Kristensmith

Skeletal Muscle Relaxants Important Notes

1. Skeletal Muscle Relaxants Classification

• Drugs acting centrally
  • Diazepam, Baclofen
• Drugs acting peripherally at the neuromuscular junction
  • Competitive blockers
    • D-tubocurarine, Pancuronium, Rocuronium
• Depolarising blockers
  • Succinylcholine
• Drugs acting directly on muscle
  • Dantrolene

2. Succinylcholine

• It is depolarizing peripherally acting muscle relaxant
• Induces rapid, complete, and predictable paralysis with spontaneous recovery
• The onset of action – 1-1.5 min
• Adverse drug reactions
  • Post-operative muscel pain
  • Hyperkalaemia
  • Cardiac arrhythmias
  • Malignant hyperthermia

3. Non-depolarizing muscle relaxant

• Long acting – d-tubocurarine, Pancuronium
• Intermediate-acting – vecuronium, atracurium
• Short-acting – mivacurium

4. Tubocurarine

• Releases histamine from mast cells
• This contributes to hypertension, flushing, and bronchospasm
• Tubocurarine is administered 4
• In case of poisoning, neostigmine is used

Skeletal Muscle Relaxants Long Essays

Question 1. Classify skeletal muscle relaxants. Describe the pharmacological actions, therapeutic uses, and adverse effects of d-tubocurarine.
or
List two classes of skeletal muscle relaxants acting at the neuromuscular junction. Mention two therapeutic uses of peripheral-acting muscle relaxants.

Answer:

Skeletal muscle relaxants:

• Skeletal muscle relaxants are drugs that act peripherally at the neuromuscular junction or muscle fiber itself or centrally in the cerebrospinal axis to reduce muscle tone and/or cause paralysis.

Skeletal muscle relaxants Classification:

1. Peripherally acting muscle relaxants.

• Neuromuscular blocking agents.
  • Non-depolarizing blockers.
    • Long acting – d-tubocurarine, pancuronium.
    • Intermediate-acting – vecuronium, atracurium
    • Short-acting – mivacurium.
  • Depolarizing blockers.
    • Succinylcholine, Decamethonium

2. Directly acting agents.

• Dantrolene sodium, Quinine.

3. Centrally acting agents.

• Mephenesin congeners- Mephenesin, carisoprodol.
• Benzodiazepines – Diazepam.
• GABA derivatives – baclofen.
• Central α₂ agonist – Tizanidine.

4. Tubocurarine:

It is a peripherally acting, non-depolarizing skeletal muscle relaxant.

Read And Learn More: Pharmacology Question and Answers

Pharmacological Actions:

1. Skeletal muscle.

• Intravenous injection initially causes muscular weakness followed by flaccid paralysis.
• It acts at the neuromuscular junction preventing the combination of acetylcholine released from the motor never ending with its receptors.

2. CVS

• Causes hypotension.

3. Histamine – causes its release.

4. Autonomic ganglia.

• In high doses, blocks the autonomic ganglia and adrenal medulla resulting in hypotension.

5. GIT

• Enhances postoperative paralytic ileus after abdominal operations.

Skeletal muscle relaxants Uses:

• As an adjuvant to general anesthesia.
• In dentistry for setting mandibular fractures.
• Assisted ventilation of critically ill patients in the ICU.
• To avoid convulsions and trauma from electroconvulsive therapy.
• In severe cases of tetanus and status epilepticus.

Skeletal muscle relaxants Adverse Effects:

• Respiratory paralysis and prolonged apnea.
• Flushing
• Hypotension and cardiovascular collapse.
• Precipitation of asthma with histamine release.

Skeletal Muscle Relaxants Short Essays

Question 1. Compare d-tubocurarine and succinylcholine.

Answer:

Question 2. Compare succinylcholine and pancuronium.

Answer:

Question 3. Describe the uses of centrally and peripherally acting skeletal muscle relaxants.

Answer:

Uses of centrally acting skeletal muscle relaxants:

• During acute muscle spasms, it is used along with anal¬gesics.
• Used to cure torticollis, backache, and neuralgia.
• Used to relieve anxiety and tension.
• Used in spastic neurological disorders like hemiplegia, and paraplegia.
• During tetanus IV diazepam is given.
• During electroconvulsive therapy, diazepam is used to suppress convulsions.
• Used in orthopedic surgery like mandibular fractures.

Uses of peripherally acting skeletal muscle relaxant:

• As an adjuvant to general anesthesia.
• To promote skeletal muscle relaxation during abdominal surgery.
• In dentistry to treat the mandibular fracture.
• Used in severe cases of tetanus and status epilepticus.
• Useful in laryngoscopy, bronchoscopy esophagoscopy, and tracheal intubation.
• To facilitate artificial ventilation of critically ill patients in the ICU.

Question 4. Succinylcholine.

Answer:

Succinylcholine is a peripherally acting skeletal muscle relaxant.

• It is depolarizing neuromuscular blocking agent

Succinylcholine Mechanism of action:

Succinylcholine
↓
Stimulation of nicotinic receptors
↓
Depolarization of skeletal muscle membrane.
↓
Persistent depolarization.
↓
Results In flaccid paralysis

• This Is PHASE – 1 block.
• At high doses, dual block occurs.

Phase -1 block
↓
Initial depolarization
↓
Phase – 2 Nondepolarizing block.

Succinylcholine Adverse Effects:

• Increases intraocular pressure.
• Postoperative muscle pain – common
• Hyperkalemia.
• Cardiac arrhythmia.
• Apnea.
• Malignant hyperthermia – genetically determined
  .

Skeletal Muscle Relaxants Short Answers

Question 1. Pancuronium.

Answer:

Pancuronium is a peripherally acting skeletal muscle relaxant

• It is a long-acting, non-depolarizing competitive neuro-muscular blocking agent

Pancuronium Uses:

• As an adjuvant to general anesthesia.
• Used to promote skeletal muscle relaxation during abdominal surgery.
• Used in the treatment of mandibular fractures.
• In severe cases of tetanus and status epilepticus.
• Duration of action – 60 – 120 min.
• The onset of action – 4 – 6 min.
• Dose – 0.04 – 0.1 mg/kg of body weight

Question 2. Lioresal.

Answer:

It is the trad$ name of baclofen, which is an analog of the inhibitory transmitter GABA.

Lioresal Mechanism:

• The primary site of action is the spinal cord.
• It depresses poly-synaptic and mono-synaptic reflexes.

