pharmacology l 2

8/14/2019 Pharmacology L 2

1/76

Pharmacology L-2

A F m Nazmus Sadat


2/76


3/76

Ligand:

A molecule which binds to a receptor is called a ligand.

It may be,Peptide (eg. neurotransitter), a hormone, a

pharmaceutical drug, a toxin,

when such binding occurs, the receptor goes into a

conformational change which ordinarily initiates acellular response.

However, some ligands merely block receptors without

inducing any response (e.g. antagonists).Ligand-induced changes in receptors result in

physiological changes which constitute the biological

activity of the ligands.


4/76

Agonists versus antagonists

Not every ligand that binds to a receptor alsoactivates the receptor. The following classes of

ligands exist: (Full) agonists are able to activate the receptor

and result in a maximal biological response.Most natural ligands are full agonists.

Partial agonists do not activate receptorsthoroughly, causing responses which are partialcompared to those of full agonists.

Antagonists bind to receptors but do not activatethem. This results in receptor blockage,inhibiting the binding of other agonists.

Inverse agonists reduce the activity of receptorsby inhibiting their constitutive activity.
http://en.wikipedia.org/wiki/Agonisthttp://en.wikipedia.org/wiki/Receptor_antagonisthttp://en.wikipedia.org/wiki/Receptor_antagonisthttp://en.wikipedia.org/wiki/Agonist


5/76

Examples of agonist Full agonists bind (have affinity for) and activate a

receptor, displaying full efficacy at that receptor. One

example of a drug that acts as a full agonist isisoproterenol which mimics the action ofadrenaline atadrenoreceptors. Another example is morphine,which mimics the actions of endorphins at -opioidreceptors throughout the central nervous system.

Partial agonist: (such as buspirone, aripiprazole,buprenorphine, ornorclozapine) also bind and activatea given receptor, but have only partial efficacy at thereceptor relative to a full agonist.

An inverse agonist is an agent which binds to thesame receptor binding-site as an agonist for thatreceptor and reverses constitutive activity of receptors.Inverse agonists exert the opposite pharmacologicaleffect of a receptor agonist.
http://en.wikipedia.org/wiki/Dissociation_constanthttp://en.wikipedia.org/wiki/Efficacyhttp://en.wikipedia.org/wiki/Isoproterenolhttp://en.wikipedia.org/wiki/Epinephrinehttp://en.wikipedia.org/wiki/Adrenergic_receptorhttp://en.wikipedia.org/wiki/Adrenergic_receptorhttp://en.wikipedia.org/wiki/Endorphinhttp://en.wikipedia.org/wiki/%CE%9C-opioid_receptorhttp://en.wikipedia.org/wiki/%CE%9C-opioid_receptorhttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Buspironehttp://en.wikipedia.org/wiki/Aripiprazolehttp://en.wikipedia.org/wiki/Buprenorphinehttp://en.wikipedia.org/wiki/Clozapinehttp://en.wikipedia.org/wiki/Efficacyhttp://en.wikipedia.org/wiki/Efficacyhttp://en.wikipedia.org/wiki/Clozapinehttp://en.wikipedia.org/wiki/Buprenorphinehttp://en.wikipedia.org/wiki/Aripiprazolehttp://en.wikipedia.org/wiki/Buspironehttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/%CE%9C-opioid_receptorhttp://en.wikipedia.org/wiki/%CE%9C-opioid_receptorhttp://en.wikipedia.org/wiki/Endorphinhttp://en.wikipedia.org/wiki/Adrenergic_receptorhttp://en.wikipedia.org/wiki/Adrenergic_receptorhttp://en.wikipedia.org/wiki/Epinephrinehttp://en.wikipedia.org/wiki/Isoproterenolhttp://en.wikipedia.org/wiki/Efficacyhttp://en.wikipedia.org/wiki/Dissociation_constant


6/76

E l f i t t


7/76

Examples of agonist ont. A co-agonist works with other co-agonists to produce

the desired effect together. NMDA receptor activation

requires the binding of both of its glutamate andglycine co-agonists. An antagonist blocks a receptorfrom activation by agonists.

A selective agonist is selective for one certain type ofreceptor. It can additionally be of any of theaforementioned types.

A physiological agonist is a substance that createsthe same bodily responses, but does not bind to thesame receptor.

Receptors can be activated or inactivated either byendogenous (such as hormones andneurotransmitters) or exogenous (such as drugs)agonists and antagonists, resulting in stimulating orinhibiting a biological response.
http://en.wikipedia.org/wiki/Receptor_antagonisthttp://en.wikipedia.org/wiki/Physiological_agonism_and_antagonismhttp://en.wikipedia.org/wiki/Endogenoushttp://en.wikipedia.org/wiki/Hormonehttp://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Exogenoushttp://en.wikipedia.org/wiki/Medicationhttp://en.wikipedia.org/wiki/Medicationhttp://en.wikipedia.org/wiki/Exogenoushttp://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Hormonehttp://en.wikipedia.org/wiki/Endogenoushttp://en.wikipedia.org/wiki/Physiological_agonism_and_antagonismhttp://en.wikipedia.org/wiki/Receptor_antagonist


8/76


9/76

Types of receptorDepending on their functions and ligands, several types of

receptors may be identified:

- Some receptor proteins are peripheral membrane proteins.

- Many hormone and neurotransmitter receptors aretransmembraneproteins: transmembrane receptors areembedded in the phospholipidbilayer of cell membranes, that

allow the activation ofsignal transduction pathways in responseto the activation by the binding molecule, orligand. Metabotropicreceptors are coupled to G proteins and affect the cell

indirectly through enzymes which control ion channels.

Ionotropicreceptors contain a central pore which functions as a ligand-gated ion channel.

- Another major class of receptors are intracellularproteins suchas those for steroid and intracrinepeptide hormone receptors.These receptors often can enter the cell nucleus and modulategene expression in response to the activation by the ligand.
http://en.wikipedia.org/wiki/Ligand_(biochemistry)http://en.wikipedia.org/wiki/Peripheral_membrane_proteinhttp://en.wikipedia.org/wiki/Hormone_receptorhttp://en.wikipedia.org/wiki/Neurotransmitter_receptorhttp://en.wikipedia.org/wiki/Transmembrane_receptorhttp://en.wikipedia.org/wiki/Transmembrane_receptorhttp://en.wikipedia.org/wiki/Phospholipid_bilayerhttp://en.wikipedia.org/wiki/Phospholipid_bilayerhttp://en.wikipedia.org/wiki/Cell_membranehttp://en.wikipedia.org/wiki/Signal_transductionhttp://en.wikipedia.org/wiki/Ligand_(biochemistry)http://en.wikipedia.org/wiki/Metabotropic_receptorhttp://en.wikipedia.org/wiki/Metabotropic_receptorhttp://en.wikipedia.org/wiki/G_proteinhttp://en.wikipedia.org/wiki/Enzymehttp://en.wikipedia.org/wiki/Ion_channelhttp://en.wikipedia.org/wiki/Ionotropic_receptorhttp://en.wikipedia.org/wiki/Ionotropic_receptorhttp://en.wikipedia.org/wiki/Intracellularhttp://en.wikipedia.org/wiki/Steroidhttp://en.wikipedia.org/wiki/Intracrinehttp://en.wikipedia.org/wiki/Peptide_hormonehttp://en.wikipedia.org/wiki/Cell_nucleushttp://en.wikipedia.org/wiki/Gene_expressionhttp://en.wikipedia.org/wiki/Gene_expressionhttp://en.wikipedia.org/wiki/Cell_nucleushttp://en.wikipedia.org/wiki/Peptide_hormonehttp://en.wikipedia.org/wiki/Intracrinehttp://en.wikipedia.org/wiki/Steroidhttp://en.wikipedia.org/wiki/Intracellularhttp://en.wikipedia.org/wiki/Ionotropic_receptorhttp://en.wikipedia.org/wiki/Ionotropic_receptorhttp://en.wikipedia.org/wiki/Ion_channelhttp://en.wikipedia.org/wiki/Enzymehttp://en.wikipedia.org/wiki/G_proteinhttp://en.wikipedia.org/wiki/Metabotropic_receptorhttp://en.wikipedia.org/wiki/Metabotropic_receptorhttp://en.wikipedia.org/wiki/Ligand_(biochemistry)http://en.wikipedia.org/wiki/Signal_transductionhttp://en.wikipedia.org/wiki/Cell_membranehttp://en.wikipedia.org/wiki/Phospholipid_bilayerhttp://en.wikipedia.org/wiki/Phospholipid_bilayerhttp://en.wikipedia.org/wiki/Transmembrane_receptorhttp://en.wikipedia.org/wiki/Transmembrane_receptorhttp://en.wikipedia.org/wiki/Neurotransmitter_receptorhttp://en.wikipedia.org/wiki/Hormone_receptorhttp://en.wikipedia.org/wiki/Peripheral_membrane_proteinhttp://en.wikipedia.org/wiki/Ligand_(biochemistry)


10/76

Potency of Agonist

The potency of an agonist is usually defined by

its EC50 value.This can be calculated for a given agonist by

determining the concentration of agonistneeded to elicit half of the maximum biologicalresponse of the agonist.

Importance:- Elucidating an EC50 value is usefulfor comparing the potency of drugs with similar

efficacies producing physiologically similareffects. The lower the EC50, the greater thepotency of the agonist the lower theconcentration of drug that is required to elicitthe maximum biological response.
http://en.wikipedia.org/wiki/Potencyhttp://en.wikipedia.org/wiki/Half_maximal_effective_concentrationhttp://en.wikipedia.org/wiki/Efficacyhttp://en.wikipedia.org/wiki/Efficacyhttp://en.wikipedia.org/wiki/Half_maximal_effective_concentrationhttp://en.wikipedia.org/wiki/Potency


11/76

Therapeutic index

When a drug is used therapeutically, it is important tounderstand the margin of safety that exists between

the dose needed for the desired effect and the dosethat produces unwanted and possibly dangerous sideeffects.

This relationship, termed the therapeutic index, is

defined as the ratio LD50:ED50.In general, the narrower this margin, the more likely it isthat the drug will produce unwanted effects. Thetherapeutic index has many limitations, notably thefact that LD50 cannot be measured in humans and,

when measured in animals, is a poor guide to thelikelihood of unwanted effects in humans.Nevertheless, the therapeutic index emphasizes theimportance of the margin of safety, as distinct from thepotency, in determining the usefulness of a drug.
http://en.wikipedia.org/wiki/Therapeutic_indexhttp://en.wikipedia.org/wiki/Median_lethal_dosehttp://en.wikipedia.org/wiki/Effective_dosehttp://en.wikipedia.org/wiki/Effective_dosehttp://en.wikipedia.org/wiki/Median_lethal_dosehttp://en.wikipedia.org/wiki/Therapeutic_index


12/76

Receptor antagonist

A receptor antagonist is a type of receptor

ligand or drug that does not provoke a

biological response itself upon binding to a

receptor, but blocks or dampens agonist-

mediated responses.

