SILDENAFIL (VIAGRA)

Therapeutic Class: Drug for erectile dysfunction

Pharmacologic Class: Phosphodiesterase (PDE)-5 inhibitor

ACTIONS AND USES: Sildenafil acts by relaxing smooth muscles in the corpora cavernosa, thus allowing increased blood flow into the penis. The increased blood flow results in a firmer and longer lasting erection in about 70% of men taking the drug. The onset of action is relatively rapid, less than 1 hour, and its effects last up to 4 hours. Sildenafil blocks the enzyme phosphodiesterase-5. Sildenafil is also used for the treatment of pulmonary arterial hypertension. Blocking phosphodiesterase-5 in pulmonary vascular smooth muscle causes vasodilation and reduction in arterial hypertension. The drug improves exercise capacity in these patients. An off-label indication for sildenafil is the treatment of Raynaud’s phenomenon resistant to vasodilator therapy.

ADMINISTRATION ALERTS: Avoid administration of sildenafil with meals, especially high-fat meals, because absorption is decreased. Avoid grapefruit juice when administering sildenafil.

ADVERSE EFFECTS: Sildenafil is well tolerated and adverse effects are usually transient and mild. Common adverse effects include headache, dizziness, flushing, rash, and nasal

congestion. The most serious adverse effect, hypotension, occurs in patients concurrently taking organic nitrates for angina and can result in myocardial infarction (MI) and sudden cardiac death. Sildenafil can produce blurred vision, increased sensitivity to light, or changes in color perception. Priapism, a sustained erection lasting longer than 6 hours, has been reported with sildenafil use and this may lead to permanent damage to penile tissues. Contraindications: Sildenafil is contraindicated in patients taking nitrates and in those with hypersensitivity to the drug. These drugs are contraindicated in patients with severe cardiovascular disease, recent MI, stroke, heart failure, dysrhythmias, and in the presence of anatomic deformities of the penis.

INTERACTIONS: Drug–Drug: Cimetidine, erythromycin, and ketoconazole will increase serum levels of sildenafil and necessitate lower drug doses. Use with nitrates will result in hypotension. Protease inhibitors (ritonavir, amprenavir, others) will cause increased sildenafil levels, which may lead to toxicity. Rifampin may decrease sildenafil levels, leading to decreased effectiveness.

Herbal/Food: Administration of sildenafil with high-fat meals decreases the absorption of the drug. Grapefruit juice increases the plasma concentrations of sildenafil and may cause adverse effects. 

Treatment of Overdose: There is no specific treatment for overdose.

RELATED;

1.  BENIGN PROSTATIC HYPERPLASIA

REFERENCES

FIBRINOLYTIC DRUGS

INTRODUCTION: Fibrinolytic drugs rapidly lyse thrombi by catalyzing the formation of the serine protease plasmin from its precursor zymogen, plasminogen. These drugs create a generalized lytic state when administered intravenously. Thus, both protective hemostatic thrombi and target thromboemboli are broken down. Myocardial Infarction describes the use of these drugs in one major application.

PHARMACOLOGY: Streptokinase is a protein (but not an enzyme in itself) synthesized by streptococci that combines with the proactivator plasminogen. Streptococci

This enzymatic complex catalyzes the conversion of inactive plasminogen to active plasmin.

Urokinase is a human enzyme synthesized by the kidney that directly converts plasminogen to active plasmin. Plasmin itself cannot be used because naturally occurring inhibitors in plasma prevent its effects. However, the absence of inhibitors for urokinase and the streptokinase-proactivator complex permits their use clinically. Plasmin formed inside a thrombus by these activators is protected from plasma antiplasmins, which allows it to lyse the thrombus from within.

