Professional Documents
Culture Documents
UNIT -1
Sources of drugs
Drugs are obtained from different sources
Most of the drugs that are currently used are manufactured synthetically
Recently drugs are synthesized by genetic technologies like human recombinant gene
technology
Ex
Erythropoietin
Cimetidine Antacid
Phenitoin Anti-epileptic
Phenobarbitone Hypnotic
2
Dosage forms
Some antibiotics are available in tablet, capsules or suspension form for oral
administration
For ex
But when the same amount of the drug is administered into the body by oral route in
tablet form, the bioavailability is about is 0.62
On the other hand, the bioavailability of digoxin elixir administered orally is 0.80
Route of administration
To produce a pharmacological effect it is very important for the drug to reach the site of
action
This depends on the transfer of drugs across one or more membrane barriers
There are some drugs which are not absorbable from one site but get into the circulation
from another
Some drugs absorbed from the gastrointestinal tract pass the intestinal mucosa and the
small intestine but metabolized by the gut wall (such as chlorpromazine , dopamine) or
by the liver ( such as lignocaine, pethidine, propranolol)
Slowly absorbed drug may have delayed onset of effect and may even fail to achieve
effective concentration
4
Drugs may act on the cell membrane, inside or outside the cell to produce their effect
1.Through receptor
4. By physical action
5. By chemical interaction
Receptor
It is a macromolecular site on the cell with which an agonist binds to bring about a
change
Affinity
Efficacy
Its the ability of a dung to elicit a response after binding to the receptor
Agonist
Antagonist
An antagonist is a substance that binds to the receptor and prevents the Action of agonist
on the receptor
It has affinity but no intrinsic activity
Partial agonist
It binds to the receptor but has low intrinsic activity
Inverse agonist
Some drugs , after binding to the receptors produce opposite to those produced by a pure
agonist
Eg
Various receptor are have been identified, isolated and extensively studied
Site
The receptors may be present in the cell membrane, in the cytoplasm or on the nucleus
Nature receptors
Function of Receptors
For the above e function , the receptor has two functional domains (areas)
The drug – receptor interaction has been considered to be similar to lock and key
relationship where the drug specifically fits into the particular receptor ( lock) like a key.
Interaction of the agonist with the receptor brings about changes in the receptor which in
turn conveys the signal to the effectors system
The final response is brought about by the effecter system through second messengers.
The agonist itself is the first messenger
The entire process involves a chain of events triggered by drug receptor interaction
Drugs may act by inhibition of various enzymes, thus altering the enzyme- mediated
reactions
Ex
Ex
Omeprazole, digoxin
Drugs may interfere with the movement of ions across specific channels
Ex
Calcium channel blockers and potassium channel blockers
7
4. Physical action.
The action of a drug could result from its physical properties like
Radioactivity - I 131
5. Chemical interaction
Drugs like antimicrobials alter the metabolic pathway in the micro- organisms resulting
in destruction of the micro-organisms
Ex
Cholinergic receptor
10
GABA Receptor
11
Opium receptor
12
Neurotransmitter
14
Secondary messengers
15
TRK RECEPTOR
18
Nuclear receptor
19
Regulation of receptor
20
Def
The chemi
from one
21
CLASSIFICATION
A. Amino acids
The neurotransmitters of this group are involved in fast synaptic transmission & are
inhibitory and excitatory in action
Ex
GABA, Glycine, glutamate (glutamic acid) and aspirate(aspartic acid)
B. Amines
Ex
C. Others
2. Depending on function
A. Expiatory neurotransmitter
B. Inhibitory neurotransmitter
A .Expiatory neurotransmitter
It is responsible for the conduction of impulse from the presynaptic neuron to the post-
Ex
Acetyl choline, adrenaline
B. Inhibitory neurotransmitters
The inhibitory neurotransmitter inhibits the conduction of impulse from the presynaptic
neuron to the post-synaptic neuron