Lioresal Uses:

• Reduces spasticity in neurological disorders like multiple sclerosis.
• Improves bladder and bowel functions in patients with spinal lesions.
• Tried in trigeminal neuralgia.

Lioresal Adverse effects:

• Drowsiness, weakness, ataxia,
• Abrupt withdrawal causes anxiety, palpitation, and hallucinations.
• Dose: 10 mg BD to 25 mg TDS

Viva Voce:

1. Diaphragm is most resistant to succinylcholine

Cholinergic System Important Notes

1. Divisions of the autonomic system

• The autonomic nervous system is divided into
  • Sympathetic
  • Parasympathetic divisions
• Sympathetic is concerned with preparing the organisms for fight and flight
• Parasympathetic is mainly concerned with the vegetative functions
• Both divisions consist of
  • Preganglionic nerve
  • Ganglion
  • Post ganglionic nerve
  • An effector organ
• Neurotransmitters released by them are

2. Cholinergic receptors

3. Actions on stimulation of acetylcholine

• Decrease in heart rate
• Increase in glandular secretion
• Contraction of smooth muscles
• Constriction of the pupil (Miosis)
• These actions are blocked by atropine

4. Cholinergic drugs

• They are also called parasympathomimetics
• They are
  • Choline esters – Acetylcholine, Methacholine, Carbachol, Bethenechol
  • Alkaloids – Pilocarpine, Muscarine
  • Anti choiineesterases
    • Reversible – Physostigmine, Neostigmine
    • Irreversible – Organophosphates

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5. Drugs causing miosis

• Cholinergic drugs – Pilocarpine, physostigmine, neostigmine
• Anti adrenergic drugs – ergotamine, dibutamine
• Opioids – morphine, codeine

6. Pilocarpine

• Causes miosis, and ciliary muscle contraction and lowers intraocular pressure
• Increases secretion such as sweating, salivation
• Causes fall in BP at small doses and rise in BP at high dose
• Used only in the eye as 0.5-4% drops

7. Neostigmine

• Increases secretions
• So used in the treatment of xerostomia

Cholinergic System Long Essays

Question 1. Classify cholinergic drugs. Mention the mechanism of action, uses, and adverse effects of neostigmine.

Answer:

Cholinergic Drugs:

These drugs are those which produce action similar to that of acetylcholine, either by directly interacting with cholinergic receptors or by increasing the availability of acetylcholine at these sites.

Cholinergic Drugs Classification:

1. Directly acting:
   • Choline esterases. Example: Acetylcholine, bethanechol
   • Alkaloids. Example: pilocarpine, muscarine.
2. Indirectly – acting:
   • Reversible – Example: physostigmine, neostigmine.
   • Irreversible – organophosphates.

Neostigmine:

Mechanism of action:

• Neostigmine is a synthetic reversible anticholi¬nesterase agent
• It resembles the structure of acetylcholine.
• Thus it binds to acetylcholinesterases and inactivates them.
• Due to it acetylcholine (Ach) is not hydrolyzed and gets accumulated in the body.
• This produces cholinergic effects.

Pharmacological actions:

Neostigmine produces more marked effects on skeletal muscle and stimulates ganglia.

Pharmacological Uses:

1. In myasthenia gravis.
   • Neostigmine – 15 mg tab 6 hourly is used.
   • It acts by.
     • Anticholinesterase activity.
     • Direct stimulation of nicotine receptors increases the amount of acetylcholine released.
2. Curare poisoning.
   • Neostigmine reverses the effect of muscle relaxants. It is given 0.5 – 2 mg IV.
3. Postoperative paralytic ileus and urinary retention.
   • Neostigmine 0.5 – 1 mg is given subcutaneously.

Pharmacological Adverse effects:

• Muscarinic effect: Salivation, lacrimation, urination, GI distress, emesis.
• Nicotinic effect: Cramps, weakness, muscle paralysis, hypertension, tachycardia, pallor, and mydriasis.
• CNS: Restlessness, headache, tremors, drowsiness, confusion, ataxia, generalized weakness, coma, convulsions.

Cholinergic System Short Essays

Question 1. Irreversible Anticholinesterases.

Answer:

Irreversible anticholinesterases are powerful inhibitors of acetylcholinesterase.

• They bind with the enzyme permanently by covalent bonds.
• They are lipid soluble and highly absorbed by all routes.

Irreversible anticholinesterases Mechanism of action:

• The structure of acetylcholinesterase contains an anionic site and an ecstatic site.
• Irreversible anticholinesterases bind only at the es¬teratic site.
• This causes the accumulation of acetylcholine in the tissues.

Irreversible anticholinesterases Drugs Included are:

1. Organophosphates – floss, parathion, malathion.
2. Carbamates – carbaryl, propoxur.

Irreversible anticholinesterases Use:

1. Echothiophate – an organophosphate.
   • Used as eyedrops in glaucoma.
2. Organophosphate.
   • Used in agricultural and domestic insecticides.
   • Organophosphorous poisoning may be accidental, suicidal, or homicidal.
   • It may lead to acute or chronic toxicity.

Organophosphorous poisoning:

Question 2. Compare neostigmine and physostigmine.

Answer:

Question 3. Therapeutic uses of reversible anticholinesterases.

Answer:

Reversible anticholinesterases include.

• Neostigmine
• Physostigmine
• Pyridostigmine
• Edrophonium.
• Rivastigmine
• Donepezil.

Cholinergic System Short Answers

Question 1. Drugs used in myasthenia gravis.

Answer:

Drugs used in myasthenia gravis are:

• Reversible anticholinesterase – neostigmine.
• Glucocorticoids.
• Immunosuppressants – Azathioprim, cyclosporine.

Question 2. Neostigmine – used in myasthenia gravis.

Answer:

Neostigmine is used in myasthenia gravis due to.

1. Anticholinesterase activity.
   • Binds to acetylcholinesterase and inactive them.
   • Due to it acetylcholine is not hydrolyzed and gets accumulated in tissues.
2. Direct stimulation of nicotinic receptors.
   • This increases the amount of release of acetylcho¬line during each nerve impulse.
   • Enhances acetylcholine levels at neuromuscular junctions by preventing its destruction.
   • This results in an increase in the force of contraction and muscle power.
   • Dose: 15 mg tab 6 hourly.

Question 3. Neostigmine – used in d-tubocurarine poisoning.

Answer:

D-tubocurarine molecules bind to nicotinic receptors and prevent the binding of acetylcholine on these receptors.

• This blocks the actions of acetylcholine.
• Thus, in curare poisoning muscle weakness occurs followed by flaccid paralysis.
• Neostigmine 0.5 – 2 mg IV given reverses the effects of muscle paralysis.
• It reverses the action of d-tubocurarine.

