Nov 28, 2010

Anesthetic Agents & Anesthesia

  • Anesthesia is the loss of sensation by giving anesthetic agents.
  • Agents which cause the loss of sensation are called as anesthetic agents.
These are of two types;
  • These cause loss of sensation but animal is conscious.
  • These cause loss of sensation due to unconsciousness.
Objectives of Anesthesia
  • Sensory block to have analgesia. In this, sensory stimuli from the periphery are blocked.
  • Mental block to have hypnosis or Amnesia (animal know nothing, what is happening around). Activity of CNS is blocked.
  • Motor block to have muscle relaxation
  • Reflex block to have hyporeflexia
  • In case of local anesthetics, only one purpose is not the case of interest which is the mental block.
Stages of Anesthesia
  • Based on ether anesthesia, there are following stages of anesthesia;
  • Excitement stage (voluntary movements occur)
  • Delirium stage (involuntary movements occur)
  • Surgical Stage
  • Medullary paralysis
There are 3 stages of anesthesia;
  • Induction
  • Maintenance
  • Recovery
Ideal Properties of Anesthetic Agent
  • It should cause rapid & smooth induction and recovery.
  • It should be easy to maintain anesthesia (light or deep).
  • It should be non-toxic and safe to internal organs.
  • It should be non-irritant.
  • It should be non-inflammable and non-explosive.
  • Myocardial sensitization to epinephrine should be least.
  • It should be compatible with other drugs.
  • It should be easily available, cheap and easy to administer.
Pre-anesthetic Agents
These are the drugs given before anesthesia.
Why to give?
  • To reduce anxiety of patient
  • To reduce the amount of anesthetic agent
  • To reduce the adverse effects of anesthetic agent
  • To reduce the toxicity problems
  • To reduce secretions especially Bronchial & Salivary
  • To increase analgesia
  • Opiods (Morphine, Mepridine) which induce analgesia
  • Tranquilizers (Xylazine, Acepromazine) which reduce anxiety
  • Anticholinergic drugs (Atropine sulphate, scopolamine) which reduce secretions
  • Muscle relaxants (Gallamine, Pancuronium, d-tubocurarine, succinylcholine)
Medication during Anesthesia
  • To reduce Blood pressure
  • To induce muscle relaxation
  • To stop bleeding
Post-Anesthetic Medication
  • Analgesics
  • Anti-inflammatory
  • Anti-microbial
  • Cholinergic drugs to relieve retention of urine E.g. Bethanicol

Nov 27, 2010

Introduction to Pharmacology of CNS

CNS consists of two main organs;
  • Brain
  • Spinal Cord
  • This is the information superhighway of the body. It carries information up to the brain and instructions back down.
It consists of following parts;
  • Mostly deals with movement. It regulates and coordinates movement, posture and balance. Also involved in learning movement
  • The cerebrum or cortex is the largest part of the human brain, associated with higher brain function such as thought and action.
  • Midbrain/ Mesencephalon- the rostral part of the brain stem, which includes the tectum and tegmentum
  • It is involved in functions such as vision, hearing, eyemovement, and body movement.
Types of Drugs in CNS
  • In CNS, synapses are the main junctions at the neuronal terminals.
  • Drugs are based on the type of neurotransmitters which are of 2 types;
  • Excitatory
  • Inhibitory
  • Drugs stimulating the excitatory neurotransmitters are called stimulants. E.g. Ach, Dopamine, epinephrine and nor-epinephrine.
  • Drugs stimulating inhibitory neurotransmitters are called depressants. E.g. GABA (gamma amino butyric acid)(Brain), Glycine (spinal cord).
  • Depressants are mainly used in human practice.
Stages of Stimulation
Stages of Depression
There is slight depression but animal is awake.
Animal is greatly depressed and seems to be asleep but can be awakened.
Slight Depression but animal behaves abnormally to external stimuli.
There is greater depression and animal is asleep and can be awakened but will again sleep. There is good analgesia.
Animal is under greater depression and asleep but cannot be awakened. There is hyporeflexia.
Dissociative Anesthetics
Animal is superficially anesthetized and there is myotonia (movement in muscles).
There is analgesia but reflexes are present.
Basal Anesthetics
This anesthesia is maintained by other agents.

