WikiVet English - User contributions [en]

Tetracyclines

2013-09-16T11:37:15Z

Shannanigans969: /* Side Effects and Contraindications */

{{review}}
[[Image: Tetracyclines.png|thumb|right|250px|The Basic Structure of Tetracyclines]]

==Introduction==
This group of antibiotics is named after the four hydrocarbon rings that make up the core of each of the drugs. Water soluble drugs are: '''Tetracycline, Oxytetracycline and Chlorotetracycline'''. Lipid soluble drugs are; '''Minocycline''' and '''Doxycycline'''.

==Mechanism of Action==
Tetracyclines work by inhibiting cell growth and so are '''bacteriostatic'''. They are brought into susceptible organisms by active uptake and then they inhibit translation. It binds to part of the ribosomal subunit and prevents tRNA from binding to the A site of the ribosome. This results in the inhibition of protein synthesis.

==Spectrum of Activity==
They are very broad antimicrobial agents.
* They are active against gram-positive bacteria, except enterococci and group D Streptococci.
* They are active against non-enteric gram-negative bactaeria. ''Pseudomonas'' and enterbacteriaceae are often resistant.
* They are active against Chlamydophila, Rickettsia, Mycoplasma and a range of protozoa.
* Resistance has now become widespread.

==Pharmacokinetic Considerations==
The water soluble tetracyclines are moderately lipophilic and the lipid soluble ones are very lipophilic. They are orally active, though presence of food decreases the absorption of the drug. This is especially the case when Ca2+ is present as it will chelate the drug. They have a wide volume of distribution but are unable to penetrate the CSF.

Water soluble forms are excreted in the bile and urine unchanged. Of the lipid soluble drugs doxcycline is excreted in the faeces by a combination of the drug in bile and through diffusion of the intestinal wall. Minocycline undergoes some metabolism in the liver before it is excreted in the bile.

==Side Effects and Contraindications==
* Due to their nature to be chelated by Ca2+ they tend to deposit in developing bones and teeth, resulting in staining and sometimes dental hypoplasia and bone deformaties. In man it is suggested not to give it to the young or pregnant animals.
* Gastrointestinal upsets are known to occur following oral administration, especially in horses and should be avoided in this species as much as possible.
* Collapse has been reported on intravenous administration of the drug.
* Nephrotoxicity has been reported because of high dose related changes in the renal tubule.
* In cattle it has been known that high doses result in fatty infiltration of the liver. This hepatotoxic nature of the drug means that they shouldn't be used if hepatic impairment is suspected.
* Oxytetracycline is irritant to tissues, especially in long-acting forms and shouldn't be used in small animals and horses.
* Doxycycline can cause oesophagitis and should be avoided if an animal is dysphagic or is vomiting.
* In man phototoxicity is a reported side-effect.

Sevoflurane

2012-09-18T09:17:56Z

Shannanigans969: /* Pharmacokinetics */

==Introduction==
'''Sevoflurane''' is very similar to [[Isoflurane|isoflurane]] but is less potent. However, it's odour is less pungent making it more suitable for mask induction, but can also be used as a maintentance agent. It is becoming more popular in veterinary anaesthesia.

==Pharmacokinetics==
Sevoflurane is also a halogenated ether. It is also stable and nonflammable. Alkaline carbon dioxide absorbents react with sevoflurane to produced a potentially toxic compound. This can be influenced by environmental temperature, sevoflurane concentrations, use of baralyme rather then sodalime, low flow rates and already exposed absorbents. The '''blood:gas partition coefficient''' is very low, meaning that has a rapid onset of action. It has a high tissue solubility however, which means that recovery is more prolonged compared to [[Isoflurane|isoflurane]] or [[Halothane|halothane]]. The '''MAC''' of sevoflurane is approximately ''2.4%'' in dogs and ''2.6%'' in cats and is therefore less potent than other agents. Sevoflurane undergoes a small amount of hepatic metabolism.

==Adverse Effects==
===Central Nervous System===
*Increases intracranial pressure due to cerebral vasodilation.

===Cardiovascular System===
*Mild myocardial contractility depression.
*Decreased arterial blood pressure and systemic vascular resistance.

===Other Systems===
*There is an increase in hepatic artery flow, but reduced in the hepatic portal vein, like isoflurane.

==Contraindications==
*It is advisable to avoid the use of sevoflurane in patients with renal disease as there is a potential for further renal damage.

