PHA THEME 1 IDA

What is pharmacodynamics?

what the drug does to the body

What is pharmacokinetics?

what the body does to the drug

examples of non specific drug actions

mylanta- neutralise stomach acid which will reduce acid reflux

1. chelating agents- bind and remove heavy metals

2. prevent absorption and helps removal (EDTA)

3. osmotic agents- alter the fluid balance in the body compartment. eg. GIT increase osmotic pressure, increase solute concentration, water move in and works as a laxative

4. surfactants- in GI help decrease, reduce surface tension and thus pain

what are 4 drug targets?

1. ion channels

2. enzymes

3. carrier molecules

4. receptors

what is the importance of selectivity?

drug interacts with only one target

what is affinity?

ability of a drug to bind to a receptor

what is efficacy?

ability substance to produce biological response when bound

what is potency?

the concentration of a drug required to give a certain response

Full vs partial agonist?

Full agonist produces maximal responce, E=1

Partial agonist, not max response, E

What is an antagonist?

They block the action of an agonist getting to the receptor to elicit a response, therefore no response is made

it has affinity, but NO efficacy

what is the response of a tissue, when a reversible antagonist is bound, but [angonist] increase?

decrease potency (Rward shift)

no change to efficacy (max response)

what is response of tissue when irreversible antagonsit bound, but [agonist] increases?

potency decrease

efficacy decrease (max)

what are some clinical agonist / antagonist?

agonist

ventolin (salbutamol) - beta adrenoreceptor

morphin- opoid receptor

adrenaline - adernoreceptor

antagonist

naloxone- mu opid receptor

how does lignocaine work?

block voltage-gated sodium channel

inhibit transmission nerve impulse block pain sensation

how does minoxidil work?

potassium channel opener

decrease calcium

vasodilation

reduce BP

how does aspiririn and ibprofin work?

arachidonic acid is converted by COX into prostaglandins which produce pain and inflammation

A&I block COX and reduce pain and inflammation

how do organophosphates and sarin gas work?

block the actions of AChE, therefore increase levels of ACh, continual signalling, leading eventually to muscle paralysis

how does cocaine work ?

prevent NA reuptake, increase [NA] in terminal

increase HR, pupil dilation...

how does amphetamine work?

it is taken up by carrier molecule, causes release of NA increase [NA] in the synapse

increase HR and pupil dilation

What is the theraputic index?

the ratio of dose between produce adverse effect to dose and desired effects (MTC:MEX)

what factors invovled in pharmacokinetics?

A- absorption

D- distribution

M- metabolism

E- elimination

factors influence distribution of drug around body?

size

lipophilic

degree of ionisation

binding to plasma proteins

permeability of capillaries

What are the routes of administration for a drug?

intravenous

intramuscular

subcutanous

oral

which route of adminsitration produces the fastest effect?

intravenous

which route of administration for a drug produces the slowest effect?

oral

What is volume of distribution?

volume which drug is distributed, related to plasma concentration amount of drug in body

what is the Vd equation?

dose/[plasma]

which two organs aid in drug eliminaiton from body?

kidney OR liver

how does liver remove drug ?

occurs via metabolism

makes lipid soluble drugs more water soluble to allow them to be excreted by kidneys by adding funcitonal groups to the drug

how does kidney remove drug?

remove unchanged drugs

1.filtration in glomerular cappiliries

2. reabsortion in pertibular capilliries

3. secrete into bowmans capsule

4. excreted

what is first order elimination kinetics?

a constant proportion (eg. a percentage) of drug is eliminated per unit time

what is zero order elimination kinetics?

rate of elminiation is not proportional

does zero or first order have larger theraputic window?

first order is easier to keep within the theraputic window

what is a neurotransmitter?

chemical subtance mediates transmission of umpulse from nerve

What is myesthenia gravis?

Autoimmune disorder destroys ACHR, decreasing # the available receptors to bind to results in muscle weakness

what is parkinson's disease?

caused by:

decrease dopamine levels in basal ganglia & substantia nigra

decrease simulation of dopamine receptors

Characterized by:

Movement disorder associated with impaired voluntary movements

such as resting tremor, slowed movement, rigidity of facial muscles, and shuffling gait, and reduction in capacity for language

what is schoziphrenia?

due to exessive dopaminergic activty in mesolimibic and mesofrontal regions in the brain

this causes increase stimulation of dopamine receptors

characcterized as:

psychotic disorder

ppl seen to withdraw from reality, illogical patterns of thinking, delusions, hallucinations, varying degress of emotional, behavioural, intellectual disturbances.

what is a potential treatment for mayesthenia gravis?

AChE inhibitors

how do we treat parkinson disease?

give LDOPA (levodopa), converted into dopamine

how do we treat schizophrenia?

dopamine receptor antagonists

what is a side effect of antipsychotic drugs?

symptoms of parkinsons disease bec blocking dopamine receptors

what neurotransmitter does the sympathetic nervous system release?

noradrenaline

what neurotransmitter does the parasympathetic nervous system release?

Achetylcholine

which nerves activate the fight or flight response?

sympathetic system

which nerves activate the rest/ digest response?

parasympathetic system

what are some physiological effects of due to sympathetic innervation?

increase:

HR

BP

decrease:

GIM

pupil dilation

bronchodilation

vasoconstriction

what are some physiological effects of due to parasympathetic innervation?

increase:

GIM

decrease:

HR

BP

pupil constriction

bronchoconstriction

what is the cycle of noradrenaline?

made from pre-cursor AA tyrosine

released from pre

binds to alpha/ beta receptors on post

taken back up into cell

which receptors do noradrenaline bind to on the blood vessels?

alpha adreno receptors

which receptors do noradrenaline bind to on the heart?

beta adreno receptors

which receptors do noradrenaline bind to on the GI?

alpha and beta adrenoreceptors

which drug prevents removal of NA back into the nerve?

cocaine

which drug prevents the release of NA from the nerve?

amphetamine

which receptors do acetylcholine bind to on skeletal muscles?

nicotinic receptors

which receptors do acetylcholine bind to on the heart, GIT, lung ?

muscarinic receptors

How is acetylcholine synthesized?

