Anti-tussives, Histamine and Anti-histamine, Anti-asthmatic drugs, Anti-migraine drugs, Anti thyroid drugs

Cough medicine (Anti-tussive drugs)

Cough medicine often contains cough suppressants or expectorants.

A cough medicine or cough and cold medicine, also known as linctus when in syrup form, is a medicinal drug used in those with coughing and related conditions. There is no good evidence for or against the use of over-the-counter cough medications in those with a cough.^[1] While they are used by 10% of American children weekly, they are not recommended in Canada and the United States in children 6 years or younger because of lack of evidence showing effect and concerns of harm.

There are a large number of different cough and cold medications. Some include: Benilyn, Sudafed, Robitussin and Vicks among others. Most contain a number of active ingredients. These may include combinations of: antihistamines, antitussives (cough suppressants), expectorants, decongestants and antipyretics

Effectiveness

The efficacy of cough medication is questionable, particularly in children. A 2012 Cochrane review concluded that "There is no good evidence for or against the effectiveness of OTC medicines in acute cough" Some cough medicines may be no more effective than placebos for acute coughs in adults, including coughs related to upper respiratory tract infections. The American College of Chest Physicians states that cough medicines are not designed to treat whooping cough, a cough that is caused by bacteria and can last for months. No over the counter cough medicines have been found to be effective in cases of pneumonia

There is not enough evidence to make recommendations for those who have a cough and cancer They are not recommended in those who have COP or chronic bronchitis.

Pharmaceuticals

• Dextromethorphan may be modestly effective in decreasing cough in adults with viral upper respiratory infections. However, in children it has not been found to be effective.
• Codeine was once viewed as the gold standard in cough suppressants but this position is now questioned. Some recent placebo-controlled trials have found however that it may be no better than placebo for some etiologies including acute cough in children. It is thus not recommended for children. Additionally there is no evidence that hydrocodone is useful in children
• A number of other commercially available cough treatments have not been shown to be effective in viral upper respiratory infections. These include in adults: antihistamines antihistamine-decongestant combinations, benzonatate, and guaifenesin; and in children: antihistamines, decongestants for clearing up the nose, or combinations of these.

Histamine antagonist

From Wikipedia, the free encyclopedia

A histamine antagonist (commonly called an antihistamine) is that drug which inhibits the actions of histamine by either blocking its attachment to histamine receptors, or inhibiting the enzymatic activity of histidine decarboxylase which catalyzes the transformation of histidine into histamine (atypical antihistaminics). Histamine antagonists are commonly used for the relief of allergies caused by intolerance of proteins.

Antihistamines ≠ Histamine action by blocking attachment to histamine®

i.e.                                          Antihistamines≠

Histidine   >>      Histamine

Clinical effects

Histamine produces increased vascular permeability, causing fluid to escape from capillaries into tissues, which leads to the classic symptoms of an allergic reaction— a runny nose and watery eyes.

Antihistamines suppress the histamine-induced wheal response (swelling) and flare response (vasodilation) by blocking the binding of histamine to its receptors on nerves vascular smooth muscles, glandular cells, endothelium, and mast cells. They exert a competitive antagonism to histamines

Itching and sneezing are suppressed by antihistamine blocking of H1-receptors on nasal sensory nerves.

Clinical: H₁- and H₂-receptor antagonists

H₁-receptor antagonists

In common use, the term antihistamine refers only to compounds that inhibit action at the H₁ receptor (and not H₂, etc.).

Rather than "true" antagonists H₁-antihistamines are actually inverse agonists at the histamine H₁-receptor. Clinically, H₁ antagonists are used to treat allergic reactions. Sedation is a common side-effect, and some H₁ antagonists, such as diphenhydramine and doxylamine, are also used to treat insomnia.

Second-generation antihistamines cross the blood–brain barrier to a much lower degree than the first generation antihistamines. The main benefit is that they primarily affect peripheral histamine receptors, and therefore are less sedating. However, high doses can still induce the CNS drowsiness.

Examples include the following:

Cyclizine, Chlorpheniramine, Chlorodiphenhydramine, Cyproheptadine and Triprolidine

ANTI ASTHMA DRUGS

Medications used to treat asthma are divided into two general classes: quick-relief medications used to treat acute symptoms; and long-term control medications used to prevent further exacerbation.^[104]

Salbutamol metered dose inhaler commonly used to treat asthma attacks.