In pharmacology, antagonists have affinity

but no efficacy for their cognate receptors

and binding will disrupt the interaction and

inhibit the function of an agonist orinverse agonist at receptors.
http://en.wikipedia.org/wiki/Ligand_(biochemistry)http://en.wikipedia.org/wiki/Drughttp://en.wikipedia.org/wiki/Receptor_(biochemistry)http://en.wikipedia.org/wiki/Agonisthttp://en.wikipedia.org/wiki/Pharmacologyhttp://en.wikipedia.org/wiki/Dissociation_constanthttp://en.wikipedia.org/wiki/Efficacyhttp://en.wikipedia.org/wiki/Agonisthttp://en.wikipedia.org/wiki/Inverse_agonisthttp://en.wikipedia.org/wiki/Inverse_agonisthttp://en.wikipedia.org/wiki/Agonisthttp://en.wikipedia.org/wiki/Efficacyhttp://en.wikipedia.org/wiki/Dissociation_constanthttp://en.wikipedia.org/wiki/Pharmacologyhttp://en.wikipedia.org/wiki/Agonisthttp://en.wikipedia.org/wiki/Receptor_(biochemistry)http://en.wikipedia.org/wiki/Drughttp://en.wikipedia.org/wiki/Ligand_(biochemistry)


13/76

Antagonists mediate their effects by binding tothe active site sites on receptors or they mayinteract at unique binding sites not normallyinvolved in the biological regulation of thereceptor's activity.

Antagonist activity may be reversible or

irreversible depending on the longevity of theantagonistreceptor complex which in turndepends on the nature of antagonist receptorbinding.

The majority of drug antagonists achieve theirpotency by competing with endogenous ligandsor substrates at structurally defined binding

sites on receptors.


14/76

Competitive antagonist:

reversibly bind to receptors at the same binding site (active site)as the endogenous ligand or agonist, but without activating thereceptor.

Agonists and antagonists "compete" for the same binding site onthe receptor. Once bound, an antagonist will block agonistbinding.

The level of activity of the receptor will be determined by the

relative affinity of each molecule for the site and their relativeconcentrations.

High concentrations of a competitive agonist will increase theproportion of receptors which the agonist occupies, higherconcentrations of the antagonist will be required to obtain the

same degree of binding site occupancy.The interleukin-1 receptor antagonist, IL-1Ra is an example of a

competitive antagonist. The effects of a competitive antagonistmay be overcome by increasing the concentration of agonist.Often (though not always) these antagonists possess a verysimilar chemical structure to that of the agonist.

N titi t i t
http://en.wikipedia.org/wiki/Binding_sitehttp://en.wikipedia.org/wiki/Affinityhttp://en.wikipedia.org/wiki/Interleukin-1http://en.wikipedia.org/wiki/IL1rahttp://en.wikipedia.org/wiki/IL1rahttp://en.wikipedia.org/wiki/Interleukin-1http://en.wikipedia.org/wiki/Affinityhttp://en.wikipedia.org/wiki/Binding_site


15/76

Non-competitive antagonists

Non-competitive antagonists are also known as allostericantagonists. These antagonists bind to a distinctly separatebinding site from the agonist, exerting their action to that

receptor via the other binding site.Cyclothiazide has been shown to act as a reversible non-

competitive antagonist of mGluR1 receptor. Thus, they do notcompete with agonists for binding.

The bound antagonists may result in a decreased affinity of anagonist for that receptor, or alternatively may preventconformational changes in the receptor required for receptoractivation after the agonist binds.

No amount of agonist can completely overcome the inhibition

once it has been established. In functional assays of non-competitive antagonists, depression of the maximal response ofagonist dose-response curves, and in some cases, rightwardshifts, is produced. The rightward shift will occur as a result of areceptor reserve and inhibition of the agonist response will only

occur when this reserve is depleted.
http://en.wikipedia.org/wiki/Allosterichttp://en.wikipedia.org/wiki/Cyclothiazidehttp://en.wikipedia.org/wiki/Metabotropic_glutamate_receptor_1http://en.wikipedia.org/wiki/Metabotropic_glutamate_receptor_1http://en.wikipedia.org/wiki/Cyclothiazidehttp://en.wikipedia.org/wiki/Allosteric


16/76

Uncompetitive antagonists

Uncompetitive antagonists differ from non-competitive

antagonists in that they require receptor activation byan agonist before they can bind to a separate

allosteric binding site.

This type of antagonism produces a kinetic profile in

which "the same amount of antagonist blocks higherconcentrations of agonist better than lower

concentrations of agonist".

Memantine, used in the treatment ofAlzheimer's disease

, is an uncompetitive antagonist of the NMDA receptor.

Partial agonists and inverse agonists
http://en.wikipedia.org/wiki/Memantinehttp://en.wikipedia.org/wiki/Alzheimer%27s_diseasehttp://en.wikipedia.org/wiki/NMDA_receptorhttp://en.wikipedia.org/wiki/NMDA_receptorhttp://en.wikipedia.org/wiki/Alzheimer%27s_diseasehttp://en.wikipedia.org/wiki/Memantine


17/76

Partial agonists and inverse agonists

Partial agonists are defined as drugs which, at a given receptor,might differ in the amplitude of the functional response that theyelicit after maximal receptor occupancy.

Although they are agonists, partial agonists can act as acompetitive antagonist if co-administered with a full agonist, asit competes with the full agonist for receptor occupancy andproducing a net decrease in the receptor activation observedwith the full agonist alone.

Clinically, their usefulness is derived from their ability to enhancedeficient systems while simultaneously blocking excessiveactivity. Exposing a receptor to a high level of a partial agonistwill ensure that it has a constant, weak level of activity, whetherits normal agonist is present at high or low levels. In addition, ithas been suggested that partial agonism prevents the adaptive

regulatory mechanisms that frequently develop after repeatedexposure to potent full agonists or antagonists.

Buprenorphine, a partial agonist of the -opioidreceptor, bindswith weak morphine-like activity and is used clinically as ananalgesic in pain management and in reversing morphine

addiction as an alternative to methodone in the treatment ofdrug addiction.
http://en.wikipedia.org/wiki/Agonisthttp://en.wikipedia.org/wiki/Competitive_antagonisthttp://en.wikipedia.org/wiki/Agonisthttp://en.wikipedia.org/wiki/Buprenorphinehttp://en.wikipedia.org/wiki/Opioid_receptorshttp://en.wikipedia.org/wiki/Opioid_receptorshttp://en.wikipedia.org/wiki/Analgesichttp://en.wikipedia.org/wiki/Methodonehttp://en.wikipedia.org/wiki/Methodonehttp://en.wikipedia.org/wiki/Analgesichttp://en.wikipedia.org/wiki/Opioid_receptorshttp://en.wikipedia.org/wiki/Opioid_receptorshttp://en.wikipedia.org/wiki/Buprenorphinehttp://en.wikipedia.org/wiki/Agonisthttp://en.wikipedia.org/wiki/Competitive_antagonisthttp://en.wikipedia.org/wiki/Agonist


18/76

Inverse Agonist

An inverse agonist can have effects similar to anantagonist, but causes a distinct set of downstream

biological responses.Constitutively active receptors which exhibit intrinsic or

basal activity can have inverse agonists, which notonly block the effects of binding agonists like a

classical antagonist, but inhibit the basal activity ofthe receptor. Drugs previously classified asantagonists are now beginning to be reclassified asinverse agonists because of the discovery of

constitutive active receptors.Antihistamines, originally classified as antagonists of

histamine H1 receptors have been reclassified asinverse agonists.

R ibilit
http://en.wikipedia.org/wiki/Inverse_agonisthttp://en.wikipedia.org/wiki/Receptor_(biochemistry)http://en.wikipedia.org/wiki/Antihistaminehttp://en.wikipedia.org/wiki/Histaminehttp://en.wikipedia.org/wiki/Histamine_H1_receptorhttp://en.wikipedia.org/wiki/Histamine_H1_receptorhttp://en.wikipedia.org/wiki/Histaminehttp://en.wikipedia.org/wiki/Antihistaminehttp://en.wikipedia.org/wiki/Receptor_(biochemistry)http://en.wikipedia.org/wiki/Inverse_agonist


19/76

Reversibility

Many antagonists are reversible antagonists that, like mostagonists, will bind and unbind a receptor at rates determined byreceptor-ligandkinetics.

Irreversible antagonists covalently bind to the receptor target andgenerally cannot be removed; inactivating the receptor for theduration of the antagonist effects is determined by the rate ofreceptor turnover, the rate of synthesis of new receptors.

Phenoxybenzamine is an example of an irreversible alpha blockerit permanently binds to adrenergic receptors, preventingadrenaline and noradrenaline from binding.

Inactivation of receptors normally results in a depression of themaximal response of agonist dose-response curves and a right

shift in the curve occurs where there is a receptor reservesimilar to non-competitive antagonists. A washout step in theassay will usually distinguish between non-competitive andirreversible antagonist drugs as effects of non-competitiveantagonists are reversible and activity of agonist will be

restored.
http://en.wikipedia.org/wiki/Receptor-ligand_kineticshttp://en.wikipedia.org/wiki/Receptor-ligand_kineticshttp://en.wikipedia.org/wiki/Covalent_bondhttp://en.wikipedia.org/wiki/Phenoxybenzaminehttp://en.wikipedia.org/wiki/Alpha_blockerhttp://en.wikipedia.org/wiki/Adrenergic_receptorhttp://en.wikipedia.org/wiki/Adrenergic_receptorhttp://en.wikipedia.org/wiki/Adrenalinehttp://en.wikipedia.org/wiki/Noradrenalinehttp://en.wikipedia.org/wiki/Noradrenalinehttp://en.wikipedia.org/wiki/Adrenalinehttp://en.wikipedia.org/wiki/Adrenergic_receptorhttp://en.wikipedia.org/wiki/Adrenergic_receptorhttp://en.wikipedia.org/wiki/Alpha_blockerhttp://en.wikipedia.org/wiki/Phenoxybenzaminehttp://en.wikipedia.org/wiki/Covalent_bondhttp://en.wikipedia.org/wiki/Receptor-ligand_kineticshttp://en.wikipedia.org/wiki/Receptor-ligand_kineticshttp://en.wikipedia.org/wiki/Receptor-ligand_kinetics


20/76

Efficacy & AffinityEfficacy is the capacity to produce a desired size of an effect

underideal oroptimal conditions.

In pharmacology, intrinsic activity or efficacy refers to the ability ofa drug-receptor complex to produce a functional response.

Efficacy must be distinguished from the affinity, which is ameasure of the ability of the drug to bind to its molecular target,and the EC50, which is a measure of the potency of the drug.

High efficacy agonists can produce the maximal response of thereceptor system while occupying a relatively low proportion ofthe receptors in that system. While Agonists of lower efficacyare not as efficient at producing a response from the drug-

bound receptor agonist: affinity and high efficacy

antagonist : affinity without efficacy

partial agonist: affinity and low efficacy, in a system with a small

number of receptors

EC50
http://en.wikipedia.org/wiki/Idealhttp://en.wikipedia.org/wiki/Optimalhttp://en.wikipedia.org/wiki/Dissociation_constanthttp://en.wikipedia.org/wiki/EC50http://en.wikipedia.org/wiki/Agonisthttp://en.wikipedia.org/wiki/Receptor_antagonisthttp://en.wikipedia.org/wiki/Receptor_antagonisthttp://en.wikipedia.org/wiki/Agonisthttp://en.wikipedia.org/wiki/EC50http://en.wikipedia.org/wiki/Dissociation_constanthttp://en.wikipedia.org/wiki/Optimalhttp://en.wikipedia.org/wiki/Ideal


21/76

EC50The term half maximal effective concentration (EC50) refers to

the concentration of a drug or antibody which induces aresponse halfway between the baseline and maximum. It is

commonly used as a measure of drug potency.The EC50 of a graded dose response curve therefore represents

the concentration of a compound where 50% of its maximaleffect is observed. The EC50 of a quantal dose response curverepresents the concentration of a compound where 50% of the

population exhibit a response.It is also related to IC50 which is a measure of a compound'sinhibition (50% inhibition). For competition binding assays andfunctional antagonist assays IC50 is the most commonsummary measure of the dose-response curve. Foragonist/stimulator assays the most common summary measureis the EC50.