Adrenergic Blocking Agents...Pharmacology

  • Adrenergic blocking agents are drugs that selectively inhibit specific receptor sites from sympathetic stimulation.
  • Blocking agents may interact with specific alpha and beta receptors. The release of nor-epinephrine from storage sites may be blocked.
Types of Adrenergic Blocking Agents
Adrenergic blocking agents are of two types;
  • α-Blockers
  • β-Blockers
  • Phenoxybenzamine is the prototype drug which blocks α-1 and α-2 receptors.
  • Phentolamine, Tolezoline…… blocks α-1 and α-2 receptors
  • Przosine, Doxazosine, Terazosine….. Blocks α-1 receptors
  • Atipamazole…. blocks α-2 receptors
  • Propranalol is the prototype drug which blocks both types of beta receptors.
  • Timolol, Ndolol, Pindolol also block the both types of beta receptors.
  • Atinilol, Esmalol blocks beta-1 receptors.
  • Butamoxine blocks beta-2 receptors.
  • Labetalol, Carvedalol block both alpha & beta receptors.
Therapeutic Uses
  • Phenoxybenzamine blocks α-1 and α-2 receptors by making covalent bond, It is irreversible inhibition.
  • Other alpha blockers are reversible inhibitors.
  • For hypertension, these drugs are used.
  • Orthostatic Hypotension…In standing condition, hypotension occurs due to these drugs. So, initial dose should be given before bed.
  • Pheochromocytoma….Tumor of chromafin cells in adrenal glands, so, adrenaline quantity increased and Blood pressure remains constantly high. To diagnose it, phenoxybenze is used which will lower the blood pressure.
  • To remove the toxicity of α-2 agonists, alpha-2 antagonists are used.
  • These are used as anti-hypertensive drugs. E.g. propranalol
  • Timolol is used to treat glaucoma by decreasing the intraocular pressure.

Adrenergic Drugs..Pharmacology

  • Sympathomimetic drugs are substances that mimic the effects of the sympathetic nervous system, such as catecholamines, epinephrine (adrenaline), norepinephrine (noradrenaline), dopamine, etc. Such drugs are used to treat cardiac arrest and low blood pressure, or even delay premature labor, among other things.
  • These drugs act at the postganglionic sympathetic terminal, by directly activating postsynaptic receptors, blocking breakdown and reuptake, or stimulating production and release of catecholamines.
There are two types of adrenergic drugs.
  • Direct Acting Drugs
  • Indirect Acting Drugs
Direct Acting Drugs
These are of two types
Natural compounds (catecholamines)
These include;
  • Epinephrine
  • Nor-epinephrine
  • Dopamine
  • If these catecholamines are released from nerve fibers, these are called neurotransmitters.
  • If released from glands, these are called as hormones.
  • If released from the outside, these are called as drugs.
Synthetic Compounds
These are of further two types;
These stimulate α receptors. These include;
  • Phenylephrine, Methoxyline (stimulate α-1 receptors)
  • Clonidine, Detomedine, Xylezene (stimulate α-2 receptors)
  • Isoprotalenol (stimulate β-1 & β-2 receptors)
  • Dobutamine (stimulate β-1 receptors)
  • Terbutalin, Sulbutamol, Clenbutarol (stimulate β-2 receptors)
Indirect Acting Drugs
  • These increase level of nor-epinephrine on receptors. These stop removal of nor-Epinephrine by stopping re uptake or by increasing the release of nor-epinephrine from the storage vesicles. These are divided into 3 categories;
  • These enhance release of Nor-epinephrine from the endings. These include Tyramine, Amphetamine and Ephedrine (mixed).
Uptake Inhibitors
  • These drugs block and reverse the activity of nor-epinephrine transporter (NET). NET is a transport protein present on surface of some cells that clears adrenaline and nor-adrenaline from the extracellular space and into the cells, thus terminating the signaling effect.
  • These drugs include cocaine, Triphenylamine.
MAO Inhibitors (MAOI)
  • Adrenaline and nor-adrenaline are metabolized by the enzyme monoamine oxidase. These drugs inhibit the activity of this enzyme, thus producing sympathomimetic effects.
  • These drugs include Isocarboxazid, Phenelzine, Iproclozide, Procarbazine, Hydralazine and Phenoxypropazine.
Prototype Drug
Prototype drug in adrenergic drugs is;
  • Adrenaline b/c it stimulates all four types of receptors.
  • Nor-adrenaline cannot stimulate β-2 receptors.
  • Others stimulate only 1 or 2 receptors.
Therapeutic Uses
  • Asthma can be treated by β-2 agonists.
  • Cardiac arrest can be treated by β-1 agonists.
  • Retention of Urine
  • To decrease the intestinal motility
  • Vasoconstriction to increase blood flow and treat nasal congestion
  • Spray of α-1 agonist during surgery to decrease bleeding from small blood vessels
  • To enhance the duration of action of local anesthetics, adrenaline is used which decrease the absorption of anesthetic by causing vasoconstriction.
  • Cocaine is used as local anesthetic but vasoconstrictor is not used along with it b/c it is itself a vasoconstrictor.
  • Stimulate CNS E.g. Cocaine
  • Some used in allergic reactions
  • Some used to delay the labor condition of uterus near parturition to manage the delivery at proper time.
  • Glycogenolysis and gluconeogenesis are increased by stimulation of β-receptors in liver, muscles and adipose tissue.