{{unfinished}}
[[Category:To Do - Drugs]][[Category:To Do - Anaesthesia]]
[[Category:Inhalation Anaesthetic Agents]]

Isoflurane

2012-09-18T09:13:58Z

Shannanigans969: /* Pharmacokinetics */

==Introduction==
'''Isoflurane''' is currently the most commonly used inhalation agent in veterinary practice. Similarly to [[Halothane|halothane]] it's main use is as a maintenance agent after induction with an [[Injectable Agents|injectable agent]] but, again, can be used to induce patients. However, it does not have a pleasant odour and so many patients will breath hold. Isoflurane is licenced in most companion animals.

==Pharmacokinetics==
Isoflurane is a nonflammable and stable anaesthetic that, at room temperature, is a liquid and so requires passage through a [[Vaporisers|vaporiser]]. Unlike [[Halothane|halothane]], it does not require a preservative, nor does it undergo ultraviolet degradation. The '''blood:gas partition coefficient''' is lower than that of halothane, meaning that is poorly blood soluble. This means that it causes rapid induction , recovery and depth of anaesthesia. The '''MAC''' for isoflurane is approximately ''1.3%'' in dogs and ''1.6%'' in cats, making it ''less potent'' than halothane, but it is less tissue soluble. There is minimal metabolism to isoflurane, but any that occurs is in the liver.

==Adverse Effects==
===Central Nervous System===
*Isoflurane does not mar the cerebral circulation's response to carbon dioxide. This means that hyperventilation can be used to decrease ICP in these patients.

===Cardiovascular System===
*Myocardial contractility depression.
*Heart rate may increase, which helps control cardiac output in the face of depression of myocardial contractility.
*Decresase in arterial blood pressure due to decreased vascular resistance.

===Respiratory System===
*Ventilation depression.

===Other Systems===
*Decreases flow through the hepatic portal vein but increased flow through the hepatic artery, so hepatic damage is less likely.
*Like halothane, isoflurane can cause malignant hyperthermia in susceptible patients.

==Contraindications==
*Isoflurane should not be used in patients with a susceptilbility to malignant hyperthermia.
*It potentiates non-depolarising neuromuscular blocking agents.

{{unfinished}}
[[Category:Inhalation Anaesthetic Agents]]
[[Category:To Do - Anaesthesia]][[Category:To Do - Drugs]]

Isoflurane

2012-09-18T09:12:53Z

Shannanigans969: /* Pharmacokinetics */

==Introduction==
'''Isoflurane''' is currently the most commonly used inhalation agent in veterinary practice. Similarly to [[Halothane|halothane]] it's main use is as a maintenance agent after induction with an [[Injectable Agents|injectable agent]] but, again, can be used to induce patients. However, it does not have a pleasant odour and so many patients will breath hold. Isoflurane is licenced in most companion animals.

==Pharmacokinetics==
Isoflurane is a nonflammable and stable anaesthetic that, at room temperature is a liquid and so requires passage through a [[Vaporisers|vaporiser]]. Unlike [[Halothane|halothane]], it does not require a preservative, nor does it undergo ultraviolet degradation. The '''blood:gas partition coefficient''' is lower than that of halothane, meaning that is poorly blood soluble. This means that it causes rapid induction , recovery and depth of anaesthesia. The '''MAC''' for isoflurane is approximately ''1.3%'' in dogs and ''1.6%'' in cats, making it ''less potent'' then halothane, but it is less tissue soluble. There is minimal metabolism to isoflurane, but any that occurs is in the liver.

==Adverse Effects==
===Central Nervous System===
*Isoflurane does not mar the cerebral circulation's response to carbon dioxide. This means that hyperventilation can be used to decrease ICP in these patients.

===Cardiovascular System===
*Myocardial contractility depression.
*Heart rate may increase, which helps control cardiac output in the face of depression of myocardial contractility.
*Decresase in arterial blood pressure due to decreased vascular resistance.

===Respiratory System===
*Ventilation depression.

===Other Systems===
*Decreases flow through the hepatic portal vein but increased flow through the hepatic artery, so hepatic damage is less likely.
*Like halothane, isoflurane can cause malignant hyperthermia in susceptible patients.

==Contraindications==
*Isoflurane should not be used in patients with a susceptilbility to malignant hyperthermia.
*It potentiates non-depolarising neuromuscular blocking agents.