• Short-acting beta₂-adrenoceptor agonists (SABA), such as salbutamol (albuterol) are the first line treatment for asthma symptoms. They are recommended before exercise in those with exercise induced symptoms.
• Anticholinergic medications, such as ipratropium bromide, provide additional benefit when used in combination with SABA in those with moderate or severe symptoms. Anticholinergic bronchodilators can also be used if a person cannot tolerate a SABA.
• Older, less selective adrenergic agonists such as inhaled epinephrine have similar efficacy to SABAs. They are however not recommended due to concerns regarding excessive cardiac stimulation.

Long–term control

Fluticasone propionate metered dose inhaler commonly used for long-term control.

• Corticosteroids are generally considered the most effective treatment available for long-term control .Inhaled forms such as beclomethasone are usually used except in the case of severe persistent disease, in which oral corticosteroids may be needed. It is usually recommended that inhaled formulations be used once or twice daily, depending on the severity of symptoms.
• Long-acting beta-adrenoceptor agonists (LABA) such as salmeterol and formoteroll can improve asthma control, at least in adults, when given in combination with inhaled corticosteroids.In children this benefit is uncertain. When used without steroids they increase the risk of severe side-effects and even with corticosteroids they may slightly increase the risk.
• Leukotriene antagonists (such as montelukast and zafirlukast) may be used in addition to inhaled corticosteroids, typically also in conjunction with LABA. Evidence is insufficient to support use in acute exacerbations. In children they appear to be of little benefit when added to inhaled steroids. In those under five years of age, they were the preferred add-on therapy after inhaled corticosteroids by the British Thoracic Society in 2009.^[123]
• Mast cell stabilizers (such as cromolyn sodium) are another non-preferred alternative to corticosteroids.

ANTI-MIGRAINE DRUGS

Migraine is a serious, potentially life-threatening neurological disease that affects nearly 32 million Americans, the majority of whom are women. The hallmark symptom of migraine is an escalating, often unbearable, debilitating headache that is commonly described as intense throbbing or pulsating pain in one area of the head. The pain may be accompanied by extreme sensitivity to light and sound, nausea, and vomiting. In some people, migraines are preceded by visual disturbances known as auras that may include flashing lights, zigzag lines, or temporary blindness.

Migraine medications do not cure migraines. Instead, migraine drugs treat the symptoms using one of two approaches. Some migraine drugs relieve symptoms. Other migraine drugs are used to prevent a migraine attack.

Many migraine sufferers rely on simple pain relievers to get through an attack. These range from over-the-counter analgesics like acetaminophen to anti-inflammatories like naproxen or ibuprofen to prescription barbiturate combinations and narcotics. While this type of treatment provides relief, it doesn't target the physiological processes that underlie a migraine attack.

Migraine symptoms occur, in part, because of the dilation of blood vessels in the brain. Until recently, migraine sufferers had few choices when it came to drugs to counteract this effect. But newer migraine drugs known as Triptans cause constriction of blood vessels and also bring about a general interruption in the chain of chemical events that leads to a migraine.

At some point, a migraine sufferer may need to move on to preventative therapy. This usually becomes necessary when migraine attacks happen more than once a week and/or abortive medications fail to work more than half the time.

No migraine drugs specifically prevent migraines. But many drugs used for other conditions can help keep migraines at bay. These include certain blood pressure medications as well as some antidepressants, anti-seizure drugs, and herbals.

For what conditions are migraine medications used?

Some of the migraine medications used to treat or prevent migraine headaches are also used for other conditions. Antidepressants, anticonvulsants, antihistamines, and narcotic pain relievers are all used in migraine therapy. There are some migraines drugs, though, that are used because they directly target the pain pathways associated with migraine headaches rather than pain pathways in general.

What are the different types of migraine medications?

Migraine medications fall into two major categories. The first contains drugs which abort or stop migraines from progressing once they begin. The earlier these drugs are used in a migraine attack, the better they work. The second category contains drugs which prevent migraines from happening.

Over-the-counter migraine medications used to address pain include analgesics, NSAIDS, and caffeine, including:

• Aspirin
• Naproxen
• Ibuprofen
• Acetaminophen
• Or combinations of these

One drawback to using analgesics and NSAIDs is that taking them daily can make headaches worse due to medication overuse.