Adrenergic Receptors..Pharmacology

Two types of receptor sites are theorized to explain adrenergic effects.
  • Alpha-receptors are associated mainly with increased contractibility of vascular smooth muscle and intestinal relaxation.
  • The alpha1 is located at postsynaptic effector sites to stimulate transmitter release in smooth muscle. For example, the smooth muscle of peripheral blood vessels is contracted in alpha1 stimulation.
  • The alpha2 receptor site is located presynaptic on axon terminals to inhibit the release of nor-epinephrine (the transmitter). The effects of alpha2 stimulation results in relaxation of the intestinal tract--motility and tone are decreased.
  • Beta-receptors are associated with vasodilation and relaxation of nonintestinal smooth muscle and cardiac stimulation.
  • Beta1 Stimulation of beta1 receptor sites results in cardiac stimulation and lipolysis.
  • Beta2 Stimulation of beta2 receptor sites causes bronchodilation, relaxation of blood vessels (usually in skeletal muscles), and muscle glycogenolysis.
Alpha Receptor Site: Important features of the site include in order of importance:
  • An anionic site - which binds the positive ammonium group.
  • One hydrogen bonding area
  • A flat area non-polar area for the aromatic ring.
Beta Receptor Site: Important features of the site include in order of importance - also see the graphic on the left:
  • An anionic site - shown as Asp anionic negative acid group which binds the positive ammonium group.
  • Two hydrogen bonding areas - shown as two Serine with alcohol (OH) groups hydrogen bonding to the phenol OH groups of the NE.
  • A flat area non-polar area for the aromatic ring.
  Receptor Subtype
NE, EP, dobutamine, xamoterol
atenolol, metoprolol.
 Adipose tissue
  beta1, beta 3?

Vascular Smooth Muscle
 beta 2
 EP, salbutamol, terbutaline, salmeterol
Airway Smooth Muscle
  beta 2
 terbutaline, salbutamol, salmeterol and zinterol,
 Smooth muscle contraction
 alpha 1
 NE, EP, phenylephrine, oxymetazoline)
prazosin, doxazocin
 Inhibition of
transmitter release Hypotension, anaesthesia, Vasoconstriction
 alpha 2
clenbuterol, alpha-methylnoradrenaline, dexmedetomidine, and mivazerol, clonidine, clenbuterol
yohimbine, idazoxan, atipamezole, efaroxan, and rauwolscine

Receptor Sites
 vasodilation (b2)
 iris dilation
 cardioacceleration (b1)
 intestinal relaxation
 intestinal relaxation (b2)
 intestinal sphincter
 uterus relaxation(b2)
 bladder sphincter contraction
 bronchodilation (b2)

Nov 26, 2010

Family Oestridae..Genus Oestrus (Nasal Bot Flies)