Anistreplase (anisoylated plasminogen streptokinase activator complex; APSAC) consists of a complex of purified human plasminogen and bacterial streptokinase that has been acylated to protect the enzyme’s active site. When administered, the acyl group spontaneously hydrolyzes, freeing the activated streptokinase-proactivator complex. This product allows for rapid intravenous injection, greater clot selectivity (ie, more activity on plasminogen associated with clots than on free plasminogen in the blood), and more thrombolytic activity. Plasminogen can also be activated endogenously by tissue plasminogen activators (t-PAs). These activators preferentially activate plasminogen that is bound to fibrin, which confines fibrinolysis to the formed thrombus and avoids systemic activation. Human t-PA is manufactured as alteplase by means of recombinant DNA technology.

Reteplase is another recombinant human t-PA from which several amino acid sequences have been deleted. Reteplase is less expensive to produce than t-PA. Because it lacks the major fibrin-binding domain, reteplase is less fibrinspecific than t-PA.

Tenecteplase is a mutant form of t-PA that has a longer half-life, and it can be given as an intravenous bolus. Tenecteplase is slightly more fibrin-specific than t-PA.

INDICATIONS & DOSAGE: Administration of fibrinolytic drugs by the intravenous route is indicated in cases of pulmonary embolism with hemodynamic instability, severe deep venous thrombosis such as the superior vena caval syndrome, and ascending thrombophlebitis of the iliofemoral vein with severe lower extremity edema. Thromboticdisorders

These drugs are also given intra-arterially, especially for peripheral vascular disease. Thrombolytic therapy in the management of acute myocardial infarction requires careful patient selection, the use of a specific thrombolytic agent, and the benefit of adjuvant therapy. Streptokinase is administered by intravenous infusion of a loading dose of 250,000 units, followed by 100,000 units/h for 24–72 hours. Patients with antistreptococcal antibodies can develop fever, allergic reactions, and therapeutic resistance. Drug resistance

Urokinase requires a loading dose of 300,000 units given over 10 minutes and a maintenance dose of 300,000 units/h for 12 hours. Alteplase (t-PA) is given by intravenous infusion of 60 mg over the first hour and then 40 mg at a rate of 20 mg/h. Reteplase is given as two intravenous bolus injections of 10 units each, separated by 30 minutes. Tenecteplase is given as a single intravenous bolus of 0.5 mg/kg. Anistreplase (where available) is given as a single intravenous injection of 30 units over 3–5 minutes. Recombinant t-PA has also been approved for use in acute ischemic stroke within 3 hours of symptom onset. In patients without hemorrhagic infarct or other contraindications, this therapy has been demonstrated to provide better outcomes in several randomized clinical trials. Clinicaltrials

The recommended dose is 0.9 mg/kg, not to exceed 90 mg, with 10% given as a bolus and the remainder during a 1 hour infusion. Streptokinase has been associated with increased bleeding risk in acute ischemic stroke when given at a dose of 1.5 million units, and its use is not recommended in this setting.

RELATED;

1.  VEIN DISORDERS  

2.  NOSE BLEEDING

3.  BLOOD CLOTTING AND IT'S PREVENTION

REFERENCES

ALLOPURINOL

Therapeutic Class: Drug for gout

Pharmacologic Class: Xanthine oxidase inhibitor

ACTIONS AND USES: Allopurinol is an older drug used to control the hyperuricemia that causes severe gout and to reduce the risk of acute gout attacks. It is also approved to prevent recurrent kidney stones in patients with elevated uric acid levels. It may be used prophylactically to reduce the severity of the hyperuricemia associated with antineoplastic and radiation therapies, both of which increase serum uric acid levels by promoting nucleic acid degradation. This drug takes 1 to 3 weeks to bring serum uric acid levels to within the normal range. Allopurinol is available by the PO and IV routes. IV administration is usually reserved for patients with high uric acid levels resulting from cancer chemotherapy. 

ADMINISTRATION ALERTS: Give with or after meals. Tablets may be crushed and mixed with food or fluids. Pregnancy category C.

