pharmacology- intro

define pharmacology

science of drugs; their mechanisms of action, how their effects are measured, their discovery, design and development and their actions on organisms and the actions of organisms on them

define therapeutics

branch of pharmacology aiming to treat and manage disease while reducing pain

define pharmacy

the practice of formulating drugs for distribution as use of medicine

define toxicology

study of the harmful effects of chemical agents on living organisms

define drug

an exogenous chemical substance (other than nutrients or essential dietary ingredients) that produces a biological effect when administered to a living organism by mimicing or blocking the action of endogenous molecules

explain the different ways of naming drugs?

chemical name (uses chemical structure e.g. propanoic acid), common name (e.g. ibuprofen), proprietary/trade name (brand name e.g. nurofen)

what type of drug is ibuprofen

cyclooxygenase inhibitor that acts as an analgesic

what type of drug is an analgesic

painkiller

what do antihypertensive drugs treat

hypertension by lowering blood pressure to prevent heard attack

MOA, therapeutic use and proprietary name: propranolol

blocks action of adrenaline and noradrenaline at B-1 and B-2 receptors thus blocks sympathetic nervous system (beta andrenergetic receptor antagonist)

treats cardiovascular conditions, neurological conditions and physical signs of anxiety

inderal

MOA, therapeutic use and proprietary name: salbutamol

binds to B-2 andrenergetic receptors on airway smooth muscle to relax muscle airway openings

treats asthma

ventoli

MOA, therapeutic use and proprietary name: sildenafil

PDE5 inhibitor keeping cGMP active for longer by blocking PDE5

relaxes smooth muscle allowing blood flow in to penis causing erection and sexual arousal abd relaxes blood vessels in lungs preventing P.A.H.

viagra (sex) revatio (pulmanory arterial hypertension)

MOA, therapeutic use and proprietary name: fexofendanine

selective peripheral H1 receptor acting as an inverse agonist to prevent runny nose by inactivating H1

prevents histamine by binding with H1 in blood vessels of airways and skin. inactive H1 prevents sneezing, cough, and runny nose

relieves allergy symptoms and skin conditions. non drowsy as it does not cross the BBB thus no CNS activity

allevia

MOA, therapeutic use and proprietary name: fluoxetine

SSRI that blocks reabsorbtion of serotonin into presynaptic neurone thus increasing its availability in the synaptic cleft

treats mental health conditions e.g. MDD

prozac

effects of a beta-1 blockade

decreases heart rate, decrease myocardial contractility, decrease AVN conduction, decrease renin from kidneys

outline the mechanism of drug-protein interactions

• complimentarity between drugs and ligands depends on the steric factors (size and flexibility) of the drug

• strength of bonding it determined by type of bond at the bonding site (hydrogen/covalent etc.)

• most drugs bind reversibly to target protein by hydrophobic interactions and hydrogen bonds + weaker van der waal forces

• irreversible bonds occur via covalent bonding and thus are more likely to produce toxic effect e.g. snake venom

• bonding leads to formation of a ligand-protein complex which alters the protein activity due to conformational changes

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target proteins of drugs e.g.

receptors for neurotransmitters or hormones, enzymes, ion channels, carrier/ transport molecules, RNA/DNA

define a ligand in pharmacology

a molecule (e.g. hormone or neurotransmitter) that binds to a target molecule to produce a certain chemical effect e.g. blocking a signal

how are drugs modelled in silico

using modern computer modelling techniques

what is needed for drugs to be useful therapeutically

• drugs must be selective in its action as the drug-protein interaction e.g. an antihypertensive drug that lowers b.p. but causes severe gastrointestinal problems will not be useful

• drugs are complimentary/specific to their binding protein

define a non-selective drug

when a drug has multiple molecular targets

define pharmacodynamics (PD)

the concequences of a drug’s action on a molecular level on the physiology of an organism

• must be considered alongside pharmacohynamics

define pharmacokinetics (PK)

how the drug is affected by an organism e.g. how it travels to its site of action, how its metabolised and how it is distributed to different organisms

state the 4 elements of pharmacokinetics

absorbtion, distribution, metabolism and excretion

how is absorption of drugs affected by the stomach and give an example

absorbtion of drugs is affected by whether the drug can remain stable in the acidic stomach environment and the individual’s characteristics e.g. patients with liver damage cannot metabolise drugs as effectively as a patient with a healthy liver

→ paracetamol and other oral drugs must withstand pH 2 from the stomach acid other wise they will be destroyed and not reach the ilium in the GI to be absorbed into the blood stream.

→ drugs must be fat soluble due to the phospholipid bilayer of the ilium to enter the circulatory system

→ due to the high water content of blood, drugs must be water soluble too

define bioavailability

fraction of an administered drug that reaches the systemic circulation in an unchanged and active form

define absorbtion in PK and what it is affected by

determines how much and how quickly a drug enters blood plasma

influenced by - molecular size, lipid solubility and thus its ionization, chemical stability (some drugs cannot be taken orally as they will be destroyed in the stomach)

explain key points of distribution in PK

drugs are distributed around the body in blood plasma which then diffuses through the tissues dissolved in the extracellular fliud (ECF)

the ability of a drug to dissolve in plasma or ECF is determined by its water sollubility

concentration of a drug in blood plasma is the assumed drug concentration at the site of action

factors interfering with drug distribution in the body

• blood circulation

• whether the drug binds to protein in blood plasma, specifically albumin since drugs that bind to albumin get trapped in blood

• whether the drug dissolved into fat cells as these will be inactive

• whether the drug can gain access to the organ it acts on i.e. whether it crosses the BBB. most drugs struggle to cross the BBB since blood vessels pack tightly to prevent bacteria from organs

how is drug distribution in the body measured

volume of distribution (Vd) which is apparent volume the drug would occupy if the total amount is administed was dissolved in solution at the same concentration as that found in blood plasma

Vd = amount administered / concentration in plasma

larger Vd means more drug has left the plasma and entered the body tissues/fats

which drugs are not intended to cross the BBB

local anaesthetics should not be distributed but rather compartmentalised to minimise side effects these do not have systemic (throughout body) actions

what are the main sites of metabolism

kidneys, liver and cells

what do metabolism and excretion under PK determine

how long the effects of a drug last since drugs are metabolised in the liver and then excreted by kidneys

factors affecting metabolism and excretion under PK

• liver health

• effectivity of liver enzymes e.g. may be different due to genetic differences

• whether the metabolites are active e.g. codein metabolised to morphine

• whether the metabolites are toxic e.g. paracetamol toxicity due to a harmful metabolite rather than the drug itself

what is a prodrug

a drug that must be converted by the liver to be activated and used e.g. codein metabolised to morphine for sedative effects

methods of excretion

urine, faeces, sweat, bile and breath

how is a drug’s half life defined

the time it takes for the plasma concentration to fall by half

what type of graph does a drug’s half life follow

monoexponential decline

define clearance

related to drug’s half life and defined as the volume of blood plasma cleared of the drug in unit time e.g. ml of plasma per minute / plasma per hour