Question 4. Oximes in organophosphorus poisoning.

Answer:

Oximes are cholinesterase reactivators.

• They restore neuromuscular transmission in organo-phosphorous poisoning.
• They provide more reactive OH groups which react with phosphorylated enzymes to form oxime phosphonate.
• This releases the binding and sets the acetylcholi¬nesterase enzyme-free.
• They must give immediately or within a few minutes become the complex undergoes aging & then the enzyme cannot be released.

Question 5. Name a few oximes.

Answer:

• Pralidoxime
• Obidoxime
• Diacetyl; monoxime.

Question 6. Physostigmine is used in atropine poisoning.

Answer:

Atropine has the following CNS effects.

1. Stimulation of medullary centers.
2. Depression of vestibular excitation.
3. Blockade of cholinergic overactivity.

• • At higher doses it causes.
  • Palpitation.
  • Excitement, psychotic behavior, ataxia, delirium, hallucination.
  • Hypotension, weak and rapid pulse.
  • Respiratory depression.
  • Physostigmine given 1-3 mg subcutaneously or IV antagonizes CNS and peripheral effects.

Viva Voce:

1. Physostigmine is used in atropine poisoning
2. Neostigmine is used in curare poisoning
3. Neostigmine is used in myasthenia gravis

Adverse Side Effects Important Notes

1. Cummulation

• • Accumulation of a drug in the body if the rate of administration is more than elimination resulting in toxicity
  • Example: digitalis

2. Tolerance

• • Requirement of a large dose of a drug to produce a given response
  • It may be natural or acquired

3. Tachyphylaxis

• • It is the rapid development of tolerance
  • The dose of the drug is repeated in quick succession resulting in a marked reduction in response
  • This is seen with directly acting catecholamines
  • Example: ephedrine, tyramine, amphetamine, 5-HT

4. Idiosyncrasy

• • It is the unpredictability of drug reaction due to other than immune reactions
  • It is genetically determined

5. Side effect

• • It is the undesired effect produced by the administration of a therapeutic dose of a drug

6. Teratogenic drugs

• • Drugs that cause fetal malformations when taken during the first trimester of pregnancy
  • They are:

7. Dependence

• • A state, psychic and
  • Sometimes also physical results from the interaction between a living organism and a drug characterized by a compulsion to take the drug
    • Drugs causing psychic and physical dependence
    • Barbiturates
    • Alcohol morphine
• Drugs cause more psychic but less physical dependence
• • Amphetamine
  • Opioid antagonist
• Drugs causing only psychic dependence
• • Cocaine
  • Caffeine
  • Cannabis

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Adverse Side Effects Long Essays

Question 1. Write in detail about Drug Toxicity in men.
(or)
Adverse drug reactions.

Answer:

Drug Toxicity Definition:

• WHO has defined an adverse drug reaction as any response to a drug that is noxious and unintended and that occurs at doses used in men for prophylaxis, diagnosis, or therapy.

Adverse drug reactions Types:

1. Side-effects:

• • These are unwanted but unavoidable pharmacodynamic effects of drug occurring at therapeutic doses. They are predictable and common.
  • Example: Sedation caused by promethazine

2. Secondary effects:

• • Corticosteroids cause immunosuppression which leads to latent TB.

3. Toxic effects:

• • These are results of Examplecessive action of the drug due to prolong usage or overdosage.
  • Overdosage may be accidental, suicidal absolute, or relative.
  • They are predictable & dose related.
  • Organs affected commonly are CNS, CVS, kidney, liver, lung, skin & blood-forming organs.
  • Poisoning can occur when the dose of the drug crosses the therapeutic index.

Adverse drug reactions Treatment:

• • Maintain airway by adequate ventilation.
  • Maintain BP and pulse rate.
  • Terminate the Exampleposure to the drug.
  • Exampleposure of the patient to fresh air.
  • Gastric lavage is done in case of ingested poison.
  • Preventing absorption of ingested poisons by use of suspension of 20-40 g of activated charcoal in 200 ml of water.
  • Inducing. diuresis.

4. Intolerance:

• • It is a characteristic toxic effect of a drug at a therapeutic dose.
  • Indicates a low threshold of the individuals to the action of the drug.
  • Example: Single dose of triflupromazine induces. Muscular dystonia in some individuals.

5. Idiosyncrasy:

• • It is genetically determined abnormal reactivity to a chemical.
  • It is a type of intolerance of some patients to specific drugs.
  • Some drugs without any genetic cause lead to ad- verse effects.
  • Such drugs are also included in it.
  • Example: Chloramphenicol causing agranulocytosis.
  • Some patients may be highly sensitive to even low doses while others may be highly insensitive even to high doses of the drug.

6. Drug Allergy:

• • The drug can induce cell-mediated or humoral-mediated immunity.
  • The drug or its metabolite acts as an antigen and induces an immunological reaction.
  • Organs affected by it are the skin, respiratory tract, gastrointestinal tract, blood and blood vessels.

Drug Allergy Types:

• Type 1 – Anaphylactic reaction.
• Type 2 – Cytolytic reaction
• Type 3 – Arthus reactions
• Type 4 – Delayed hypersensitivity reaction.

7. Photosensitivity:

• It is a cutaneous reaction resulting from drug-induced sensitization of the skin to UV radiation.

Photosensitivity Types:

• Phototoxic.
  • Drug or its metabolite accumulates in the skin, absorbs light, and undergoes photochemical reactions followed by photobiological reactions, resulting in local tissue damage and sunburn.
  • Example: Tetracyclines.
• Photoalergic.
  • Drug or its metabolite induces a cell-mediated immune response on Exampleposure to UV resulting in contact dermatitis.
  • Example: Sulphonamides.

8. Drug dependence/Addition:

• Drug dependence.
  • It is a state of compulsive use of drugs in spite of the knowledge of the risks associated with its use
  • Example: Alcohol.
• Addiction.
  • It is the dependence of a person on a drug to an Exampletent that influences the behavior and mood of the person.
  • Example: Barbiturates.

9. Teratogenicity.

• • It is an ability of a drug to cause fetal abnormalities when administered to a pregnant lady.
  • Depending on the stage of pregnancy during which the teratogen is administered, it can produce various abnormalities.

• • Example: ACE inhibitors can cause hypoplasia of organs.

10. Drug withdrawal reactions.

• • Certain drugs on sudden cessation result in adverse effects.
  • It may cause a worsening of the clinical condition.
  • Example: Acute adrenal insufficiency may be precipitated by abrupt cessation of corticosteroid therapy.