Concentration measures typically follow a Sigmoidal curve,increasing rapidly over a relatively small change inconcentration. The point at which the effectiveness slows withincreasing concentration is the IC50. This can be determined

mathematically by derivation of the best-fit line.
http://en.wikipedia.org/wiki/Potencyhttp://en.wikipedia.org/wiki/Dose_response_curvehttp://en.wikipedia.org/wiki/IC50http://en.wikipedia.org/wiki/IC50http://en.wikipedia.org/wiki/Sigmoid_functionhttp://en.wikipedia.org/wiki/Sigmoid_functionhttp://en.wikipedia.org/wiki/IC50http://en.wikipedia.org/wiki/IC50http://en.wikipedia.org/wiki/Dose_response_curvehttp://en.wikipedia.org/wiki/Potency


22/76


23/76

Antagonists will block the binding of an agonist at a receptor

molecule, inhibiting the signal produced by a receptor-agonistcou lin .
http://en.wikipedia.org/wiki/Agonisthttp://en.wikipedia.org/wiki/Receptor_(biochemistry)http://en.wikipedia.org/wiki/Receptor_(biochemistry)http://en.wikipedia.org/wiki/Agonist


24/76

Side effectSide effect can mean:

Adverse drug reaction, an unintended

consequence specifically arising from drug

therapy

Therapeutic effect, an unintended but desirable

consequence of any kind of medical treatment

Adverse effect (medicine), an unintended, and

undesirable, consequence of any kind of

medical treatment
http://en.wikipedia.org/wiki/Adverse_drug_reactionhttp://en.wikipedia.org/wiki/Therapeutic_effecthttp://en.wikipedia.org/wiki/Adverse_effect_(medicine)http://en.wikipedia.org/wiki/Adverse_effect_(medicine)http://en.wikipedia.org/wiki/Therapeutic_effecthttp://en.wikipedia.org/wiki/Adverse_drug_reaction


25/76

An adverse drug reaction (abbreviated ADR) or

adverse drug event (abbreviated ADE) is an

expression that describes the unwanted,negative consequences associated with the

use of given medications.

An ADR is a particular type ofadverse effect. Themeaning of this expression differs from the

meaning of "side effect", as this last expression

might also imply that the effects can be

beneficial. The study of ADRs is the concern of

the field known aspharmacovigilance.

Cl ifi ti
http://en.wikipedia.org/wiki/Medicationhttp://en.wikipedia.org/wiki/Adverse_effect_(medicine)http://en.wikipedia.org/wiki/Pharmacovigilancehttp://en.wikipedia.org/wiki/Pharmacovigilancehttp://en.wikipedia.org/wiki/Adverse_effect_(medicine)http://en.wikipedia.org/wiki/Medication


26/76

Classification

ADRs may be classified by e.g. cause and severity.

Cause

Type A: Augmented pharmacologic effects

Type B: Bizarre effects (oridiosyncratic)

Type C: Chronic effects

Type D: Delayed effects

Type E: End-of-treatment effects

Type F: Failure of therapy

Types A and B were proposed in the 1970s, and theother types were proposed subsequently when the

first two proved insufficient to classify ADRs.

Seriousness and Severity
http://en.wikipedia.org/wiki/Idiosyncratic_drug_reactionhttp://en.wikipedia.org/wiki/Idiosyncratic_drug_reaction


27/76

Seriousness and Severity

The American Food and Drug Administration definesa serious adverse event as one when the patient

outcome is: Death

Life-Threatening

Hospitalization (initial or prolonged) Disability - significant, persistent, or permanent

change, impairment, damage or disruption in thepatient's body function/structure, physical activities

or quality of life. Congenital Anomaly - or - Requires Intervention

to Prevent Permanent Impairment or Damage
http://en.wikipedia.org/wiki/Food_and_Drug_Administrationhttp://en.wikipedia.org/wiki/Food_and_Drug_Administration


28/76

Severity is a point on an arbitrary scale ofintensity of the adverse event in question.

The terms "severe" and "serious" whenapplied to adverse events are technicallyvery different. They are easily confused butcan not be used interchangeably, require

care in usage.A headache is severe, if it causes intense

pain. There are scales like "visual analog

scale" that help us assess the severity. Aheadache, on the other hand, can hardlyever be serious, unless it also satisfies thecriteria for seriousness, listed above.

O ll D Ri k


29/76

Overall Drug Risk

While no official scale exists yet to communicate

overall drug risk, the iGuard Drug Risk Rating

System is a five color rating scale similar to the

Homeland Security Advisory System:

Red (High Risk)

Orange (Elevated Risk)

Yellow (Guarded Risk)

Blue (General Risk) Green (Low Risk)
http://en.wikipedia.org/wiki/IGuardhttp://en.wikipedia.org/wiki/Homeland_Security_Advisory_Systemhttp://en.wikipedia.org/wiki/Homeland_Security_Advisory_Systemhttp://en.wikipedia.org/wiki/IGuard


30/76

Location

Adverse effects may be local, i.e. limited to a

certain location, or systemic, where amedication has caused adverse effects

throughout the systemic circulation.

For instance, some ocularantihypertensivescause systemic effects, although they are

administered locally as eye drops, since a

fraction escapes to the systemic circulation.
http://en.wikipedia.org/wiki/Systemic_circulationhttp://en.wikipedia.org/wiki/Ocular_antihypertensivehttp://en.wikipedia.org/wiki/Ocular_antihypertensivehttp://en.wikipedia.org/wiki/Eye_drophttp://en.wikipedia.org/wiki/Eye_drophttp://en.wikipedia.org/wiki/Ocular_antihypertensivehttp://en.wikipedia.org/wiki/Ocular_antihypertensivehttp://en.wikipedia.org/wiki/Systemic_circulation


31/76

Mechanisms

As research better explains the

biochemistry of drug use, less ADRs areType B and more are Type A. Common

mechanisms are:

Abnormal pharmacokinetics due to genetic factors

co morbid disease states

Synergistic effects between either a drug and a disease

two drugs

Abnormal pharmacokinetics
http://en.wikipedia.org/wiki/Geneticshttp://en.wikipedia.org/wiki/Synergistichttp://en.wikipedia.org/wiki/Synergistichttp://en.wikipedia.org/wiki/Genetics


32/76

Abnormal pharmacokinetics

Co morbid disease states: Various diseases,

especially those that cause renal orhepatic

insufficiency, may alter drug metabolism.

Resources are available that report changes

in a drug's metabolism due to disease states.

Genetic factors: Abnormal drug metabolism

may be due to inherited factors of either

Phase I oxidation or Phase II conjugation.

Pharmacogenomics is the study of theinherited basis for abnormal drug reactions.
http://en.wikipedia.org/wiki/Renal_failurehttp://en.wikipedia.org/wiki/Liver_failurehttp://en.wikipedia.org/wiki/Pharmacogenomicshttp://en.wikipedia.org/wiki/Pharmacogenomicshttp://en.wikipedia.org/wiki/Liver_failurehttp://en.wikipedia.org/wiki/Renal_failure


33/76

Phase I reactions: Inheriting abnormal alleles ofcytochromeP450 can alter drug metabolism.

Inheriting abnormal butyrylcholinesterase (pseudocholinesterase) may affect metabolismof drugs such as succinylcholine.

Phase II reactions: Inheriting abnormal N-

acetyltransferase which conjugated some drugsto facilitate excretion may affect the metabolismof drugs such as isoniazid, hydralazine, andprocainamide.

Inheriting abnormal thiopurineS-methyltransferase may affect the metabolism ofthe thiopurine drugs mercaptopurine and

azathioprine.
http://en.wikipedia.org/wiki/Azathioprinehttp://en.wikipedia.org/wiki/Allelehttp://en.wikipedia.org/wiki/Cytochromehttp://en.wikipedia.org/wiki/Cytochrome_P450http://en.wikipedia.org/wiki/Cholinesterase_enzymehttp://en.wikipedia.org/wiki/Cholinesterase_enzymehttp://en.wikipedia.org/wiki/Succinylcholinehttp://en.wikipedia.org/wiki/Acetyltransferasehttp://en.wikipedia.org/wiki/Acetyltransferasehttp://en.wikipedia.org/wiki/Isoniazidhttp://en.wikipedia.org/wiki/Hydralazinehttp://en.wikipedia.org/wiki/Procainamidehttp://en.wikipedia.org/wiki/Thiopurine_methyltransferasehttp://en.wikipedia.org/wiki/Thiopurine_methyltransferasehttp://en.wikipedia.org/wiki/Thiopurine_methyltransferasehttp://en.wikipedia.org/wiki/Thiopurinehttp://en.wikipedia.org/wiki/Mercaptopurinehttp://en.wikipedia.org/wiki/Azathioprinehttp://en.wikipedia.org/wiki/Azathioprinehttp://en.wikipedia.org/wiki/Mercaptopurinehttp://en.wikipedia.org/wiki/Thiopurinehttp://en.wikipedia.org/wiki/Thiopurine_methyltransferasehttp://en.wikipedia.org/wiki/Thiopurine_methyltransferasehttp://en.wikipedia.org/wiki/Thiopurine_methyltransferasehttp://en.wikipedia.org/wiki/Procainamidehttp://en.wikipedia.org/wiki/Hydralazinehttp://en.wikipedia.org/wiki/Isoniazidhttp://en.wikipedia.org/wiki/Acetyltransferasehttp://en.wikipedia.org/wiki/Acetyltransferasehttp://en.wikipedia.org/wiki/Succinylcholinehttp://en.wikipedia.org/wiki/Cholinesterase_enzymehttp://en.wikipedia.org/wiki/Cholinesterase_enzymehttp://en.wikipedia.org/wiki/Cytochrome_P450http://en.wikipedia.org/wiki/Cytochromehttp://en.wikipedia.org/wiki/Allele


34/76

Interactions with other drugs: The risk of

drug interactions is increased with polypharmacy.

Protein binding: These interactions are usually

transient and mild until a new steady state is

achieved. These are mainly for drugs withoutmuch first-pass liver metabolism. The principal

plasma proteins for drug binding are:

albumin

1-acid glycoprotein

lipoproteins

Synergistic effects
http://en.wikipedia.org/wiki/Drug_interactionhttp://en.wikipedia.org/wiki/Polypharmacyhttp://en.wikipedia.org/wiki/Albuminhttp://en.wikipedia.org/wiki/Albuminhttp://en.wikipedia.org/wiki/Polypharmacyhttp://en.wikipedia.org/wiki/Drug_interaction


35/76

Synergistic effects

Synergy (from the Greeksyn-ergo,

meaning working together) is the term used todescribe a situation where the final outcome of

a system is greater than the sum of its parts.

The opposite of synergy is antagonism, thephenomenon where two agents in combination

have an overall effect that is less than that

predicted from their individual effects.
http://en.wikipedia.org/wiki/Greek_languagehttp://en.wikipedia.org/wiki/Antagonismhttp://en.wikipedia.org/wiki/Antagonismhttp://en.wikipedia.org/wiki/Greek_language


36/76

Synergy can also mean:

A mutually advantageous conjunction where

the whole is greater than the sum of theparts.

A dynamic state in which combined action isfavored over the sum of individual component

actions.Behavior of whole systems unpredicted by the

behavior of their parts taken separately. More

accurately known as emergent behavior.The cooperative action of two or more stimuli or

drugs.

Drug synergism occurs when drugs can interact in ways
http://en.wikipedia.org/wiki/Emergent_behaviorhttp://en.wikipedia.org/wiki/Emergent_behaviorhttp://en.wikipedia.org/wiki/Drughttp://en.wikipedia.org/wiki/Drug


37/76

Drug synergism occurs when drugs can interact in waysthat enhance or magnify one or more effects, or sideeffects, of those drugs.