{{unfinished}}
[[Category:Inhalation Anaesthetic Agents]]
[[Category:To Do - Anaesthesia]][[Category:To Do - Drugs]]

Inhalation Anaesthetic Agents Overview

2012-09-17T15:52:18Z

Shannanigans969: /* Introduction */

==Introduction==
'''Inhalation anaesthetics''' are commonly used after induction with [[Injectable Agents|injectable agents]] but can also themselves be used for the induction of anaesthesia. However, inhalation agents are poor analgesics and have varying muscle relaxant ability. As expected, if used alone, much higher concentrations of inhalation agents are required to produce general anaesthesia than if used in combination with analgesics and/or muscle relaxants - a '''balanced anaesthetic technique''''. They are unusual in respect to most other drugs, as they are adminstered and removed via the same route i.e. as the patient breathes. This also allows for easy adjustment to the depth of anaesthetic of a patient as it does not rely on the metabolism of the agent.

==General Properties==
Most inhalation agents are ''halogenated'' organic compounds, but nitrous oxide is an inorganic compound. This improves the stability of the agent and increases the potency of the agent. They exist as either '''vapours''' or '''gases''' depending on their state at room temperature and sea level pressures - a vapor is liquid under these conditions and requires a [[Vaporisers|vaporiser]] to produce the gaseous form required for inhalation. Nitrous oxide is one of the very few gases in clincal use.

==General Pharmacokinetics==
To produce a state of general anaesthesia, it is necesary to reach a partial pressure in the brain sufficient to depress the central nervous system. This means that the depth of anaesthesia is based on the partial pressure of agent in the brain. This is reached by diffusion of agent from inhaled air to the brain via alveolar air and blood. Diffusion occurs until an equilibium has been reached, which occurs rapidly bettween the alveoli and blood, and blood and brain. This means that the alveolar partial pressure is almost identical to that in the blood, and therefore brain.

===Changes in anaesthetic depth===
Factors that affect depth of anaesthesia include -
*Inspired concentration of the agent.
*Ventilation
*Agent solubility both in blood and tissues.
*The patient's cardiac output.

===Metabolism and Elimination===
Elimination of inhalation agents is mostly via the lungs as the patient breathes out. However, there are varying degress of hepatic metabolism.

===Minimum Alveolar Concentration===
'''Minimum Alveolar Concentration''' (MAC) is a measure of the potency of an inhalation agent. It is the minimum alveolar concentration of agent required to produce immobility of 50% of patients when exposed to a noxious stimuli. Therefore, the lower the MAC, the more potent the agent.

==Agents in this Class==
*[[Halothane]]
*[[Isoflurane]]
*[[Sevoflurane]]
*[[Desflurane]]
*[[Nitrous Oxide]]

[[Category:Inhalation Anaesthetic Agents|A]]

Inhalation Anaesthetic Agents Overview

2012-09-17T15:51:10Z

Shannanigans969: /* Introduction */

==Introduction==
'''Inhalation anaesthetics''' are commonly used after induction with [[Injectable Agents|injectable agents]] but can also themselves be used for the induction of anaesthesia. However, inhalation agents are poor analgesics and have varying muscle relaxant ability. As expected, if used alone, much higher concentrations of inhalation agents are required to produce general anaesthesia then if used in combinations with analgesics and/or muscle relaxants - a '''balanced anaesthetic technique''''. They are unusual in respect to most other drugs, as they are adminstered and removed via the same route i.e. as the patient breathes. This also allows for easy adjustment to the depth of anaesthetic of a patient as it does not rely on the metabolism of the agent.

==General Properties==
Most inhalation agents are ''halogenated'' organic compounds, but nitrous oxide is an inorganic compound. This improves the stability of the agent and increases the potency of the agent. They exist as either '''vapours''' or '''gases''' depending on their state at room temperature and sea level pressures - a vapor is liquid under these conditions and requires a [[Vaporisers|vaporiser]] to produce the gaseous form required for inhalation. Nitrous oxide is one of the very few gases in clincal use.

==General Pharmacokinetics==
To produce a state of general anaesthesia, it is necesary to reach a partial pressure in the brain sufficient to depress the central nervous system. This means that the depth of anaesthesia is based on the partial pressure of agent in the brain. This is reached by diffusion of agent from inhaled air to the brain via alveolar air and blood. Diffusion occurs until an equilibium has been reached, which occurs rapidly bettween the alveoli and blood, and blood and brain. This means that the alveolar partial pressure is almost identical to that in the blood, and therefore brain.

===Changes in anaesthetic depth===
Factors that affect depth of anaesthesia include -
*Inspired concentration of the agent.
*Ventilation
*Agent solubility both in blood and tissues.
*The patient's cardiac output.

===Metabolism and Elimination===
Elimination of inhalation agents is mostly via the lungs as the patient breathes out. However, there are varying degress of hepatic metabolism.

