pharmacology Flashcards
which system does bronchodilation and bronchoconstriction respectively?
beta2 sympathetic receptore in lungs dilates blood vessel as to increase blood flow to the lungs to allow flight and fight response
m3 receptors of the Parasympathetic nervous system constricts the bronchi to reduce blood flow as to direct it towards the GIT to rest and Digest
what is the main diffrence between the receptors at the skeletal muscle and smooth and cardiac muscle?
regarding the Parasym. system the skeletal muscle have the Nm receptors (nicotinic)
the smooth and cardiac have M receptors (muscuranic)
explain acetylcholine receptors (the parasympathetic receptors)
two types
N (nicotinic)
these are Ligand gated Na+/K+
two subtypes Nn(in autonomic ganglia and adrenal medulla) and Nm (skeletal muscular junction)
Muscuranic receptors (G protien coupled receptors)
what are the major 4 types of receptors in the body?
1) Ligand gated receptors (channel linked receptors)
2) G-protien coupled receptor (most common and important)
3) enxyme Linked receptors ( kinase receptors)
4) nuclear receptors
What is a ligand?
Any substance or molecute that activates (agonist) or deactivates (antagonist) the receptots is known as a ligand
explain GPCR’s
more than 1000 gpcr’s are known in human body.
the ligands for these receptors can be anything upto hormones pheremones seretonin dopamine odors neurotransmitters, light sensitive compounds etc
structre- seven helic structure
as th name indicated GPCR’s are coupled with the G protien.
What is G protien?
G protiens are specialized protiens that have the ability to bind the GTP and GDP
all G protiens that are associated with the Gpcrs are heteromeric that means they have 3 subunits in them. (alpha, beta and gamma)
when inactive it binds GDP (to the alpha subunit)
Explain the signaling pathway for GPCR’s
ligand binds to GPCR= goes confirmational change= alpha subunit exchange GDP to GTP
now alpha unit will dissociates and then go to regulate the another target protien.
now the target protien will relay another message by the use of secondary messenger
now again GTP hets hydrolysed to GDP and everything goes back to normal :)
now lets take can example
lets take adrenaline. here adrelanline receptor is a GPCR and ligand is adrenaline molecule
the target protien here will be Adenylate CYClase.
adenyl cyclase will have atp attached and then it will get converted to cAMP (in this case the secondary messenger)
now this messenger will tell the organ to do stuff (increase heart rate blood flow etc)
cAMP activates protien kinase A
how many type og G protiens are there? note gpcs have G protiens. GPCR and G protiens are separate entities that works together.
there are 4
Gs = starts AC
Gi = Inhbits AC
Go
Gq = activates phospholipase c pathway
Gs and Gi these have adenyl cyclase (AC) pathway
explain IP3 DAG pathway (Gq pathway or the phosphatidylinositol pathway)
ligand = g receptor activate = gdp to gtp = Gq goes and activates phospholipase C = Ph. C breaks down to IP3 and DAG = IP3 goes to rer and release calcium = DAG remain in cell membrane and activates phosphokinase C
What type of GPCR receptor is M3? (parasympathetic) (muscuranic) (present in bronchus)
its a Gq receptor (follows IP3 and DAG as secondary messenger)
(Bronchospasm)
Gq increase intracellular calcium thus causing contraction of smooth muscle of bronchiole causing vasoconstrriction
here the ligand is acetycholine / related drug
what type of GPCR is beta 2 ? (adrenergic/sympathetic)
its a Gs coupled (use cAMP and PKA) (bronchodilation)\
here the ligand is adrenaline/epinephrine/related drug
What is Methacholine?
stimulate M3 receptor in bronchi (parasym,VC)
it is given as a challenge test for asthma :)
what is Ipratropium and tiotropium?
the are antagonists for the M receptors of the pns or cholinergic or acetylcholine receptors.\
these cause vasodilation and prevent vasoconstriction.
blocks the M receptor
These are ANTICHOLINERGICS DRUGS. or ANTAGONISTS.
dont confuse these with the Beta agonist even though the function is same these BLOCKS the M and they ACTIVATED the beta
explain albuterol/salbutamol.
also explain salmeterol
all these are beta2 agonist used for bronchodilation in case of asthma.
salbutamol is short acting while salmeterol is long
NEVER GIVE LONG ACTING AGONISTS ALONE.
combine with inhaled corticosteroids
Why long acting bronchodilators/ beta 2 agonist such as salmeterol should never be given as a monotherapy and shoud always be combined with corticosteroids?
or
why is monotherapy of LABA (salmeterol fometerol)is contradicted in case of asthma?