11. Carcinogenicity and mutagenicity.

• • It refers to the capacity of a drug to cause cancer and genetic defects.
  • It generally takes several years to develop
  • Example: Anticancer drugs, and radioisotopes.

12.  Drug-induced diseases – iatrogenic diseases.

• • They are functional disturbances caused by drugs that persist even after the causative drug has been withdrawn.
  • Example: Hepatitis by isoniazid.

Adverse Side Effects Short Essays

Question 1. Anaphylactic reaction.

Answer:

It is the type 1 hypersensitivity reaction.

• It is the only type of allergic reaction that the dentist may have to treat by himself.

Anaphylactic reaction Mechanism:

The drug or its metabolite act as an antigen
↓
It induces the synthesis of IgE antibodies which get fixed on mast cells.
↓
On Exampleposure of the drug, antigen-antibody complExample is formed.
↓
It causes the degranulation of mast cells which results in the release of
histamine, leukotrienes, prostaglandins, and platelet-activating factor
↓
Results in clinical manifestations of anaphylaxis.

Anaphylactic reaction Clinical features:

• Bronchospasm.
• Laryngeal edema.
• Hypotension.
• Urticaria.
• Itching.
• Angioedema.
• Rhinitis.
• Anaphylactic shock.
  • Example: Penicillin, cephalosporin, lignocaine, procaine, etc.
• Skin tests are carried out to detect it.

Question 2. Drug nomenclature.

Answer:

A drug can have three names.

1. Chemical name.
2. Non-proprietary name and
3. Proprietary name.

Adverse Side Effects Short Answer

Question 1. Drug resistance.

Answer:

It refers to the unresponsiveness of a microorganism to an antimicrobial agent.

Drug resistance Types:

1. Natural resistance.
   • Some microbes have always been resistant to certain antimicrobial agents.
   • Example: Gram-negative bacilli are unaffected by penicillin G.
2. Acquired resistance.
   • It is the development of resistance by an organism due to the use of antimicrobial agents over a period of time.
   • Example: Gonococci resistant to penicillin.

Question 2. Drug cumulation.

Answer:

When the rate of administration is more than the elimination rate, the drug will cumulate in the body and causes toxicity.

Example: Prolonged use of chloroquine causes retinal damage.

• The sometimes cumulative effect is desired.

Example: Use of phenytoin in the treatment of epilepsy.

• Substances like lead can remain deposited in bone without producing toxic effects.

Drug cumulation Prevention:

• Stop drug administration.
• Select the proper route of administration
• Check liver and kidney function before and during administration.

Question 3. Teratogenetic agents

Answer:

• Drugs that cause fetal malformations when taken during the first trimester of pregnancy
• They are:
  • Thalidomide
  • Amelia, phocomelia
  • Phenytoin
  • Cleft lip and palate, microcephaly
  • Tetracycline
  • Hypoplasia of teeth
  • Aspirin
  • Premature closure of ductusarterious

Viva Voce:

• Toxicity occurs at overdosage or prolonged dosage
• Side effects occur at the therapeutic dose
• Idiosyncrasy is genetically determined
• The first trimester is the most vulnerable period for teratogenicity

Pharmacodynamics Important Notes

1. Therapeutic index
   • It helps in the assessment of the safety of drugs
   • The larger the therapeutic index, the safer the drug
   • Penicillin has a larger therapeutic index
2. Affinity
   • It is the ability of the drug to bind to a receptor
3. Agonist
   • A drug that initiates pharmacological reaction after combining with receptors
   • It has
     • More affinity
     • High intrinsic activity
4. Antagonist
   • A drug that bonds to receptors but it is not capable to produce any action
   • It produces receptor blockade
   • It has
     • Affinity same as an agonist
     • Poor intrinsic activity
5. Partial agonist
   • A drug with
     • Affinity equal to agonist
     • Less intrinsic activity
6. Additive effect
   • Two drugs with the same effect produce an effect that is equal to the sum of the effects of individual drug
   • Example: ephedrine+aminophylline in bronchial asthma
7. Synergism
   • Two drugs with the same effect produce an effect that is greater than the sum of the effects of individual drug
   • Example: procaine + adrenaline
8. Antagonism

Pharmacodynamics Long Essays

Question 1. Describe the principles & mechanism of action of drugs with examples. Add a note of enzyme induction.

Answer:

Principle:

• Drugs produce their effects by interacting with the physiological systems of the organisms.
• By such interactions, drugs modify the rate of functions of various systems but do not change the basic functions.

Types of Drug Action:

Mechanism of drug action:

• Physical action.
  • Glucocorticoids
    • The action of drug results from its physical properties.
    • Adsorption-activated charcoal in poisoning.
    • Mass of the drug – bulk laxatives like psyllium.
    • Osmotic property – osmotic diuretics, mannitol.
    • Radioactivity – Radioiodine 1131
• Chemical action.
  • Drugs interact according to simple chemical reactions.

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• Through enzymes:
  • Drugs can either increase/stimulate or decrease/inhibit enzymatic action.

• Through receptors.
  • Drugs may act by interacting with receptors in the body.
  • Receptors have specificity & selectivity.
  • Similarly, drugs are relatively selective.
  • Receptors may be present in the cell membrane, in the cytoplasm or in the nucleus.
  • Example: Adrenaline binds at adrenergic receptors.
• Through ion channels.
  • Drugs may interfere with the movement of ions across specific channels
  • Example: calcium channel blockers.
• By altering metabolic processes.
  • Drugs may alter the metabolic pathway in the mi- cro-organism resulting in the destruction of the micro-organisms.
  • Example: Sulphonamides interfere with bacterial folic acid synthesis.

Enzyme induction:

• The synthesis of microsomal enzymes, mainly cytochrome P450 can be enhanced by certain drugs & environmental pollutants.
• This is called enzyme induction.
• It speeds up the biotransformation of the inducing drug.
  • Example: phenobarbital, rifampicin, and alcohol.
• It involves microsomal enzymes in the liver as well as other organs.
• Increase the rate of metabolism by 2-4 fold.
• Induction takes 4-14 days to reach the peak.

Enzyme induction Consequences:

• Decreased intensity of action of drugs that are inactivated by metabolism.
• Increased intensity of action of drugs that are activated by metabolism.
• Development of tolerance to drugs.
• May result in toxicity & therapeutic failure.
• May result in diseases
  • Example: Antiepileptics enhance the breakdown of Vit. D – re- sulting in osteomalacia.
• Intermittent use of an inducer may interfere with the adjustment of the dose of another drug.
• Some endogenous substrates are metabolized faster.

