Migraine Medication /s Or Migraine Treatment

Migraine Medication

 Introduction

Migraine is a type of headache which usually occurs in adolescents or young adults.Headache of migraine occur on one side of the head or in the whole head and 60-80% of migraine headache are familial.Migraine is more common in female than in males.Migraine headache occurs in attacks and each attacks of headache usually last from a few hours to 2 days while the frequency of attacks may varry from one or more attacks in a week to one attack in a year.Migraine is usually precipitated by emotional or physical stress apart from this migraine can also be precipitated by missed meals ,sleep disturbances,menstrual periods,alcohol,foods and oral contraceptives.Severity of Headache varies in different patients it may he throbbing pain or some time it may be dull.migrainenmay also be assoiciated woth vomiting and nausea.it may be preceded or accompanied by certain neurological symptoms such as luminous visual hallucination.Migraine occur due to the involement of trigeminal the perivascular spaces.This perivascular oedema mau cause the stretching of pain receptors in the dural membrane,causing headache of migraine.Also it has been found that sometimes during migraine,amplitude of pulsation of temporal arteries is increased .During aura there is abnormal release of serotinin from the platelets,but during headache of migraine serum serotinin fall below normal.

There is another type of migraine headache which is more common in males than in females which is called Cluster Headache in this type of headahe there is very severe pain around an eye with redness of the eye and watering from the nose and eye .Usually occurs in people age 30 or more and its attack usually occur after every 12-18 months.Attack occur usually at night and each attack last 1-2 hours.They remain for one to three weeks during each cluster.

Classifiacation Of Migriane Drugs / Migraine Medication /s
There are two group of Migraine Medication /s Which are ,

(A) Drugs For the treatment of Acute Attack

(1)5-HT1 Agonist:

Zolmitriptan
Sumatriptan
Rizatriptan
Naratriptan

(2)Other Migraine Medication /s

Ergotamine
Paracetamol
Opioids
Dihydroergotamine
NSAIDs

(B)Prophylactic Drugs

Aspirin
Pizotifine
Propranolol
Amitryptyline
Fluoxetine
Flunarizine
Cyproheptadine
Clonidine
Methylsergide
Sertraline

Ergotamine

Ergotamine is one of the best Migraine Medication and It is an alkaloid obtained from a fungus known as cleviceps purpurea.This Fungus infest the rye and some other grains and grasses.
Pharmacokinetics

It is given orally,sublingually,inhalationaly,by rectal route and by intramuscular injection.When given orally it is absorb from the intestine and its absorption is variable.After metabolism the drugs is excreted in urine.Caffeine increases its absorption from the intestine.

Adverse Effects:

Nausea ,vomiting and diarrhea are the most common adverse effects.
Large doses can cause spasm of the blood vessels of the arms and legs thatmay lead to their gangrene.Rarely gangrene of intestine can occur due to spasm of mesentric artieries.

Contraindications

Perilheral vascular disease such as Reynaud disease and buerger disease.in these disease arteries of the limb are narrowed .
Collagen disease.
Ischemic heart disease
Its better to avoid in pregnant women though there is no evidence of harmful effects.

Triptans

These are a group of drugs that are recently being most commonly used in acute attack of migraine.Their mechanism of action appears to be similar to that of ergot alkaloids.

Sumatriptan

It is a 5HT1B and 5HT1D agonist and it is a great Migraine Medication which is effective in both migraine headache and cluster headache.its effectivenessin these conditions is equal to or more than that of ergot alkaloids.

Pharmacokinetics
When given orally only 15% of sumitriptan is absorbed into the systemic circulation.its plasma half life is two to three hours.it can be used orally,subcutaneously and as a nasal spray.

Adverse effects:
Sumitriptan is well tolerated .it can cause mild degree of abnormal sensation such as dizziness,muscle weakness,tingling,pain in the chest ,pain in the neck and pain at the site of injection.
As it is short acting several doses of drug maybe need during a prolonged attack of migraine.However no more than two doses should be given per day.

Other triptans

Naratriptan

It is also a 5HT1B and 5HT1D agonist.
Use 2.5mg of naratriptan orally after an attack of migraine .
When used orally 40-70% of drug is absorbed from the intestine into systemic circulation.
If migraine recurs then 2.5mg can be used again after 4 hours of intial dose.
If the patient doesn’t respond to the first dose don’t use it again for the same attack.
A maximum of 5mg can be used per day.
Not recommended for patient below 18 year of age.
Plasma half life is about 6 hours
Mechanism and adverse reactions are similar to that of sumitriptan.

Rizatriptan

This drug is also a 5HT1B and 5HT1D agonist and is also a best Migraine Medication .
Mechanism and adverse effect are similar to that of sumatriptan.
when used orally 40-70% absorbed from the small intestine into the systemic circulation.
10mg can be used orally at the onset of an attack and if the migraine recurs then a second dose can be given after 2 hours of the first dose.
Keep that mind if the patient doesn’t respond to first dose then second dose is not used.
Maximum daily dose is 20mg and it is not recommended for children below 18 years.

Almotriptan

Daily recommended Dose is 25 mg.
It is used in a dose of 12.5mg orally as soon as possible after the onset of migraine attack.
For recurrence of migraine a second dose should not be given before 2 hours of the first dose.
If there is no response to the first dose,second dose is not given for the same attack .
It is not recommended in children below 18 years.

Eletriptan

It is used in a dose of 40mg orally as soon as possible after the onset of migraine attack and repeated after 2 hours if recurs.
A second dose is not used if there is no response to the first dose.

Contraindications of triptans

Almotriptan is contraindicated in severe hypertension.