Chronic use of LABAs causes tolerance due to downregulation of β2-adrenoceptors. This is associated with an increased risk of mortality in patients with asthma. Therefore the use of LABAs alone is contraindicated. The downregulation of β2-adrenoceptors by chronic use of LABAs can impair the response to SABAs when they are need for acutre relief of symptoms during an asthma attack.
Inhaled corticosteroids are used to control the inflammatory processes underlying asthma. Corticosteroids also upregulate β2-adrenoceptor expression. Combination of inhaled corticosteroids with LABAs reduces the risk of development of tolerance to β2-adrenoceptor agonists. Therefore, LABAs are only used concomitantly with corticosteroids.
Anticholinesterase ecplain.
Anticholinesterases are drugs that prolong the existence of acetylcholine after it is released from cholinergic nerve endings by inhibiting both acetylcholinesterase and butyrylcholinesterase.
Explain anticholinesterase poisioning.
Anticholinesterase poisoning is defined as the presence of nicotinic and/or muscarinic clinical features in combination with either (a) a history of exposure to an organophosphate or carbamate insecticide, or (b) a decreased level of serum pseudocholinesterase.
high acetylcholine remains. High pns function. N and M recetors activated highly.
one such organophosphate is Parathion.
Parathion=organophosphate poisioning = ache blocks =high acetycholine=high parasympathetic= symptoms of para,
diarrhoea urination miosis bronchospasm bradycardia emesis (vomiting) lacrimation sweating and salivation
what is asthma?
it is Bronchial Hyperreactivity.
narrowing of airway=increased muscus secretion.
name the two type of asthma.
Extrinsic Asthma
type 1 hypersensitivity
trigger are environmental antigens
IgE mediated
Intrinsic Asthma
non immune
trigger can be cold weather aspirin etc.
no IgE mediated
Name all cateogries of drugs that can be used to treat asthma.
1 corticosteroids 2 Beta agonnist 3 Muscuranic blockers 4 Mast cell stabilizers (chromolyn sodium) 5 Methylxanthine (theophylline) 6 antileukotrines 7 Monoclonal AB aginst IgE
2 , 3 , 5 are bronchodilators
1 , 4, 7 are anti-inflammatory agents
6 in leukotrine antagonist
How do Aspirin (NSAIDS) induces asthma?
Aspirin Blocks COX
low COX. Arachidonic acid shifts to form more leucotrines (LOX)
high leukotrines high hypersensitivity rxn
Name Corticosteroids for Asthma.
inhaled ICS
FLuticasone
oral is predni-sone
IV is predni-so-lone (L for long vien :P)
What are Methylxanthines?
Xanthines are a class of drug derived from purine base produces by both plants and animals
They work as to increase the cAMP in the tissues which in turn causes bronchodilation.
(asthma and copd)
Name some Methylxanthines.
Theophylline
Aminophylline
Theobromine
Caeffine
how do Adenosine causes bronchoconstriction?
the Adenosine receptors are Gi ones. they decrease the cyclic AMP and thus causes bronchoconstriction :)
rememner each smooth muscle cell have various receptors fo diffrent ligands :)
how methylxanthines increase cAMP in cells?
these inhibits the phosphodiestrase.
no PDE= cAMP does not get broken down.
= high cAMP
why Methylxanthines are called the enemy of Adenosine?
both of their functions are opposite. adenosine BC (inhibits cAMP through Gi) methyxanthind BD (increase cAMP through PDE inhibition)
Adenosine Treats Cardiac Arrythmias and causes Asthma
theophylline (xanthine) Cause arrythmia but Treats Asthma :)
NEVER COMBINE THESE TWO DRUGSSSSSS