Enzyme induction Uses:

• Congenital nonhemolytic jaundice.
• Cushing’s syndrome.
• Chronic poisoning.
• Liver disease.

Question 2. Discuss factors modifying drug action with examples.

Answer:

Factors Modifying Drug Action:

• Drug Factors:

1. Route of administration.

• It may modify the speed & intensity of drug response.
• Example: Magnesium sulfate.

2. Presence of another drug.

• Drugs may interact with each other & modify the response.
  • Example: Hydralazine + propranolol used in hypertension.
• Succinylcholine – induces arrhythmias in digitalized patients.

3. Cumulation.

• When the rate of elimination of the drug is slower than the rate of administration, the drug gets cumulated in the body.
  • Example: Digoxin cumulates & results in toxicity.
• Chloroquine cumulate & cause retinal damage.

4. Dose.

• The dose of the drug can modify the drug response.
• An increase in dose increases drug response but only till the maximum is reached.
• Further increase in dose may lead to adverse effects.
• Example: Neostigmine.
  • Therapeutic doses-enhances muscle power
  • Higher doses cause muscle paralysis.

2. Sex.

• Smaller body size & hormonal effects in females may influence drug action.
• Example: Some antihypertensive drugs like clonidine may interfere with sexual functions in males but not in females.
• Some drugs are prohibited in pregnancy and lactation.

3. Species & race.

• Different response to drugs occurs in different species & races.

Drug Action Examples:

• Rabbits are resistant to atropine.
• Blacks require a high dose while mangoes require a low dose of atropine to dilate their pupils.

4. Body weight.

• It influences the concentration of the drug attained at the site of action.
• Accordingly, the dose is calculated as follows.

\(\text { Dose }=\frac{\text { Body weight }(\text { in } \mathrm{kg})}{70} \times \text { average adult dose }\)

. Drug Action Environment.

• Exposure to insecticides, carcinogens, and tobacco smoke induces drug metabolism.
• Food interferes with the absorption of drugs.
• Example: Tetracycline forms complexes with calcium. Present in food & are poorly absorbed.

6. Drug Action Genetic factors.

• Drug response is mediated genetically.
• It occurs due to variations in the amount of drug-metabolizing enzymes.
  • Example: Acetylation of drugs like INH, and hydralazine.
• Their acetylation differs in fast and slow acetylators.
• Slow acetylators may develop lupus erythematosus with hydralazine.

7. Emotional/psychological states.

• Doctor-patient relationship influences the drug response.
• Example: Use of placebo.

8. Pathological state.

• The presence of certain diseases influences drug response.

9. Tolerance.

• It refers to the requirement of a higher dose of a drug to produce a given response.
• It may be natural or acquired.
• Example: Tolerance develops to the sedative action of chlorpromazine.

10. Drug dependence.

• It is a drug response that always includes a compulsion to take a drug on a continuous or periodic basis in order to experience its psychic effects & sometimes to avoid the discomfort of its absence.
• Example: Alcohol, barbiturates.

Pharmacodynamics Short Essays

Question 1. Pharmacodynamics.

Answer:

Pharmacodynamics Definition:

Pharmacodynamics is the study of the actions of drugs on the body and their mechanisms of action.

Question 2. Placebo.

Answer:

Placebo is the inert dosage form with no specific biological activity.

• It is a dummy preparation
• It is a Latin word that means “I will please”.
• It may induce physiological responses.
  • Example: Placebo can release endorphins in the brain causing analgesia.
• It supplements pharmacological effects.
• Placebo effects are variable.
• Example: Placebo may induce sleep on the first night but not subsequently.

Placebo Uses:

• In clinical trials to minimize bias.
• To relieve subjective symptoms.

Factors Influencing it:

1. Patient factor.
   • Patients with neurotic symptoms respond well.
2. Drug factor.
   • The response can be affected by the drug presentation or route of administration.
   • Example: the color of the drug, injections.
3. Doctor factors.
   • The doctor’s personality and doctor-patient relationship may affect the response.
   • Example: Lactose, sucrose, injections of distilled water.

Question 3. Drug antagonism.

Answer:

Drug antagonism Definition:

One drug decreasing or inhibiting the action of another drug is called antagonism.

Drug antagonism Types:

Question 4. Drug Synergism.

Answer:

• When the action of one drug is increased or facilitated by another drug the combination is synergistic

Drug Synergism Types:

1. Additive
   • Effect of two drugs are in same direction Side effects of each may be different
   • But the combination is better-tolerated Effect of A + B = effect of A+ effect of B
   • Example: aspirin + Paracetamol- used as analgesic
2. Supra additive
   • The effect of the combination is greater than the individual effects
   • Effect of A+ B> effect of A+ effect of B
   • One component given alone is inactive
   • Example: acetylcholine + physostigmine

Pharmacodynamics Short Answers

Question 1. Drug synergism.

Answer:

When the action of one drug is increased or facilitated by another drug, the combination is synergistic.

Drug synergism Types:

1. Additive.
   • The effect of the two drugs is in the same direction.
   • Effect of A + B = effect of A+ effect of B.
     • Example: Aspirin + paracetamol – used as analgesic.
2. Supra-additive (potentiation)
   • The effect of the combination is greater than the individual effects.
   • Effects of A+B > effect of A+ effect of B.
     • Example: Acetylcholine + physostigmine.

Question 2. Drug antagonism.

Answer:

Drug antagonism Types:

1. Physical antagonism.
2. Chemical antagonism.
3. Physiological antagonism.
4. Antagonism at the receptor level.
   • Reversible.
   • Irreversible.
5. Non-competitive antagonism.

Question 3. Tachyphylaxis.

Answer:

Tachyphylaxis is the rapid development of tolerance.

• When a drug is given repeatedly at short intervals, tolerance develops & is known as tachyphylaxis.
• These drugs act by displacing noradrenaline from sympathetic nerve endings.
• There may be slow dissociation of the drug from the receptor, thereby blocking the receptor.
• Other mechanisms involve the internalization of receptors, homeostatic adaptation, etc.
• Example: Epinephrine given repeatedly in bronchial asthma may not give desired response.

Question 4. Bioassay.

Answer:

Bioassay is the determination of the amount of biological activity in a unit’s quality of preparation.

Bioassay Indications:

• When the chemical composition of a substance is not known.
• When the chemical assay method is too complex.
• When drugs differ in composition but have the same action.
• When the active principle is unknown.