ADVERSE EFFECTS: The most frequent and serious adverse effects are dermatologic and include micropapular rash and rare cases of fatal toxic epidermal necrolysis and Stevens–Johnson syndrome. A rare, sometimes fatal, hypersensitivity syndrome may occur and includes a skin rash, fever, hepatitis, leukocytosis, and progressive renal failure. Other possible adverse effects include drowsiness, headache, vertigo, nausea, vomiting, abdominal discomfort, malaise, diarrhea, retinopathy, and thrombocytopenia. 

Contraindications: Contraindications include hypersensitivity to allopurinol and idiopathic hemochromatosis. Use cautiously in patients with impaired hepatic or renal function, history of peptic ulcers, lower GI tract disease, bone marrow depression, and pregnancy.

INTERACTIONS Drug–Drug: Alcohol may inhibit the renal excretion of uric acid. Ampicillin and amoxicillin may increase the risk of skin rashes. An enhanced anticoagulant effect may be seen with the use of warfarin, and toxicity risks increase for azathioprine, mercaptopurine, cyclophosphamide, and cyclosporine. The risk of ototoxicity is increased when allopurinol is used with thiazides and angiotensin-converting enzyme (ACE) inhibitors. Aluminum antacids taken concurrently with allopurinol may decrease its effects. An increased effect may be seen with phenytoin and anticancer drugs, necessitating the need for altered doses of these medications.

RELATED;

1.  GOUT

REFERENCES

ANTIEMETIC AGENTS

 

Introduction:  Nausea and vomiting may be manifestations of a wide variety of conditions, including adverse effects from medications; systemic disorders or infections; pregnancy; vestibular dysfunction; central nervous system infection or increased pressure; peritonitis; hepatobiliary disorders; radiation or chemotherapy; and gastrointestinal obstruction, dysmotility, or infections.  

Pathophysiology:  The brainstem “vomiting center” is a loosely organized neuronal region within the lateral medullary reticular formation and coordinates the complex act of vomiting through interactions with cranial nerves VIII and X and neural networks in the nucleus tractus solitarius that control respiratory, salivatory, and vasomotor centers.  High concentrations of muscarinic M₁, histamine H₁, neurokinin1 (NK1), and serotonin 5-HT3  receptors have been identified in the vomiting center.  There are four important sources of afferent input to the vomiting center:  

1)    The “chemoreceptor trigger zone” or area postrema is located at the caudal end of the fourth ventricle.  This is outside the blood-brain barrier but is accessible to emetogenic stimuli in the blood or cerebrospinal fluid.  The chemoreceptor trigger zone is rich in dopamine D₂ receptors and opioid receptors, and possibly serotonin 5-HT₃ receptors and NK1 receptors.  

2)     The vestibular system is important in motion sickness via cranial nerve VIII.  It is rich in muscarinic M1  and histamine H1 receptors.  

3)     Vagal and spinal afferent nerves from the gastrointestinal tract are rich in 5-HT3 receptors.  Irritation of the gastrointestinal mucosa by chemotherapy, radiation therapy, distention, or acute infectious gastroenteritis leads to release of mucosal serotonin and activation of these receptors, which stimulate vagal afferent input to the vomiting center and chemoreceptor trigger zone.  

4)     The central nervous system plays a role in vomiting due to psychiatric disorders, stress, and anticipatory vomiting prior to cancer chemotherapy.   Identification of the different neurotransmitters involved with emesis has allowed development of a diverse group of antiemetic agents that have affinity for various receptors.

REFERENCES

SEDATIVE-HYPNOTICS

INTRODUCTION:  Sedation is a condition of drowsiness due to reduced central nervous system response to various environmental stimuli and manufests as reduced mental alertness.  

Hypnosis means initiation and maintanance of sleep situation.  Therefore a sedative-hypnotic is a drug that calms you down and leads to initiation and maintainance of sleep.  An effective  sedative  (anxiolytic) agent should reduce anxiety and exert a calming effect. The degree of central nervous system depression caused by a sedative should be the minimum consistent with therapeutic efficacy.  A  hypnotic  drug should produce drowsiness and encourage the onset and maintenance of a state of sleep. Hypnotic effects involve more pronounced depression of the central nervous system than sedation, and this can be achieved with many drugs in this class simply by increasing the dose. Graded dose-dependent depression of central nervous system function is a characteristic of most sedative-hypnotics.