===Minimum Alveolar Concentration===
'''Minimum Alveolar Concentration''' (MAC) is a measure of the potency of an inhalation agent. It is the minimum alveolar concentration of agent required to produce immobility of 50% of patients when exposed to a noxious stimuli. Therefore, the lower the MAC, the more potent the agent.

==Agents in this Class==
*[[Halothane]]
*[[Isoflurane]]
*[[Sevoflurane]]
*[[Desflurane]]
*[[Nitrous Oxide]]

[[Category:Inhalation Anaesthetic Agents|A]]

Anti-Protozoal Drugs

2011-12-05T17:03:15Z

Shannanigans969: /* Other Anti-protozoal Drugs */

{{toplink
|linkpage =WikiDrugs
|linktext =WikiDrugs
|sublink1 = Antiparasitic Drugs
|subtext1 = Antiparasitic Drugs
|pagetype = Drugs
}}

In the UK the major group of protozoa of significant economic importance are the [[coccidia]]. As such the pharmaceutical industry have spent a lot of money developing anti-coccidial drugs to ensure that production isn't affected. This group of drugs will be the many topic on this page but other groups of drugs that have anti-protozoal action will also be discussed.

==Anti-Coccidial Agents==

It must be remembered that very few drugs are licensed to treat avian coccidiosis, '''toltrazuril''' is one of the exceptions. The following drugs are thus used to prevent infections occuring.

===Ionophores - Monensin, salinomycin, narasin===
* The most popular drug group to treat avian coccidiosis, they have been developed from the fermentation products of ''Streptomyces'' moulds.
* They work by allowing an influx of sodium ions into the sporozoite, this leads to a water influx. The sporozoite uses up all its energy trying to restore its ion and water balance, eventually structural damage occurs and the organism dies.
* They are particular useful for avian coccidiosis because:
** They suppress clinical and subclinical coccidia
** As the entire coccidia population is not destroyed it allows natural immunity to develop
** They reduce oocyst build up in the litter
** They exert little selection pressure on the coccidia and so resistance develops slowly
* Some of these drugs are '''highly toxic to horses, turkeys and gamebirds'''.

===Other Agents===

Numerous chemicals have anticoccidial activity; they include '''nicarbazin, decoquinate, robenidine, diclazuril, clopidol''' and '''halofuginone'''. All these drugs will either kill the coccidia or stop it from reproducing. These drugs must therfore be used with care as they have a high selection pressure on the parasites, which can result in resistance. For that reason a lot of these drugs are only liscensed in combination therapy.

===Anticoccidial Programmes===
The aim of these programmes is to ensure that the birds in question develop natural immunity, without their production being affected, whilst ensuring that resistance doesn't develop in the population. This means that continous use of the same drug can not be used.

A '''shuttle programme''' is the alternative. This means that in a bird's growing period it experiences a number of different drugs in sequence. These programmes try to balance risk, productivity and cost. They are obviously very complex and only skilled specialists develop them for use on poultry farms.

==Other Anti-protozoal Drugs==

* The antibiotic [[Macrolides and Lincosamides|clindamycin]] and atovaquone (no license for animals) are used in man to treat Babesia infections.
* Complex chemotherapy protocols are used to treat Leishmania.
* [[Nitroimidazoles|Metronidazole]] is used to treat ''Treponema hyodysenteriae, [[Trichomonas foetus]], Histomonas'' and ''Giardia''.
* Fenbendazole is used to treat ''Encephalitozoon caniculi'' and Giardia.

Anti-Protozoal Drugs

2011-12-05T17:00:07Z

Shannanigans969: /* Anticoccidial Programmes */

{{toplink
|linkpage =WikiDrugs
|linktext =WikiDrugs
|sublink1 = Antiparasitic Drugs
|subtext1 = Antiparasitic Drugs
|pagetype = Drugs
}}

In the UK the major group of protozoa of significant economic importance are the [[coccidia]]. As such the pharmaceutical industry have spent a lot of money developing anti-coccidial drugs to ensure that production isn't affected. This group of drugs will be the many topic on this page but other groups of drugs that have anti-protozoal action will also be discussed.

==Anti-Coccidial Agents==

It must be remembered that very few drugs are licensed to treat avian coccidiosis, '''toltrazuril''' is one of the exceptions. The following drugs are thus used to prevent infections occuring.