All of 5HT1 Agonist are contraindicated in agina pectoris,because they produce spasm of coronary arteries.

Zolmitriptan is contraindicated in wolf-parkinson-white syndrome.

Sumatriptan,rizatriptan,almotriptan,eletriptan,and zolmitriptan are short acting drugs and therefore several doses of these drugs are required during a prolonged attack.

Noratriptan and almotriptan are contraindicated in severe hepatic and renal diseases and in peripheral vascular diseases.

NSAIDS

All NSAIDs can be used as a Migraine Medications in the treatment of acute attack of migraine.
Opioids may be used in severe cases of migraine not responding to other drugs.As they cause addiction ,care should be taken during their use.

Prophylactic Migraine Medication /s

Following are the important Migraine Medication /s that can be used in the prevention of migraine.

Drugs          Prophylactic Dose
Aspirin        300mg twice daily
Prpranolol   80-240mg/Day in 3-4 doses
Imipramine 10-150mg daily in single dose
Amitriptyline 10-150mg daily in single dose
Fluoxetine    20-60mg in a single dose
Sertraline     50-200mg in a single dose
Clonidine      0.2-0.6mg daily
Mrthylsergide maleate 4-8 mg daily
Verapamil      80-160mg daily
Ergonovine maleate 0.6-2mg daily
Cyprophetadine   12-20mg daily.

Quinolones and Fluoroquinolones

Quinolones & Fluoroquinolones

 

Introduction:

Quinolones and Fluoroquinolones are a group of synthetic broad spectrum antibiotics.These antibiotics were also isolated from natural resources. One of the most important member of quinolone group of antibiotic was Nalidix Acid.The Problem with this compound was that it was narrow spectrum and it has moderate gram negative activity but it has no gram positive activity.Apart from this issue the nalidix acid was poorly distributed in the body and that is why quinolones are not effective for systemic bacterial infections.so with the passage of time scientist added flourine with mother compound i.e Nalidix acid to improve their activity  so “a group of broad spectrum antibiotics which are flourinated analogues of nalidix acid are called fluoroquinolones ”
These antibiotics are the most famous drugs these days because of their good absorption and spectrum of activity against all type of bacteria and these agents can be effectively used in systemic infections.

Why they are so important ?

A)Very Good Oral Absorption.
B)Very good distribution means deep peneteration in the tissues very effiently.because of their deep penetretion they can kill intracellular organisms.e.g chlamydia,TB,Legionella,brucella.
C)Newer agents are very broad spectrum.
D)They have high potency.
E)They are very well tolerated (Very safe drugs compare to other antibiotic drugs)

What is the mechanism of action of quinolones on bacteria?
OR
How does quinolone work?
OR

Mechanism of action of Quinolones and Fluoroquinolones :

  • These drugs are bactericidal But the question is how they kill the bacteria ?
    Quinolones And Fluoroquinolones are acting on enzymes called topoisomerases or DNA Gyrase.They inhibit bacterial replication by interfering with their DNA replication pathway. DNA is the core genetic material of the cells, and is responsible for correct functioning of the cell. During protein synthesis and DNA replication, the double-stranded DNA must unwind into one stranded structure, that allows for complementary base pairing to occur and synthesis of messenger RNA to procede. Normally This moving of DNA within the bacterium is completed by enzymes called DNA topoisomerase type 2 or DNA gyrase There are two functional Domains Of Topoisomerase 2 enzyme i.e Nuclease domain And Ligase domain.Basically this DNA gyrase (Nuclease Domain) cut the one side of two stranded DNA  and then (Ligase domain ) reseal it after unwinding.This Process continue and the bacteria keep growing but quinolones and fluoroquinolones inhibit or didn’t allow the enzyme Ligase sub doamin to refix or reseal the broken or cut edge of DNA and that is why the bacteria is unable to replicate or even synthesize proteins.First & Second Generation fluoroquinolones Work On this Enzyme .
  • There is another enzyme which is called topoisomerase type 4 which is little different from the type 2 enzyme they also have two domains but the nulcease domain has two sub domain which is responsible for cutting of untangled DNA into fragments the mechanism of fluoroquinolones is same like Topoisomerase 2 they inhibit the function of Ligase and make it dysfunctional.Nuclease domain keep on cutting the DNA into fragments but the ligase is not able to reseal it and the DNA Convert into small fragments and bacteria die.Third and Fourth generation Work Best on both type 2 and type 4 Topoisomerases.And that is the reason Third and Fourth Generation drugs are more broad spectrum in activity .
  • Initially the quinolone and fluoroquinoles first and second generation drugs were best work on gram negative bacteria.but the newer group work on both gram negative and gram positive .

 

  • Mnemonics For Mechanism:
  • Quinolones & Fluoroquinolones: Topple the Queen“: Quinolone interferes withTopoisomerase II.

Classification of quinolones and fluoroquinolones

The first generation i.e Nalidix acid is only quinolone other 3 classes are flouroquinolones.All Other compounds are the derivaties of Nalidix acid.Following are some classes of quinolones and fluoroquinolones ;

  • A)First Generation:
  • Nalidix acid
    B)Second Generation :
  • Ciprofloxacin
  • Norfloxacin
  • Ofloxacin
  • Lomefloxacin
  • Enoxacin
    Norfloxacin don’t absorb very well and they are not used most commonly While ciprofloxacin is the most commonly used drug in this class.
    C)Third Generation :
  • Levofloxacin
  • Gatifloxacin
  • Sparfloxacin
    (D)Fourth Generation :
  • Moxifloxacin
  • Trovafloxacin

Spectrum of activity 

1)First Generation Nalidix acid is moderatly effective (Not very effective) against gram negative bacteria.This drug is not used these day because of poor distribution in the body so it is use in rare uncomplicated urinary tract infections.because this drug is eliminated from the body through renal system and it concentrate into urinary system.

