Page 1 of 1: pharmac extracts..

skjeev · Credits: 8220 My Scrapbook

hi, i am starting here everyday 1/2 chapters from katzung,since i dont have any other book.and 2nd revision is boring!and every day..little by little...want to finsh by july last week..all additional info welcome!that way it will be complementary.
main focus will be imp points and drugs names.

today-

introduction and drug metabolism-

introduction:
nature of drugs:
1.size-smallest..lithium MW 7;largest..thrombolytics..heparin30000
2.drug receptor bonds-literally all kind..covalent,weak electrostatic,much weaker hydrogen,vander waals,hydrophobic.dont ask examples..not given here.
drug movement in the body:
1.permeation-aqueous diffusion[thru water filled pores...upto size of small protein]
2.lipid diffusion-thru membranes and other lipid structures
both 1&2-r passive so,governed by Fick's law.
3.special carrier mediated- similar mechanisms that of endogenous substances
once carriers get saturated it stops,but not governed by Fick's.eg..probenecid inhibits special carriers for uric acid and penicillin..so u know where they r used!
4.endocytosis ,pinocytosis-permit very large /lipid insoluble chemicals to enter;eg.peptides,B12 with IF,Fe with transferrin.
Fick's law:it predicts rate of movement across a barrier-
Rate=concentration gradient x[permeability coeff/thickness] x surface area.

water and lipid solubility of drugs:
water is dipole so attracts charged molecules,forms shell around the drug molecule.so drug has charge...it will dissolve...
lipid solubility inversly proportional to charge on the drug.
and so fraction of molecules un-ionised for weak acids AND ionised for weak bases will determine..lipid solubility-
SO Handerson Hasselbalch equation helps here.
log[ionised/nononised]=pKa-pH for weak acids

nonionised/ionised...for weak bases

if one knows pKa value and pH of the body fluids[approximate]...we can tell whether the drug will pass thru certain barriers by calculating the fractions.

absorption of drugs:

routes-not something anybody wants to know more!
blood flow-same
concentration-same

distribution-

determinants -
size of organ[determines concentration gradient-smaller ones get saturated fast so lower gradient..brain,comapred to skeletal muscle...greater capacity...maintains higher gradient even with greater amount of drug.]
blood flow[determines rate...how fast?]
solubility...higher lipid solubility tissue uptake[cells] faster
binding..to tissue/plasma proteins will restrict the drug in one place,and the other will hav lower distribution.

skjeev · Credits: 8220 My Scrapbook

Metabolism:

it can termnate/activate.
most drugs r relatively lipid soluble.
types of metablic reactions-

phaseI:

oxidation[cytochrome P450 group of enzymes-Mixed Function Oxidases]
reduction
deamination
hydrolysis

phase II:

are synthetic reactions involve-conjugation of subgroups to hydroxyl,amino,and sulfhydryl.subgroups added are-glucuronate,acetate,glutathione,glycine,sulfate and methyl groups.
these make the drug less lipid soluble and relatively polar so it can b excreted.

skjeev · Credits: 8220 My Scrapbook

sites of metabolism:LIVER..kidneys,intestinal wall,blood..

DETERMINANTS OF BIOTRANSFORMATION RATE:

there is variation in how a drug is metabolised in different individuals.they r-
genetic
drug induced
age
disease related
gender
smoking

Genetic factors:

1.hydrolysis of esters:everyone knows succinyl choline
2.acetylation of amines:N-acetylation is the method by which INH,hydralazine,procainamide are metabolised.persons in whom it is deficient[autosomal recessive]-r called slow acetylators...will experience toxic effects of those drugs.
3.oxidation..rates of phenformin,dextrometharphan,metoprolol,some tcas.

other drugs:

enzyme induction and inhibitions:..everyone knows..if anybody can contribute welcome

Inhibitor of intestinal P-glycoprotein-
it is a [P-gp]important drug modulator in intestine mucosa...functions to expel drugs into lumen ...also found in blood brain barrier annd in multiple drug resistant cancer cells.
these inhibitors make it look like bioavailability increasing..so toxic plasma levels reached even with nontoxic doasge..eg:verapamil,mibefradil[ccb],grapefruit juice.

and drugs affected by inhibitors r -digoxin,cyclosporin,saquinavair.

FINALLY in metabolism-

should know about paracetamol.[antidote??]

skjeev · Credits: 8220 My Scrapbook

Eliminition of drugs-

1st order:half life if is constant
0 order:rate of elimination constant

imp phenytoin & aspirin at high doses AND ethanol...follow zero order.

i am done for the day!tomarrow pharmakinetic and dynamics..sure takes long time to type..hope i will not give up!

skjeev · Credits: 8220 My Scrapbook

Pharmaco dynamics-

must knows are-

EFFICACY-[bit confusing!]
THE MAXIMUM EFFECT A DRUG CAN BRING ABOUT REGARDLESS OF THE DOSE.
...in the text he says-
E max is the maximal effect an agonist can produce if the dose is taken to very high levels.

measured with graded dose-response curve[a graph of increasing responses to increasing doses of a drug.and cant measure with quantal dose-response curve.

It is determined by nature of receptor and its effector system.[partial agonists less efficacious than full]

so what is the role of dose???

skjeev · Credits: 8220 My Scrapbook

POTENCY-
THE DOSE OR CONCENTRATION REQUIRED TO BRING ABOUT 50 % OF DRUG'S MAXIMAL EFFECT.
that dose is EC50.

It can be measured by both quantal and dose response curves.[quantal being-fraction of population that shows a specified responce to increasing doses of a drug.ED50,TD50&LD 50..SO numbers obtained of potencies will not be identical]

It is determined by affinity of the receptor for the drug.

now the Kd-

it is the concentration of drug that results in binding to 50% of receptors.
ie higher the Kd value...lower the affinity.

Spare receptors-when EC50 IS LESS THAN Kd...these exist.
this might result by t mechanisms-
the effect of drug-receptor interaction may persist for a much longer time than the interaction itself
2nd..actual no of receptors may exceed the no of effector molecules available.

IMPORTANCE-presence of spares increases sensitivity to the agonists ..

skjeev · Credits: 8220 My Scrapbook

all the graphs...go through at least once.

signalling mechanisms-

1.thr' intracellular receptors..direct!

2.thr' receptor located on membrane spanning enzymes:eg,insulin-tyrosin kinase.

3.thr' receptor located on membrane spanning molecules that bind to separate intracellular tyrosine kinase molecules called Janus kinases...which on activation phosphorylate STAT molecules..which travel to nucleus ..where they regulate transcription.

4.thr' receptors located on membrane ion channels:mainly thr' changing the electric potential.

5.thr' receptors linked to effectors via G proteins...

skjeev · Credits: 8220 My Scrapbook

go thr' G protein table...

symp and parasymp-

G[q]-
alpha 1
muscarinic 1 & 3

G[s]-
all beta's

G[i]-
alpha 2 and muscarinic 2

About others-

like

1.dopamine:-
D1-G[s]
D2-G[i]

2.Histamine:-
H1-G[q]
H2-G[s]

3.5HT:-[any body with more info welcome]
5HT1D-G[i]
5HT2A-G[q]

4.angiotensin:G[q]

5.prostcyclin,glucagon-G[s]

vivek_patel · Credits: 2336 My Scrapbook

good

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