PHARMACOLOGY IMPORTANT
LONG QUESTIONS (15 MARKS)
(PART 1: QUESTION NO. 1-7)
PREPARED
BY MR. ABHIJIT DAS
1.
What do you mean by parenteral route?
What are advantages of parenteral routes over oral route? Classify parenteral
route.
2. Define
absorption of drugs. Give a note on different processes of absorption of drugs
and factors affecting the absorption process.
3. Define
biotransformation of a drug. Describe various processes of drug metabolism.
4. Explain
the various factors affecting the dose and action of drugs.
5. Define
cholinergic drugs. Classify it with suitable suitable examples. Give a note on
pharmacological action of acetylcholine.
6. What
do you mean by sympathomimetics and parasympathomimetics? Classify
anti-cholinergic drugs. Discuss pharmacological action of atropine on eye, CVS,
glands and smooth muscles.
7. Define
adrenergic drugs & classify them. Describe about pharmacological action,
adverse effect and use of adrenaline.
8. Write
down the definition, classification, mechanism of action, pharmacological
action and use of local anaesthetics.
9. Explain
general anaesthetics. Briefly describe the different stages of general
anaesthesia. Write a note on barbiturates.
10.
What are NSAIDS? Classify them. Write
the mechanism of action, pharmacological action and uses of aspirin.
11.
what is the difference between narcotic
and non-narcotic analgesics? Classify opiod
analgesics. Give a note on pharmacological actions, ADME, side effects
and therapeutic effects of morphine.
12.
Define epilepsy. Describe shortly
different types of epilepsy. Classify anti epileptic drugs. Write the mechanism
of action and adverse effects of phenytoin.
13.
What is sedative? Classify the drugs
used as sedative-hypnotics. Give an account of pharmacological action, ADME,
adverse reactions and therapeutic uses of barbiturates.
14.
Define diuretics. Classify it. Write
down the pharmacological action, adverse effect and use of furosemide.
15.
What do you mean by cardiac glycosides?
Write the mechanism of action, pharmacological action, adverse effects and uses
of digoxin.
16.
Enumerate the drugs used for the
treatment of peptic ulcer and describe pharmacological action, toxicities of H2
blockers.
17.
What is purgative? Classify it with
example. Give a note on irritant purgatives.
18.
Define chemotherapeutic agents and
antibiotics. Write the mechanism of action of penicillins and a note on
semi-synthetic penicillins. Or Classify penicillins and describe their method
of action, toxicity and therapeutic uses.
19.
What is tuberculosis? Classify anti
tubercular drugs with examples. Give a note on firstline anti tubercular drugs.
20.
What is amoebiasis? Classify antiamoebic
drugs. Discuss about the mechanism of action, pharmacokinetics, side effects
and uses of metronidazole.
21.
What is cancer? Classify anti cancer
drugs. Discuss shortly the mechanism of action of anti metabolites and
alkylating agents.
1. WHAT DO YOU MEAN BY PARENTERAL ROUTE? WHAT ARE ADVANTAGES OF
PARENTERAL ROUTES OVER ORAL ROUTE? CLASSIFY PARENTERAL ROUTE.
ANS:
A route of
administration is the path by which a drug is taken into the body. The choice
of appropriate route in a given situation depends both on drug as well as
patient related factors. In addition, some drugs are maximally absorbed through
a particular route as compared to another route.
PARENTERAL
ROUTE
Par=without
Enteron=intestine
So,
parenteral route means a route which is other than GIT route. In this route the
drug administration is merely done by injection, inhalation, and topical application.
The drug will go directly into the tissue fluid or blood without having to
cross the intestinal mucosa.
ADVANTAGES OF PARENTERAL ROUTE:
i.
It is
useful for poorly absorbed drugs.
ii.
Immediate
onset of action.
iii.
Useful
in emergency condition.
iv.
Useful when
the patient is unconscious.
v.
Accurate
dose can be given.
CLASSIFICATION OF PARENTERAL ROUTE
i.