2)Second Generation
They become more effient against gram negative as compare to Nalidix acid.And Also have some less gram positive coverage but keep in mind it doesn’t work on streptococcus pneumoniae .
Ciprofloxacin is also effective against atypical organism like chalymdia ,mycoplasma both of these organism cause respiratory tract infections.
Means second generation has expanded its spectrum from moderate to more effective against gram negative bacteria some added benefits to gram positive bacteria and to atypical organisms.

Ciprofloxacin show more activity against pseudomonas aeruginosa than other fluoroquinolones.

Ciprofloxacin and ofloxacin are also good against Mycobacterium tuberculosis,mycobacterium Fortuitum and Mycobacterium Kansasii.but if use alone these are effective against M.avium infection.So for M.avium treatment they have to be combined with other antituberculous drugs.

Norfloxacin shows least activity against both gram postive and gram negative organisms.

Uses / Indications Of Ciprofloxacin

Where not to use this antibiotic ?
Don’t use this antibiotic more often because of the development of resistant strain and due to over usage, ciprofloxacin is failing against bacteria because of development of resistance.
Every doctor know there is one resistance type of organism i.e MRSA (Methicillin resistance staphylococcus aureus )it is resitant to many other antibiotic and the latest news is even ciprofloxacin is failing on this .
Don’t use this antibiotic in Pneumococcus and Enterococcus infections .

Where to Use Ciprofloxacin ?
A)GIT :Its very effective in traveller diarhea caused by toxic ecoli.
B)Ciprofloxacin is more effective in cystic fibrosis due to infection by pseudomonas auregenosa.
Usually flouroquinolones is contraindicated in children under the age of 18 because in animal model it is approved that flouroqinolones can damage the cartilages and they can produce arthropathy so it should not be used in pregnant women.

C)Ciprofloxacin and Ofloxacin are effective in treatment of typhoid fever .

D)Ciprofloxacin can be used to eradicate the nasopharyngeal carrier -state with meningococci.

E)Ciprofloxacin is the drug of choice in the treatment and prevention of anthranx.

3)Third Generation: Levofloxacin
Good against gram negative but has more activity against gram positive including streptococcus pnemoniea means levofloxacin can be used in pnemonia and that is why this is also called respiratory quinolones .
Levofloxacin is also effective against chlamydia ,mycoplasma and atypical pnemonia.

Levofloxacin and sparfloxacin show improved activity against streptococci and also effective against penicillin resistant pneumococci.

Levofloxacin
DON’T Use this antibiotic
if you are allergic to this drug or other drugs of this class like ciprofloxacin,norfloxacin,moxifloxacin.

Avoid taking antacids, vitamin or mineral supplements, sucralfate  or didanosine powder or chewable tablets within 2 hours before or after you take levofloxacin.

Before taking levofloxacin, tell your doctor if you have muscle weakness ,kidney or liver disease,or trouble breathing,seizures,joint problems, diabetes, myasthenia gravis, a history of head injury of brain tumor, a condition called pseudotumor cerebri, a personal or family history of Long QT syndrome,low levels of potassium in your blood,or if you have ever had an allergic reaction to an antibiotic.

Levofloxacin may cause swelling or tearing of a tendon, especially in the Achilles’ tendon of the heel. These effects may be more likely to occur if you are over 60, or if you have had a kidney,heart, or lung transplant.
if you take steroid medication, Stop taking levofloxacin and call your doctor at once if you have sudden pain, swelling, tenderness, stiffness.

Uses of levofloxacin
Levofloxacin is used to treat bacterial infections that cause bronchitis or pneumonia,means that action of this drug is more extended against pneumococci and also used to treat people who have been exposed to anthrax or plague.
Levofloxacin is also used to treat bacterial infections of the sinuses,skin,kidneys, bladder, or prostate.

4)Fourth Generation.Moxifloxacin
Levofloxacin and moxifloxacin both are called respiratory quinolones .
Its spectrum of activity further broaden against gram positive cocci and gram positive bacilli .
Moxifloxacin can kill the anaerobic organisms and that is why this can be used in mixed infections .

Moxifloxacin ,Gatifloxacin,Sparfloxacin and Gemifloxacin are effective against gram positive organism especially against pneumococci and to some extent staphylococci.

Moxifloxacin Uses
Moxifloxacin is used to treat a variety of bacterial infections. It works by stopping the growth of bacteria.

Moxifloxacin is used to treat bacterial infections, including:
community acquired pneumonia,throat, sinus, and lung infections stomach infections skin infections

Autonomic Nervous System Pharmacology & Adrenergic Antagonists

Autonomic Nervous System PharmacologyAutonomic Nervous System Pharmacology

Short introduction Of Nervous System:

The nervous system is divided into two;
A) Central Nervous System
B) Peripheral Nervous System
Central Nervous system composed of brain and spinal cord.While The peripheral nervous system includes neurons located outside the brain and spinal cord.i.e any nerves that enter or leave the CNS.
The Peripheral nervous system is subdivided into Two;A)Efferent B)Afferent
A)Efferent:The Efferent neurons carry signals away from brain and spinal cord to the peripheral tissues.
B)Afferent:The afferent neurons bring information from periphery to the CNS.These neurons provide sensory input to modulate the function of the efferent division through the reflex arc or neural pathways that mediate reflex action.
The efferent division further divided into;
A)Autonomic System

B)Somatic

In this Chapter we will Discuss about Autonomic Nervous system in detail.