This is sometimes exploited in combination preparations,

such as codeine mixed with acetaminophen oribuprofen to enhance the action of codeine as a painreliever. This is often seen with recreational drugs,where 5-HTP(5-Hydroxytryptophan), a serotoninprecursor often used as an antidepressant, is oftenused prior to, during, and shortly after recreational useofMDMA(3,4-methylenedioxy-N-methylamphetamine)as it allegedly increases the "high" and decreases the"comedown" stages of MDMA use (although most

anecdotal evidence has pointed to 5-HTP moderatelymuting the effect of MDMA). Other examples includethe use ofcannabis with LSD, where the activechemicals in cannabis enhance the hallucinatoryexperience of LSD-use.
http://en.wikipedia.org/wiki/Drughttp://en.wikipedia.org/wiki/Codeinehttp://en.wikipedia.org/wiki/Acetaminophenhttp://en.wikipedia.org/wiki/Ibuprofenhttp://en.wikipedia.org/wiki/5-HTPhttp://en.wikipedia.org/wiki/MDMAhttp://en.wikipedia.org/wiki/Cannabishttp://en.wikipedia.org/wiki/LSDhttp://en.wikipedia.org/wiki/LSDhttp://en.wikipedia.org/wiki/Cannabishttp://en.wikipedia.org/wiki/MDMAhttp://en.wikipedia.org/wiki/5-HTPhttp://en.wikipedia.org/wiki/Ibuprofenhttp://en.wikipedia.org/wiki/Acetaminophenhttp://en.wikipedia.org/wiki/Codeinehttp://en.wikipedia.org/wiki/Drug


38/76

Nice to read

(5-Hydroxytryptophan or5-HTP is a naturally-occurringamino acid, a precursorto the neurotransmitterserotoninand an intermediate in tryptophanmetabolism. It ismarketed in the United States and other countries as adietary supplement for use as an antidepressant,

appetite suppressant, and sleep aid.MDMA (3,4-methylenedioxy-N-methylamphetamine),

most commonly known today by the street nameEcstasy (often abbreviated E, X, orXTC), is asemisynthetic member of the amphetamine class of

psychoactive drugs, a subclass of the phenethylamines.[3] MDMA also falls under many other broad categoriesof substances, including stimulants, psychedelics, andthe empathogenic-entactogens. )
http://en.wikipedia.org/wiki/Amino_acidhttp://en.wikipedia.org/wiki/Precursor_(chemistry)http://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Serotoninhttp://en.wikipedia.org/wiki/Tryptophanhttp://en.wikipedia.org/wiki/Metabolismhttp://en.wikipedia.org/wiki/United_Stateshttp://en.wikipedia.org/wiki/Antidepressanthttp://en.wikipedia.org/wiki/Appetite_suppressanthttp://en.wikipedia.org/wiki/Sleep_aidhttp://en.wikipedia.org/wiki/Semisynthetichttp://en.wikipedia.org/wiki/Amphetaminehttp://en.wikipedia.org/wiki/Phenethylamineshttp://en.wikipedia.org/wiki/MDMAhttp://en.wikipedia.org/wiki/Stimulantshttp://en.wikipedia.org/wiki/Psychedelic_drughttp://en.wikipedia.org/wiki/Empathogen-entactogenhttp://en.wikipedia.org/wiki/Empathogen-entactogenhttp://en.wikipedia.org/wiki/Psychedelic_drughttp://en.wikipedia.org/wiki/Stimulantshttp://en.wikipedia.org/wiki/MDMAhttp://en.wikipedia.org/wiki/Phenethylamineshttp://en.wikipedia.org/wiki/Amphetaminehttp://en.wikipedia.org/wiki/Semisynthetichttp://en.wikipedia.org/wiki/Sleep_aidhttp://en.wikipedia.org/wiki/Appetite_suppressanthttp://en.wikipedia.org/wiki/Antidepressanthttp://en.wikipedia.org/wiki/United_Stateshttp://en.wikipedia.org/wiki/Metabolismhttp://en.wikipedia.org/wiki/Tryptophanhttp://en.wikipedia.org/wiki/Serotoninhttp://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Precursor_(chemistry)http://en.wikipedia.org/wiki/Amino_acid


39/76

An example of negative effects of synergy isif more than one depressant drug is used

that affects the central nervous system(CNS), for example alcohol and Valium.

The combination can cause a greater

reaction than simply the sum of theindividual effects of each drug if they wereused separately. In this particular case, themost serious consequence of drug synergy

is exaggerated respiratory depression,which can be fatal if left untreated.

Toxicity
http://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Alcoholhttp://en.wikipedia.org/wiki/Valiumhttp://en.wikipedia.org/wiki/Respiratory_depressionhttp://en.wikipedia.org/wiki/Respiratory_depressionhttp://en.wikipedia.org/wiki/Valiumhttp://en.wikipedia.org/wiki/Alcoholhttp://en.wikipedia.org/wiki/Central_nervous_system


40/76

ToxicityToxicity is the degree to which a substance is able to

damage an exposed organism. Toxicity can refer to

the effect on a whole organism, such as a human,

bacterium, or plant, as well as the effect on a

substructure of the organism, such as a cell

(cytotoxicity) or an organ (organotoxicity) such as theliver(hepatotoxicity).

A central concept oftoxicology is that effects are dose-

dependent; even water can lead to water intoxication

when taken in large enough doses, whereas for evena very toxic substance such as snakevenom there is

a dose below which there is no detectable toxic effect.

Types of toxicity
http://en.wikipedia.org/wiki/Organismhttp://en.wikipedia.org/wiki/Humanhttp://en.wikipedia.org/wiki/Bacteriumhttp://en.wikipedia.org/wiki/Cell_(biology)http://en.wikipedia.org/wiki/Liverhttp://en.wikipedia.org/wiki/Toxicologyhttp://en.wikipedia.org/wiki/Dosehttp://en.wikipedia.org/wiki/Water_intoxicationhttp://en.wikipedia.org/wiki/Snakehttp://en.wikipedia.org/wiki/Venom_(poison)http://en.wikipedia.org/wiki/Venom_(poison)http://en.wikipedia.org/wiki/Snakehttp://en.wikipedia.org/wiki/Water_intoxicationhttp://en.wikipedia.org/wiki/Dosehttp://en.wikipedia.org/wiki/Toxicologyhttp://en.wikipedia.org/wiki/Liverhttp://en.wikipedia.org/wiki/Cell_(biology)http://en.wikipedia.org/wiki/Bacteriumhttp://en.wikipedia.org/wiki/Humanhttp://en.wikipedia.org/wiki/Organism


41/76

Types of toxicity

There are generally three types of toxic entities;

chemical, biological, and physical.

Chemicals include inorganic substances such as

lead, hydrofluoric acid, and chlorine gas,

organic compounds such as methyl alcohol,

most medications, and poisons from living

things.

Biological toxic entities include those bacteria
http://en.wikipedia.org/wiki/Inorganichttp://en.wikipedia.org/wiki/Leadhttp://en.wikipedia.org/wiki/Hydrofluoric_acidhttp://en.wikipedia.org/wiki/Chlorinehttp://en.wikipedia.org/wiki/Organic_compoundhttp://en.wikipedia.org/wiki/Methanolhttp://en.wikipedia.org/wiki/Methanolhttp://en.wikipedia.org/wiki/Organic_compoundhttp://en.wikipedia.org/wiki/Chlorinehttp://en.wikipedia.org/wiki/Hydrofluoric_acidhttp://en.wikipedia.org/wiki/Leadhttp://en.wikipedia.org/wiki/Inorganic


42/76

Biological toxic entities include those bacteriaand viruses that are able to induce disease inliving organisms.

Biological toxicity can be complicated to measurebecause the "threshold dose" may be a singleorganism. Theoretically one virus, bacterium orworm can reproduce to cause a seriousinfection.

However, in a host with an intact immune systemthe inherent toxicity of the organism is balanced

by the host's ability to fight back; the effectivetoxicity is then a combination of both parts ofthe relationship. A similar situation is alsopresent with other types of toxic agents.
http://en.wikipedia.org/wiki/Virushttp://en.wikipedia.org/wiki/Wormhttp://en.wikipedia.org/wiki/Infectionhttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Biological_agenthttp://en.wikipedia.org/wiki/Biological_agenthttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Infectionhttp://en.wikipedia.org/wiki/Wormhttp://en.wikipedia.org/wiki/Virus


43/76

Physically toxic entities include things not usually

thought of under the heading of "toxic" by many

people: direct blows, concussion, sound and vibration,

heat and cold, non-ionizing electromagnetic radiation

such as infrared and visible light, and ionizing radiationsuch as X-rays and alpha, beta, and gamma radiation.
http://en.wikipedia.org/wiki/Oscillationhttp://en.wikipedia.org/wiki/Electromagnetic_radiationhttp://en.wikipedia.org/wiki/Ionizing_radiationhttp://en.wikipedia.org/wiki/X-rayshttp://en.wikipedia.org/wiki/Alpha_rayshttp://en.wikipedia.org/wiki/Beta_rayshttp://en.wikipedia.org/wiki/Gamma_rayshttp://en.wikipedia.org/wiki/Gamma_rayshttp://en.wikipedia.org/wiki/Beta_rayshttp://en.wikipedia.org/wiki/Alpha_rayshttp://en.wikipedia.org/wiki/X-rayshttp://en.wikipedia.org/wiki/Ionizing_radiationhttp://en.wikipedia.org/wiki/Electromagnetic_radiationhttp://en.wikipedia.org/wiki/Oscillation


44/76

Acute Toxicity

Acute toxicity looks at lethal effects following oral,

dermal or inhalation exposure. It is broken into

five categories of severity where Category 1

requires the least amount of exposure to be

lethal and Category 5 requires the mostexposure to the be lethal.


45/76

Oral Toxic Category

a. Category 1: LD50 5 mg/kg of bodyweight

b. Category 2: LD50 50 mg/kg of bodyweight

c. Category 3: LD50 300 mg/kg of bodyweight

d. Category 4: LD50 2000 mg/kg of bodyweight

e. Category 5: LD50 5000 mg/kg of bodyweight

*substances beyond category 5 are notdefined, though they cannot legally be defined

as orally toxic.


46/76

2. Dermal

a. Category 1: LD50 50 mg/kg of bodyweight

b. Category 2: LD50 200 mg/kg of bodyweight

c. Category 3: LD50 1,000 mg/kg of bodyweight

d. Category 4: LD50 2,000 mg/kg of bodyweight

e. Category 5: LD50 5,000 mg/kg of bodyweight

*substances beyond category 5 are notdefined, though they cannot legally be defined

as dermally toxic.


47/76

3. Inhalation Gases

a. Category 1: LC50 100 ppmV

b. Category 2: LC50 500 ppmVc. Category 3: LC50 2,500 ppmV

d. Category 4: LC50 20,000 ppmV

e. Category 5: not defined though isexpected to have an equivalent of

category 5 oral and dermal


48/76

4. Inhalation Vapours

a. Category 1: LC50 0.5 mg/l

b. Category 2: LD50 2.0 mg/lc. Category 3: LD50 10 mg/l

d. Category 4: LD50 20 mg/l

e. Category 5: not defined though isexpected to have an equivalent of



49/76

5. Inhalation Dust and Mists

Category 1: LC50 0.05 mg/l

Category 2: LD50 0.5 mg/l

Category 3: LD50 1.0 mg/l

Category 4: LD50 5 mg/l

Category 5: not defined though isexpected to have an equivalent of


Teratogenicity


50/76

Teratogenicity

The term teratology generally refers to disfiguring

birth defects or malformations.Another term for this is dysmorphology, meaning "the

study of abnormal form."