===Ionophores - Monensin, salinomycin, narasin===
* The most popular drug group to treat avian coccidiosis, they have been developed from the fermentation products of ''Streptomyces'' moulds.
* They work by allowing an influx of sodium ions into the sporozoite, this leads to a water influx. The sporozoite uses up all its energy trying to restore its ion and water balance, eventually structural damage occurs and the organism dies.
* They are particular useful for avian coccidiosis because:
** They suppress clinical and subclinical coccidia
** As the entire coccidia population is not destroyed it allows natural immunity to develop
** They reduce oocyst build up in the litter
** They exert little selection pressure on the coccidia and so resistance develops slowly
* Some of these drugs are '''highly toxic to horses, turkeys and gamebirds'''.

===Other Agents===

Numerous chemicals have anticoccidial activity; they include '''nicarbazin, decoquinate, robenidine, diclazuril, clopidol''' and '''halofuginone'''. All these drugs will either kill the coccidia or stop it from reproducing. These drugs must therfore be used with care as they have a high selection pressure on the parasites, which can result in resistance. For that reason a lot of these drugs are only liscensed in combination therapy.

===Anticoccidial Programmes===
The aim of these programmes is to ensure that the birds in question develop natural immunity, without their production being affected, whilst ensuring that resistance doesn't develop in the population. This means that continous use of the same drug can not be used.

A '''shuttle programme''' is the alternative. This means that in a bird's growing period it experiences a number of different drugs in sequence. These programmes try to balance risk, productivity and cost. They are obviously very complex and only skilled specialists develop them for use on poultry farms.

==Other Anti-protozoal Drugs==

* The antibiotic [[Macrolides and Lincosamides|clindamycin]] and atovaquone (no liscense for animals) are used in man to treat Babesia infections.
* Complex chemotherapy protocols are used to treat Leishmania.
* [[Nitroimidazoles|Metronidazole]] is used to treat ''Treponema hyodysenteriae, [[Trichomonas foetus]], Histomonas'' and ''Giardia''.
* Fenbendazole is used to treat ''Encephalitozoon caniculi'' and Giardia.

Sulphonamides

2011-12-03T14:50:40Z

Shannanigans969: /* Spectrum of Activity */

{{review}}
==Introduction==
Sulphonamides are derivatives of sulphanilamide, an active metabolite of the pro-drug and dye prontosil. Commonly used ones are: '''sulphadiazine, sulphaquinoxaline, sulphadimethoxine, sulphadoxine''' and '''sulphanilamide'''.

==Mechanism of Action==
Sulphonamides act by competing with an essential precursor in folic acid synthesis in bacteria. Bacteria need to synthesise folic acid in order to grow as they are unable to obtain it from their 'diet' like mammals can. Since the bacterium is unable to synthesize RNA or DNA, due to its lack of folic acid, its growth is inhibited. As such, sulphonamides are '''bacteriostatic'''.

==Spectrum of Activity==
These are generally broad spectrum antibiotics.
* They are active against aerobic gram-positive cocci and some rods.
* They are active against gram-negative rods, including enterobacteriaceae.
* They are active against the anaerobes, ''Actinomyces'' and ''Fusobacterium'', but inactive against clostridial species and anaerobic cocci.
* Resistance is now widespread.
* Drugs which contain a PABA nuclear core, such as procaine, antagonise their actions.

==Pharmacokinetic Considerations==
* Sulphonamides are lipophilic weak acids of varying pKas.
* Most are absorbed readily from the gut, except Succinylsulphathiazole and Phthalylsuphathiazole.
* They tend to distribute widely throughout the body as the non-ionised form is able to cross cell membranes.
* The extent of binding to plasma proteins is very dependent on the individual drug and species involved and can vary between 20 and 90%.
* They are eliminate both by hepatic metabolism and renal excretion, the rate of both in each species and for each drug varies. This results in very different half-lives of each drug in each species.
* They are unable to work in pus or tissue debris as they contain thymidine and purines. This means that the bacteria can utilise these rather than folic acid for continued growth. This means that the drug will become obselete in such a circumstance.

==Side Effects and Contraindications==
Major reactions to sulphonamides are uncommon but the following are the most common of the side effects recorded:
* Rapid intravenous injection can lead to muscle weakness, ataxia and collapse. This has only been recorded in cattle and horses.
* They can precipitate in tubular fluid resulting in renal tubular damage.
* Dobermans have had serious allergic reactions to them including immune-mediated polyarthritis, thrombocytopenia and haemolytic anaemia.
* Severe hepatotoxicity has been noted in some dogs.
* Long dosage regimens of Sulphonamides have resulted in keratoconjunctivitis sicca/'dry eye' in dogs.
* Sulphonamides inhibit thyroid gland function and so mild signs of hypothyroidism have been seen in dogs that have had intesive dosage regimens.