Autonomic Nervous System Pharmacology

ANS is further classified into three
(1)Sympathetic
(2)Parasympathetic
(3)Enteric.

●Sympathetic and parasympathetic NS are working against each other.
●Under stress sympathetic Nervous system activate while in Relax position your parasympathetic nervous system activates.e.g When You are lying on your bed.
I will take advantage of Dr.Najeeb Very Famous Example.

Scenario Example : A Person walking on the road suddenly a very big dog appears behind him in a very hostile Manner.The sympathetic nervous system Will Activate & his body will prepare for fight or flight.Here his body will prepare for flight because the dog is big and dangerous but if the dog is too small your body will prepare for fight and the dog sympathetic nervous system will activate and the dog will run away.
Taking the first example we will see the sympathetic N.S of The Person.

Question: How the sympathetic N.S Will be activated?
How Adrenergic System Start ?

Note :
1)Sympathetic preganglionic fibers release acetylcholine as a neurotransmitter at neuro effector organs.Means All the neurons Coming out of CNS are cholinergic.
2)Sympathetic Postganglionic fiber release Norepinephrine as a neurotransmitter.

3)The acetylcholine release in the 2 example will act on adrenal medulla and adrenal medulla will then release Epinephrine.The epinephrine released by adrenal medulla to the general circulation will act on all the receptors in the body.

Q)How adrenergic Receptor Work?

This is very important because a lot of drugs act on this area
The main neurotransmitter here is Norepinephrine This N.E is synthesized in the nerve ending.Basically, Amino acids come from absorption of food from GIT into the General circulation.This amino acid converted into tyrosine in the blood and then taken up intracellularly into nerve ending where tyrosine converts into Dopa with the help of Tyrosine Hydroxylase enzyme.The Dopa then converted into Dopamine by an enzyme which is called Dopa decarboxylase enzyme.The Dopamine then Stored in the vesicles if not stored the dopamine is destroyed in the cytosol by MAO(Monoamine oxidase) enzyme so that’s why they are stored in the vesicles.In the vesicle, the dopamine converts into Norepinephrine if the neuron is adrenergic but if the neuron is dopaminergic the dopamine inside the vesicle will and store and will release as such.Here the neuron is adrenergic so the Norepinephrine will release in the nerve ending.
》Now the Ca+ Channels will open intracellular Calcium Level will increase.
There is a protein on the wall of vesicles which is called synaptobrevin
And the other protein on the membrane of the neuron  i.e Syntaxin.
Whenever sympathetic nervous system release Norepinephrine some of the N.E work on presynaptic membrane (alpha 2 AR)and causes inhibition of the cyclic AMP and Increase outflux of potassium (k+) from the nerve ending which control the release of N.E

How Norepinephrine Release

Q)What Happens to N.E after Using?

》There is a special reuptake mechanism and unlike cholinergic system in which the acetylcholine is destroyed by acetylcholinesterase enzyme.But in this case, the N.E is reuptake to the cell.After Reuptake there is a 50 % chance for N.E to take back by vesicle or destroyed by MAO Enzyme.
》Small Amount of N.E is methylated by an enzyme COMPT Which cause methylation some very small amount of NE comes into General circulation.

Q)How Drugs Act On This Whole System?/ Autonomic Nervous System Pharmacology

Following are some of the drugs which work on this system and show their effects.

Sympatholytic Drugs/adrenergic antagonist:

These drugs work on the above system and reduce the release of Norepinephrine.

1)Methyl Tyrosine:(CH5-Tyrosine)

The mechanism of action of methyl tyrosine is same like that of tyrosine.This drug enters into the system just like tyrosine and will work/bind on methyl hydroxylase enzyme.The enzyme will not work properly and eventually less dopamine will produce so fewer N.E will produce Less N.E means adrenergic activity decreases so this drug is sympatholytic, or adrenergic antagonist.

2)Reserpine: 

This Drug Work On dopamine transporter on the vesicle and Don’t let dopamine to enter into the vesicle and we know that dopamine outside the vesicle will be destroyed by MAO enzyme.There will no or less N.vesicle.So after action potential, the Nerve ending will not release N.E because of empty vesicle.This drug is called resperine.

3)Bretylium & Guanadrel:

These drugs Don’t allow the vesicle to fuse with the membrane of neuron and don’t let the vesicle to expel N.E.So Less N.E release from the neve terminal.

4)Alpha Methyl Dopa:

This drug is taken up by the transport mechanism i same like tyrosine.It is going to fool the dopa. Dopa work/bind on this Drug (Alpha methyldopa) instead of dopa decarboxylase enzyme.The drug continuously fooling this system up to the end and in the end no N.E release but instead the nerve terminal release alpha methyl N.E. so When action potential generated alpha methyl norepinephrine will release into the synaptic cleft.

Note: These drugs decrease the activity of norepinephrine but by binding direct into the normal Mechanism.These drugs don’t work on receptor.

Drugs That Block the receptor:

These drugs are also called adrenergic receptor blockers/antagonist:
These drugs also decrease the effect of N.E but by blocking the receptor on which N.E act.

Adrenergic Receptor Blockers/Antagonists

Sources: Lippincott Illustrated Reviews Pharmacology

                     Doctor Najeeb Lectures.

We Will Discuss Sympathomimetic Drugs In The Upcoming Posts.Keep Sharing Our Contents.

Pharma Chapter 2 :Routes of drug administration:

Routes of drug administration

Routes of drug administration

Routes of drugs administration are the strategies that are used to administer a specific drug to a patient.They are divided into 2 main types.

1)Enteral

2)Parenteral

Enteral Routes:

Administration of drugs through the gastro intestinal tract is known as enteral route of administration.it is further divided into 3 varieties.

