Low infection risk
- Very simple for self administration
cons
- Harsh environment – stomach/duodenum
- First pass metabolism
What is first pass metabolism?
Reduced bioavailability of drug due to loss by metabolism or excretion
- Intestinal lumen
- Intestinal wall
- Liver (main organ)
- Lungs (main organ)
Avoided by drug into a region of gut that does not drain into hepatic portal vein.
What are the Pros and cons of topical
Parenteral administration
Pros – local effects, low systemic effects
- Limited first pass metabolism
- Low infection risk
- Suited to low continuous – long period administration
- Risk of systemic absorption – direct absorption to blood
- Process of lipid permeation (drug must be lipid soluble, small molcular size and use a carrier molecule)
What are teh types of injection?
-Intravascular (IV, IA) – drugs enters directly into blood stream
- INtramuscual r(IM) drug injected into skeletal muscle
- subcutaneous (SC) – drug absorbed from subcutaneoyse tissue
- dermal (ID) – dermal vascular layer
- depot injection (slow release formulations)
What are the Pros and cons injections
Parenteral administration
Cons – high infection rapid, targeting risks
Pros – rapid bioavailability for IV and IA and avoids first pass metabolism
What is bioavailability?
Proportion of active drug that reaches the systemic circulation and is free to bind to its target
Over time the plasma conc. Reduces as used up
What effects bioavailability?
- Route of administration
- Formulation – enteric coating
- Bioavailability is not a measure of how effective a drug is
IV – rapid but short term -slow release – less absorbed but over long term
What factors that effect distribution of drugs?
1.Protein binding
2. blood flow
3. membrane permeation/ tissue solubility
How is distribution effected by protein binding?
• Dynamic equilibrium for most drugs
• Partly bound to plasma protein and partly in plasma water
• Binding is reversible
Only the UNBOUND fraction can cross membranes or bind to receptor
Bound drug is locked in the plasma
What can unbound or free drugs do – compared to bound drugs?
-Diffuse through capillary walls
- produce pharmacological effect
- metabolised and excreted
- subtle changes in binding have profound effects
- particular problem in elderly amlnourished patients
Bound drugs – are locked in the plasma
How does blood flow effect distribution?
-primariy through ciculatory system
- tissue perfusion rate per tissue is important
What is lipophilicity?
-Charged molecules, ions, ionised molecule diffuse less efficiently
- uncharged, non-ionised drugs have better access to membrane bound compartments
What are the two phases of metabolism?
-Phase 1 – produces toxic metabolites
- Phase 2 – converts toxins to soluble metabolites for excretion
Normal occur sequentially but phase 2 can precede phase 1 and can occur with the absence of phase 1
What is phase 1 of metabolism?
-Involves oxidisation, reduction and hydrolysis reactions
- Chemical reactions change polarisation of substance, increase water solubility, reduce pharmacological activity and may activate prodrugs
What is phase 2 of metabolism?
Conjugation -a ding of endogenous substance
1.make water soluble and 2. biologically inactive
Convert drug/toxin by covalently joining them to other molecules
What is excretion?
mainly kidney and renal
-Filtrtatoin
- only unbound drugs, metabolites can be processed via glomerular filtration
- proximal convoluted tubule cells actively secrete into nephron
- reaborption of lipophilic drugs – unionised at urine pH
- other routes – biliary, saliva, breat milk, sweat and tears
What is biliary excretion?
Enteropheptic circulation
-principle route of excretion – kepatocyte uptake -> bile -> duodenum -> excretion in faeces
But – gut can convert drug to original form – can be resabsorded across intestinal wall – re-circulate in blood and be metabolised in liver again and re-secreted into bile
What is a drug elimination half-life?
Half life – t ½
Time taken to decrease plasma concentration to 50%
What is enterohepatic circulation?
the movement of bile acid molecules from the liver to the small intestine and back to the liver
What is potency?
Concentration of a drug necessary to produce a given response
Eg. Two drugs that bind to the same receptor may not activate it to an equal extent, one may be more potent.
What is affinity for a receptor?
Strength of the ligand – receptor interaction at molecular level
Strong or weak binding
What is efficacy?
Drug ability to produce maximum possible effect when it binds to a receptor.
Some drugs fully activate the receptor once they reach a suitable concentration.
Full agonist – trigger max response once reach a sufficient concentration
What is a full agonist?
trigger max response once reach a sufficient concentration