===Hepatotoxicity===
*some of these casue hepatic necrosis in susceptible animals
*has been associated with a reduced capability of detoxifying the metabolites
*Doberman Pinscher breed appears to be susceptible
[[Category:Hepatotoxicity,_Drug_induced]]
[[Category:To_Do_-_Clinical]]

Pharmacodynamics

2011-11-12T15:45:16Z

Shannanigans969: /* Self-antagonism */

{{review}}
{{toplink
|linkpage =WikiDrugs
|linktext =WikiDrugs
|sublink1 = Basic Concepts of Pharmacology
|subtext1 = Basic Concepts of Pharmacology
|pagetype = Drugs
}}
'''Pharmacodynamics is the actions of drugs on the body.'''

For drugs to act upon the body the must be able to exert some chemical influence upon a cell to result in a physiological response. They are capable of doing this by binding to a target molecule (usually proteins).

There are four main kinds of targets for the drugs to bind to:

* '''Receptors''' - these are protein molecules that are capable of responding to endogenous chemical signals. They are usually found on the cell membrane, in the cytoplasm or on the nucleus and other organelles.
* '''Enzymes''' - both intracellular and extracellular ones.
* '''Ion Channels'''
* '''Transport proteins'''

==Agonists==

An agonist can be defined as '''a drug that binds to a target molecule and results in activation of the receptor and thus a tissue response'''.

* An agonist forms a complex with the receptor. This complex is '''dynamic''' as the agonist will continously associate and dissociate with the receptor. The agonist will continue to do this and thus produce a response, until the concentration of the agonist is reduced to a level at which binding no longer occurs.

* The rate of complex formation is dependent on two factors: '''agonist concentration''' and the '''number of free receptors'''.

* The '''affinity''' of a drug to a receptor varies and can be compared using the '''equilibrium constant or KA'''.

This can be defined as the concentration of a drug which results in 50% of receptors being bound in equilibrium or when '''K1=K-1'''.

<big>'''Drug + Number of Free Receptors = Drug-Receptor Complexes'''</big>

Where '''K1''' is the rate constant in a forward direction (association rate constant)
and '''K-1''' is the rate constant in a backward direction (dissociation rate constant)

Therefore a drug that has a higher affinity to a receptor has a lower '''KA''' value.

* The biological response of resulting from an agonist is proportional to the number of receptors occupied. The size of a response can be measured and plotted against the dose/concentration of the agonist. As the size of a response normally increasee in a non-linear manner (until the maximum is reached) the response is normally plotted against the log of the concentration.

'''Please Insert Appropriate Graphs'''

From these graphs two figures can be achieved, the '''ED50''' or '''EC50'''. The ED50 is the effective dose at which 50% of a maximal response occurs or 50% of individuals respond. The EC50 is the same but is the effective concentration. Agonists with higher affinities will have a lower concentration and so EC50 than an agonist with a lower affinity. The first drug is therfore said to be more '''potent'''.

The '''potency''' of a drug is very important clinically as it will determine the dose needed to have the desired clinical effect. Often if a drug is more potent it is usally more selective to which target molecules it binds to.

===Full and Partial Agonists===

* A full agonist is defined as an agonist that is capable of producing the maximal response of a tissue. To achieve this the number of receptors occupied varies and in some cases very few receptors need occupying. This is called the '''spare receptor hypothesis''' and is very relevant when thinking about multiple drugs working at the same receptor site simultaneously.

* A partial agonist is unable to produce the maximum tissue response however great the dose or concentration of the drug. It must be remembered that a partial agonistmay have a greater, lesser or equal affinity to a receptor site compared to a full agonist.

The difference between the full and partial agonist is it's '''efficacy'''. This is defined as the strength of the tissue response that results from the formation of a agonist-receptor complex. The efficacy of the partial agonist is lower than that of the full agonist.

It is still unclear why molecules that are chemically very similar have differing efficacies. Only now are the mechanisms behind it being gradually understand. This however doesn't mean that we ignore efficacy. It is of great practical importance as some drugs of equal affinity for a specific receptor may have widely differing efficacy.

===Inverse Agonists===

These are agonists that bind to receptors that are continuely activated (even if no ligand is present) and result in the reduction of the level of activation. They therefore have a negative efficacy.

===Effector Linkage Mechanisms===

Once the agonist binds to the receptor the cell response can be formed in three different ways:
* By the opening of a ligand gated ion channel
* By an intracellular second messenger system
* By DNA transcription

==Antagonists==

An antagonist can be defined as '''a drug that inhibits the action of an agonist'''.