RELATED;

1.  ZOLPIDEM  

2.  DEPRESSION  

3.  MANAGEMENT OF SLEEP DISORDERS

4.  BENZODIAZEPINES

5.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

DANTROLENE SODIUM

Therapeutic Class: Skeletal muscle relaxant

Pharmacologic Class: Direct-acting antispasmodic; calcium release blocker

ACTIONS AND USES: Dantrolene is often used for spasticity, especially for spasms of the head and neck. It directly relaxes muscle spasms by interfering with the release of calcium ions from storage areas inside skeletal muscle cells. It does not affect cardiac or smooth muscle. Dantrolene is especially useful for muscle spasms when they occur after spinal cord injury or stroke and in cases of cerebral palsy or multiple sclerosis. Stroke: Multiple sclerosis

Occasionally, it is useful for the treatment of muscle pain after heavy exercise. It is also used for the treatment of malignant hyperthermia.

ADMINISTRATION ALERTS: Use oral suspension within several days because it does not contain a preservative. IV solution has a high pH and therefore is extremely irritating to tissue. Pregnancy category C. Drugsin relation to pregnancy

ADVERSE EFFECTS: Adverse effects include muscle weakness, drowsiness, dry mouth, dizziness, nausea, diarrhea, tachycardia, erratic blood pressure, photosensitivity, and urinary retention.

Warning: This drug has the potential for hepatoxicity. Liver dysfunction may be evidenced by abnormal chemical blood enzyme levels. The risk of hepatic injury is increased in females over 35 years of age and after 3 months of therapy. Therapy should be discontinued after 45 days with no observable benefit. 

Contraindications: Patients with impaired cardiac or pulmonary function or hepatic disease should not take this drug. 

INTERACTIONS: Drug–Drug: Dantrolene interacts with many other drugs. For example, it should not be taken with over-the-counter (OTC) cough preparations and antihistamines, alcohol, or other CNS depressants. Verapamil and other calcium channel blockers that are taken with dantrolene increase the risk of ventricular fibrillation and cardiovascular collapse.

RELATED;

1.  Rh disease of the newborn

REFERENCES

PHENYTOIN

 

Introduction:  Phenytoin is the oldest, non-sedative, antiseizure drug, introduced in 1938 after a systematic evaluation of compounds such as phenobarbital that altered electrically induced seizures in laboratory animals. It was known for decades as diphenylhydantoin. 

Molecular structure:  Phenytoin is a diphenyl-substituted hydantoin with the structure shown below. It has much lower sedative properties than compounds with alkyl substituents at the 5 position.  A more soluble prodrug of phenytoin, fosphenytoin, is available for parenteral use; this phosphate ester compound is rapidly converted to phenytoin in the plasma.

Mechanism of Action:  Phenytoin has major effects on several physiologic systems.  It alters Na⁺, K⁺,  and Ca²⁺ conductance, membrane potentials, and the concentrations of amino acids and the neurotransmitters norepinephrine, acetylcholine, and γ-aminobutyric acid (GABA).  Phenytoin also blocks the persistent Na⁺ current, as do several other AEDs including valproate, topiramate, and ethosuximide.  In addition, phenytoin paradoxically causes excitation in some cerebral neurons.  A reduction of calcium permeability, with inhibition of calcium influx across the cell membrane, may explain the ability of phenytoin to inhibit a variety of calcium-induced secretory processes, including release of hormones and neurotransmitters.

Clinical Uses:  Phenytoin is effective against partial seizures and generalized tonic-clonic seizures. In the latter, it appears to be effective against attacks that are either primary or secondary to another seizure type. 