  • Larvae of these flies spend most of their time in the nasal passage of sheep & Goat. So called nasal bots
  • Adult flies are having short life span (1 week) whereas larvae having 1 year or more of life span.
  • Adult flies are 1cm in size and of grey color.
  • Small dark spots are present on the abdomen with a covering of short brown hair.
  • Size of Larvae is 3cm and color is yellowish white. Larva is tapering anteriorly with prominent step posteriorly.
  • Body is segmented having dark transverse bands dorsally (each segment).
Nasal Bot fly injecting larvae
Life Cycle
  • Adult female is viviparous and produce larvae.
  • Sheep become infected by squirting of jet of liquid containing larvae.
  • During the flight, fly deliver 25 larvae.
  • Newly emerged larva is 1mm in length.
  • Larva migrates from nasal passage to frontal sinuses.
  • Larva feed on mucous secreted by movement of larva.
  • In the nasal passage, larva mould to L2.
  • In the frontal sinuses, larva completes their development and then migrates to nostrils where they are active throughout the year.
  • Become dormant in winter season if temperature is below 18.
  • From the nostrils, L3 larvae fall on the ground and from larva, pupa develops.
  • From the pupa, adult emerges. Adult having very short life span
  • Survive for only 1 week and during this period, produce about 500 larvae.
Pathogenic effects
  • Itching and Irritation
  • Rubbing the nostrils against hard objects
  • Nasal discharge which later on becomes mucopurulent
  • In coordination, convulsions
  • Also called false gid (signs resembling coenurus cerebralis)
  • Cause swelling of eyes in human called as keratoconjunctivitis and inflammation of lips called stomatitis
  • Loss of weight
  • Refoxanide, Ranide…. 1ml/25kg BW subcutaneously
  • Nitroxynil, Trodex….1ml/20kg BW subcutaneously
  • Ivermectin………….1ml/50kg BW subcutaneously
Regular use of insecticidal drugs should be followed.

Family Oestridae..Genus Hypoderma (Warble Flies)

These are hairy flies.
Adult flies having primitive and non-functional mouth parts.
Adult life span is short.
Larva having functional mouth parts and long life span
There are 3 important generas;
  • Hypoderma
  • Oestrus
  • Gaterophilus
Genus Hypoderma
  • Also called warble flies
  • Cause great economic losses
  • Affect cattle, buffalo, sheep, goat, equines and sometimes human beings.
  • These flies are present mainly in lower Punjab areas.
  • Species include;
  • H. Bovis
  • H. Liniatum
  • These flies resemble honey bees.
  • Have one pair of wings, Yellow orange abdomen having yellow orange hair with a broad band of black hair in middle.
  • Larva size is 2.5-3cm and color is dirty white when emerges but becomes dark brown later on.
  • Larva is barrel shaped and segmented body. Each segment bears spines.
  • Larva is tapering interiorly and color of pupa is black.
Life cycle
  • Adult flies are active during warm month of the year and lay eggs.
  • Egg attaches to the lower region of the leg having hairs. H.Bovis has single eggs but H.Liniatum eggs are in a row of 6. Eggs of H.Bovis are above hock region and that of H.Liniatum are below hock region.
  • Egg hatch and larva develop (L1). Size of L1 larva is 1mm. L1 crawl down the Hair, Penetrate Hair follicles and reaches the Diaphragm region. This migration is aided by paired mouth hooks and secretion of proteolytic enzymes.
  • From the diaphragm, L1 move toward resting site during autumn. Resting site of H.Bovis is epidural fat of spinal canal and that of H.Liniatum is sub mucosa of esophagus.
  • They spend winter over there.
  • With the onset of spring season, L1 mould to L2 and become active and move toward skin of back.
  • With the onset of summer season, L2 mould to L3. L3 can be seen under the skin. These come out of the skin and fall on the ground. They move in the soil for some time.
  • From the larva, pupa and from the pupa, adult emerges.
  • Adult copulate, female lay eggs and then die within 1-2 weeks.
Pathogenic Effects
  • Creates disturbance and cause restlessness for the animals and human beings due to buzzing noise
  • Greenish yellow gelatinous mass is formed on the damaged skin of back and it is called as Butcher Jelly.
  • Due to buzzing noise, meat production is reduced and also milk production.
Treatment & Control
  • Ivermectin…. Ivotec, Ivomec (1ml/50kg B.W subcutaneously)
  • Use insecticides;
  • Organo Chlorine…… DDT, hexachlorocyclohexane/ benzene hexachloride
  • Organic phosphate…. Trichlorofen, neguvan, cumafex, neocidal, diazinon and asuntal
  • Synthetic pyrethroid...Cypermethrine and Ecoflee
  • Carbamates
  • To treat toxicity, Atropine sulphate is used.