Antagonists bind to similar receptors as agonist but crucially they don't activate any intracellular events and so there is no tissue response. It's effect is produced by reducing the amount or capability of an agonist to bind to it's target molecule.

Antagonists like agonists bind to receptors in a dynamic fashion, and so it is the antagonists affinity to the receptor that determines it's inhibitory response. The amount of inhibition thus depends on the concentration of the drug at the target site and the number of free receptor sites.

===Competitive Antagonism===

====Reversible Competitive Antagonism====

Here the antagonist competes with the agonist for the occupation of the receptor site. Since less agonist is able to bind to the target molecule the size of the tissue response will decrease. As the dose/concentration of the antagonist increases so the size of the tissue response will further decrease.

The formation of receptor complexes is dynamic in it's nature and so if the agonist' dose/concentration is increased it will out-compete the antagonist for receptor occupation and the size of the tissue response will start to increase. Therefore the antagonists action is reversible.

====Irreversible Competitive Antagonism====

This form of antagonism essentially works in the same manner as above except for one crucial difference. The antagonist forms very strong bonds to the receptor sit meaning that it dissociates very slowly or not at all. This means that increasing the amount of agonist present is unable to out-compete the antagonist as receptor sites are always full.

A partial agonist can effectively act as an antagonist when it is present in very high concentrations as it out-competes the full agonist for the receptor site.

===Non-Competitive Antagonism===

Here the agonist binds to its receptor but the antagonist acts further along the sequence of events resulting in a tissue response. As this chain is blocked the agonist is incapable of producing a response.

===Pharmacokinetic Antagonism===

The antagonist reduces the effect of another drug by reducing its absorption or increasing its rate of metabolism or increasing its rate of excretion.

===Self-antagonism===

If some drugs are repeatedly given its effect can decrease. This is called '''tachyphylaxis''' or '''desensitisation'''. If a gradual decrease in response to a drug occurs this is called '''tolerance''' and if the drug loses total therapeutic efficacy it is deemed '''refractory'''. Many types of mechanisms occur to cause this phenomenon, the most important include:

* change in receptor type
* loss of receptors
* exhaustion of cell mediators
* increased metabolic degradation of the drug
* physiological adaptation
* active extrusion of the drug from cells

===Chemical Antagonism===

This is where the interaction of two drugs results in the failure of an biological activity.

===Physiological Antagonism===

This occurs when two drugs have opposing actions on the body and so their actions cancel each other out.

Pharmacodynamics

2011-11-12T15:44:40Z

Shannanigans969: /* Self-antagonism */

{{review}}
{{toplink
|linkpage =WikiDrugs
|linktext =WikiDrugs
|sublink1 = Basic Concepts of Pharmacology
|subtext1 = Basic Concepts of Pharmacology
|pagetype = Drugs
}}
'''Pharmacodynamics is the actions of drugs on the body.'''

For drugs to act upon the body the must be able to exert some chemical influence upon a cell to result in a physiological response. They are capable of doing this by binding to a target molecule (usually proteins).

There are four main kinds of targets for the drugs to bind to:

* '''Receptors''' - these are protein molecules that are capable of responding to endogenous chemical signals. They are usually found on the cell membrane, in the cytoplasm or on the nucleus and other organelles.
* '''Enzymes''' - both intracellular and extracellular ones.
* '''Ion Channels'''
* '''Transport proteins'''

==Agonists==

An agonist can be defined as '''a drug that binds to a target molecule and results in activation of the receptor and thus a tissue response'''.

* An agonist forms a complex with the receptor. This complex is '''dynamic''' as the agonist will continously associate and dissociate with the receptor. The agonist will continue to do this and thus produce a response, until the concentration of the agonist is reduced to a level at which binding no longer occurs.

* The rate of complex formation is dependent on two factors: '''agonist concentration''' and the '''number of free receptors'''.

* The '''affinity''' of a drug to a receptor varies and can be compared using the '''equilibrium constant or KA'''.

This can be defined as the concentration of a drug which results in 50% of receptors being bound in equilibrium or when '''K1=K-1'''.

<big>'''Drug + Number of Free Receptors = Drug-Receptor Complexes'''</big>

Where '''K1''' is the rate constant in a forward direction (association rate constant)
and '''K-1''' is the rate constant in a backward direction (dissociation rate constant)

Therefore a drug that has a higher affinity to a receptor has a lower '''KA''' value.

* The biological response of resulting from an agonist is proportional to the number of receptors occupied. The size of a response can be measured and plotted against the dose/concentration of the agonist. As the size of a response normally increasee in a non-linear manner (until the maximum is reached) the response is normally plotted against the log of the concentration.