Etymology
http://en.wikipedia.org/wiki/Birth_defecthttp://en.wikipedia.org/wiki/Birth_defect


51/76

Etymology As early as the 17th century, Teratology referred to a discourse

on prodigies and marvels, of anything so extraordinary as toseem abnormal.

In 19th century, it acquired a meaning closer related tobiological deformities, mostly in the field of botany. Currently, itsmost instrumental meaning is that of the medical study ofteratogenesis, congenital malformations or grossly deformedindividuals. Monsteris a pejorative term for a grossly deformed

individual, although it is interesting to note that, etymologically,this word is related to demonstration, and used to simply meansomething worth looking at, for being unusual, withoutnecessarily being pejorative.

Teratology as a medical term was popularized in the 1960s byDr. David W. Smith of the University of Washington MedicalSchool, one of the researchers who became known in 1973 forthe discovery ofFetal alcohol syndrome. With greaterunderstanding of the origins of birth defects, the field ofteratology now overlaps with other fields of basic science,including developmental biology, embryology, and genetics.

Teratogenesis
http://en.wikipedia.org/wiki/Congenital_disorderhttp://en.wikipedia.org/wiki/Pejorativehttp://en.wikipedia.org/wiki/University_of_Washingtonhttp://en.wikipedia.org/wiki/Fetal_alcohol_syndromehttp://en.wikipedia.org/wiki/Developmental_biologyhttp://en.wikipedia.org/wiki/Embryologyhttp://en.wikipedia.org/wiki/Geneticshttp://en.wikipedia.org/wiki/Geneticshttp://en.wikipedia.org/wiki/Embryologyhttp://en.wikipedia.org/wiki/Developmental_biologyhttp://en.wikipedia.org/wiki/Fetal_alcohol_syndromehttp://en.wikipedia.org/wiki/University_of_Washingtonhttp://en.wikipedia.org/wiki/Pejorativehttp://en.wikipedia.org/wiki/Congenital_disorder


52/76

g Birth defects are known to occur in 3-5% of all

newborns. They are the leading cause of infantmortality in the United States, accounting for more

than 20% of all infant deaths. Seven to ten percent ofall children will require extensive medical care todiagnose or treat a birth defect. And althoughsignificant progress has been made in identifyingetiologic causes of some birth defects, approximately

65% have no known or identifiable cause. It was previously believed that the mammalianembryo

developed in the impervious uterus of the mother,protected from all extrinsic factors. However, after the

thalidomide disaster of the 1960s, it became apparentand more accepted that the developing embryo couldbe highly vulnerable to certain environmental agentsthat have negligible or non-toxic effects to adultindividuals.
http://en.wikipedia.org/wiki/Mammalianhttp://en.wikipedia.org/wiki/Embryohttp://en.wikipedia.org/wiki/Thalidomidehttp://en.wikipedia.org/wiki/Embryohttp://en.wikipedia.org/wiki/Embryohttp://en.wikipedia.org/wiki/Thalidomidehttp://en.wikipedia.org/wiki/Embryohttp://en.wikipedia.org/wiki/Mammalian


53/76

4. The access of adverse influences to developing tissues


54/76

p g

depends on the nature of the influence. Several factors

affect the ability of a teratogen to contact a developing

conceptus, such as the nature of the agent itself, route

and degree of maternal exposure, rate of placental

transfer and systemic absorption, and composition of the

maternal and embryonic/fetal genotypes.

5. There are four manifestations of deviant development(Death, Malformation, Growth Retardation and Functional

Defect).

6. Manifestations of deviant development increase in

frequency and degree as dosage increases from the NoObservable Adverse Effect Level (NOAEL) to a dose

producing 100% Lethality (LD100).

Studies designed to test the teratogenic potential of environmentalt i l d l t ( t bbit d


55/76

agents use animal model systems (e.g., rat, mouse, rabbit, dog,and monkey). Early teratologists exposed pregnant animals toenvironmental agents and observed the fetuses for grossvisceral and skeletal abnormalities. While this is still part of theteratological evaluation procedures today, the field ofTeratology is moving to a more molecularlevel, seeking themechanism(s) of action by which these agents act.Genetically modified mice are commonly used for this purpose.

In addition, pregnancy registries are large, prospective studiesthat monitor exposures women receive during their pregnanciesand record the outcome of their births. These studies provideinformation about possible risks of medications or otherexposures in human pregnancies.

Understanding how a teratogen causes its effect is not onlyimportant in preventing congenital abnormalities but also hasthe potential for developing new therapeutic drugs safe for usewith pregnant women.

Teratogenic agents
http://en.wikipedia.org/wiki/Molecularhttp://en.wikipedia.org/wiki/Genetically_modifiedhttp://en.wikipedia.org/wiki/Genetically_modifiedhttp://en.wikipedia.org/wiki/Molecular


56/76

g g

A wide range of different chemicals and environmental

factors are suspected or are known to be teratogenic

in humans and in animals. A selected few include: Ionizing radiation: atomic weapons, radioiodine,

radiation therapy

Infections: cytomegalovirus, herpes virus,

parvovirus B-19, rubella virus (German measles),

syphilis, toxoplasmosis,

Venezuelan equine encephalitis virus

Metabolic imbalance: alcoholism, endemic cretinism,diabetes, folic acid deficiency, hyperthermia,

phenylketonuria, rheumatic disease and

congenital heart block, virilizingtumors

Drugs and environmental chemicals:
http://en.wikipedia.org/wiki/Atomic_weaponshttp://en.wikipedia.org/wiki/Radioiodinehttp://en.wikipedia.org/wiki/Radiation_therapyhttp://en.wikipedia.org/wiki/Cytomegalovirushttp://en.wikipedia.org/wiki/Herpes_virushttp://en.wikipedia.org/wiki/Parvovirushttp://en.wikipedia.org/wiki/Rubellahttp://en.wikipedia.org/wiki/Syphilishttp://en.wikipedia.org/wiki/Toxoplasmosishttp://en.wikipedia.org/wiki/Venezuelan_equine_encephalitis_virushttp://en.wikipedia.org/wiki/Alcoholismhttp://en.wikipedia.org/wiki/Cretinismhttp://en.wikipedia.org/wiki/Diabeteshttp://en.wikipedia.org/wiki/Folic_acid_deficiencyhttp://en.wikipedia.org/wiki/Hyperthermiahttp://en.wikipedia.org/wiki/Phenylketonuriahttp://en.wikipedia.org/wiki/Rheumatic_diseasehttp://en.wikipedia.org/wiki/Heart_blockhttp://en.wikipedia.org/wiki/Virilizationhttp://en.wikipedia.org/wiki/Virilizationhttp://en.wikipedia.org/wiki/Virilizationhttp://en.wikipedia.org/wiki/Virilizationhttp://en.wikipedia.org/wiki/Heart_blockhttp://en.wikipedia.org/wiki/Rheumatic_diseasehttp://en.wikipedia.org/wiki/Phenylketonuriahttp://en.wikipedia.org/wiki/Hyperthermiahttp://en.wikipedia.org/wiki/Folic_acid_deficiencyhttp://en.wikipedia.org/wiki/Diabeteshttp://en.wikipedia.org/wiki/Cretinismhttp://en.wikipedia.org/wiki/Alcoholismhttp://en.wikipedia.org/wiki/Venezuelan_equine_encephalitis_virushttp://en.wikipedia.org/wiki/Toxoplasmosishttp://en.wikipedia.org/wiki/Syphilishttp://en.wikipedia.org/wiki/Rubellahttp://en.wikipedia.org/wiki/Parvovirushttp://en.wikipedia.org/wiki/Herpes_virushttp://en.wikipedia.org/wiki/Cytomegalovirushttp://en.wikipedia.org/wiki/Radiation_therapyhttp://en.wikipedia.org/wiki/Radioiodinehttp://en.wikipedia.org/wiki/Atomic_weapons


57/76

g

13-cis-retinoic acid, isotretinoin(Accutane),

temazepam (Restoril; Normisson), nitrazepam

(Mogadon), nimetazepam (Ermin), aminopterin,androgenic hormones, busulfan, captopril,

enalapril, chlorobiphenyls(PCBs), Dioxin,

coumarin, cyclophosphamide, diethylstilbestrol,diphenylhydantoin(Phenytoin,Dilantin,

Epanutin), ethanol, ethidiumbromide, etretinate

, hexachlorophene, lithium, methimazole,

organic mercury, penicillamine, tetracyclines,

thalidomide, trimethadione, uranium,

methoxyethyl ethers and valproicacid.

The status of some of the above substances (e.g.
http://en.wikipedia.org/wiki/Retinoic_acidhttp://en.wikipedia.org/wiki/Isotretinoinhttp://en.wikipedia.org/wiki/Isotretinoinhttp://en.wikipedia.org/wiki/Temazepamhttp://en.wikipedia.org/wiki/Nitrazepamhttp://en.wikipedia.org/wiki/Nimetazepamhttp://en.wikipedia.org/wiki/Aminopterinhttp://en.wikipedia.org/wiki/Androgenichttp://en.wikipedia.org/wiki/Busulfanhttp://en.wikipedia.org/wiki/Captoprilhttp://en.wikipedia.org/wiki/Enalaprilhttp://en.wikipedia.org/wiki/Polychlorinated_biphenylhttp://en.wikipedia.org/wiki/Polychlorinated_biphenylhttp://en.wikipedia.org/wiki/Polychlorinated_dibenzodioxinshttp://en.wikipedia.org/wiki/Coumarinhttp://en.wikipedia.org/wiki/Cyclophosphamidehttp://en.wikipedia.org/wiki/Diethylstilbestrolhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Ethanolhttp://en.wikipedia.org/wiki/Ethidium_bromidehttp://en.wikipedia.org/wiki/Ethidium_bromidehttp://en.wikipedia.org/wiki/Etretinatehttp://en.wikipedia.org/wiki/Hexachlorophenehttp://en.wikipedia.org/wiki/Lithiumhttp://en.wikipedia.org/wiki/Methimazolehttp://en.wikipedia.org/wiki/Mercury_(element)http://en.wikipedia.org/wiki/Penicillaminehttp://en.wikipedia.org/wiki/Tetracyclineshttp://en.wikipedia.org/wiki/Thalidomidehttp://en.wikipedia.org/wiki/Trimethadionehttp://en.wikipedia.org/wiki/Uraniumhttp://en.wikipedia.org/wiki/Ethershttp://en.wikipedia.org/wiki/Valproic_acidhttp://en.wikipedia.org/wiki/Valproic_acidhttp://en.wikipedia.org/wiki/Valproic_acidhttp://en.wikipedia.org/wiki/Valproic_acidhttp://en.wikipedia.org/wiki/Ethershttp://en.wikipedia.org/wiki/Uraniumhttp://en.wikipedia.org/wiki/Trimethadionehttp://en.wikipedia.org/wiki/Thalidomidehttp://en.wikipedia.org/wiki/Tetracyclineshttp://en.wikipedia.org/wiki/Penicillaminehttp://en.wikipedia.org/wiki/Mercury_(element)http://en.wikipedia.org/wiki/Methimazolehttp://en.wikipedia.org/wiki/Lithiumhttp://en.wikipedia.org/wiki/Hexachlorophenehttp://en.wikipedia.org/wiki/Etretinatehttp://en.wikipedia.org/wiki/Ethidium_bromidehttp://en.wikipedia.org/wiki/Ethidium_bromidehttp://en.wikipedia.org/wiki/Ethanolhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Diethylstilbestrolhttp://en.wikipedia.org/wiki/Cyclophosphamidehttp://en.wikipedia.org/wiki/Coumarinhttp://en.wikipedia.org/wiki/Polychlorinated_dibenzodioxinshttp://en.wikipedia.org/wiki/Polychlorinated_biphenylhttp://en.wikipedia.org/wiki/Polychlorinated_biphenylhttp://en.wikipedia.org/wiki/Enalaprilhttp://en.wikipedia.org/wiki/Captoprilhttp://en.wikipedia.org/wiki/Busulfanhttp://en.wikipedia.org/wiki/Androgenichttp://en.wikipedia.org/wiki/Aminopterinhttp://en.wikipedia.org/wiki/Nimetazepamhttp://en.wikipedia.org/wiki/Nitrazepamhttp://en.wikipedia.org/wiki/Temazepamhttp://en.wikipedia.org/wiki/Isotretinoinhttp://en.wikipedia.org/wiki/Isotretinoinhttp://en.wikipedia.org/wiki/Isotretinoinhttp://en.wikipedia.org/wiki/Isotretinoinhttp://en.wikipedia.org/wiki/Retinoic_acid