Injections
ii.
Inhalation
iii.
Transdermal
route
INJECTIONS
Injection
means the act of putting a drug into a person’s body using a needle and a
syringe.
1.
Intravenous
– This involves the administration of drugs directly into a vein. It is useful
in case of emergency.
2.
Intraspinal
– This involves the administration of a drug within the vertebral column.
3.
Intraarterial
– This involves direct administration of a drug to an artery.
4.
Intracerebroventricular
– This involves direct administration of a drug to the cerebral ventricles.
This route bypasses the blood-brain barrier.
5.
Intracardiac-This
route is used as an emergency route during an cardiac arrest. Ex- Adrenaline
injection into heart.
6.
Intradermal-
Administration of drugs into dermis of the skin.
7.
Intraarticular-
Administration of drugs into the joints.
8.
Intralymphatic-
Administration of drugs into the lymph node.
9.
Intraperitoneal-
Administration of drugs into the peritoneal cavity.
10.
Intramuscular
– Administration of drugs deep into the muscle tissue.
11.
Subcutaneous-
Drugs are administered under the skin.
INHALATION
Ø Volatile
liquid and gases are given by inhalation for systemic action.
Ø Absorption
takes place from surface of alveoli to blood circulation.
Ø Action
is very rapid
Ø Ex:
General anaesthetics
TRANSDERMAL
ROUTE
The
transdermal route is commonly referred to as ‘the patch’ because the medication
is contained in a patch that will be absorbed through the skin. The patches
will deliver the contained drug at a constant rate into systemic circulation.
The
drug is held in a reservoir between an backing film and a rate controlling
micropore membrane. So the drug will be delivered at a constant and predictable
rate.
2. DEFINE ABSORPTION OF DRUGS. GIVE A NOTE ON DIFFERENT PROCESSES OF
ABSORPTION OF DRUGS AND FACTORS AFFECTING THE ABSORPTION PROCESS.
ANS:
Absorption
is a process of transfer of drug from the site of administration to the
systemic circulation.
DIFFERENT PROCESSES OF ABSORPTION
OF DRUGS
A.
Passive transfer:
1. Simple
diffusion
2. Filtration
B.
Specialized transfer:
1. Active
transport
2. Facilitated
diffusion
3. Pinocytosis
Ø SIMPLE DIFFUSION/PASSIVE TRANSPORT
Substances
can be transported from higher concentration to lower concentration.
It
does not require the assistance of membrane proteins.
Ex-
passive transport of small non polar drugs
Ø FILTRATION
Only
water soluble substances can be transported
through this process through aqueous pores present
in the cell membrane.
Molecules will move from area of higher concentration to area of lower concentration.
Ø ACTIVE TRANSPORT
Active
transport is the movement of drug molecules from an area of lower concentration
to an area of higher concentration against the concentration gradient.
Active
transport requires cellular energy(ATP) to make this happen.
Ø FACILITATED DIFFUSION
It
is the process of transport done by the help of carrier protein.
Being passive, facilitated diffusion doesn’t require chemical energy from ATP.
Ø PINOCYTOSIS
In this process cells engulf fluids or macromolecules from the surroundings.
FACTORS AFFECTING THE ABSORPTION
PROCESS
1.
LIPOPHILICITY
Lipid solubility of the drug affect drug absorption
from the GI tract.
Lipid soluble drugs are absorbed more rapidly than
water soluble drugs.
2.
PHYSICAL
STATE
Physical
state of drugs is one of the most important factors affecting their absorption.
It
has been observed that liquid drugs are well absorbed than solid drugs. Also,
aqueous solutions are more quickly absorbed than oily solutions. Gasses are
more quickly absorbed through lungs.
3.
DEGREE
OF IONIZATION
Unionized drugs are easily absorbed than ionized
drugs.
Different drugs are either acidic or basic and are
present in ionized or unionized form.
Acidic drugs are unionized in the acidic medium and
basic drugs are unionized in the basic medium. That’s why acidic drugs are
quickly absorbed from the acidic compartment.