1)Oral

2)Sublingual

3)Rectal

(A)ORAL ROUTE:

In This method the drug is taken within the mouth so enclosed,usually with the help of some water or alternative fluid.

Benefits:

1)It is convenient.

2)it is generaly economical as compared to other routes

3)This is the most typically used method of drug administration.

Limitations/Drawbacks:

1)Some drugs are not absorbed within the git,For example gentamicin,or streptomycin.Due to which its tough to administer in oral dosage type.

2)This method needs cooperation of patient.

3)Some drugs are destroyed by digestive enzymes of stomach or intenstine e.g benzyl penicillin and insullin.

4)Vomiting may occur due to unhealthy style,smell or iritant effect of the drug on the gastric mucous membrane.example are aspirin and indomethacin, which cause irrition of the stomach mucous membrane while castor oil has bad smell and quinine has bitter taste.

5)Food reduce absorption of some medicine e.g iron and tetracycline.while sure medication absorption is increased by food.e.g Griseofulvin.

6)Certain Drugs could inhibits the motility of stomach and intestine e.g opiods and antimuscarinics.thus they will delay their own absorption which of alternative medication given long with them.

7)When two or a lot of medication are given together,they can interfer with the absorption of one another.calcium, aluminium,magnesium,and iron can decrease the absorption of tetracyclines,because they react with chemicals to form insoluble salts.

8)First pass metabolism occur in oral route due to which only a part of drug could reach into the circulation.e.g oral administration of propranolol may cause metabolism of 70th of medication by first pass metabolism and so only 30 minutes of drug reached the circulation.

(B)SUBLINGUAL ROUTE:
Some drus with high lipid solubility can be chewed and then kept under the tongue.this is causes rapid absorption of drugs from the sublingual and other blood vessels of the oral mucosa.thus a quick effect of the drug will be produced.Following Drugs can be used by sublingual route.
1)Ergotamine
2)Nitroglycerin
3)Nifedipine

ADVANTAGES/BENEFITS:
1)Patient can use the drug himself with out assistance.
2)It is economical.
3)Administration of drug by this route produces a rapid effect because it is quickly absorbed into systemic circulation.
4)As the drug join the systemic circulation directly ,first pass effect does not occur.
5)The effect of the drug given by sublingual route can be terminated by spitting the tablet or swallowing it.

LIMITATIONS/DISADVANTAGES:
1)We can’t use this method in a person suffering from nausea.
2)Cooperation of patient is essential.
3)Drug can cause irritation of the mucosa with excessive saliva formation,and thus its swallowing can occur .This will prevent aim of sublingual administration.
4)We Can’t give it to an unconscious person.

(C)RECTAL ROUTE:
Administration of All form of Drugs into the rectum is known as Rectal route while of the dosage form is solid it is called suppository,while if this is liquid then it is called enema.Rectal Route can be used for both local and systemic administration.
E.g Indomethacin a pain relieving drug, can be used in the form of suppository to produce systemic effect.while corticosteroids can be used locally into the rectum for its inflamatory conditions.
About 50% of drug administered from rectal route is absorbed into portal circulation,and other 50% is absorbed into the systemic circulation.

ADVATAGES/BENEFITS:
1.This can be use in unconcious person
2.This also can be used in uncooperative child.
3.Those who are suffering from nausea can take take drugs through this route.
4.Those drugs which cause irritation of the stomach can be given through this route .e.g Aminophylline and indomethacine

LIMITATIONS:
1.Some people are embarrased to use this route.
2.Drugs absorbed into portal circulation can undergo fiest pass.
3.It requires the cooperation of a concious person.
4.Absorption of drug can be unpredictable through this route.
5.Repeated use of this route can cause irritation of rectal mucosa.

(2)PARENTERAL ROUTES:

Par means besides,Renteral means gastrointestinal tract.So Administration of drugs by routes other then enteral routes are known as parenteral routes.Most often ,the term parenteral is used when a drug is given by intravenous(IV),intramuscular(IM),subcutaneous(SC) injection.Here we will use the term parenteral for any route of drug administration other than enteral (From GIT).It Can be further divided into the following three Types:
1.Injection
2.inhalation
3.Topical

1)INJECTIONS:
Here the drug is administered with the help of a special instrument know as a syringe or by an infusion apparatus.The following types of injections are commonly employed.
1.intravenous (IV)
2.intramuscular(IM)
3.Subcutaneous (SC)
4.Intradermal
5.Intrathecal
6.intra-articular

Intravenous Route:
The drug is injected into a peripheral vein.Effects of the drugs may occur immediately .intravenous administration of a drug can be done bu two methods.
A)Bolus
B)infusion
Bolus:In this method injection is made into a vein with the help a syringe,
Infusion: infusion is done with the help of an infusion apparatus.Drugs With Short Duration of action can be given by intravenous infusion.e.g Dopamine,dobutamine etc.Similarly large quantities of fluid can also be given by intravenous infusion. Eg Normal Saline or dextrose solution etc.

Advantages:
1.It is highly effective and reliable route of drug administration.
2.A large volume of drug can be given by this method.
3.Effects of the drugs occur rapidly; this route is often used in emergency conditions.
4.An irritant Drug can be injected by this route the drug will be imediately diluted by the blood,and thus its irritant effect is reduced.
5.Rate of IV infusion of the drug can be controlled according to the response of the patient.Sodium nitroprusside can be given intravenous infusion for sever hupertension,and the rate of infusion can be adjusted according to the blood pressure of the patient.