Pharmacokinetics:  Absorption of phenytoin is highly dependent on the formulation of the dosage form. Particle size and pharmaceutical additives affect both the rate and the extent of absorption.  Absorption of phenytoin sodium from the gastrointestinal tract is nearly complete in most patients, although the time to peak may range from 3 to 12 hours.  Phenytoin is highly bound to plasma proteins. Drug concentration in cerebrospinal fluid is proportionate to the free plasma level. Phenytoin accumulates in brain, liver, muscle, and fat. Phenytoin is metabolized to inactive metabolites that are excreted in the urine. Only a very small proportion of the dose is excreted unchanged.  The elimination of phenytoin is dose-dependent. At very low blood levels, phenytoin metabolism follows first-order kinetics. However, as blood levels rise within the therapeutic range, the maximum capacity of the liver to metabolize phenytoin is approached.

Therapeutic Levels & Dosage:  The therapeutic plasma level of phenytoin for most patients is between 10 and 20 mcg/mL.  A loading dose can be given either orally or intravenously; the latter, using fosphenytoin, is the method of choice for convulsive status epilepticus.  When oral therapy is started, it is common to begin adults at a dosage of 300 mg/d, regardless of body weight. This may be acceptable in some patients, but it frequently yields steady-state blood levels below 10 mcg/mL, which is the minimum therapeutic level for most patients. If seizures continue, higher doses are usually necessary to achieve plasma levels in the upper therapeutic range.  Because of its dose-dependent kinetics, some toxicity may occur with only small increments in dosage. The phenytoin dosage should be increased each time by only 25–30 mg in adults, and ample time should be allowed for the new steady state to be achieved before further increasing the dosage.

RELATED;

1.  CARBAMAZEPINE

REFERENCES

CARBAMAZEPINE

 

Introduction:  Closely related to imipramine and other antidepressants, carbamazepine is a tricyclic compound effective in treatment of bipolar depression.  It was initially marketed for the treatment of trigeminal neuralgia but has proved useful for epilepsy as well.

Molecular structure:  Although not obvious from a two-dimensional representation of its structure, carbamazepine has many similarities to phenytoin.  The ureide moiety (–N–CO–NH 2) in the heterocyclic ring of most antiseizure drugs is also present in carbamazepine. Three dimensional structural studies indicate that its spatial conformation is similar to that of phenytoin.

Mechanism of Action:  The mechanism of action of carbamazepine appears to be similar to that of phenytoin. Like phenytoin, carbamazepine shows activity against maximal electroshock seizures. Carbamazepine, like phenytoin, blocks Na⁺ channels at therapeutic concentrations and inhibits high-frequency repetitive firing in neurons in culture.  It also acts presynaptically to decrease synaptic transmission.  Potentiation of a voltage-gated K⁺  current has also been described. These effects probably account for the anticonvulsant action of carbamazepine. Binding studies show that carbamazepine interacts with adenosine receptors, but the functional significance of this observation is not known.

Clinical Uses:  Although carbamazepine has long been considered a drug of choice for both partial seizures and generalized tonic-clonic seizures, some of the newer antiseizure drugs are beginning to displace it from this role. Carbamazepine is not sedative in its usual therapeutic range. The drug is also very effective in some patients with trigeminal neuralgia, although older patients may tolerate higher doses poorly, with ataxia and unsteadiness. Carbamazepine is also useful for controlling mania in some patients with bipolar disorder.

RELATED;

1.  EPILEPSY

2.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

MISUSE OF DRUGS AND POSSIBILITIES OF TOXICITY

MISUSE OF DRUGS AND POSSIBILITIES OF TOXICITY:  Drug toxicity is one of the negative outcomes of drug use today.  This fatal scenario has dramatically increases with increasing pharmaceutical products on the market and continuous use of traditional medications, and Over The Counter (OTC) medications.  The increase in pharmaceutical products is in fact not the problem but instead an advantage that, we stand a chance to win many microbial infections and disease conditions however, due to irrational use of such medical products, we stand high chances of getting toxicities form such products.  On this page, we are going to look at the way drugs can be misused by patients and or medical workers and the possibility to develop adverse effects and or toxicities form them.  If you have not been following me in the previous discussions, you may also want to read about;  Dynamics of drugs in the human body and then, Concurrent use of over the counter medications.