4.
PARTICL
SIZE
It has been studied that smaller particle
sized drugs are better absorbed than larger particle sized drugs.
Smaller
particle size provides greater surface area of a given weight of drug thus
improving the process of absorption.
5.
PH
Acidic pH favors acidic drug absorption and basic pH
is better for basic drugs. That means, acidic drugs are rapidly absorbed from
stomach.
On the other hand, basic drugs are not absorbed
until they reach the small intestine.
6.
CONCENTRATION
Passive
diffusion depends on concentration gradient. So, concentrated forms of drugs
are quickly absorbed than dilute solutions. Higher concentration of drugs helps
better absorption of those drugs.
7.
SURFACE
AREA
Larger
the surface area of the absorbing membrane, more will be the absorption.
Drugs
can be easily absorbed from the small intestine than the stomach due to large
surface area of the small intestine.
The
absorption of drugs through sublingual route is faster. That means absorption
of drugs from highly vascular membrane will be faster.
8.
ROUTE
OF ADMINISTRATION
Some
drugs are well absorbed through parenteral route than oral route.
Bioavailability
of drugs administered through parenteral route is always more than the
bioavailability of drugs administered through oral route.
Certain
drugs are degraded in the GI tract by acid and are ineffective orally. So
enteric coated tablets can be used to overcome acid lability.
9.
PRESENCE
OF FOOD
Foods can interact with the drugs to alter their
rate of absorption.
Ex-antihyperlipidemic drugs are better absorbed when
taken with the food.
10.
PHARMACEUTICAL
FACTORS
DISINTEGRATION:
Disintegration is the breaking up of the dosage form
into smaller particles. So, when disintegration occurs rapidly, rapid will be
the absorption.
DISSOLUTION:
After disintegration, drugs dissolve in the gastric
juices, which is called dissolution. When rapid is the dissolution, rapid will
be the absorption.
11.
GI
MOBILITY
GI mobility should be optimal for oral drug
absorption. That means it should be neither increased nor decreased.
Different situations may alter the GI mobility.
Diarrhea causes rapid peristalsis (GIT movement), thus the process of
absorption is affected. Constipation affects disintegration so decreases
mobility.
3. DEFINE BIOTRANSFORMATION (DRUG METABOLISM) OF A DRUG. DESCRIBE
VARIOUS PROCESSES OF DRUG METABOLISM.
ANS:
METABOLISM/BIOTRANSFORMATION
Metabolism
means modification of drug by enzymes to make the drug ineffective.
It
is needed to convert lipid-soluble compounds to water soluble compounds so that
they will be easily excreted. That’s why most hydrophilic (water-soluble) drugs
are little biotransformed and are largely excreted unchanged.
The
primary site for drug excretion is liver. Other
sites are kidney, intestine, lungs etc.
Liver
does it mainly through two metabolic reactions called phase
1 and phase 2.
PHASE
1 REACTIONS
Phase
1 reactions are all about making a drug more hydrophilic. These reactions
involve introduction or unmasking of a polar functional group so in phase 1 we
are going to see oxidation, reduction, hydrolysis, cyclization and
decyclization.
OXIDATION
Ø The
enzyme system which oxidizes the drug is called ‘cytochrome
P-450 system’.
Ø
This reaction involves addition of
oxygen/negatively charged radical or removal of hydrogen/positively charged
radical.
Ø
Oxidations are the most important drug
metabolizing reactions.
Ø
Types of oxidation: Microsomal oxidation
and NON-microsomal oxidation.
Ø
Microsomal Oxidation- Catalyzed by
enzymes present in the microsome of liver
a)
Hydroxylation – addition of hydroxyl
group.
Ex – phenytoin Ã
hydroxyl phenytoin
b)
Dealkylation – removal of alkyl group
Ex - codeinÃ
morphine
c)
S-Oxidation – addition of sulfoxide
group
Ex- CimentidineÃ
cimentidine sulfoxide
Ø
Non-microsomal Oxidation- catalyzed by
enzymes present in the endoplasmic reticulum of liver.