LIMITATIONS:
1.This Reguire the help of a trained person,who is familiar with technique.
2.Proper asceptic precautionhave to be observed during the procedure.
3.This method is often expensive
4.some drugs can cause irritation of the vien wall and thrombophelbitis e.g diazepam.
5.The drug is directly administered into the systemic circulation thats why serious adverse effects can occur.Hence injection should be given slowly,and response of the patient should be carefully monitored.if the ADR occur asministeration of the drug should be immediately stpped.

INTRAMUSCULAR ROUTE:
In this method the drug is directly injected into a  skeletal muscle with the help of a syringe.Commonly injection is made into one of the following skeletoal muscle;
1.Vastus lateralis
2.Gluteus maximus
3.Deltoid
Absortion of drug is more feom deltoid and vastus lateralis than from Gluteus maximus due to better blood supply of the former two skeletal muscles,Drugs in aqueous solutions are more rapidly absorbed than those in oily solutions.Action of some drugs can be prolonged by combining them with some other substances e.g the effect of penicillin can be prolonged by combining it with procaine.This will cause slow absorption of penicillin from the site of injection.Thus intramuscular injection of procaine penicillin is effective for about 24 hours.intramuscular injection of oily solutionof penicillin will also prolonged its effects due to slow absorption of the drugs from the site of injection.

Benefits/Advantages:
1.This is reliable route ,liquid preparation produce their effects in 10-30 minutes.
2.certain depot preparations can be used by this route that are effective for a prolonged period.1 intramuscular injec of medroxyprogesterone may act as contraceptivr for about three months.One intramuscular injection of benzathine penicillin may be effective for about 1 month.
3.Rate of absorption of drug is more rapid as compared to the subcutaneous route.

Limitations:
1.A person trained for the technique is required for injection.
2.Only a limited amount of drug can be used by this route.
3.some drugs may cauee irritation of skeletol muscles,eg penicillin may cause pain when administered through an intramuscular injection.
4.If ADR (Adverse drug reactions)occur after its administration it can’t be removed from the site of injection.
5.Proper aseptic precautions are essential during the procedure.

Subcutaneous Route:
Drug is inected under the skin with a syringe.absorption of drug is slow in this method as compare to intramuscular route.
Advantages:
1.It is reliable route.
2.Self injection is possible.
Disadvantes:
1.Drug may cause irritation of the subcutaneous tissue.
2.Poor absorption of drug occurs in peripheral circulatory failure.
3.Poor absorption.

2)INHALATION:
Drug is inhaled into the lungs and then its absorption occurs into the systemic circulation from alveoli.Drugs Can be inhaled by the following methods.

A)Powder inhalation:
Some drugs can be inhaled as a fine powder with the help of a special apparatus known as spinhaler.Sodium cromoglycate can be used by this method for the prevention of bronchial asthma.

B)Gas inhalation:Most of the general anaesthetics are available as a volatile liquids.Their inhalation causes rapid absorption of drugs into the blood circulation from the alveoli.There is a rapid distribution of drug from the blood into the brain .this causes loss of consciousness ,for example suh an effect is produced by halothane ,enflurane etc.

C)Aerosol Inhalation:
The drug particle in this method are suspended in a gas.Particle size of a drug is 2-5 micrometers.e.g Terbutaline,Salbutamol,Ipratropium,Corticosteroids etc can be used as aerosolfor the treatment of asthma.Drug particles are distributed uniformly in a gas that us present in a compressed form in a special appartus known as inhaler.Drug is used by inhalation from the inhaler.

ADVANTAGES:
1.Aerosoland powders affect the lungs,and they have minimum systemic effects.
2.General anaesthetic are rapidly absorbed from the lungs,and they are also excreted from the lungs,thus their administration can be easily controlled.
3.Nitrous oxide is a gas with good analgesic effect.though it does not produce full anaesthesia,it can be used by the patient himself during painful conditions e.g during labour.

DISADVANTAGES:
1.Patient may not be able to use the apparatus properly.
2.Drug can cause irritation of the bronchial tract.
3.A special Apparatus is required.
4.Obsteuction of the bronchial tree with mucous plugs may interfere with the effect of drug.

TOPICAL ROUTE:
Drug is applied locally on skin ,eye,ear,nose oral cavity urinary bladder,rectum and vigina.Drugs can be applied on the skin for local or systemic effects .eg nitroglycerin can be used in the form of an ointment or a sticking plaster on the skin to produce its systemic effects.

ADVANTAGES:
1.Patient can use it himself.
2.High local concentration of drug can be achieved usually without its systemic effects.

DISADVANTAGES:
1.Some drugs can cause allergic reaction e.g certain antimicrobials.
2.Systemic absorption of drugs can occur from the local site of application.This can produce adverse effects on various parts of the body like administration of atropine or beta blocker in the eye.use of corticosteroids on skin can cause sufficient absorptioninto the blood to produce their systemic effects.

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                     Routes Of Drug Administration

General Pharmacology Definitions And Basic Concepts

Pharmacology

1)PHARMACOLOGY:

It is a branch of science that Deal with interaction of drugs with living organisms.Pharmacology incorporates the information of history,source,physical and chemical properties,compounding,biochemical and physiological effects,mechanism of action,absorption,distribution,biotransformation,excretion,and restorative and different employments of medications.

