pharmacology semester 1

all pharmacology

what is pharmacology

study of drugs and their affects in the body

indications

what the drugs are used to treat

mechanism of action

how the drug works

adverse effects

harmful symptoms

interactions

the way the drug interacts with food and other medications

depagloflozin indication

type 2 diabetes

depagloflozin class

SGLT2 inhibitor

depagloflozin indication

reduces reuptake of glucose from the kidneys, increases excretion of glucose and reduces blood glucose levels

adverse effects

UTI and dehydration

what is a drug

any chemical agent that effects the way the body functions whether that be physically or mentally

difference between a drug and a medicine

• medicines are drugs that have theraputic purposes

• not all drugs are medicines - alcohol, caffine, recreational drugs

asthma target

b2 andrenergic receptors in the lungs

types of drugs (class) - asthma

short acting b2 agonist: salbutamol

mechanism of action - salbutamol

stimulates the b2 receptors in lungs are relaxes the smooth muscle in the bronchioles

how drugs are administered

orally - tablet, capsule

intravenously - injection

transdermally - patch, cream, gel

branches of pharmacology

pharmacokinetics

pharmacodynamics

pharmacokinetics

• what the body does to the drug

• absorption into the blood stream - speed

• distribution into the body - once drug enters the blood stream

• metabolism of drug metabolites - once drug is broken down into smaller drug metabolites

• excretion from the body

pharmacodynamics

what the drug does to the body - understanding the mechanism of action

mechanisms of action

physiological effect

what type, how much, how often you take

neurofen/ibproufen

reduce pain, inflammation, and fever

who shouldnt take ibproufen

people with bad kidneys

important drug characteristics

physical nature - formulation

degree of ionization

relative lipid soluability

molecular size and shape

selectivity

physical nature - formulation

solid, liquid or gas

relative lipid solubility

small, lipophilic drugs cross the membrane easily

through diffusion/facillitated diffusion or active transport

should be fat loving

why do you want a drug that is somewhat lipophilic

• if it is too lipophilic it will just stay in the lipid membrane and not move through into the cells

molecular size

• varies widely

• small ions to large chains

• low molecular weight (less than 500g/mol) v high molecular weight (more than 500g/mol)

• some drugs are small ions

if the drug size is too big

it has to be injected

molecules crossing blood brain barrier

only small lipophillic (hydrophobic) molecules cross the blood brain barrier (BBB)

how does a drug get through the BBB

• to pass through the small tight junctions around brain cells, the drug needs to be very small and lipophillic

drugs fitting into their targets

drugs and their targets are 3d structures - they have to be the right size to fit into their targets

some chemical bonds in the 3d drug can rotate which gives rise to different configurations of the bonds

drug targets in our bodies will generally mold around the drug

biological activity of drugs

• drugs interact with their targets via chemical bonds or forces

• changed chemical groups change biological effects

• drug development SAR

selectivity ideal drug

binds to one receptor in one tissue making one single effect

selectivity of drugs

drugs bind preferentially to the target and are less likely to bind to other molecules in the body

degree of ionisation

to do with whether the drugs have a positive or a negative charge

small molecules

classic drug molecules

produced by chemical synthesis

biopharmeceuticals

• large biological agents

• produced in living cells - in labs

• proteins

• stem cells

• gene therapies

different protiens for drugs

hormones

monoclonal antibodies

vaccines

monoclonal antibodies

• antibodies are protiens made by the immune system to target a specific protein

• monoclonal antibodies (mABs) are made in a lab to target one single binding site on a single antigen

• very selective

how monoclonal antibodies work

they alter signalling

• andogenous ligand can bind to the receptor and cause signalling within the cell

• if a monoclonal antibody binded to that same receptor, the receptor would be blocked and prevent the ligand from binding into the receptor and prevent signalling from occuring

• sometimes the monoclonal antibody is directed at the ligand - attaching to the ligand and forming a complex which prevents the lignads form going into the recpetor

• monoclonal antiobodies can also bind to a receptor and actually activate the in cell signalling even more - heightening the affects of the receptor

difference between small molecules and proteins

• difficult to replicate exact copies with protien drugs

• small molecules are stable and last

• protein molecules are unstable and can be changes with outside conditions - short shelf life

• likliness to cause an immune response in the body

how do drugs cause biological changes

change the environment

antiacids and alginates

bind to the target and cause physiological changes

antiacids

work by counteracting and neutralising any excess stomach acid

alginates

form a raft that floats on top of stomach contents and doesnt allow acid to come up

what is a drug target

a molecule in the body or other organism, usually a protien which a drug binds to and which then mediates biochemical and physiological changes

endogenous ligand

normally proteins have endogenous molecules (endogenous ligands) that bind to and interact with them

ligand is the normal molecule in the body which will bind to the target receptor

drug target: ion channels

regulate the movement of ions across membranes

very fast (miliseconds)

important in:

• neurotransmisson

• cardica conduction

• muscle contrations

• secretory processes

g protein coupled receptors

transmembrane receptors - cross the membrane multiple times

activate intracellular signalling molecules known as G proteins

most abundant receptors in the body

fast effects - seconds

g protein activation

when a drug binds to the receptor it will activate a g protein inside of the cell which will further lead to the intracellular response

transmembrane receptors linked with enzymatic domains

ligand binding leads to the activation of enzymatic domains

slower effects (hours)

several groups of linked enzymatic domains

most common group are tyrosine kinase receptors

activation of the ezymatic domains

• enzymatic domain in the cell

• once the drug binds the receptors will couple up and join through dimerisation

• these joined receptors will attach phosphate groups to eachother which activates the receptor

intracellular receptors

• small lipophillic signalling molecules can diffuse through the plasma membrane

• bind to DNA and alter gene transcription

• slow effects (hours)

characteristics of ligands for intracellular receptors

• ligands for the intracellular receptors are usually small lipophilic ligands which are able to enter into the cell

• easily diffuse into plasma membrane

• can alter gene transcription - binding to DNA

drug target - intracellular receptorm- thyroid hormones

example - receptors for thyroid hormones

thyroid hormones are small lipophilic molecules

bind to transcription factors in the cytoplasm or the nucleus

ligand receptor complex usually dimerises in the nucleus

alters gene expression

drug target - enzymes

catalyst in the body - breaks things down

drugs usually inhibit the activity of the enzyme

how does a drug inhibit an enzyme

• in many different ways

• if the drug takes up the enzymes active site it is called a competitive inhibitor

• non competitive - when the drug binds to another part of the enzyme and changes the active site shape

extracellular target - acetylcholinesterase (ALZHEIMERS)

alzheimers - inhibiting this enzymes stops the break down of acetylcholine

more hangs around in the synapse for longer which increases acetylcholine levels

helps with memory

intracellular target - HMG-COA reductase

• inhibits an enzyme with a drug in order to decrease cholesterol production in the liver

• lower risk of heart disease and stroke

drug affects on target

• activation of receptor can be done by a ligand which can be enhanced by an agonist which will act as a ligand and increase the reaction caused by the receptor

• antagonist bind to receptors and block the effects of the ligand which decreases receptor and intracellular affect

• also partial agonists which are molecules which bind to a receptor and produce only a partial response

• can bind to all receptors but only activate some of them

different types of adrenergic receptors

alpha 1

beta 1

beta 2

increasinf heart rate receptor

B2 and B1

increasing contractility

B1 and B2

bronchodilation

B2

vasoconstriction - arterioles

a1 and a2

skeltal muscle arterioles dilation

B2

veins vasoconstriction

a1 and a2

vasodilation veins

B2

increased blood glucose - liver

B2

increased blood glucose - skeletal muscle

B2

increased contractility in skeletal muscle

B2

decreased GI motility

a1 and a2

increasing renin secretion

B1

bladder sphincter contraction

a1

catecholamines

dopamine, nonadrenaline, adrenaline

sympathatomimetic

mimics sympathetic activity

a or B agonists

sympatholytics

inhibits sympathetic activity

a or B receptor antagonist

oxymetazoline pathway

intranasal

oxymetazoline receptor and action

a1 antagonist

oxymetazoline indication

nasal congestion

oxymetazoline effect

effects blood vessels

arteriole and veins are constricted because they are part of a1 receptor group

oxymetazoline adverse effects

increased BP

rebound congestion with continued use - more than 3-5 days

down regulation of receptors in nose

increased vasodilation upon stopping the drug - compensatory

prazosin - receptor

a1 antagonist

prozasin indication

hypertension benign prostatic hyperplasia

Prazosin action

blocks the a1 receptors and causes vasodilation

causes drop in BP which helps with hypertension

benign prostatic hyperplasia

there is an enlarged prostate which can make urination harder

typically sympathetic stimulation will tighten the urinary sphincter around the urethra

in hyperplasia the urethra is tightened because of the enlarged prostate which causes the urinary sphincter to be tighter

Prazosin adverse effects

nasal congestion

hypotension

salbutamol receptor

B2 agonist

salbutamol adverse effects

tremor - mainly in high doses

tachycardia - a heart tremor as it can sometimes activate the B2 receptors in the heart

salbutamol indications

asthma and COPD

B antagonists

also called beta blockers and often have the suffix “olol”

B antagonists selectivity

they are non selective and with antagonise B1 and B2

propanolol selectivity

selesctively agonises B1

what effect to deta blockers have on the heart

decrease in heart rate and contractility

beta blockers on kidney

decrease renin secretion - lowers BP

beta blockers in lungs

can cause bronchoconstriction - only if beta blockers effects B2

liver and skeletal muscles

effects blood glucose control

blood vessels - beta blockers

cause vasoconstriction in skeletal muscles

cold extermities

if a beta blocker is lipophillic

can cross BBB and cause sedation

beta blockers - bladder

can cause incontenence

cholinergenic synapse - neurotransmitter

acetylcholine is released into the synapse for this type of receptor

ACH binds to the cholinergenic receptors on the post synaptic neuron

what is ACh broken down by after has binded to cholinergenic receptors

AChE - acetyl cholinesterase

• this breaks it down into choline and acetate

• therefore, the choline ca n be reabsorbed back into the pre synaptic neuron