58/76

diphenylhydantoin) is subject to debate, and many

other compounds are under varying degrees of

suspicion. These include Agent Orange, nicotine,aspirin and otherNSAIDs. Other compounds are

known as severe teratogens based on veterinary work

and animal studies, but aren't listed above because

they have not been studied in humans, e.g.cyclopamine. Teratogenic effects also help to

determine the pregnancy category assigned by

regulatory authorities; in the United States, a

pregnancy category of X, D, or C may be assigned ifteratogenic effects (or other risks in pregnancy) are

documented or cannot be excluded.
http://en.wikipedia.org/wiki/Agent_Orangehttp://en.wikipedia.org/wiki/Nicotinehttp://en.wikipedia.org/wiki/Aspirinhttp://en.wikipedia.org/wiki/NSAIDhttp://en.wikipedia.org/wiki/Cyclopaminehttp://en.wikipedia.org/wiki/Pregnancy_categoryhttp://en.wikipedia.org/wiki/Pregnancy_categoryhttp://en.wikipedia.org/wiki/Cyclopaminehttp://en.wikipedia.org/wiki/NSAIDhttp://en.wikipedia.org/wiki/Aspirinhttp://en.wikipedia.org/wiki/Nicotinehttp://en.wikipedia.org/wiki/Agent_Orange


59/76


60/76

Teratogenic outcomes

Exposure to teratogens can result in a

wide range of structural abnormalities

such as cleft lip, cleft palate, dysmelia,

anencephaly, ventricularseptaldefect. In

most cases, specific agents produce a

specific teratogenic response.

Cleft lip (cheiloschisis) and cleft palate

( l t hi i ) hi h l t th
http://en.wikipedia.org/wiki/Cleft_liphttp://en.wikipedia.org/wiki/Cleft_palatehttp://en.wikipedia.org/wiki/Dysmeliahttp://en.wikipedia.org/wiki/Anencephalyhttp://en.wikipedia.org/wiki/Ventricular_septal_defecthttp://en.wikipedia.org/wiki/Ventricular_septal_defecthttp://en.wikipedia.org/wiki/Ventricular_septal_defecthttp://en.wikipedia.org/wiki/Ventricular_septal_defecthttp://en.wikipedia.org/wiki/Ventricular_septal_defecthttp://en.wikipedia.org/wiki/Ventricular_septal_defecthttp://en.wikipedia.org/wiki/Anencephalyhttp://en.wikipedia.org/wiki/Dysmeliahttp://en.wikipedia.org/wiki/Cleft_palatehttp://en.wikipedia.org/wiki/Cleft_lip


61/76

(palatoschisis), which can also occur together

as cleft lip and palate are variations of a

type of clefting congenital deformity caused

by abnormal facial development duringgestation. This type of deformity is

sometimes referred to as a cleft. A cleft is a

sub-division in the body's natural structure,

regularly formed before birth. A cleft lip orpalate can be successfully treated with

surgery soon afterbirth. Cleft lips or palates

occur in somewhere between one in 600-800

births.

The term harelip is no longer used to

describe the condition as it is considered

offensive.

Anencephaly is a cephalic disorderthat resultsfrom a neural tube defect that occurs when
http://en.wikipedia.org/wiki/Congenital_deformityhttp://en.wikipedia.org/wiki/Gestationhttp://en.wikipedia.org/wiki/Clefthttp://en.wikipedia.org/wiki/Surgeryhttp://en.wikipedia.org/wiki/Birthhttp://en.wikipedia.org/wiki/Birthhttp://en.wikipedia.org/wiki/Surgeryhttp://en.wikipedia.org/wiki/Clefthttp://en.wikipedia.org/wiki/Gestationhttp://en.wikipedia.org/wiki/Congenital_deformityhttp://en.wikipedia.org/wiki/Cephalic_disorderhttp://en.wikipedia.org/wiki/Neural_tube_defecthttp://en.wikipedia.org/wiki/Neural_tube_defecthttp://en.wikipedia.org/wiki/Cephalic_disorder


62/76

from a neural tube defect that occurs whenthe cephalic (head) end of the neural tubefails to close, usually between the 23rd and26th day ofpregnancy, resulting in the

absence of a major portion of the brain, skull,and scalp. Children with this disorder areborn without a forebrain, the largest part ofthe brain consisting mainly of thecerebral hemispheres (which include theisocortex, which is responsible for higherlevel cognition, i.e., thinking). The remainingbrain tissue is often exposed - not covered bybone or skin.

There is no cure or standard treatment foranencephaly and the prognosis for affected

individuals is poor. Most anencephalic babiesdo not survive birth, accounting for 55% ofnon-aborted cases. If the infant is not stillborn, then he or she will usually die within a fewhours or days after birth from

cardiorespiratory arrest.
http://en.wikipedia.org/wiki/Neural_tube_defecthttp://en.wikipedia.org/wiki/Pregnancyhttp://en.wikipedia.org/wiki/Scalphttp://en.wikipedia.org/wiki/Childrenhttp://en.wikipedia.org/wiki/Forebrainhttp://en.wikipedia.org/wiki/Telencephalonhttp://en.wikipedia.org/wiki/Isocortexhttp://en.wikipedia.org/wiki/Cognitionhttp://en.wikipedia.org/wiki/Stillbirthhttp://en.wikipedia.org/wiki/Stillbirthhttp://en.wikipedia.org/wiki/Cognitionhttp://en.wikipedia.org/wiki/Isocortexhttp://en.wikipedia.org/wiki/Telencephalonhttp://en.wikipedia.org/wiki/Forebrainhttp://en.wikipedia.org/wiki/Childrenhttp://en.wikipedia.org/wiki/Scalphttp://en.wikipedia.org/wiki/Pregnancyhttp://en.wikipedia.org/wiki/Neural_tube_defect


63/76

drug interaction

A drug interaction is a situation in which a substance affects theactivity of a drug, i.e. the effects are increased or decreased, or theyproduce a new effect that neither produces on its own. Typically,interaction between drugs come to mind (drug-drug interaction).However, interactions may also exist between drugs & foods (drug-food interactions), as well as drugs & herbs (drug-herb interactions).

Generally speaking, drug interactions are to be avoided, due to thepossibility of poor or unexpected outcomes. However, druginteractions have been deliberately used, such as co-administeringprobenecid with penicillin prior to mass production of penicillin.Because penicillin was difficult to manufacture, it was worthwhile tofind a way to reduce the amount required. Probenecid retards theexcretion of penicillin, so a dose of penicillin persists longer whentaken with it, and it allowed patients to take less penicillin over acourse of therapy.
http://en.wikipedia.org/wiki/Medicationhttp://en.wikipedia.org/wiki/Probenecidhttp://en.wikipedia.org/wiki/Penicillinhttp://en.wikipedia.org/wiki/Penicillinhttp://en.wikipedia.org/wiki/Probenecidhttp://en.wikipedia.org/wiki/Medication


64/76


65/76

Metabolic drug interactions Many drug interactions are due to alterations in drug metabolism.[1] Further, human

drug-metabolizing enzymes are typically activated through engagement ofnuclear receptors.[1]

One notable system involved in metabolic drug interactions is the enzyme systemcomprising the cytochromeP450oxidases. This system may be affected by eitherenzyme induction or enzyme inhibition, as discussed in the examples below.

Enzyme induction - drug A induces the body to produce more of an enzyme whichmetabolises drug B. This reduces the effective concentration of drug B, which maylead to loss of effectiveness of drug B. Drug A effectiveness is not altered.

Enzyme inhibition - drug A inhibits the production of the enzyme metabolising drug B,thus an elevation of drug B occurs possibly leading to an overdose.

Bioavailability - drug A influences the absorption of drug B. The examples described above may have different outcomes depending on the

nature of the drugs. For example, if Drug B is a prodrug, then enzyme activation is

required for the drug to reach its active form. Hence, enzyme induction by Drug Awould increase the effectiveness of the drug B by increasing its metabolism to itsactive form. Enzyme inhibition by Drug A would decrease the effectiveness of Drug B.

Additionally, Drug A and Drug B may affect each other's metabolism.
http://en.wikipedia.org/wiki/Drug_metabolismhttp://en.wikipedia.org/wiki/Nuclear_receptorhttp://en.wikipedia.org/wiki/Cytochrome_P450_oxidasehttp://en.wikipedia.org/wiki/Cytochrome_P450_oxidasehttp://en.wikipedia.org/wiki/Cytochrome_P450_oxidasehttp://en.wikipedia.org/wiki/Enzyme_induction_and_inhibitionhttp://en.wikipedia.org/wiki/Drug_metabolismhttp://en.wikipedia.org/wiki/Enzyme_induction_and_inhibitionhttp://en.wikipedia.org/wiki/Drug_overdosehttp://en.wikipedia.org/wiki/Bioavailabilityhttp://en.wikipedia.org/wiki/Absorption_(Pharmacokinetics)http://en.wikipedia.org/wiki/Prodrughttp://en.wikipedia.org/wiki/Prodrughttp://en.wikipedia.org/wiki/Absorption_(Pharmacokinetics)http://en.wikipedia.org/wiki/Bioavailabilityhttp://en.wikipedia.org/wiki/Drug_overdosehttp://en.wikipedia.org/wiki/Enzyme_induction_and_inhibitionhttp://en.wikipedia.org/wiki/Drug_metabolismhttp://en.wikipedia.org/wiki/Enzyme_induction_and_inhibitionhttp://en.wikipedia.org/wiki/Cytochrome_P450_oxidasehttp://en.wikipedia.org/wiki/Cytochrome_P450_oxidasehttp://en.wikipedia.org/wiki/Cytochrome_P450_oxidasehttp://en.wikipedia.org/wiki/Nuclear_receptorhttp://en.wikipedia.org/wiki/Drug_metabolism


66/76

Drug tolerance occurs when a subject's

reaction to a psychoactive drug (such as a

painkiller or intoxicant) decreases so that larger

doses are required to achieve the same effect.Drug tolerance can involve both

psychological drug tolerance and physiological

factors.

Tachyphylaxis is a medical term referring to therapid development of drug tolerance.
http://en.wikipedia.org/wiki/Psychoactive_drughttp://en.wikipedia.org/wiki/Psychological_drug_tolerancehttp://en.wikipedia.org/wiki/Physiological_tolerancehttp://en.wikipedia.org/wiki/Physiological_tolerancehttp://en.wikipedia.org/wiki/Psychological_drug_tolerancehttp://en.wikipedia.org/wiki/Psychoactive_drug


67/76

A psychoactive drug orpsychotropic substance is a chemical substance that actsprimarily upon the central nervous system where it alters brain function, resulting intemporary changes in perception, mood, consciousness and behaviour. These drugsmay be used recreationally to purposefully alter one's consciousness, as entheogensfor ritual or spiritual purposes, as a tool for studying or augmenting the mind, ortherapeutically as medication.