2)Drugs:

A drug is a comprehensively characterized as any substance specialist that causes changes in natural Functions in a living organism.some medications are framed inside living organism,such as hormones(insulin)Neurotransmitters(noradrenaline),etc.Drugs That are brought into the body from outside are known as xenobiotics.Most of the medications tie with a particular particle in a living being and cause an adjustment in its biological function by invigorating it.This atom directs a few capacities in the living life form and is known as receptor.There are some different medications that rear with the receptor yet don’t bring about its stimulation.they additionally keep the agonsit from authoritative with the receptors,such medications are known as antagonists.The sub-atomic weight of the most medications weight from 100-1000.However there are a few medications whose sub-atomic weight is very less, for example, that of lithium which is just 7.there are some drugs that have a high sub-atomic weight for example,alteplase has a sub-atomic weight of 59050.

3)Dose:

A determined measure of medication endorsed to be taken at one time.

4)Pharmacokinetics:

Branch Of Pharmacology That manage the absorption,distribution,metabolism and excretion of drugs.

5)Pharmacodynamics:

Branch Of Pharmacology Which  manages the physioligical and biochemical impacts of drugs and their system of activity.

6)Pharmacotherapeutics:

Pharmacotherapeutics manage the utilization of medications for counteracting and treating disease.

7)Toxicology:

It is a part of pharmacology that arrangement with the unfriendly impact of medications on living organisms.in expansion to drugs utilized as a part of therapy,it additionally manages numerous different chemicals that might be in charge of household,envionmental or industrial intoxications.

8)Medical Pharmacology:

It is a branch science and pharmacology which manage the substances used to prevent,diagnose and treat infections.

9)Pharmacognosy:

It is a branch of pharmacology which manages the organic and monetary components of common medications and their constituents.

10)Clinical pharmacology:

It is the scientific investigation of medications taken by Human being.

11)Pharmacy:

It is a branch of health sciences that arrangement with the preparation,dispensing and legitimate usage of medications.

12)Pharmacopoeia:

Pharmacopeia is a book that contains a list of item utilized as a part of prescription with descriptions,chemical tests for deciding their character and purity,and formulas for specific mixtures of these substances.it additionally for the most part contains an announcement of normal dosage.we commonly refers to two sorts of pharmacopeia.
1)British Pharmacopoeia(BP)
2)United States Pharmacopeia (USP)

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Chf medications Or Drugs Used For Congestive Heart Failure

chf medications

Chf medications or Drugs Used For Congestive Cardiac Failure/Heart Failure

To understand how chf medications work we have to first understand the normal physiology of heart.what happens to failing heart and what are the natural ways to avoid heart failure .We will also highlight some chf medications and possible management proctocols .

Cardiac/Heart Failure :

In Congestive Cardiac/Heart failure the heart fails to supply enough blood to the tissues due to decrease in cardiac out put.cardiac output depends upon the following four factors;
1)Preload
2)After load
3)Force Of heart contractility
4)Heart rate

Preload:

It can be defined as the volume of blood which flows into the heart and causes its stretch.stretching of the heart upto a certain point increases its force of contraction,as is explained by the frank starling law.thus increase in blood flow to the heart will increase its force of contraction upto a certain limit.beyond this point further increase in blood volume will lead to failure of the heart.a common example of this type of heart failure occurs in case of valvular incompetence.

Afterload:

It is the resistance offerd by the arterial system to the left ventricular contraction.increase in the arterial resistance causes the left ventricle to contract with more force.This out put load on the left ventricle and it is hypertrophied and thus ultimately fails.A common example of this occurs in chronic hypertension.here increase in arterial resistance causes decrease in systolic blood flow to kidney and other organs of the body.Decrease in renal blood flow leads to stimulation of renin secretion that causes formation of angiotensin 2.Angiotnesin 2 causes generalised vasoconstriction and increased release of aldosterone.Aldosterone causes retention of salt and water in the body by increasing their reabsoprtion from the distal renal tubules.this results in increase in the blood volume that further increase load on the heart.ultimately heart failure occurs.

Cardiac contractility:

Weaknes of the myocardium of the right and left ventricle will lead to decrease force of their contraction.coronary artery disease may lead to chronic right or left ventricle failure.acute myocardial infarction may lead to acute right or left ventricular failure.

Heart rate :

Any factor which decrease the force of contraction of the left ventricle will lead to decrease in cardiac output.This will cause relfex sympathetic nervous system stimulation,causing increase in the heart rate.

chf medications are used to control these four factors which ultimately decrease the chances of heart failure .

SIGNS AND SYMPTOMS OF CARDIAC FAILURE:

1)Tachycardia
2)Shortness of breath
3)Decrease in exercise tolerence
4)Pulmonary oedema
5)Cardiomegaly
6)Peripheral oedema

CLASSIFICATIOM OF DRUGS: chf medications 

Drugs Used For Congestive Cardiac Failure or chf medications are ,

1)Drugs used to decrease preload:
A)Diuretics
B)organic nitrate
2)Drugs which decrease after load
A)Hydralazine
B)Minoxidil
3)Drugs which decrease both preload and afterload:
A)Captopril
B)Enalapril
C)Lisinopril
D)Fosinopril
E)Quinapril
4)Positive ionotropic drugs:
They can be further divided into three groups;
1)Cardiac glycosides:
A)Digoxin
B)Digitoxin
C)Ouabin
D)Lanatoside.
2)Phosphodiestrase inhibitors:
A)inamrinonone (Amrinone)
B)Milrinone
3)Sympathomimetics:
A)Dopamine
B)Dobutamine
C)Depoxamine
D)Xamoterol

How to Manage Chronic Heart Failure:

Following steps should be taken for the managment of chronic heart failure:
1)Rest-Physical activity should be avoided
2)Hypertension and other underlying conditions should be treated.
3)Reduce weight if overweighted.
4)Reduce salt in diet.
5)Mild cardiac failure can be treated with diuretics for example frusemide in order to prevent K+ Loss amiloride or another K+ Sparing diuretic can be used with frusemide or other loop diuretics.
6)If cardiac failure is not controlled with diuretics then angiotensin converting enzyme inhibitors can be used,provided there is no hyptension.if hypotension is present then organic nitrates cannbe used.
7)Digoxin or other cardiac glycoside can be used if heart failure is not adequately controlled by the above methods.