Ø Barbiturates, imipramine, phenothiazines, imipramine, ibuprofen, paracetamol etc are oxidized in this way.
REDUCTION
Ø This
reaction involves removal of oxygen or addition of hydrogen.
Ø Warfarin,
halothane, chloramphenicol etc are reduced.
HYDROLYSIS
Ø Hydrolysis
is any chemical reaction in which a molecule of water breaks one or more
chemical bonds.
Ø Hydrolysis
occurs in liver, intestine, plasma etc.
Ø Ex-
aspirin, procaine, lidocaine etc are hydrolyzed
CYCLIZATION
Ø This
is formation of ring structure from a straight chain compound.
Ø Ex-
proguanil
DECYCLIZATION
Ø This
is opening up of ring structure of the cyclic drug molecule.
Ø Ex-
phenytoin, barbiturates etc.
PHASE
2 REACTIONS
If
metabolites from phase 1 are still too lipophilic they can undergo conjugation
reaction which involves addition of a polar group.
GLUCURONIDE
CONJUGATION
Ø Compounds
with a hydroxyl or carboxylic acid group are easily conjugated with glucuronic
acid.
Ø Ex-
chloramphenicol, aspirin, paracetamol, morphine, metronidazole etc.
Ø Glucuronidation increases the molecular weight of the drug which favours it’s excretion in bile.
ACETYLATION
Ø Compounds
having amino or hydrazine residues are conjugated with the help of acetyl
coenzyme-A
Ø Ex-
sulfonamides, isoniazide, hydralazine, clonazepam, procainamide etc.
METHYLATION
Ø
The amines and phenols can be
methylated.
Ø
Ex- adrenaline, histamine, nicotinic
acid, methyl dopa, captopril, etc.
SULFATE
CONJUGATION
Ø The
phenolic compounds and steroids are sulfated by sulfotransferase.
Ø Ex-
chloramphenicol, methyl dopa, sex steroids etc.
GLYCINE
CONJUGATION
Ø Drugs
having carboxylic acid group are conjugated with glycine.
Ø Ex-
salicylates
4. EXPLAIN THE VARIOUS FACTORS AFFECTING THE DOSE AND ACTION OF DRUGS.
ANS:
A
variety of host and environmental factors affect the drug response. Hence
knowing various factors modifying drug action is essential as it will help in
deciding proper desired drug effects with the optimum dosage of drugs.
The
important factors which modify the effect of a drug are :
ROUTE
OF ADMINISTRATION
Ø Bioavailability
of a particular drug when given through IV route is greater than the
bioavailability of that particular drug when given through oral route. So when
a drug is given through IV route shows better action.
Ø A
drug may have entirely different uses through different routes.
Ex-
Magnesium sulfate when given orally causes purgation but when given intravenously
it produces hypotension.
CUMULATION
Ø Accumulation
of a drug in the body following its repeated administration is termed as
cumulation. So if rate of administration is more than the rate of elimination,
then the drug will accumulate in the body. Hence slowly eliminated drugs
produce cumulative toxicity.
Ø Ex-
prolonged use of chloroquine causes retinal damage.
Ø Sometimes
cumulative effect is desired.
Ex- Phenobarbitone in
the treatment of epilepsy.
AGE
Ø The
newborn has low glomerular filtration rate and tubular transport is immature.
Ø Similarly,
hepatic drug metabolizing system is not properly developed in newborns. Infants
below one year are devoid of enzymes that metabolize drugs.
Ø Drug
absorption may also be altered in newborns because of lower gastric acidity.
Ø Similarly,
in geriatric patients (older patients), administered drug dosages should be
selected carefully due to their inability to metabolize drugs.
Ø The
dosage of children is calculated on the basis of their age.
YOUNG’S
FORMULA
Child
Dose= (Age/Age+12) X Adult Dose
DILLING’S
FORMULA
Child
Dose= (Age/20) X Adult Dose
GENDER
Ø Generally,
males weigh more than females. So females get lesser dose than males.