Family Muscidae..Genus Glossina (TseTse Flies)

  • Also called TseTse flies
  • Some classify it in family muscidae and some in Glossinidae family.
  • It is found in Africa on more than 10 million kilometer area.
  • It is important vector of many Human & Animal diseases.
  • Adult flies are long, narrow and yellow to dark brown in color.
  • Size is 6-15mm and mouth is projecting forward.
  • Wings held over the abdomen like a pair of close scissors when at rest.
  • Mouth parts are composed of U-shaped Labium with rasp labella which lie at the terminal region of Labium and upper sharp labrum.
  • B/W Labium and Labrum, Hypopharynx is present which carries salivary duct and delivers anticoagulant to Host tissue.
  • In the center of the wings, there lies hatchet or cleaver.
Life Cycle
  • Female is viviparous and produce 8-12 larvae in its life time.
  • Maturation of larva takes place in 10 days.
  • Size of larva is 8-10mm.
  • Color of larva is creamy white and segmented body and ear shaped Protuberance which is used for respiration.
  • From the larva, pupa develops. Pupa stage is 4-5 weeks. Pupa is barrel shaped and Dark brown in color.
  • From the pupa, adult emerges. Adult requires several blood meals for a period of 16-20 days before ovary matures and egg laying starts.
Pathogenic Effects
  • Create great restlessness for animal and human beings.
  • It causes production losses.
  • These flies are important vectors of Trypanosomiasis (human & animals).
Treatment & Control
  • Use insecticides;
  • Organo Chlorine…… DDT, hexachlorocyclohexane/ benzene hexachloride
  • Organic phosphate…. Trichlorofen, neguvan, cumafex, neocidal, diazinon and asuntal
  • Synthetic pyrethroid...Cypermethrine and Ecoflee
  • Carbamates
  • Destroy the bushes.
  • Killing of the game animals which act as reservoir of infection because these animals provide blood to flies is necessary.
  • Trap the flies with black cloth and kill them. It is the best method.

Nov 24, 2010


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A variable is any observable event that can vary;
  • Weight
  • Age of an animal 
  • Number of cases of disease
Study variable
A study variable is any variable that is being considered in an investigation
Response and explanatory variables
A response variable is one that is affected by another (explanatory) variable
Effects of dry cat food on the occurrence of urolithiasis, cat food is the explanatory variable and urolithiasis is the response variable
Types of association
Association is the degree of dependence or independence between two variables.
Main types of association
  • Non-statistical association
  • Statistical association