Bioassay Methods:

• Direct comparison on the same tissues.
• Direct assay on several animals.
• Indirect assays.

Viva Voice:

1. The larger the therapeutic index the safer the drug
2. Drug efficacy refers to the maximal response that can be elicited by the drug
3. Drug potency refers to the amount of drug needed to produce a certain response

Routes Of Drug Administration Important Notes

1. Routes of drug administration

2. Parenteral routes

3. Transcutaneous routes are:

• lantophoresis
• Jet injections
• Adhesive units

Pharmacological Principles

4. Transmucosal routes are:

• Sublingual – Example: nitroglycerine
• Trans nasal – Example: dDAVP
• Trans rectal – Example: indomethacin, aminophylline

5. Drugs that should not be given by IV route are

• Paracetamol
• Diclofenac
• Chloroquine
• Adrenaline

6. Prodrug

• They are inactive as such and need conversion in the body to one or more metabolites
• Advantages
  • More stable
  • Better bioavailability
  • Fewer side effects.
  • Less toxicity

Read And Learn More: Pharmacology Question and Answers

• Examples:

Routes Of Drug Administration Long Essays

Question 1. Describe various routes of drug administration their merits & demerits with suitable Examples.

Answer:

Routes of Drug Administration:

Pharmacological Principles

1. Routes of Drug Administration Systemic:

1. Oral/enteral
2. Parental Includes.
   • Subcutaneous
   • Intramuscular
   • Intravenous
   • Intradermal.
3. Sublingual.
4. Rectal.
5. Cutaneous.
6. Inhalation.

2. Routes of Drug Administration Local:

1. Topical
2. For deeper tissues
3. Arterial supply.

Question 2. Discuss the intravenous routes of administration.

Answer:

Oral Route of administration:

• It is the most commonly used route.
• Its effectiveness is facilitated by.

1. The large surface area of the GIT.
2. Mixing of its contents.
3. Differences in pH at different parts of the gut.

Intravenous Route of administration :

• It is a type of parenteral drug administration where.

1. Drugs are injected directly into the bloodstream through veins.
2. Drugs are injected as a bolus or infused slowly over hours into superficial veins.

Pharmacological Principles

Routes Of Drug Administration Short Essays

Question 1. Sublingual route of administration
(or)
Mention different routes of drugs. Write in detail about the sublingual route.

Answer:

Sublingual Route of administration:

• The tablet or pellet is placed under the tongue.
• When the drug is dissolved, it is directly absorbed across the sublingual mucosa.
• But the drug should be lipid soluble.

Sublingual Route of administration Merits/Advantages:

• Rapid absorption.
• Once desired effect is achieved, the drug can be spat out.
• Bypass first-pass metabolism by the liver.

Sublingual Route of administration Demerits/Disadvantages:

• Incoveneint to patient.
• Only lipid-soluble, nonirritating drugs can be given.
• May cause buccal ulceration.

Sublingual Route of administration Examples:

• Glyceral trinitrate.
• Buprenorphine.
• Desamino-oxytocin.

Routes Of Drug Administration Short Answer

Question 1. Enumerate routes of administration with suitable Examples.

Answer:

Question 2. Enteric-Coated Tablets.

Answer:

To make the drug more acceptable through the oral route, tablets are coated with substances like cellulose acetate, phthalate, gluten, etc.

These are not digested by gastric acid but get disintegrated in the alkaline juices of the intestine.

Enteric-Coated Tablets Advantages:

• As it is not digested by gastric acid, it prevents gastric irritation.
• Avoid the destruction of drugs by the stomach.
• Retard absorption.
• Prolong duration of action.
• Provide a higher concentration of the drug in the small intestine.
• Reduces frequency of administration.
• Maintain the therapeutic concentration of the drug.

Enteric-Coated Tablets Disadvantages:

• Expensive.
• Failure of preparation causes the release of the entire drug within a short time.
• This leads to toxicity.

Question 3. Parenteral Route.

Answer:

It refers to a drug injected directly into tissue fluid or blood without having to cross the intestinal mucosa.

Parenteral Route Advantages:

• Rapid action.
• Can be used in unconscious & uncooperative patients.
• Avoid gastric irritation.
• Used in patients who are unable to swallow tablets.
• Bypass first-pass metabolism.
• No interferences of gastric juices.

Parenteral Route Disadvantages:

• More chances of systemic toxicity.
• Invasive, painful.
• Preparations have to be sterilized.
• Assistance required.
• Examplepensive.
• Injury to nerves & other tissues may occur.

Parenteral Route Routes – include:

1. Subcutaneous.
2. Intradermal.
3. Intramuscular.
4. Intravenous.

Question 4. Intravenous route.

Answer:

Intravenous route Examples:

Question 5. Transdermal route.

Answer:

The transdermal route requires adhesive units.

Pharmacological Principles

• These are adhesive patches of various shapes and sizes which deliver the contained drug at a constant rate into systemic circulation via stratum corneum of epithelium.
• The drug is held in a reservoir between an outer layer and a porous membrane.
• The membrane is smeared with an adhesive impregnated with a priming dose of the drug.
• The drug is protected by another film which is to be peeled off just before application.
• The drug gets diffused for percutaneous absorption into circulation.

Transdermal route Advantages:

• Prolonged duration of action.
• Good patient compliance.
• Provide contsnt plasma drug eleves.

Transdermal route Disadvantage:

• Local irritation & erythema may occur.
• Sites of Application:
• Chest, abdomen, upper arm, back mastoid region, and scrotum.

Transdermal route Examples:

• Hyoscine
• Nitroglycerine
• Fentanyl
• Nicotine
• Estradiol.

Question 6. Inhalation.

Answer:

Volatile liquids and gases are given by inhalation.

Inhalation Mechanism:

• Inhaled gases may act on the pulmonary epithelium and mucous membranes of the respiratory tract.
• They are absorbed through these membranes.
• When administration is discontinued, the drug diffuses back and is rapidly eliminated in Examplepired air.

Inhalation Examples:

• General Anaesthesia, salbutamol.

Question 7. New drug delivery system.

Answer:

1. Ocusert.
   • They are thin elliptical units that contain the drug in a reservoir which slowly releases the drug through a membrane by diffusion.
   • Example: Pilocarpine used in glaucoma.
2. Transdermal patches.
   • The drug is held in between an outer layer and a porous membrane.
   • Example: Fentanyl.
3. Progestasert.
   • Inserted into the uterus for delivering progesterone.
4. Prodrug.
   • The inactive form of the drug gets metabolized to an active form.
   • Example: levodopa.
5. Computerized miniature pumps.
   • Programmed to release drugs at a definite rate.
   • Example: insulin.