Prescription drugs used to provide relief from pain include NSAIDs and narcotics. Like over-the-counter medications, prescription drugs often come in combinations. A barbiturate called butalbital is often used in combination with acetaminophen, and caffeine with or without codeine (a narcotic). Barbiturates are a sedative and may be useful to help people sleep off the pain.

While analgesics, NSAIDs, and narcotics relieve pain, they don't address the underlying physiology -- primarily the dilation of blood vessels in the brain. Two classes of migraine drugs do: the ergotamines and the more recently available triptans.

Ergot alkaloids -- such as ergotamine tartrate and dihydroergotamine mesylate  are potent drugs that constrict blood vessels. Because nausea is a possible side effect of these migraine drugs, some people take ergotamines in combination with other drugs to prevent nausea.

Triptans target serotonin receptors. These drugs cause constriction of blood vessels and bring about a general interruption in the chain of chemical events that lead to a migraine. Triptans include:

• Almotriptan
• Eletriptan
• Frovatriptan
• Naratriptan
• Rizatriptan
• Sumatriptan
• Zolmitriptan

While specific triptans differ in their ability to prevent a recurrence of migraine headache, they are generally equally effective in their ability to provide relief. Triptans are more migraine-specific than the earlier ergotamines.

Another migraine drug used to abort the pain of a migraine is a combination product containing the vasoconstrictor isometheptene mucate, the sedative dichloralphenazone, and the analgesic acetaminophen. The FDA has classified isometheptene mucate as "possibly" effective for migraines, pending further review.

Antihistamines are also used to ease migraine symptoms. These drugs counteract the effect of histamine, a substance that dilates blood vessels and causes an inflammatory response in the body -- the same kinds of response seen during a migraine attack. Antihistamines are broadly grouped into sedating and nonsedating types. An example of a sedating type is diphenhydramine; an example of the nonsedating type is loratadine.

There are no drugs that specifically prevent migraines. But certain blood pressure medications as well as some antidepressants, antiseizure drugs, and herbals have been used for that purpose. It sometimes takes weeks of trial and error to arrive at an optimal dose for these medications and even longer for the drugs to exert their full effect. Preventative migraine medications include:

Beta-blockers

• Atenolol

Calcium channel blockers

• Diltiazem
• Nimodipine
• Verapamil

Carbimazole(Anti-thyroid Drugs)

Carbimazole is used to treat hyperthyroidism. Carbimazole is a pro-drug as after absorption it is converted to the active form, methimazole. Methimazole prevents the thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4 (thyroxine)

Clinical use

Therapy for hyperthyroidism generally starts at a high daily dose of 15–40 mg continued until the patient has normal thyroid function, and then reduced to a maintenance dose of 5–15 mg. Treatment is usually given for 12–18 months followed by a trial withdraw.

The onset of anti-thyroid effect is rapid but the onset of clinical effects on thyroid hormone levels in the blood is much slower. This is because the large store of pre-formed T3 and T4 in the thyroid gland and bound to thyroid binding globulin (99% bound) has to be depleted before any beneficial clinical effect occurs.

Precautions

Some people are allergic to azole(s). Some azole drugs have adverse side-effects. Some azole drugs may disrupt estrogen production in pregnancy, affecting pregnancy outcome.

Carbimazole should be used judiciously in pregnancy as it crosses the placenta. It has (rarely) been associated with congenital defects, including aplasia cutis of the neonate but is not contra-indicated. However, it more predictably may cause fetal hypothyroidism so (in minimal doses) it can be used in order to control maternal hyperthyroidism. There are reported cases of goiter and choanal atresia in fetus.  Furthermore, breast feeding is possible but only if lowest effective dose is used and neonatal development is closely monitored.

Adverse effects

Whilst rashes and pruritus are common, these can often be treated with antihistamines without stopping the carbimazole. For those patients where sensitivity reactions can not be controlled, propylthiouracil may be used as an alternative; cross-sensitivity between these drugs is rare.

Its most serious rare side effect is bone marrow suppression causing neutropenia and agranulocytosis. This may occur at any stage during treatment and without warning; monitoring of white cell count is not useful. Patients are advised to immediately report symptoms of infection, such as sore throat or fever, so that a full blood count test may be arranged. If this confirms a low neutrophil count, discontinuation of the drug leads to recovery. However failure to report suggestive symptoms or delays in considering the possibility of immunosuppression and its testing, can lead to fatalities.