Inhibitory neurotransmitter is released from the presynaptic axon terminal due to the
22
When IPSP is developed, the action potential is not generated in the post-synaptic neuron
Ex
Acetyl choline
Nor-adrenaline
Dopamine
Serotonin
GABA
Histamine
Glycine
Glutamate
Substance P
Nitric acid
1 . ACETYLE CHOLINE
It is a cholinergic transmitter
Site of secretion
23
Neuromuscular junction
Cerebral cortex
Basal ganglia
Thalamus
Synthesis
Acetate activating reaction
Acetate + Co-Enzyme-A + ATP ------------------------------------- Acetyl CoEn-A
Choline acetylase
Acetyl CoEn-A + CHOLINE -- --------------------------------- ACETYLCHOLINE
Receptor
1. Nicotinic receptor
The nicotinic receptors are located on postganglionic cell bodies in the autonomic ganglia
at neuromuscular junctions of skeletal muscle and on neurons of CNS
2. Muscarinic receptors
These are of five types M1, M2, M3, M4 and M5 of which the first three are well defined
The muscarinic receptors are located on smooth h muscle, cardiac muscle, gland cell and
some neurons of CNS
24
Function
Excitatory function
It is synthesized in axon terminals and stored inside the vesicles
Excitatory function
Opening of legand gated Na channels
Ach has very quick and potent action
It also destroyed immediately after executing the action
It is destroyed by the enzyme acetyl-cholinesterase
This enzyme is present in basal lamina of the synaptic cleft
2. Nor-adrenaline
It is the neurotransmitter in adrenergic nerve fibers
Site of secretion
25
In many places, it is the excitatory chemical mediator and in very few places, it causes
Inhibition
It is believed to be involved in dreams, arousal and elevation of moods
Synthesis
It is synthesized from the amino acid tyrosine in the chromaffin cells of adrenal medulla
These hormones are formed from phenylalanine, but phenylalanine has to be converted
into tyrosine
Uptake of tyrosine from blood into the chromaffin cells of adrenal medulla by active
Transport
RECEPTOR
The action of nor-adrenaline are executed by binding with receptors called adrenergic
Receptors
1. Alpha1 receptor
Mode of action
27
It exert their actions by activating the secondary messenger IP3 through phospholipase C
2.Alpha 2 receptor
It exert their effects by inhibiting adenyl cyclase and reducing intracellular CAMP
1. Beta1- receptor
These mediate the actions of both adrenaline and nor-adrenaline almost equally
2. Beta2 receptor
Both B1 and B2 receptors produced their actions by activating adenyl cyclase through G
protein and increasing intracellular cyclic AMP
3. SEROTONINE
It is also called Enteramine as GIT contains 80-90% of all the 5 HT in the body
Hypothalamus
Cerebellum
Limbic system
Midbrain
28
Spinal cord
GIT
Lungs
Platelets
Retina
Synthesis
Tryptophan hydroxylase
Tryptophan --------------------------------------------- 5-Hydroxy-tryptophan (5 HTP)
O2
decarboxylase
5- Hydroxy- tryptamine (5 HT) --------------------------- 5HT
MAO
5-HT -------------------------------------------5- Hydroxy- indole acetic acid (5HIAA)
Serotonin receptor
It is contained mainly in the brainstem neurons that innervate practically all other areas of
the CNS
In general 5 HT has
An excitatory effect on motor pathways
The presence of descending serotonergic neurons in the brainstem and spinal cord is
essential for the analgesic action of morphine
4. GABA
It is an inhibitory neurotransmitter in synapses particularly in CNS
Mechanism of action
29
Presynaptic inhibition
It is also known as indirect inhibition and it occurs because of the failure of presynaptic
axon terminal to release the excitatory neurotransmitter substance
The most important inhibitory neurotransmitter is gamma amino butyric acid (GABA)
and Glycine
The transmitter receptor complex opens the ligand gated potassium channels instead of
sodium channels
The K channels which are more in the cell body of post-synaptic neurons more to ECF
Simultaneously Cl channels also open and Cl ions which are more in ECF move inside
the cell body of post-synaptic neurons
The exit of K ions and influx of Cl ions cause more negativity inside, leading to hyper
polarization
30
Receptors
Opening of ion channels known as chloride channels and conduction of chlorine influx of
Cl ions
2. GABA B ( G- protein coupled receptor)