Acetyl CoA + choline forms to makE ACh

released from the pre synaptic

binds to nicotinic / muscarinic receptors

broken down by AChE

Reaction is catalysed by choline acetyltransferase

are receptors on blood vessels innervated by ACh?

what receptors present?

blood vessels not innervated by ACh

but muscarinic receptors present

what is an antagonist of ACh on GI smooth muscle and what effects does it have?

atropine antagonises ACh at the muscarinic receptor

what is an antagonist of ACh on skeletal muscle and what effects does it have?

tubocurarine (competitive anatag) of nico receptor

results in relaxation of muscle-> paralysis

what are the effect of atropine binding to muscarinic receptors on the pupil?

atropine is competitive muscarinic receptor antagonist

blocks the actions of ACh

results in pupil dilation

what is the action of AChE?

it is an enzyme that breaks down ACH (involved in removal process)

what are the actions of organophosphates- like malathion (insecticide) and sarin (nerve gas)?

irreversible anticholinesterases

prevents the actions of AChE

results in build up of ACH in NMJ

leads to NMJ depolarising blockade (too much ACh in system)

leads to reduced HR, BP, bronchoconstriction and paralysis

how is serotonine removed?

removed by active uptake using SERT-> serotonin reuptake transporter

what is the effect of 5HT on blood vessels?

vasoconstriction (some areas may cause dilation)

what is the effect of 5HT on platelets?

aggregation

what is the effect of 5HT on GITs?

contraction-> increase motility

what is the effect of 5HT on the lungs?

bronchoconstriction

what is the effect of 5HT on the CNS?

wakefulness

pain

appetite

mood

vomiting

what is the effect of 5HT on sensory nerves?

stimulatory

what is the theraputic mechainsm for depression?

SSRIs- selective serotonin reuptake inhibitors prevent the uptake of 5HT back into pre-synaptic nerve terminal

what are some side effects of SSRIs?

Insomnia, anxiety, nausea, diarrhoea

what is nitric oxide?

biologically active gas

NT

synthesised on demand

what are the actions of NO in blood vessels?

vasodilaiton

decrease platelet aggregation

what are the actions of NO in ntiregic nerves?

neurotransmission

erection

what are the actions of NO when released by macrophages?

host defence

targets and kills pathogens

what is a constitutibve form of NO?

NO that is always present

present under physiological conditions

what consitituve forms of NO are present?

eNOS- NO present in the endothelial cell

nNOS- NO present in nitregic nerves

what is the inducible form of NO?

nitric oxide that is expressed in response to stimuli not present all the time

what inducible form of NOS present?

iNOS- inducible NO, expressed in response to pathological stimuli, produces a huge amount

what is angina?

coronary artery disease-> accumulation lipids in blood vessels, narrowing of BV which causes spasms during angina attacks, results in insufficient blood flow and oxygen to heart results in chest pain and breathlessness, serious can lead to heart attack

what is used to treat angina?

NO donors, results in cornary vasodilation, results in increase blodflow and increase oxygen supply and reduces the symptoms patient experiencing

what is pulmonary hypertension?

high BP limited to the pulmonary vasculature (affects arteries in lungs and heart)

what treatment used for pulmonary hyperntesnion?

inhaled NO

results in pulmonary vasodilation

limit NO to pulmonary vasculature, not interfere with other areas of the body

are prostaglandins/leukotrienes stored or synthesised on demand?

P/L are synthesised on demand

what generates prostaglandins and leukotrienes?

local tissues, blood vessels, platelets, lungs, mast cells

how are Prostaglandins and Leukotrienes synthesised?

Phospholipids -> arachidonic acid ->

1. action of lipoxygenase -> leukotrienes

OR

2. action of cyclooxygenase-> Prostaglandins

what are the actions of leukotrienes?

very strong bronchoconstrictors

increase vascular permeability

what are the actions of PGE2?

vasodilator

increase sensistivty to pain

increase fever

decrease gastric secretions

what are COX inhibitors used for (aspirin & ibprofin)?

COX inhibit formation of Prostaglandins

therfore results in anti-inflammatory, antipyretic, analgesic effects (decrease pain and fever)

are histamines stored or synthesied on demand?

stores in mast cells

where is [histamine] high?

lungs, skin GIT

what is histamines major actions?

mediator for allergic reacitons

what is the effect of histamine on the lungs?

bronchoconstriction

what is the effect of histamine on the blood vessels?

vasodilation

increase vascular permeability

what is the effect of histamine on the stomach?

increases gastric acid secretion

what is the effect of histamine on the GIT?

increase motility

what is the effect of histamine on sensory nerves?

stimulatory

what is the effect of histamine on the CNS?

arousal/ wakefulness

nasuea/ vomiting

what are the effect of histamine receptor antagonists in the stomach?

reduces gastric acid secretions

therefore reduces peptic ulcers

what are the effects of histamine receptor antagonists and its effects on allergic reactions?

decrease vasodilation & vascular permeability -> REDUCES PERMEABILITY

decreases stimulation in sensory nerves -> REDUCES ITCHING AND PAIN