Because psychoactive substances bring about subjective changes in consciousnessand mood that the user may find pleasant (e.g. euphoria) or advantageous (e.g.

increased alertness), many psychoactive substances are abused, that is, usedexcessively, despite risks or negative consequences. With sustained use of somesubstances, physical dependence may develop, making the cycle of abuse evenmore difficult to interrupt. Drug rehabilitation can involve a combination ofpsychotherapy, support groups and even other psychoactive substances to break thecycle of dependency.

In part because of this potential for abuse and dependency, the ethics of drug use arethe subject of a continuing philosophical debate. Many governments worldwide have

placed restrictions on drug production and sales in an attempt to decrease drugabuse.
http://en.wikipedia.org/wiki/Chemical_substancehttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Brainhttp://en.wikipedia.org/wiki/Perceptionhttp://en.wikipedia.org/wiki/Mood_(psychology)http://en.wikipedia.org/wiki/Consciousnesshttp://en.wikipedia.org/wiki/Behaviourhttp://en.wikipedia.org/wiki/Recreational_drug_usehttp://en.wikipedia.org/wiki/Consciousnesshttp://en.wikipedia.org/wiki/Entheogenshttp://en.wikipedia.org/wiki/Medicationhttp://en.wikipedia.org/wiki/Substance_abusehttp://en.wikipedia.org/wiki/Physical_dependencehttp://en.wikipedia.org/wiki/Drug_rehabilitationhttp://en.wikipedia.org/wiki/Psychotherapyhttp://en.wikipedia.org/wiki/Psychotherapyhttp://en.wikipedia.org/wiki/Drug_rehabilitationhttp://en.wikipedia.org/wiki/Physical_dependencehttp://en.wikipedia.org/wiki/Substance_abusehttp://en.wikipedia.org/wiki/Medicationhttp://en.wikipedia.org/wiki/Entheogenshttp://en.wikipedia.org/wiki/Consciousnesshttp://en.wikipedia.org/wiki/Recreational_drug_usehttp://en.wikipedia.org/wiki/Behaviourhttp://en.wikipedia.org/wiki/Consciousnesshttp://en.wikipedia.org/wiki/Mood_(psychology)http://en.wikipedia.org/wiki/Perceptionhttp://en.wikipedia.org/wiki/Brainhttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Chemical_substance


68/76

Uses of psychoactive substances

Psychoactive substances are used by humans for a number of different purposes. These uses vary widely between cultures. Some substances may have controlled or i llegal uses while others may have shamanic purposes, and stillothers are used medicinally. Other examples would be social drinking or sleep aids. Caffeine is the world's most widely consumed psychoactive substance, but unlike many others, it is legal and unregulated in nearly all jurisdictions. InNorth America, 90% of adults consume caffeine daily.[6]

[edit] Anesthesia

Main article:Anesthesia General anestheticsare a class of psychoactive drug used on patients to block pain and other sensations. Most anesthetics induce unconsciousness, which allows patients to undergo medical procedures like surgerywithout physical

pain or emotional trauma.[7] To induce unconsciousness, anesthetics affect the GABAandNMDAsystems. For example, halothaneis a GABA agonist,[8]andketamineis an NMDA receptor antagonist.[9]

[edit] Painkillers

Main article:Analgesics Aspirin

Psychoactive drugs are often prescribed to manage pain. As the subjective experience of pain is regulated by endorphins , neurochemicals that are endogenousopioids, pain can be managed using psychoactives that operate on thisneurotransmitter system. This class of drugs includesnarcotics, like morphineandcodeine,[10]and also NSAIDs(which don't affect endorphins) such as aspirinandibuprofen.

[edit] Psychiatric medications

Main article: Psychiatric medications

Zoloft, anantidepressant(and anti-anxiety) medication

Psychiatric medications are prescribed for the management ofmental and emotional disorders. There are 6 major classes of psychiatric medications:

Antidepressants, which are used to treat disparate disorders such as clinical depression,dysthymia,anxiety,eating disordersandborderline personality disorder.[11] Stimulants, which are used to treat disorders such asattention deficit disorderand narcolepsyand to suppress the appetite.

Antipsychotics, which are used to treat psychoses,schizophreniaandmania.

Mood stabilizers, which are used to treatbipolar disorderand schizoaffective disorder.

Anxiolytics, which are used to treat anxiety disorders.

Depressants, which are used as hypnotics, sedatives, and anesthetics.

[edit] Recreational drugs

Main article: Recreational drug use Many psychoactive substances are used for their mood and perception altering effects, including those with accepted uses in medicine and psychiatry. Classes of drugs frequently used recreationally include:

Stimulants, which elevate thecentral nervous system. These are used recreationally for theireuphoriceffects.

Hallucinogens(psychedelics, dissociatives and deliriants), which induce perceptual and cognitive distortions.

Hypnotics, which are used recreationally because they induce inebriation.

Analgesics, which are used recreationally because of theireuphoriceffects.

Inhalants, in the forms of gas aerosols, or solvents, which are inhaled as a vapor because of their stupefying effects. Many inhalants also fall into the above categories (such as Nitrous Oxide which is also an anelgesic)

Examples include caffeine,alcohol,cocaine, LSD, and cannabis.[12]

In some sub-cultures, drug usage is seen as astatus symbol. Recreational drugs are seen as status symbols at events such as at nightclubsand parties.[13] This is true of many cultures throughout history; drugs have been viewed asstatus symbols since ancient times. For example, in ancient Egypt, gods were commonly pictured holding hallucinogenic plants.[14]

Because there is controversy about regulation of recreational drugs, there is an ongoing debate about drug prohibition. Critics of prohibition believe that regulation of recreational drug use is a violation of personalautonomyandfreedom.

[15]In the United States, critics have noted that prohibition or regulation of recreational and spiritual drug use might be unconstitutional.[16] [edit] Ritual and spiritual use

Timothy Learywas a leading proponent of spiritual hallucinogen use.

Main article: Entheogens Certain psychoactives, particularly hallucinogens, have been used for religious purposes since prehistoric times. Native Americans have usedmescaline-containingpeyotecacti for religious ceremonies for as long as 5700 years.[17]The

muscimol-containingAmanita muscariamushroom was used for ritual purposes throughout prehistoric Europe.[18]Various other hallucinogens, includingjimsonweed,psilocybin mushrooms, andcannabishave been used in religiousceremonies for centuries.[19]

The use of entheogens for religious purposes resurfaced in the West during the counterculture movementsof the 1960s and 70s. Under t he leadership ofTimothy Leary, new religious movements began to use LSDand otherhallucinogens as sacraments.[20] In the United States, the use of peyote for ritual purposes is protected only for members of the Native American Church, which is allowed to cultivate and distributepeyote. However, the genuinereligious use of Peyote, regardless of one's personal ancestry, is protected in Colorado, Arizona, New Mexico, Nevada, and Oregon.[21]