Ø Females
have a higher percent of body fat than males which can affect the volume of
distribution of certain drugs.
Ø In
women consideration must be given to menstruation, pregnancy and lactation. For
example drugs having strong stimulant effect on uterus or foetus should not be
given to menstruating and pregnant ladies.
Ø Drugs
like morphine can cross the placental barrier and depresses the foetal
respiration. So morphine should be avoided during pregnancy.
BODY
WEIGHT
Ø The
average adult dose refers to individuals of medium built (adult weighing
between 50-100 Kg.).
Ø So
for obese or lean individuals and for children dose can be calculated on body
weight basis.
Dose=
(Body Weight in Kg/70) X Adult Dose
GENETIC
FACTOR
Ø Some
patients are unable to metabolize certain medicines because of the absence of
certain enzymes required for their metabolism. Absence of certain enzymes in
some individual is the result of lack of specific genes encoding them from
their genetic set up.
Ø Deficiency
of enzyme ‘Glucose-6 Phosphate dehydrogenase’ cannot metabolize primaquin in
some individuals.
PRESENCE
OF FOOD
Ø Sometimes
presence or absence of food in GIT can modify the drug absorption process.
Ø Example
Milk
decreases the absorption of Tetracyclin.
Fat
increases the absorption of Griseofluvin.
DISEASE
Ø In
liver disease first pass metabolism of some drugs will be reduced. So the
bioavailability of drugs having high first pass metabolism will be increased
and that will produce toxicity.
Ø In
some gastrointestinal disease, the absorption of some orally administered drugs
can be altered.
METABOLISM
Ø If
a drug undergoes first pass metabolism the concentration of that drug is
generally reduced before it reaches the systemic circulation. That’s why it
shows less action. If the drug will be administered in ways to bypass first
pass metabolism then the drug will show good efficacy.
Ø Metabolic
disturbance in one’s body can drastically affect drug action. Changes in
physiological factors such as water balance, body temperature, electrolyte
balance also modify the drug effects.
Ø Example-
in case of iron deficiency anaemia, absorption of iron from the
gastrointestinal tract is maximum.
RACE
(ETHNICITY)
Ø Ethnic
differences in drug response may be due to the interaction of genetic factors
and the environmental factors. It also depends on the pathogenesis of the
disease.
Ø So
different race require different dose of a particular drug.
Ø Example-
Blacks require higher and Mongols require lower concentration of atropine and
ephedrine to dilate their pupil.
RATE
OF ABSORPTION
Ø The
rate of drug absorption determines the onset of action.
Ø Drugs
which are highly lipid soluble are absorbed fast and will show better action
than polar drugs.
PSYCHOLOGICAL
FACTOR
Ø Efficacy
of a drug can be affected by patient’s attitude and expectations.
Ø Placebo
effect: Placebo is an inert substance. It works by psychological rather than
pharmacological means and often produces responses equivalent to the active
drug.
Ø Nocebo
effect: It refers to negative psychodynamic effect evoked by loss of faith in
the medication or the doctor. Nocebo effect can oppose the therapeutic effect
of active medication.
TIME
OF ADMINISTRATION
Ø Effects
of some drug may be influenced by the setup in which it is taken.
Ø Example: Hypnotics taken at night and in quiet atmosphere may work more easily.
EFFECT
OF OTHER DRUGS
Ø ADDICTIVE
EFFECT: when the total pharmacological effect of two drugs administered
together is equal to the sum of their individual pharmacological effects, the
phenomenon is called addictive effect.
2+2=4
Example:
Ephedrine and aminophylline show addictive effect in the treatment of bronchial
asthma.
Ø SYNERGICTIC
EFFECT: It is the result of two or more drugs interacting together to produce
an effect that is greater than the cumulative effect that those drugs produce
when used individually.
2+2=10
Example:
Codeine and aspirin as analgesic.