Hyper polarization
K conduction
Altering of Ca influx
3. GABA C
5. DOPAMINE
It is secreted by nerve endings in the following areas
Basal ganglia
Hypothalamus
31
Limbic system
Retina
Sympathetic ganglia
Receptor
Synthesis
The other physiological functions of circulating dopamine are not understood clearly
Functions
Vasodilatation in mesentery
6. HISTAMINE
It is formed by decarboxylation of the amino acid known as Histidine
It is exciter neurotransmitter
Hypothalamus
Limbic cortex
Gastric mucosa
Mast cells
Spinal cord
Mechanism of action
Functions
Rise in BP
Cardiac stimulation
Behavioral arousal
Hypothermia
Vomiting
ADH release
Sensation of itching
7. GLUTAMATE (ASPARATE)
It is the most abundant amino acid in the brain and is concentrated in dorsal sensory
nerve terminals
Receptor
1. Metabotropic receptor
2. Inotropic receptor
Legend gated ion channels
3. m – GLU
8. GLYCINE
It is inhibitory neurotransmitter
It is formed and released by inhibitory inter-neurons which act on motor neurons in the
brain and spinal cord
Site of secretion
Gyycine concentration in the ventral grey matter of the spinal cord is higher than any
other amino acids
9. SUBSTANCE – P
It is a neuropeptide that acts as a neurotransmitter
The substance p is secreted by the nerve endings of pain pathway in spinal cord
10. NO
It is a neurotransmitter in the CNS
It is produced by non- neuronal cells like the endothelial cells of blood vessels
From the site of production it diffuses into the neuronal and non-neuronal cells where it
exerts its action
It also produced in the brain and is responsible for long term protestation LTP and long
term depression (opposite of LTP)
It activates guanyl cyclase in cells, producing c GMP which brings about relaxation of
vascular smooth muscle
NO is inactivated by haemoglobulin
NO is released by variety of agents such as Ach, sudden increase in tissue blood flow and
products of platelet aggregation
1. Physical dependence
2. Psychic dependence
1. Physical dependence
It is an adoptive state which causes intense physical disturbance when the administration
of the drug is stopped
These disturbances , that is withdrawal produce specific symptoms characteristic for each
drug type
35
2. Psychic dependence
Here there is a feeling of satisfaction and a psychic drive that requires periodic or
continuous use of the drug to produce a sense of well being or to avoid discomfort
Psychic dependence is specific and it varies with the individuals and with the drug
1. Opium drugs
1. The individual problems are that the drugs may adversely affect the physical and
mental health of the addict
2. Socio-cultural problems are that the drug dependence may cause loss of earning
capacity of the drug user
36
3. Socio-legal problem is prohibiting and controlling the traffic in such dangerous drugs.
Further the smuggling of dangerous drugs is to be considered as criminal activity
Tolerance
Def
Concept of can be explained in easiest possible way with the example of effect of
alcohol
After periodic consumption of alcohol the same quantity of alcohol the same can not
produce the same effect, this effect is reduced
To get the same effect, one has to consume more amount of alcohol.
Some times tolerance is observed even when drug is administered for the first time
1. Natural tolerance
2. Acquired tolerance
1. Natural tolerance
Ex
2. Acquired tolerance
It is the decrease in number and sensitivity of receptors for an agonist after prolonged
exposure to it
2. Internalization of receptor
After prolonged exposure to agonists some receptors are taken inside the cell and they
remain unavailable for action
3. Enzyme induction
Alcohol induces hepatic microsomal enzymes that are required for its own metabolism
So long term use of alcohol results in faster metabolism and elimination and reduced
action of alcohol
. Tachyphylaxis
Ex
Ephedrine stimulates release of stored nor adrenaline from the nerve endings
After repeated administrations of ephedrine, the store of nor adrenaline is exhausted and
effect of ephedrine is reduced
Previous prolonged exposure to drug can produce clinical effects that are less than what
are expected
Development of tolerance when demands increase in doses, decision is not very easy.