Question 8. Prodrug.

Answer:

• Prodrug is an inactive form of a drug that gets metabolized to the active derivative in the body.

Prodrug Advantages:

• Enhances drug availability.
• Prolongs duration of action
• Improves tolerability.
• Targets drug at the site.
• Improves stability.

Prodrug Examples:

• Levodopa – prodrug of dopamine.
• Bacampicillin – prodrug of ampicillin.
• Cyclophosphamide – prodrug of aldophosphamide.

Pharmacokinetics Important Notes

1. Pharmacokinetics
   • It is the study of drug absorption, distribution, biotransformation, and excretion
2. Bioavailability
   • It is the amount or percentage of drug that is absorbed from a given dosage form and reaches the systemic circulation following nonvascular administration
3. Biotransformation
   • It is the alteration of a drug within living organisms
   • After absorption drug circulates in the blood either in free form or bound to plasma proteins
   • The protein-bound drug is inactive and acts as a temporary store
   • The liver is the most active site for metabolizing the drugs
   • The enzymes that bring about biotransformation are microsomal enzymes
4. Routes of excretion of the drug
   • Lungs – alcohol, paraldehyde
   • Skin – arsenic, heavy metals
   • Bile – erythromycin, tetracycline, glycosides
   • Milk – erythromycin, tetracycline, penicillin
   • Saliva – metronidazole, heavy metals
   • Tears – rifampicin, minocycline
5. First order kinetics
   • Elimination of a drug occurs exponentially
   • A constant fraction of the drug disappears in each equal interval of time at the rate proportional to its plasma concentration
   • It occurs in lower dosage levels
6. Zero-order kinetics
   • When the dose exceeds a certain critical level, eliminating mechanism gets saturated
   • A fixed quantity of drug is eliminated per unit of time
7. Methods of prolonging drug action
   • Retarding absorption
   • Inhibiting drug metabolism in the liver
   • Slowing renal excretion of the drug
   • Increased protein binding of the drug in plasma
8. Drugs are transported across the membrane by
   • Passive diffusion and filtration
   • Specialized transport
9. Drug dosage
   • Clarke’s rule

\(\frac{\text { Child weight (in lbs) }}{150} \times \text { adult dose }\)

• • Young’s rule

\(\frac{\text { Age of child }}{\text { Age }+12} \times \text { adult dose }\)

Pharmacokinetics Long Essays

Question 1. Describe the various methods to prolong the duration of action of the drug.

Answer:

The duration of action of drugs can be prolonged by in-interfering with the pharmacokinetic processes.

• It has the following advantages:

1. Reduces frequency of drug administration.
2. Improves patient compliance.
3. Avoids large fluctuations in plasma concentration.
4. Maintains drug effect overnight.

Prolong The Duration Of Action Of The Drug Methods:

1. By prolonging the absorption:

• The oral route prolongs absorption by 4-6 hours.
  • Used sustained-release preparation, coating with resin, plastic, etc. Temporarily disperse the release of the active ingredient in the GIT.
  • Used the semipermeable membrane to control the release of the drug.
  • Example: Iron, dyphylline.
• Parenteral route – prolongs absorption up to days to several months.
  • Reducing solubility – Example: procaine + penicillin.
  • Use of oily solution depot progression.
  • Altering particle size – Insulin zinc suspension.
  • Pellet implantation – DOCA.
  • Statistic capsules – testosterone.
  • Inclusion of vasoconstrictor with the drug adrenaline with local anesthetics.
  • Combining with protein – protamine + zinc + in-caution.
  • Chemical alteration through esterification.
• Transdermal drug deliver:
  • Use of transdermal patch.

Read And Learn More: Pharmacology Question and Answers

2. By increasing plasma protein binding:

• Drugs that are highly bound to plasma protein are pre- pared & are released slowly in the free active form.
• Example: sulphonamides.

3. By Retarding the rate of Metabolism:

• By chemical alteration of drug – Example: addition of ethical group to estradiol.
• Inhibiting specific enzymes.
  • Inhibition of enzyme cholinesterase by posting- mine prolongs the action of acetylcholine.
  • Inhibition of enzyme peptidase in the renal tubules by cilastatin – prolongs the action of imipenem.

4. By Retarding Renal Excretion:

• Use of competitive substances, which competes for the same transport system.
• Example: Probenecid pro- longs the action of penicillin and ampicillin.

Question 2. Explain the means of biotransformation of drugs in the body with examples.

Answer:

Biotransformation:

• Biotransformation is the process of chemical alteration of the drug in the body.
• It converts the drugs into more polar, water-soluble compounds so that they are easily excreted through the kidneys.

Site of Biotransformation:

• Liver – most important organ.
• Other includes kidney, gut, mucosa, lungs, blood & skin.

Biotransformation Consequences:

1. Inactivation.
   • Active metabolites & drugs are converted to inactive or less active substances.
   • Example: Lidocaine, ibuprofen.
2. Active metabolite from an active drug.
3. Activation of the inactive drug.
   • Enzymes in biotransformation:

Reactions in Biotransformation:

1. Phase 1 reactions or non-synthetic reactions.

It converts the drug to a more polar metabolite by oxidation, reduction, or hydrolysis.

• Oxidation.
  • It involves the addition of oxygen or negatively charged radicals or either the removal of hydrogen or positively charged radicals.
  • They are mostly carried out by a group of mono-oxygenases in the liver.
  • They are the most important drug metabolizing reactions.
• Reduction.
  • It involves cytochrome P-450 enzymes working in opposite directions.
• Hydrolysis.
  • This cleavages of drug molecules by taking up a molecule of water.

\(\text { Ester }+\mathrm{H}_2 \mathrm{O} \stackrel{\text { esterase }}{\longrightarrow} \text { acid }+ \text { alcohol }\)

2. Phase 2 reactions or synthetic reactions.

1. In it, endogenous water-soluble substances combine with the drug or its phase 1 metabolite to form a highly polar conjugate.
2. Various synthetic reactions are:

• Glucuronide conjugation.
  • It is a most important synthetic reaction.
  • Carried out by a group of UDP-glucuronosyl transferases.
• Acetylation.
  • Compounds having amino or hydrazine residues are conjugated with the help of acetyl cohen- zyme-A.
• Methylation.
  • Amines & phenols can be methylated.
• Sulfate conjugation.
  • Phenolic compounds & steroids are sulfated by sulfotransferases.
• Glycine conjugation.
  • Salicylates are conjugated with glycine.
• Glutathione conjugation.
  • Serves to inactivate highly reactive quinine or epoxide intermediates formed during metabolism.
• Ribonucleoside.
  • Required for activation of many purine & pyrimidine antimetabolites used in cancer chemotherapy.