Ø ANTAGONISTIC
EFFECT: It is defined as the opposite actions of two drugs on the same
physiological system.
2+2=0
Example:
Protamine reverses the action of heparin.
TOLERANCE
Ø On
repeated administration, some drugs may prove to be ineffective at the usual
therapeutic dose.
Ø That’s
why progressive increase in the dose is required to produce the desired effect.
This phenomenon is known as drug tolerance.
Ø Example-
When Morphine or Alcohol is used for a long time, larger and larger doses must
be taken to produce the same effect.
5. DEFINE CHOLINERGIC DRUGS. CLASSIFY IT WITH SUITABLE SUITABLE EXAMPLES.
GIVE A NOTE ON PHARMACOLOGICAL ACTION OF ACETYLCHOLINE.
ANS:
CHOLINERGIC
DRUGS
These are drugs which
produce actions similar to that of ACh, either by directly interacting with
cholinergic receptors (cholinergic agonists) or by increasing availability of
ACh by destroying cholinestesase (anti cholinesterases).
CLASSIFICATION
1. CHOLINERGIC
AGONISTS
A. CHOLINE
ESTERS: Acetylcholine, Methacholine, Carbachol, Bethanechol
B. ALKALOIDS:
Pilocarpine, Arecoline
2. ANTICHOLINESTERASES
A. REVERSIBLE
I.
CARBAMATES: Physostigmine, Neostigmine,
Pyridostigmine, Edrophonium, Rivastigmine, Donepezil, Galantamine
II.
ACRIDINE: Tacrine
B. IRREVERSIBLE
I.
ORGANOPHOSPHATES: Dyflos, Echothiophate,
Parathion, Malathion, Diazinon
II.
CARBAMATES: Carbaryl, Propoxur
ACETYLCHOLINE
Acetylcholine is the
physiological neurotransmitter at ANS ganglia, postganglionic parasympathetic
nerve ending and neuromuscular junction.
Acetylcholine has two types
of receptors such as muscarinic and nicotinic.
SYNTHESIS,
STORAGE, RELEASE & DESTRUCTION OF ACETYLCHOLINE
Ø Choline, from ECF (extra cellular fluid) enters
into the axoplasm or choline obtained from the degradation of ACh in the
synaptic cleft is recycled and enters the axoplasm.
Within
the neuron, choline conjugates with Acetyl CoA and
acetylcholine is formed.
Ø After
being synthesized, the ACh molecules are stored in the synaptic vesicles.
Ø When
an action potential develops in the axon, it
causes calcium ions enter into the axon and as a
result the vesicles burst releasing ACh.
Ø Then
ACh binds to its receptors and shows action. ACh
is destroyed by hydrolysis by the enzyme cholinesterase.
Ø Then
choline is recycled and taken up by the
cholinergic neuron to form ACh again.
PHARMACOLOGICAL
ACTIONS OF ACETYLCHOLINE:
MUSCARINIC
ACTION:
ON
HEART
It acts on muscarinic
receptors of SA node & AV node and produces bradycardia
(decreased heart rate).
It also acts on atrial
muscle and weakens atrial muscular contractility.
Ventricular
contractility is also decreased but the effect is not marked.
ON
BLOOD VESSELS
On the endothelial
cells of the arterioles, there are ACh receptors but these receptors are not
connected with any parasympathetic nerve. Therefore parasympathetic stimulation
doesn’t have any effect on blood vessels.
But IV administration
of ACh causes pronounced vasodilation and fall of blood
pressure by combining with ACh receptors of endothelial cells.
ON
SMOOTH MUSCLES
Smooth muscles in most
organs are contracted by ACh.
GIT muscles contract,
Salivary glands secret, Urinary bladder contract, Bronchial muscles constrict.
ON
GLANDS
Secretion from all
parasympathetically innervated glands is increased.
Ex- Salivation, Gastric
secretion etc.
The effect on
pancreatic gland and intestinal gland is not marked.
ON
EYE
Miosis (constriction of
pupil), fall of IOP (Intraocular Pressure) occur.