WAYS OF GETTING TOXIC EFFECTS FROM DRUGS:  There are several ways we can get toxicities from the drugs we use and most of them are patient/client related.  Although in rare scenarios drug toxicities can result from medical/health workers interventions, this is a limited case because in the health care settings and following the medical protocol, there is follow-up and carefulness from more than one individual making it hard for a mistake to be done by the whole team.  Below are some of the ways we can risk getting toxicities from the drugs we use.

1.  Simultaneous use of traditional medications and pharmaceutical products:  It is noted that throughout the globe in different communities, people tend to use traditional medications to cure various disease and for some, they really work out very well even better than some of the available pharmaceutical products.  The problem however comes that some of the traditional remedies that are used may contain certain ingredients similar to those in a given pharmaceutical product and therefore this may subject additional quantities of the same drug to the patient.  To understand the way this can lead to possible toxicities, it requires one to read about Therapeutic index/window discussed in our previous modules.  Also, it will be good to read more about my article about; Sources of drugs and pharmaceutical products.

2.  Drug-drug and drug-food interactions

3.  Unknown dosages of the drug...................

RELATED;

1.  DYNAMICS OF DRUGS AND THE HUMAN BODY

2.  CONCURRENT USE OF OVER THE COUNTER MEDICATIONS

3. THERAPEUTIC INDEX/WINDOW

4.  SOURCES OF DRUGS AND PHARMACEUTICAL PRODUCTS

AMANTADINE & RIMANTADINE

INTRODUCTION: Amantadine and its α-methyl derivative, rimantadine, are tricyclic amines of the adamantane family that block the M2 proton ion channel of the virus particle and inhibit uncoating of the viral RNA within infected host cells, thus preventing its replication. They are active against influenza A only.

PHARMACOKINETICS: Rimantadine is four to ten times more active than amantadine in vitro. Amantadine is well absorbed and 67% protein bound. Its plasma half-life is 12–18 hours and varies by creatinine clearance. Rimantadine is about 40% protein-bound and has a half-life of 24–36 hours. Nasal secretion and salivary levels approximate those in the serum, and cerebrospinal fluid levels are 52–96% of those in the serum; nasal mucus concentrations of rimantadine average 50% higher than those in plasma. Amantadine is excreted unchanged in the urine, whereas rimantadine undergoes extensive metabolism by hydroxylation, conjugation, and glucuronidation before urinary excretion. Dose reductions are required for both agents in the elderly and in patients with renal insufficiency, and for rimantadine in patients with marked hepatic insufficiency.

CLINICAL SIGNIFICANCY: In the absence of resistance, both amantadine and rimantadine, at 100 mg twice daily or 200 mg once daily, are 70–90% protective in the prevention of clinical illness when initiated before exposure. When begun within 1–2 days after the onset of illness, the duration of fever and systemic symptoms is reduced by 1–2 days. The primary target for both agents is the M2 protein within the viral membrane, incurring both influenza A specificity and a mutation-prone site that results in the rapid development of resistance in up to 50% of treated individuals. 

ANTIMICROBIAL RESISTANCE: Resistant isolates with single-point mutations are genetically stable, retain pathogenicity, can be transmitted to close contacts, and may be shed chronically by immunocompromised patients. The marked increase in the prevalence of resistance to both agents in clinical isolates over the last decade, in influenza A H1N1 as well as H3N2, has limited the usefulness of these agents for either the treatment or the prevention of influenza. Cross-resistance to zanamivir and oseltamivir does not occur.

ADVERSE EFFECTA: The most common adverse effects are gastrointestinal (nausea, anorexia) and central nervous system (nervousness, difficulty in concentrating, insomnia, light-headedness); side effects are dose related and may diminish or disappear after the first week of treatment despite continued drug ingestion. More serious side effects (eg, marked behavioral changes, delirium, hallucinations, agitation, and seizures) may be due to alteration of dopamine neurotransmission; are less frequent with rimantadine than with amantadine; are associated with high plasma concentrations; may occur more frequently in patients with renal insufficiency, seizure disorders, or advanced age; and may increase with concomitant antihistamines, anticholinergic drugs, hydrochlorothiazide, and trimethoprim-sulfamethoxazole.