Methimazole

Methimazole is a drug used to treat hyperthyroidism, a condition that occurs when the thyroid gland begins to produce an excess of thyroid hormone. The drug may also be taken before thyroid surgery to lower thyroid hormone levels and minimize the effects of thyroid manipulation. Additionally, Methimazole is used in the veterinary setting to treat hyperthyroidism in cats.

Mechanism of action

Methimazole inhibits the enzyme thyroperoxidase, which normally acts in thyroid hormone synthesis by oxidizing the anion iodide (I-) to iodine (I0), facilitating iodine's addition to tyrosine residues on the hormone precursor thyroglobulin, a necessary step in the synthesis of triiodothyronine (T3) and thyroxine (T4).

It does not inhibit the action of the sodium-dependent iodide transporter located on follicular cells' basolateral membranes. Inhibition of this step requires competitive inhibitors such as perchlorate and thiocyanate

Adverse effects

Other known side effects include:

• Skin rash, itching, abnormal hair loss, upset stomach, vomiting, loss of taste, abnormal sensations.

Propylthiouracil

Mechanism of action

Propylthiouracil inhibits the enzyme thyroperoxidase, which normally acts in thyroid hormone synthesis by oxidizing the anion iodide (I^-) to iodine (I⁰), facilitating iodine's addition to tyrosine residues on the hormone precursor thyroglobulin. This is one of the essential steps in the formation of thyroxine(T4)

Propylthiouracil does not inhibit the action of the sodium-dependent iodide transporter located on follicular cells' basolateral membranes. Inhibition of this step requires competitive inhibitors, such as perchlorate and thiocyanate.

Propylthiouracil also acts by inhibiting the enzyme 5'-deiodinase (tetraiodothyronine 5' deiodinase), which converts T₄ to the active form T₃. (This is in contrast to methimazole, which shares propylthiouracil's central mechanism, but not its peripheral one.)

 

Pharmacokinetics

Side effects

One possible side effect is agranulocytosis a decrease of white blood cells in the blood. Symptoms and signs of agranulocytosis include infectious lesions of the throat, the gastrointestinal tract, and skin with an overall feeling of illness and fever. A decrease in blood platelets (thrombocytopenia) also may occur. Since platelets are important for the clotting of blood, thrombocytopenia may lead to problems with excessive bleeding. Side effects are suspected and the drug is sometimes discontinued if the patient complains of recurrent episodes of sore throat.

A more life threatening side effect is sudden, severe, fulminant hepatic failure resulting in death or liver transplantation, which occurs in up to 1 in 10,000 people taking propylthiouracil. Unlike agranulocytosis which most commonly occurs in the first three months of therapy, this side effect may occur at any time during treatment.

By; Dr. Omokhafe (Pharmacology Department)

†SUMMARY/HIGHLIGHTS†

‡Antiussives are drug substances used in suppressing cough

ᴥ Antitussives are based on the effect on the suppression of the symptoms/causatives alone except codeine which addresses the cough directly

ᴥ Many of these antitussive drugs suppress cough at the upper respiratory tract.

ᴥ Substances in these drugs help to break the mucous substances in the upper respiratory tracts (URT) to help release the irritant materials present in the URT. E.g. Antihistamines, codeine, dextromethorphan, menthol(as is used in mints).

ᴥ Expectorants are substances used in breaking the mucous and help bring out the mucous from the URT (i.e. helps to expel the mucous out of the system)

‡Drugs

  of Migraine.

ᴥ The cause is not actually known but can be aggravated by several factors and the end result is severe long-term headache.

ᴥ Examples of such factors are stress, tension, e.t.c.

ᴥ Most important drugs are;

v  Triptans

v  Ergot alkaloids (used in the constriction of blood vessels in the brain)

ᴥ Both are used in directly treating Migraines

ᴥ Others include non-steroidal anti-inflammatory drugs…

By; Kpoto Demo Judex

Drop your own Revision of the above topics and their mechanism of actions б

۝Study Questions

Write on the mechanism of action of any three of the following with examples of drugs and drug actions;

(A)   Anti-migraine drugs

(B)   Carbimazole

(C)   Linctus

(D)   Anti asthma drugs

(E)    Histamine antagonist

State their clinical significance and their adverse effects

REFRENCES

   From Wikipedia and co

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