NICOTINIC
ACTION:
AUTONOMIC
GANGLIA
Both sympathetic and
parasympathetic ganglia are stimulated.
High doses of ACh given
after atropine causes tachycardia and rise in BP.
SKELETAL
MUSCLES
Application of ACh to
muscle end plate causes muscle contaction
ON
CNS
ACh injected
intravenously doesn’t penetrate Blood-Brain-Barrier and no central effects are
seen.
However, direct
injection into the brain, produce a complex pattern of stimulation followed by
depression.
USES
Choline esters are rarely, if ever, clinically used.
ACh is not used because
of nonselective action and it is affected by rapid hydrolysis by cholinesterase.
6. WHAT DO YOU MEAN BY SYMPATHOMIMETICS AND PARASYMPATHOMIMETICS?
CLASSIFY ANTI-CHOLINERGIC DRUGS. DISCUSS PHARMACOLOGICAL ACTION OF ATROPINE ON
EYE, CVS, GLANDS AND SMOOTH MUSCLES.
ANS:
SYMPATHOMIMETICS
These are agents which stimulate
the sympathetic nervous system.
PARASYMPATHOMIMETICS
These are agents which
stimulate the parasympathetic nervous system.
ANTICHOLINERGIC
DRUGS
Anticholinergic drugs
are those which block actions of ACh on autonomic effector organs.
Though nicotinic
antagonists also block certain actions of ACh, they are generally referred to
as ‘ganglionic blockers’ and ‘neuromuscular blockers’.
CLASSIFICATION
1.
Natural alkaloids: Atropine, Hyoscine
(scopolamine).
2.
Semisynthetic derivatives: Homatropine,
Atropine methonitrate, Hyoscine butyl bromide, Ipratropium bromide, Tiotropium
bromide.
3.
Synthetic compounds
a. Mydriatics:
Cyclopentolate, Tropicamide.
b. Antisecretory-antispasmodics
i.
Quaternary compounds: Propantheline,
Oxyphenonium, Clidinium, Pipenzolate methlybromide, Isopropamide,
Glycopyrrolate.
ii.
Tertiary amines: Dicyclomine,
Valethamate, Pirenzepine.
c. Vasicoselective:
Oxybutynin, Flavoxate, Tolterodine.
d. Antiparkinsonian:
Trihexyphenidyl (Benzhexol), Procyclidine, Biperiden.
ATROPINE
Atropine, the prototype
drug of this class, is highly selective for muscarinic receptors, however some
of its synthetic substitutes do possess significant nicotinic blocking
property.
Atropine binds to the
muscarinic receptors. So muscarinic receptors are occupied by atropine. That’s
why ACh can not bind to muscarinic receptors.
Atropine is a
reversible inhibitor of ACh or muscarinic antagonist.
PHARMACOLOGICAL
ACTIONS OFATROPINE:
HEART
The prominent action of
atropine is to cause tachycardia. Atropine abolishes the effect of parasympathetic
agents on heart rate.
Therefore atropine
increases the heart rate and improves the atrioventricular conduction by
blocking the parasympathetic influences on the heart.
EYE
On local instillation,
atropine causes pupillary dilation (Mydriasis), by blocking the cholinergic
nerve supply.
The ciliary smooth
muscles are paralyzed by atropine which causes increase in focal length of the
lens.
SMOOTH
MUSCLES
All visceral smooth
muscles that receive parasympathetic motor supply are relaxed by atropine.
Atropine relaxes smooth
muscles of bronchi.
Atropine reduces tone
and motility of GIT.
GLANDS
Atropine reduces the
secretion of exocrine glands.
Atropine may block
watery salivary secretion induced by parasympathetic stimulation.
Atropine also reduces
gastric secretion and it has little effect on pancreatic and intestinal
secretions.
Atropine can reduce the
secretion of sweat as well.
BODY
TEMPERATURE
Atropine causes rise in
body temperature at higher doses due to both inhibition of sweating as well as
stimulation of temperature regulating centre in the hypothalamus.