Clinical manifestations of anticholinergic activity tend to be present in acute amantadine overdose. Both agents are teratogenic and embryotoxic in rodents, and birth defects have been reported after exposure during pregnancy.

RELATED;

1. ANTIVIRAL DRUGS  

2. DOPAMINE  

3. DRUG RESISTANCE

REFERENCES

DRUG DICOVERY AND DEVELOPMENT

DRUG DICOVERY AND DEVELOPMENT

FOOD-FOOD AND FOOD-DRUG INTERACTIONS

INTRODUCTION: Herbal and vitamin supplements can have powerful effects on the body that can influence the effectiveness of prescription drug therapy. In some cases, OTC supplements can enhance the effects of prescription drugs; in other instances, supplements may cancel the therapeutic effects of a medication. For example, many patients with heart disease take garlic supplements in addition to warfarin (Coumadin) to prevent the potential for clots forming. Because garlic and warfarin are both anticoagulants, taking them together could result in abnormal bleeding. As another example, high doses of calcium supplements may cancel the beneficial antihypertensive effects of drugs such as nifedipine, a calcium channel blocker. Few controlled studies have examined how concurrent use of natural supplements affects the therapeutic effects of prescription drugs. Patients should be encouraged to report use of all OTC dietary supplements to their health care provider.

RELATED;

1.  GINGER

REFERENCES

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

NSAIDS:  Non steroidal anti-inflammatory drugs are some of the most commonly used drugs either as Over the counter or prescribed medications.  with their affordability in terms of cost and availability of different types, these drugs are used to treat different medical conditions involving inflammation, fever and pain.

EXAMPLES:  Some of the most commonly use NSAIDs include but not limited to; Aspirin, Indomethacin, Diclofenac, Ibuprofen, and sometimes Acetaminophene is taken under this group although it has a slightly different classification.

PHARMACODYNAMICS

SIDE EFFECTS

PLASMA VOLUME EXPANDERS

ACTIONS AND USES: Dextran 40 is a polysaccharide that is too large to pass through capillary walls. It is similar to dextran 70, except dextran 40 has a lower molecular weight. Dextran 40 acts by raising the osmotic pressure of the blood, thereby causing fluid to move from the interstitial spaces of the tissues to the intravascular space (blood). Given as an IV infusion, it has the capability of expanding plasma volume within minutes after administration. Cardiovascular responses include increased blood pressure, increased cardiac output, and improved venous return to the heart. 

PHARMACOKINETICS AND INDICATIONS: Dextran 40 is excreted rapidly by the kidneys. Indications include fluid replacement for patients experiencing hypovolemic shock due to hemorrhage, surgery, or severe burns. When given for acute shock, it is infused as rapidly as possible until blood volume is restored. Dextran 40 also reduces platelet adhesiveness and improves blood flow through its ability to reduce blood viscosity. These properties have led to its use in preventing deep venous thromboses and postoperative pulmonary emboli. Pulmonary embolism

ADMINISTRATION ALERTS:

1) Emergency administration may be given 1.2 to 2.4 g/min.

2) Non-emergency administration should be infused no faster than 240 mg/min.

3) Discard unused portions once opened because dextran contains no preservatives.

4) Pregnancy category C

ADVERSE EFFECTS: Vital signs should be monitored continuously during dextran 40 infusions to prevent hypertension caused by plasma volume expansion. Signs of fluid overload include tachycardia, peripheral edema, distended neck veins, dyspnea, or cough. A small percentage of patients are allergic to dextran 40, with urticaria being the most common sign.

CONTRAINDICATIONS: Dextran 40 is contraindicated in patients with renal failure or severe dehydration. Other contraindications include severe congestive heart failure (CHF) and hypervolemic disorders.