Causal network
Non-statistical association
  • A non-statistical association between a disease and a hypothesized causal factor is an association that arises by chance
  • Frequency of joint occurrence of the disease and factor is no greater than would be expected by chance
  • Mycoplasma felis has been isolated from the eyes of some cats with conjunctivitis.
  • This represents an association between the Mycoplasma and conjunctivitis in these cats
  • Surveys have shown that M. felis also can be recovered from the conjunctivae of 80% of apparently normal
Association between conjunctivitis and the presence of M. felis arose by chance
Statistical association
  • Variables are positively statistically associated when they occur together more frequently than would be expected by chance
  • Negatively statistically associated when they occur together less frequently than would be expected by chance
Path diagrams
  • Indicating the paradigm
  • An example of causal and non-causal statistical associations
  • A = Cause of disease (explanatory variable); B and C = manifestations of disease
  • (Response variables)         causal association;          non-causal association
Infection of cattle with Haemonchus contortus
If infection of cattle with Haemonchus contortus were being investigated, then the following positive statistical associations could be found:
  • Between the presence of the parasite and Abomasal mucosal hyperplasia;
  • Between the presence of the parasite and anaemia;
  • Between Abomasal mucosal hyperplasia and anemia
The first two associations are causal and the third non-causal
Abomasal mucosal hyperplasia and infection with H. contortus are risk factors for anemia, that is, their presence increases the risk of anemia
Confounding (Latin: confundere = to mix together) is the effect of an extraneous variable that can wholly or partly account for an apparent association between variables
  • A variable that confounds is called a confounding variable or confounder
  • A confounding variable is distributed non-randomly (i.e., positively or negatively correlated with the explanatory and response variables that are being studied)
  • A confounding variable generally must:
  • Be a risk factor for the disease that is being studied;
  • Be associated with the explanatory variable, but not be a consequence of exposure to it.
The association between coffee drinking and pancreatic cancer
Schematic representation of the issue of potential confounding
Causal models
The associations and interactions between direct and indirect causes can be viewed in two ways, producing two causal 'models.
Causal model 1
The relationship of causes to their effects allows classification of causes into two types:
Sufficient cause
  • A cause is sufficient if it inevitably produces an effect (assuming that nothing happens that interrupts the development of the effect, such as death or prophylaxis).
  • A sufficient cause virtually always comprises a range of component causes; disease therefore is multifactorial.
Distemper virus-cause of distemper, although the sufficient cause actually involves
  • Exposure to the virus
  • Lack of immunity
  • Other components
It is not necessary to identify all components of a sufficient cause to prevent disease because removal of one component may render the cause insufficient
Necessary cause
If a cause is a component of every sufficient cause, then it is necessary
A necessary cause must always be present to produce an effect
Cause that is necessary but not sufficient is infection with Actinobacillus ligneresi, which must occur before actinobacillosis ('wooden tongue') can develop
Component causes therefore include factors that have been classified as
Predisposing factors:
Which increase the level of susceptibility in the host (e.g., age and immune status?)
Enabling factors:
Which facilitate manifestation of a disease (e.g., housing and nutrition?)
Precipitating factors:
Which are associated with the definitive onset of disease (e.g., many toxic and infectious agents)
Reinforcing factors:
Which tend to aggravate the presence of a disease (e.g., repeated exposure to an infectious agent in the absence of an immune response).
  • Pneumonia is a disease that has sufficient causes, none of which has a necessary component.
  • Pneumonia may have been produced in one case by heat stress where a dry, dusty environment allowed microscopic particulate matter to reach the alveoli.
  • Cold stress could produce a clinically similar result
Formulating a causal hypothesis
First step in any epidemiological investigation of cause is descriptive.
A description of time, place, and population is useful initially.
  • Associations with year, season, month, day, or even hour in the case of food poisoning investigations, should be considered.
  • Information on climatic influences, incubation periods and sources of infection
An outbreak of Salmonellosis in a group of cattle may be associated with the introduction of infected cattle feed
  • The geographical distribution of a disease may indicate an association with local geological, management or ecological factors
  • Epidemiological maps are a valuable aid to identifying geographical associations
  • The type of animal that is affected often is of considerable importance.
  • Hereford cattle are more susceptible to squamous cell carcinoma of the eye than other breeds, suggesting that the cause may be partly genetic
  • An epidemiological investigation is similar to any detective novel that unfolds a list of 'suspects' (possible causal factors), some of which may be non-statistically associated with a disease, and some statistically associated with the disease, either causally or non-causally.
Principles for establishing cause: Hill's criteria
The British medical statistician, Austin Bradford Hill, proposed several criteria for establishing a causal association including
  1. The time sequence of the events
  2. The strength of the association
  3. Biological gradient
  4. Consistency
  5. Compatibility with existing knowledge
Time sequence
  • Cause must precede effect
  • Unless bacterial infections were present before the mares became infertile (incorrect to infer the bacterial infections)
Strength of association
If a factor is causal, then there will be a strong positive statistical association between the factor and the disease.
Biological gradient
  • If a dose-response relationship can be found between a factor and a disease, the plausibility of a factor being causal is increased.
  • This is the basis of reasoning by the method of concomitant variation
  • Frequency of milking in relation to Leptospirosis
  • Smoking in relation to lung cancer
  • If an association exists in a number of different circumstances, then a causal relationship is probable.
  • This is the basis of reasoning by the method of agreement.
An example is bovine hyperkeratosis
The disease was called 'X disease' because initially the cause was unknown. It occurred in different circumstances:
  • In cattle that were fed sliced bread;
  • In calves that had been licking lubricating oil;
  • In cattle that were in contact with wood preservative.
The bread slicing machine was lubricated with similar oil to that which had been licked by the calves. The lubricating oil and the wood preservative both contained chlorinated naphthalene. This chemical was common to the different circumstances and subsequently was shown to cause hyperkeratosis
Compatibility with existing knowledge
It is more reasonable to infer that a factor causes a disease if a plausible biological mechanism has been identified than if such a mechanism is not known
Smoking can be suggested as a likely cause of lung cancer because other chemical and environmental pollutants are known to have a carcinogenic effect on laboratory animals