[edit]
http://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=3http://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=3http://en.wikipedia.org/wiki/Anesthesiahttp://en.wikipedia.org/wiki/Anesthesiahttp://en.wikipedia.org/wiki/General_anaesthetichttp://en.wikipedia.org/wiki/General_anaesthetichttp://en.wikipedia.org/wiki/Surgeryhttp://en.wikipedia.org/wiki/Surgeryhttp://en.wikipedia.org/wiki/GABAhttp://en.wikipedia.org/wiki/GABAhttp://en.wikipedia.org/wiki/NMDAhttp://en.wikipedia.org/wiki/NMDAhttp://en.wikipedia.org/wiki/NMDAhttp://en.wikipedia.org/wiki/Halothanehttp://en.wikipedia.org/wiki/Halothanehttp://en.wikipedia.org/wiki/Ketaminehttp://en.wikipedia.org/wiki/Ketaminehttp://en.wikipedia.org/wiki/Ketaminehttp://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=4http://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=4http://en.wikipedia.org/wiki/Analgesicshttp://en.wikipedia.org/wiki/Analgesicshttp://en.wikipedia.org/wiki/Pain_managementhttp://en.wikipedia.org/wiki/Endorphinshttp://en.wikipedia.org/wiki/Endorphinshttp://en.wikipedia.org/wiki/Endogenoushttp://en.wikipedia.org/wiki/Opioidshttp://en.wikipedia.org/wiki/Opioidshttp://en.wikipedia.org/wiki/Opioidshttp://en.wikipedia.org/wiki/Narcoticshttp://en.wikipedia.org/wiki/Narcoticshttp://en.wikipedia.org/wiki/Narcoticshttp://en.wikipedia.org/wiki/Morphinehttp://en.wikipedia.org/wiki/Morphinehttp://en.wikipedia.org/wiki/Codeinehttp://en.wikipedia.org/wiki/Codeinehttp://en.wikipedia.org/wiki/NSAIDhttp://en.wikipedia.org/wiki/NSAIDhttp://en.wikipedia.org/wiki/Aspirinhttp://en.wikipedia.org/wiki/Aspirinhttp://en.wikipedia.org/wiki/Ibuprofenhttp://en.wikipedia.org/wiki/Ibuprofenhttp://en.wikipedia.org/wiki/Ibuprofenhttp://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=5http://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=5http://en.wikipedia.org/wiki/Psychiatric_medicationshttp://en.wikipedia.org/wiki/Antidepressanthttp://en.wikipedia.org/wiki/Antidepressanthttp://en.wikipedia.org/wiki/Antidepressanthttp://en.wikipedia.org/wiki/Mental_disordershttp://en.wikipedia.org/wiki/Mental_disordershttp://en.wikipedia.org/wiki/Antidepressantshttp://en.wikipedia.org/wiki/Clinical_depressionhttp://en.wikipedia.org/wiki/Clinical_depressionhttp://en.wikipedia.org/wiki/Dysthymiahttp://en.wikipedia.org/wiki/Dysthymiahttp://en.wikipedia.org/wiki/Dysthymiahttp://en.wikipedia.org/wiki/Anxietyhttp://en.wikipedia.org/wiki/Anxietyhttp://en.wikipedia.org/wiki/Anxietyhttp://en.wikipedia.org/wiki/Eating_disordershttp://en.wikipedia.org/wiki/Eating_disordershttp://en.wikipedia.org/wiki/Eating_disordershttp://en.wikipedia.org/wiki/Borderline_personality_disorderhttp://en.wikipedia.org/wiki/Borderline_personality_disorderhttp://en.wikipedia.org/wiki/Borderline_personality_disorderhttp://en.wikipedia.org/wiki/Stimulantshttp://en.wikipedia.org/wiki/Stimulantshttp://en.wikipedia.org/wiki/Attention_deficit_disorderhttp://en.wikipedia.org/wiki/Attention_deficit_disorderhttp://en.wikipedia.org/wiki/Attention_deficit_disorderhttp://en.wikipedia.org/wiki/Narcolepsyhttp://en.wikipedia.org/wiki/Narcolepsyhttp://en.wikipedia.org/wiki/Anoretichttp://en.wikipedia.org/wiki/Anoretichttp://en.wikipedia.org/wiki/Antipsychoticshttp://en.wikipedia.org/wiki/Antipsychoticshttp://en.wikipedia.org/wiki/Psychoseshttp://en.wikipedia.org/wiki/Schizophreniahttp://en.wikipedia.org/wiki/Schizophreniahttp://en.wikipedia.org/wiki/Schizophreniahttp://en.wikipedia.org/wiki/Maniahttp://en.wikipedia.org/wiki/Maniahttp://en.wikipedia.org/wiki/Maniahttp://en.wikipedia.org/wiki/Mood_stabilizershttp://en.wikipedia.org/wiki/Mood_stabilizershttp://en.wikipedia.org/wiki/Bipolar_disorderhttp://en.wikipedia.org/wiki/Bipolar_disorderhttp://en.wikipedia.org/wiki/Bipolar_disorderhttp://en.wikipedia.org/wiki/Schizoaffective_disorderhttp://en.wikipedia.org/wiki/Schizoaffective_disorderhttp://en.wikipedia.org/wiki/Anxiolyticshttp://en.wikipedia.org/wiki/Anxiolyticshttp://en.wikipedia.org/wiki/Anxiety_disorderhttp://en.wikipedia.org/wiki/Depressantshttp://en.wikipedia.org/wiki/Depressantshttp://en.wikipedia.org/wiki/Hypnoticshttp://en.wikipedia.org/wiki/Sedativehttp://en.wikipedia.org/wiki/Sedativehttp://en.wikipedia.org/wiki/Anesthetichttp://en.wikipedia.org/wiki/Anesthetichttp://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=6http://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=6http://en.wikipedia.org/wiki/Recreational_drug_usehttp://en.wikipedia.org/wiki/Stimulantshttp://en.wikipedia.org/wiki/Stimulantshttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Euphoria_(emotion)http://en.wikipedia.org/wiki/Euphoria_(emotion)http://en.wikipedia.org/wiki/Hallucinogenshttp://en.wikipedia.org/wiki/Hallucinogenshttp://en.wikipedia.org/wiki/Hypnoticshttp://en.wikipedia.org/wiki/Hypnoticshttp://en.wikipedia.org/wiki/Inebriationhttp://en.wikipedia.org/wiki/Inebriationhttp://en.wikipedia.org/wiki/Analgesicshttp://en.wikipedia.org/wiki/Analgesicshttp://en.wikipedia.org/wiki/Euphoria_(emotion)http://en.wikipedia.org/wiki/Euphoria_(emotion)http://en.wikipedia.org/wiki/Euphoria_(emotion)http://en.wikipedia.org/wiki/Inhalanthttp://en.wikipedia.org/wiki/Inhalanthttp://en.wikipedia.org/wiki/Caffeinehttp://en.wikipedia.org/wiki/Caffeinehttp://en.wikipedia.org/wiki/Alcoholic_beveragehttp://en.wikipedia.org/wiki/Alcoholic_beveragehttp://en.wikipedia.org/wiki/Cocainehttp://en.wikipedia.org/wiki/Cocainehttp://en.wikipedia.org/wiki/LSDhttp://en.wikipedia.org/wiki/LSDhttp://en.wikipedia.org/wiki/Cannabishttp://en.wikipedia.org/wiki/Social_statushttp://en.wikipedia.org/wiki/Social_statushttp://en.wikipedia.org/wiki/Nightclubshttp://en.wikipedia.org/wiki/Nightclubshttp://en.wikipedia.org/wiki/Ancient_Egypthttp://en.wikipedia.org/wiki/Ancient_Egypthttp://en.wikipedia.org/wiki/Arguments_for_and_against_drug_prohibitionhttp://en.wikipedia.org/wiki/Arguments_for_and_against_drug_prohibitionhttp://en.wikipedia.org/wiki/Autonomyhttp://en.wikipedia.org/wiki/Autonomyhttp://en.wikipedia.org/wiki/Autonomyhttp://en.wikipedia.org/wiki/Libertyhttp://en.wikipedia.org/wiki/Libertyhttp://en.wikipedia.org/wiki/Libertyhttp://en.wikipedia.org/wiki/Unconstitutionalhttp://en.wikipedia.org/wiki/Unconstitutionalhttp://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=7http://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=7http://en.wikipedia.org/wiki/Timothy_Learyhttp://en.wikipedia.org/wiki/Timothy_Learyhttp://en.wikipedia.org/wiki/Entheogenshttp://en.wikipedia.org/wiki/Mescalinehttp://en.wikipedia.org/wiki/Mescalinehttp://en.wikipedia.org/wiki/Mescalinehttp://en.wikipedia.org/wiki/Peyotehttp://en.wikipedia.org/wiki/Peyotehttp://en.wikipedia.org/wiki/Peyotehttp://en.wikipedia.org/wiki/Muscimolhttp://en.wikipedia.org/wiki/Muscimolhttp://en.wikipedia.org/wiki/Amanita_muscariahttp://en.wikipedia.org/wiki/Amanita_muscariahttp://en.wikipedia.org/wiki/Amanita_muscariahttp://en.wikipedia.org/wiki/Datura_stramoniumhttp://en.wikipedia.org/wiki/Datura_stramoniumhttp://en.wikipedia.org/wiki/Datura_stramoniumhttp://en.wikipedia.org/wiki/Psilocybin_mushroomhttp://en.wikipedia.org/wiki/Psilocybin_mushroomhttp://en.wikipedia.org/wiki/Cannabis_(drug)http://en.wikipedia.org/wiki/Cannabis_(drug)http://en.wikipedia.org/wiki/Cannabis_(drug)http://en.wikipedia.org/wiki/Counterculture_of_the_1960shttp://en.wikipedia.org/wiki/Counterculture_of_the_1960shttp://en.wikipedia.org/wiki/Timothy_Learyhttp://en.wikipedia.org/wiki/Timothy_Learyhttp://en.wikipedia.org/wiki/Timothy_Learyhttp://en.wikipedia.org/wiki/LSDhttp://en.wikipedia.org/wiki/LSDhttp://en.wikipedia.org/wiki/Sacramenthttp://en.wikipedia.org/wiki/Sacramenthttp://en.wikipedia.org/wiki/Native_American_Churchhttp://en.wikipedia.org/wiki/Native_American_Churchhttp://en.wikipedia.org/wiki/Peyotehttp://en.wikipedia.org/wiki/Peyotehttp://en.wikipedia.org/wiki/Peyotehttp://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=8http://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=8http://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=8http://en.wikipedia.org/wiki/Peyotehttp://en.wikipedia.org/wiki/Native_American_Churchhttp://en.wikipedia.org/wiki/Sacramenthttp://en.wikipedia.org/wiki/LSDhttp://en.wikipedia.org/wiki/Timothy_Learyhttp://en.wikipedia.org/wiki/Counterculture_of_the_1960shttp://en.wikipedia.org/wiki/Cannabis_(drug)http://en.wikipedia.org/wiki/Psilocybin_mushroomhttp://en.wikipedia.org/wiki/Datura_stramoniumhttp://en.wikipedia.org/wiki/Amanita_muscariahttp://en.wikipedia.org/wiki/Amanita_muscariahttp://en.wikipedia.org/wiki/Muscimolhttp://en.wikipedia.org/wiki/Peyotehttp://en.wikipedia.org/wiki/Mescalinehttp://en.wikipedia.org/wiki/Entheogenshttp://en.wikipedia.org/wiki/Timothy_Learyhttp://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=7http://en.wikipedia.org/wiki/Unconstitutionalhttp://en.wikipedia.org/wiki/Libertyhttp://en.wikipedia.org/wiki/Autonomyhttp://en.wikipedia.org/wiki/Arguments_for_and_against_drug_prohibitionhttp://en.wikipedia.org/wiki/Ancient_Egypthttp://en.wikipedia.org/wiki/Nightclubshttp://en.wikipedia.org/wiki/Social_statushttp://en.wikipedia.org/wiki/Cannabishttp://en.wikipedia.org/wiki/LSDhttp://en.wikipedia.org/wiki/Cocainehttp://en.wikipedia.org/wiki/Alcoholic_beveragehttp://en.wikipedia.org/wiki/Caffeinehttp://en.wikipedia.org/wiki/Inhalanthttp://en.wikipedia.org/wiki/Euphoria_(emotion)http://en.wikipedia.org/wiki/Analgesicshttp://en.wikipedia.org/wiki/Inebriationhttp://en.wikipedia.org/wiki/Hypnoticshttp://en.wikipedia.org/wiki/Hallucinogenshttp://en.wikipedia.org/wiki/Euphoria_(emotion)http://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Stimulantshttp://en.wikipedia.org/wiki/Recreational_drug_usehttp://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=6http://en.wikipedia.org/wiki/Anesthetichttp://en.wikipedia.org/wiki/Sedativehttp://en.wikipedia.org/wiki/Hypnoticshttp://en.wikipedia.org/wiki/Depressantshttp://en.wikipedia.org/wiki/Anxiety_disorderhttp://en.wikipedia.org/wiki/Anxiolyticshttp://en.wikipedia.org/wiki/Schizoaffective_disorderhttp://en.wikipedia.org/wiki/Bipolar_disorderhttp://en.wikipedia.org/wiki/Mood_stabilizershttp://en.wikipedia.org/wiki/Maniahttp://en.wikipedia.org/wiki/Schizophreniahttp://en.wikipedia.org/wiki/Psychoseshttp://en.wikipedia.org/wiki/Antipsychoticshttp://en.wikipedia.org/wiki/Anoretichttp://en.wikipedia.org/wiki/Narcolepsyhttp://en.wikipedia.org/wiki/Attention_deficit_disorderhttp://en.wikipedia.org/wiki/Stimulantshttp://en.wikipedia.org/wiki/Borderline_personality_disorderhttp://en.wikipedia.org/wiki/Eating_disordershttp://en.wikipedia.org/wiki/Anxietyhttp://en.wikipedia.org/wiki/Dysthymiahttp://en.wikipedia.org/wiki/Clinical_depressionhttp://en.wikipedia.org/wiki/Antidepressantshttp://en.wikipedia.org/wiki/Mental_disordershttp://en.wikipedia.org/wiki/Antidepressanthttp://en.wikipedia.org/wiki/Psychiatric_medicationshttp://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=5http://en.wikipedia.org/wiki/Ibuprofenhttp://en.wikipedia.org/wiki/Aspirinhttp://en.wikipedia.org/wiki/NSAIDhttp://en.wikipedia.org/wiki/Codeinehttp://en.wikipedia.org/wiki/Morphinehttp://en.wikipedia.org/wiki/Narcoticshttp://en.wikipedia.org/wiki/Opioidshttp://en.wikipedia.org/wiki/Endogenoushttp://en.wikipedia.org/wiki/Endorphinshttp://en.wikipedia.org/wiki/Pain_managementhttp://en.wikipedia.org/wiki/Analgesicshttp://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=4http://en.wikipedia.org/wiki/Ketaminehttp://en.wikipedia.org/wiki/Halothanehttp://en.wikipedia.org/wiki/NMDAhttp://en.wikipedia.org/wiki/GABAhttp://en.wikipedia.org/wiki/Surgeryhttp://en.wikipedia.org/wiki/General_anaesthetichttp://en.wikipedia.org/wiki/Anesthesiahttp://en.wikipedia.org/w/index.php?title=Psychoactive_drug&action=edit&section=3


69/76

Administration For a substance to be psychoactive, it must cross the

blood-brain barrierso it can affect neurochemical function.Psychoactive drugs are administered in several different ways. Inmedicine, most psychiatric drugs, such as fluoxetine, quetiapine,and lorazepam are ingested orally in tablet orcapsule form.

However, certain medical psychoactives are administered viainhalation, injection, or rectal suppository/enema. Recreationaldrugs can be administered in several additional ways that are notcommon in medicine. Certain drugs, such as alcohol and caffeine,are ing

pharmacology l 2

Documents