INTERACTIONS:

Drug–Drug: There are no clinically significant interactions.

Treatment of Overdose: For patients with normal renal function, discontinuation of the infusion will result in reduction of adverse effects.

RELATED;

1. ALKALINITY AND ACIDITY OF BODY SYSTEMS

2.  HEMATOLOGICAL CONDITIONS

REFERENCES

PRAZIQUANTEL

INTRODUCTION:  Praziquantel is effective in the treatment of schistosome infections of all species and most other trematode and cestode infections, including cysticercosis. The drug’s safety and effectiveness as a single oral dose have also made it useful in mass treatment of several infections.

PHARMACOKINETICS: Praziquantel is a synthetic isoquinoline-pyrazine derivative. It is rapidly absorbed, with a bioavailability of about 80% after oral administration. Peak serum concentrations are reached 1–3 hours after a therapeutic dose. Cerebrospinal fluid concentrations of praziquantel reach 14–20% of the drug’s plasma concentration. About 80% of the drug is bound to plasma proteins. Most of the drug is rapidly metabolized to inactive mono- and polyhydroxylated products after a first pass in the liver. The half-life is 0.8–1.5 hours. Excretion is mainly via the kidneys (60–80%) and bile (15–35%).

Plasma concentrations of praziquantel increase when the drug is taken with a high-carbohydrate meal or with cimetidine; bioavailability is markedly reduced with some antiepileptics (phenytoin, carbamazepine) or with corticosteroids.

PHARMACODYNAMICS:  Praziquantel appears to increase the permeability of trematode and cestode cell membranes to calcium, resulting in paralysis, dislodgement, and death. In schistosome infections of experimental animals, praziquantel is effective against adult worms and immature stages, and it has a prophylactic effect against cercarial infection.

CLINICAL USES:  Praziquantel tablets are taken with liquid after a meal; they should be swallowed without chewing because their bitter taste can induce retching and vomiting.

A. Schistosomiasis:  Praziquantel is the drug of choice for all forms of schistosomiasis. The dosage is 20 mg/kg per dose for two ( S. mansoni and S haematobium ) or three (S. japonicum and S mekongi ) doses at intervals of 4–6 hours. High cure rates (75–95%) are achieved when patients are evaluated at 3–6 months; there is marked reduction in egg counts in those not cured. The drug is effective in adults and children and is generally well tolerated by patients in the hepatosplenic stage of advanced disease. There is no standard regimen for acute schistosomiasis (Katayama syndrome), but standard doses as described above, often with corticosteroids to limit inflammation from the acute immune response and dying worms, are recommended.

B. Clonorchiasis, Opisthorchiasis, and Paragonimiasis:  Standard dosing is 25 mg/kg three times daily for 2 days for each of these fluke infections.

C. Taeniasis and Diphyllobothriasis:  A single dose of praziquantel, 5–10 mg/kg, results in nearly 100% cure rates for T. saginata , T. solium , and D. latum infections. Because praziquantel does not kill eggs, it is theoretically possible that larvae of T solium released from eggs in the large bowel could penetrate the intestinal wall and give rise to cysticercosis, but this hazard is probably minimal.

ADVERSE REACTIONS, CONTRAINDICATIONS, & CAUTIONS:  Mild and transient adverse effects are common. They begin within several hours after ingestion of praziquantel and may persist for about 1 day. Most common are headache, dizziness, drowsiness, and lassitude; others include nausea, vomiting, abdominal pain, loose stools, pruritus, urticaria, arthralgia, myalgia, and low-grade fever. Mild and transient elevations of liver enzymes have been reported. Several days after starting praziquantel, low-grade fever, pruritus, and skin rashes (macular and urticarial), sometimes associated with worsened eosinophilia, may occur, probably due to the release of proteins from dying worms rather than direct drug toxicity. The intensity and frequency of adverse effects increase with dosage such that they occur in up to 50% of patients who receive 25 mg/kg three times in 1 day.

 

RELATED;

1.  Fungi

REFERENCES