LOCAL
ANAESTHETICS
Atropine has a mild
anaesthetic action on the cornea.
ADVERSE
EFFECTS
1. Dryness
of mouth, difficulty in swallowing
2. Blurry
vision
3. Constipation
4. Allergic
reactions
THERAPEUTIC
USES
1.
As an antispasmodic in gastrointestinal
colic (cramp like pain in small or large intestine).
2.
It is used for treating peptic ulcer.
3.
It is used as an pre-anaesthetic
medication.
4.
It is used in the treatment of
Parkinson.
7. DEFINE ADRENERGIC DRUGS & CLASSIFY THEM. DESCRIBE ABOUT
PHARMACOLOGICAL ACTION, ADVERSE EFFECT AND USE OF ADRENALINE.
ANS:
ADRENERGIC DRUGS
These are drugs that
stimulate sympathetic nerves in our body. They do this either by mimicking the
action of the neurotransmitters adrenaline (epinephrine) and noradrenaline
(norepinephrine) or by stimulating their release.
These drugs are
otherwise known as sympathomimetic drugs.
CLASSIFICATION
1.
DIRECT ACTING: Adrenaline,
Noradrenaline, Isoproterenol, Dopamine, Phenyl ephrine, Dobutamine, Clonidine,
Metaproterenol, Albuterol.
2.
INDIRECT ACTING:
A. Releasing
Agents: Tyramine, Amphetamine.
B. Uptake
Inhibitor: Cocaine
3.
MIXED ACTING: Ephedrine, Metaraminol.
Direct acting agents
combine directly with adrenergic receptors and produce effects.
Indirect acting agents
are taken up by the presynaptic neuron and cause release of NA from the
presynaptic neuron or they inhibit the reuptake of NA in the synapse.
Mixed acting agents can
combine directly with the adrenergic receptors as well as they can be taken up
by the presynaptic neuron to cause release of
NA.
ADRENALINE
Adrenaline, also known
as epinephrine, is a neurotransmitter and a drug as well.
Adrenaline is produced
both by adrenal glands and a small
number of neurons.
It plays an important role in the sympathetic nervous system (fight or flight response) by binding to adrenergic receptors (alpha & beta).
PHARMACOLOGICAL ACTIONS
OF ADRENALINE
HEART
Adrenaline causes
cardiac stimulation. Both cardiac contractility and heart rate are raised (tachycardia).
Because of its
cardiostimulatory action, adrenaline causes increased demand of oxygen and thus
can precipitate an anginal attack in susceptible patients.
Adrenaline also
increases susceptibility to ventricular fibrillation in persons suffering from
ischemic heart disease.
EYE
Mydriasis occurs due to
contraction of radial muscle of iris.
Adrenaline has complex
effects on aqueous humor. Aqueous humor production is reduced by adrenaline.
GIT
In GIT relaxation
occurs through activation of both Alpha and Beta receptors.
Peristalsis is reduced
and sphincters are constricted, but the effects are brief and has no clinical
importance.
RESPIRATORY SYSTEM
Adrenaline causes
relaxation of bronchial muscle (Bronchodilation).
Adrenaline can directly
stimulate respiratory centre but this action is rarely shown at clinically used
doses.
Toxic doses of
adrenaline causes pulmonary edema.
METABOLIC
Adrenaline produces
glycogenolysis (conversion of glycogen to glucose).
Adrenaline also causes
lipolysis which leads to rise in plasma free fatty acid.
ADVERSE EFFECTS
1.
Palpitation, anxiety, tremor may occur
after IM injection.
2.
Rise in blood pressure leading to
cerebral haemorrhage, tachycardia may occur after IV injection.
3.
Sweating, Dizziness Etc. may occur
THERAPEUTIC USES
1.
Adrenaline is used in the treatment of
cardiac arrest.
2.
It is used to treat severe allergic
reaction (anaphylaxis)
3.
It can be used in the treatment of
bradycardia.