How to manage Acute Ventricular Failure:

1)Patient should be put to complete bed rest.in severe left ventricular failure,legs should be kept dependent (Hanging from the bed)to reduce venous return from the legs.
2)A loop diuretic ,such as frusemide,should be given intravenously to produce dilatationof viens and later on diuresis.40-80 mg of frusemide can be given.Morphine can also be given intravenously to produce vasodilation as well as to reduce anxiety of the patient.

Diuretics Classification With Furosemide Pharmacology

Diuretics Classification With Furosemide PharmacologyDiuretics Classification With Furosemide Pharmacology
Diuretics:

Diuretics are Substances or drugs that are used to enhance or to modulate or to potentiate diuresis.OR Any agents or drugs that increase the volume of urine and any agents that increase the excretion of sodium (Na+) in the urine is called natriuretic or diuretics.

Classification:

(1)Thiazides diuretics
chlorothiazide
chlorthalidone
indapamide
hydrochlorothiazide
methyclothiazide
metolazone
(2)Loop diuretics
bumetanide
furosemide
ethacrynate
torsemide
(3)Potassium sparing diuretics
Amiloride hydrochloride
spironolactone
triamterene
(4)Carbonic Anhydrase inhibitors:
Acetazolamide
Methazolamide.

Furosemide:
Also known as frusemide.
Therapeutic Category:
It is one of the loop diuretic
One of the antihypertensive
Drug of choice in pulmonary oedema
Drug of choice in generalized oedema
(Oedema related to myocardial infarction and Oedema related to liver cirrhosis.
DOSAGE FORM & STRENGTHS:
It is available in solution,tablets as well as injectable form
Solution: 8,10 mg/ml
Tablet:20 mg,40mg,80mg
Injections:10 mg/ml,2ml.
Comercial Product and Trade names:
Frusemix 40mg (Abbot)
Losix 20,40 mg (Aventus)

Pharmacokinetics:

After oral adminstration absorption is satisfying,more the  40-60% of drug have absorption capability.
Onset of action:
In case of solid dosage form its onset of action is 30-60 minutes.
Peak effect is 1-2 hours
Time half: (T1/2)
Almost 1 hour
Protien Binding
More the 80% of drug have protien binding ability.

Mechanism of action:

As for mechanism of action is concern it is restricted to loop of henle and distilled part. it block Na-K+2cl- Cotransporter .Overall the drug is responsible to reinhibit the absorption of Na+,Cl-,Mg+ while on other side responsible for extretion of H+and K+ ions by tubular secretionso overall effect is reabsorption of various ions net result will decrease plasma volume inother words we can say it decrease peripheral resistance,venous return to heart,decrease diastolic blood pressure,so obviously there will be decrease heart rate ,cardiac output,and decrease systolic blood pressure.so loop diuretic have ability to decrease diastolic blood pressure by direct pathway while systolic blood pressure by indirect pathway.

Indications:
1)Acute pulmonary Oedema:

It  is most commonly related to lung directly related to deoxygenated blood ,specialy in condition like if a person is suffering from congestion of lungs so on one side it increase quantity of deoxygenated blood towards lungs while on other side due to congestion leads to increase permeability at the level of endothelial cell so liquid portion will ooze out towards interstatial area which is responsible for pulmonary oedema.
By taking support of loop diuretic peripheral resistance and venous return will decrease.this lead to decrease work load on heart obviously the contractility of heart will be decrease which in turn will decrease transportation toward lungs.

2)Generalized Oedema.

Loop diuretic specially frusemide use in generalized type of oedema relating to some pathological conditions like CHF,tachycardia,and liver cirhosis.

3)Hyperkalemia.

Loop diuretic is used in hyperkalemia because it block Na-K+2cl- Cotransporter and block K+(Potasium) to go to the blood so potasium level in blood decreases.
4)Hypertension:
Loop diuretic is used in hypertension in aged candidates while taking support of strips managment protocol for hypertension.also used to decrease Na+ intake ,Decrease alcohol consumtion specially in pregnancy.Also used in hypermagnesemia and hypernatrimia.

Adverse effects:(ADR)

Hypokalemia
Hyperurecemia
Hypocalcemia
Hypomagnesemia
Hyponatremia
Systemic alkalosis
Orthostatic hypotension
Osteoporosis if use for long time.

Precautionary measurment:

1)Monitor for possible occurence of blood dyscrasia and liver damage,monitor urine and blood pressure in diabetes.
2)Frequently monitor serum electrolyte
3)Incase of lactating mother it cross and exrete in milk so can effect the child.
4)In case of childrens may increase incidence of patent ductus arteriosis in premature infant especially with respiratory distress.
5)Persons Showing hypersensitivity reactions towards sulphonamide can show allergic reaction to frusemide.
6)Renal function:If increasing azotemia and oliguria occurs during treatment abruptly discontinue the drug.

Drug interactions:

1)Interaction of other antihypertensive drugs with frusemide increase the effects of frusemide.If use with other antihypertensive agents then reduce the dose by atleast 50%.
2)Frusemide Increase plasma lithium level and cause toxicity.
3)NSAIDs Decrease tge effects of frusemide
4)Phenytoin may reduce diuretic effect of frusemide.
4)Interaction of frusemide with thiazide diuretic can show synergistic effect that may result in profound diuresis and serious electrolyte abnormalities.