Pharmacokinetics Short Essays

Question 1. Channels of drug excretion.

Answer:

Drug & their metabolites are excreted.

1. Urine.

1. Through kidney.
2. A most important channel for the majority of drugs.
3. It takes place in three steps.

• Glomerular filtration.
  • Ionized drugs of low molecular weight are easily filtered through the glomerular membrane.
  • All nonprotein drugs are presented to the glomerulus for filtration.
• Tubular reabsorption.
  • It depends upon lipid solubility & ionization of the drug at the existing urinary pH.
• Tubular secretion.
  • It involves the active transfer of organic acids & bases by two separate classes of nonspecific transporters.

2. Faeces:

• Unabsorbed portions of the orally administered drugs are eliminated through the faeces.
• Most of the drug present in it is derived from bile.
• Certain drugs are excreted directly in the colon.

3. Exhales air:

• Gases & volatile liquids are eliminated by the lungs.

4. Saliva & sweat.

• Drugs like phenytoin and metronidazole are excreted through saliva.
• Drugs like iodide and rifampicin are excreted through sweat.

5. Milk.

• The excretion of drugs in the milk is of no significance to the mother, but the infant receives the drug during suckling.

Question 2. First pass metabolism/Pre-systemic metabolism.

Answer:

First-pass metabolism is the metabolism of the drug during its first passage from the site of absorption into the systemic circulation.

• Most of the orally administered drugs have to pass via the gut wall, portal vein & liver to enter the systemic circulation.
• Certain drugs during this process of passage get metabolized & are removed or inactivated before they reach systemic circulation.
• This process is known as first-pass metabolism.
• Its extent depends on the individual & the drug.
• Bioavailability is increased in patients with hepatic diseases.

Result of first-pass metabolism:

• Decreases bioavailability of the drug.
• Decreases the therapeutic effect of the drug.

Pre-systemic metabolism Consequences:

• The dose has to be increased.
• The route of administration has to be changed.

Examples: Phenobarbitone has low first-pass metabolism & lidocaine has high first-pass metabolism.

Question 3. Bioavailability mentions factors influencing it by oral route with examples.

Answer:

Bioavailability:

• Bioavailability is the fraction of a drug that reaches the systemic circulation following administration by any route.

Factors influencing it:

1. Disintegration & dissolution.
   • Oral drugs have to be disintegrated to be absorbed & then dissolved in gastrointestinal fluids.
   • Liquids → faster absorption→ good bioavailability.
2. Formulation.
   • Inert substances used with diluents’ slow absorption reduce bioavailability.
3. Particle size.
   • Small particles have easy absorption → better bioavailability.
4. Lipid solubility.
   • Lipid-soluble drugs- fast absorption → more bioavailability.
5. pH & ionization.
   • lionized drugs – poor absorption → less availability.
   • Acidic drugs unionized and rapidly absorbed → good bioavailability.
6. Area & vascularity of the absorbing surface.
   • Larger area – more vascularity → more absorption → more bioavailability.
7. Gastrointestinal motility.
   • Faster gastric emptying → fast passage into the intestine → more absorption→ more bioavailability.
8. Presence of food.
   • Delayed gastric emptying → delay absorption.
9. Metabolism.
   • Degradation of drugs in GIT leads to zero bioavailability.
10. Diseases.
    • Liver diseases lead to increased bioavailability.

Question 5. Various methods to prolong drug action.

Answer:

1. By prolonging the absorption

• Oral route
  • Prolongs absorption by 4-6 hours
  • Used sustained-release preparation, coating with resin, plastic, etc
  • Temporarily disperse release of the active in-gradient in the GIT
  • Use of semipermeable membrane to control the release of drug
• Parenteral route
  • Prolongs absorption upto days to several months
    • Reducing solubility
      • Use of oily solution
        • Altering particle size
          • Pellet implantation
            • Siastic capsules
              • Inclusion of vasoconstrictor with drugs like adrenaline
                • Combining with protein
                  • Chemical alteration through esterification

• Transdermal route
  • Use of the transdermal patch

2. By increasing plasma protein binding

• Drugs that are highly bound to plasma proteins are prepared and are released slowly in the free active form

3. By retarding the rate of metabolism

• By chemical alteration of drug
• Inhibiting specific enzyme

4. By retarding renal excretion

• Uses of competitive substances which compete for the same transport system

Pharmacokinetics Short Answers

Question 1. Pharmacokinetics.

Answer:

Pharmacokinetics is the study of the absorption, distribution, metabolism & excretion of drugs i.e., the movement of the drug into, within, and out of the body.

• Once a drug is administrated→ it is absorbed → enters blood distributed to different parts of the body → reaches the site of action metabolized and excreted out of the body.
• It depends upon.

1. Route of administration.
2. Dose
3. Latency of onset.
4. Time of peak action.
5. Duration of action.
6. Frequency of administration.

Question 2. Mention factors affecting bioavailability.

Answer:

1. Disintegration & dissolution of the drug.
2. Formulation.
3. Particle size.
4. pH & ionization.
5. Lipid solubility.
6. Gastrointestinal motility.
7. Presence of food.
8. Metabolism.
9. Area & vascularity of absorbing surface.
10. Diseases.

Question 3. Mention channels of excretion of drug with examples.

Answer:

Question 4. Methods of prolonging effects of the drug with examples.

Answer:

Question 5. Plasma half-life

Answer:

The plasma half-life (t1/2) of the drug is the time taken for its plasma concentration to be reduced to half its original value.

Plasma half-life Phase:

1. Initial rapid phase.
   • Due to distribution.
2. Declined phase.
   • Occurs due to elimination.

• Four to five half-lives are required for the complete elimination of the drug.

Plasma half-life Significance:

• Calculate the loading & maintenance dose of the drug.
• Indicates the duration of action of the drug.
• Guides dosing regimen.

Question 6. Drug dosage.

Answer:

A dose is the appropriate amount of a drug needed to pro- duce a certain degree of response in a patient.

Viva Voce:

1. Acidic drugs are rapidly absorbed from the stomach
2. Most of the drugs are absorbed by passive diffusion
3. Propranolol has extensive first-pass metabolism
4. Drugs are eliminated from the body by first-order kinetics or zero-order kinetics