'''Please Insert Appropriate Graphs'''

From these graphs two figures can be achieved, the '''ED50''' or '''EC50'''. The ED50 is the effective dose at which 50% of a maximal response occurs or 50% of individuals respond. The EC50 is the same but is the effective concentration. Agonists with higher affinities will have a lower concentration and so EC50 than an agonist with a lower affinity. The first drug is therfore said to be more '''potent'''.

The '''potency''' of a drug is very important clinically as it will determine the dose needed to have the desired clinical effect. Often if a drug is more potent it is usally more selective to which target molecules it binds to.

===Full and Partial Agonists===

* A full agonist is defined as an agonist that is capable of producing the maximal response of a tissue. To achieve this the number of receptors occupied varies and in some cases very few receptors need occupying. This is called the '''spare receptor hypothesis''' and is very relevant when thinking about multiple drugs working at the same receptor site simultaneously.

* A partial agonist is unable to produce the maximum tissue response however great the dose or concentration of the drug. It must be remembered that a partial agonistmay have a greater, lesser or equal affinity to a receptor site compared to a full agonist.

The difference between the full and partial agonist is it's '''efficacy'''. This is defined as the strength of the tissue response that results from the formation of a agonist-receptor complex. The efficacy of the partial agonist is lower than that of the full agonist.

It is still unclear why molecules that are chemically very similar have differing efficacies. Only now are the mechanisms behind it being gradually understand. This however doesn't mean that we ignore efficacy. It is of great practical importance as some drugs of equal affinity for a specific receptor may have widely differing efficacy.

===Inverse Agonists===

These are agonists that bind to receptors that are continuely activated (even if no ligand is present) and result in the reduction of the level of activation. They therefore have a negative efficacy.

===Effector Linkage Mechanisms===

Once the agonist binds to the receptor the cell response can be formed in three different ways:
* By the opening of a ligand gated ion channel
* By an intracellular second messenger system
* By DNA transcription

==Antagonists==

An antagonist can be defined as '''a drug that inhibits the action of an agonist'''.

Antagonists bind to similar receptors as agonist but crucially they don't activate any intracellular events and so there is no tissue response. It's effect is produced by reducing the amount or capability of an agonist to bind to it's target molecule.

Antagonists like agonists bind to receptors in a dynamic fashion, and so it is the antagonists affinity to the receptor that determines it's inhibitory response. The amount of inhibition thus depends on the concentration of the drug at the target site and the number of free receptor sites.

===Competitive Antagonism===

====Reversible Competitive Antagonism====

Here the antagonist competes with the agonist for the occupation of the receptor site. Since less agonist is able to bind to the target molecule the size of the tissue response will decrease. As the dose/concentration of the antagonist increases so the size of the tissue response will further decrease.

The formation of receptor complexes is dynamic in it's nature and so if the agonist' dose/concentration is increased it will out-compete the antagonist for receptor occupation and the size of the tissue response will start to increase. Therefore the antagonists action is reversible.

====Irreversible Competitive Antagonism====

This form of antagonism essentially works in the same manner as above except for one crucial difference. The antagonist forms very strong bonds to the receptor sit meaning that it dissociates very slowly or not at all. This means that increasing the amount of agonist present is unable to out-compete the antagonist as receptor sites are always full.

A partial agonist can effectively act as an antagonist when it is present in very high concentrations as it out-competes the full agonist for the receptor site.

===Non-Competitive Antagonism===

Here the agonist binds to its receptor but the antagonist acts further along the sequence of events resulting in a tissue response. As this chain is blocked the agonist is incapable of producing a response.

===Pharmacokinetic Antagonism===

The antagonist reduces the effect of another drug by reducing its absorption or increasing its rate of metabolism or increasing its rate of excretion.

===Self-antagonism===

If some drugs are repeadtedly given its effect can decrease. This is called '''tachyphylaxis''' or '''desensitisation'''. If a gradual decrease in response to a drug occurs this is called '''tolerance''' and if the drug loses total therapeutic efficacy it is deemed '''refractory'''. Many types of mechanisms occur to cause this phenomenon, the most important include:

* chnage in receptor type
* loss of receptors
* exhaustion of cell mediators
* increased metabolic degradation of the drug
* physiological adaptation
* active extrusion of the drug from cells

===Chemical Antagonism===

This is where the interaction of two drugs results in the failure of an biological activity.

===Physiological Antagonism===

This occurs when two drugs have opposing actions on the body and so their actions cancel each other out.