Because tolerance for effect may not be associated with tolerance for side effects
Cross tolerance
If prolonged use of one drug results in development of tolerance for another drug, it is
cross tolerance for another drug
Ex
38
Pseudo tolerance
From the prehistoric period, poisons are consumed regularly and in small quantities to
develop tolerance against them . This type of logic is not scientifically proved
DISTRIBUTION
39
40
METABOLISM
41
42
43
UNIT – 2
44
NEURO-HUMARAL TRANSMISSION
45
Synapse
It is a region including the axon terminal of a presynaptic neuron, the plasma membrane
of the postsynaptic cell
In presynaptic neurons
Ex
Synaptic cleft
Postsynaptic cells can be neurons or other cells( effecter cell in the muscle)
At synapse, electrical transmissions –action potentials along presynaptic neurons are
translated into chemical signals which lead to postsynaptic cell responses, increases or
excitation , decrease or inhibition or modulation of neuron activity or biochemistry
On postsynaptic membranes
Ex
In postsynaptic neurons
Ex
Stimulations of enzymes
Physiological action
Action potentials at presynaptic axon terminals initiate steps that release neurotransmitter
molecules into a synapse which cross the synaptic cleft and bind reversibly to
postsynaptic receptors
Receptor activators (ex drugs) are agonists and antagonists are drugs that combine with
dopamine)
In brain and spinal cord , major excitatory neurotransmitters are glutamate and aspirate
Neurohumoral transmission implies that nerves transmit their message across synapses
synthesizing it)
stimulation
47
1. Impulse conduction
2. Transmitter release
4. Postjuctional activity
1. Impulse conduction
The resting Tran membrane potential (70 mV negative inside) is established by high K
permeability of axonal membrane and high axoplasmic concentration of this ion coupled
K ions then move ort in the direction of their concentration gradient and repolarization
occurs
Ionic distribution is normalized during the refractory period by the activation of Na-K
pump
The action potential generated sets up local circuit currents which activate ionic channel
at the next excitable part of the membrane ( next node of Ranvier in myelinated fiber )
Transmitter release
synaptic vesicles
Nerve impulse promotes fusion of vesicular and axonal membranes, through Ca entry
All contents of the vesicle ( transmitter, enzymes and other proteins)are extruded in the
functional cleft
EPSP
It increase in permeability to all cations –Na or Ca influx ( through fast or slow channels)
These ionic movements are passive as the flow is down the concentration gradients
IPSP
That is K and Cl ( hydrated K ion is smaller than hydrated Na ion) only, so that K
moves out and CL moves in (in the direction of their concentration gradients ) resulting
in hyper polarization
4. Postjunctional activity
49
Following its combination with the receptor ,the transmitter is either locally degraded (ex
Ach) or is taken back into the prejunctional neuron by active uptake or diffuses away (ex
NA, GABA)
Rate of termination of transmitter action governs the rate at which responded can bet
Parasympathomimetic drugs
1. Choline esters
Acetyl choline
Methacholine - 10-30 mg , s/c
Carbachol- 0.2 – 0.5mg s/c , or 1-4mg , orally
Bethanechol- 2.5 mg s/c, 5 -30 mg orally
Polocarpine
Muscarine
Arecholine
3. A . Cholinesterase inhibitors
Physostigmine
Neostigmine
Pyrodostigmine
Benzpyrinium
Ambenonium
Edrophonium
Demecarium
Cholinergic receptor
PNS
52
53
Cholinergic system
Acetyl choline (Ach) an ester of choline, is an important neurotransmitter of the ANS
The nerves that synthesize, store and release Ach are called cholinergic
Cholinergic receptors
Muscarinic receptors are present in the heart, smooth muscles, glands , eyes and CNS
Nicotinic receptors are present in the neuromuscular junction, autonomic ganglia and
adrenal medulla
Nm receptors are present at the skeletal muscle end plate and Nn receptors at the
autonomic ganglia and adrenal medulla
3. Sweet glands – The sympathetic postganglionic nerve endings supplying the sweet
Glands
5. Adrenal medulla
Synthesis of Ach
Acetyl choline synthesized from acetyl coA and choline , catalyzed by the enzyme
choline acetyltransferase
This Ach is stored in small oval vesicles known as synaptic vesicles in the cholinergic
nerve terminals
Transmission of an impulse
When as action potential reaches the presymaptic membrane, Ach is released into the
synaptic cleft
This Ach binds to and activates the cholinergic receptor on the postsynaptic membrane
leading to the depolarization of this membrane
The Ach released into the synaptic cleft is rapidly destroyed by the acetyl cholinesterase
enzyme
Cholinesterase
Acetylcholine is hydrolyzed to choline and acetic acid by the enzymes cholinesterase
Two types of Ach enzymes are present
Cholinergic receptor
56
Parasympatholytic drugs
1. Belladonna alkaloids
Atropine
Scopolamine
Homatropine
Atropine methyl nitrate
Scopolamine methyl bromide
Homatropine methyl bromide
Methamtheline
Propantheline
Oxyphenonium
Dibutoline
Cyclopentolate
57
Sympathomimetic drugs
1.Alpha receptors
Noradrenalin
Mephentermine
Metarminol
Methoxamine
Phenylephrine
2. Beta receptor
Isoprenaline
Isoxsuprine
Nylidrine
ANERGIC RECEPTOR
59
60
61
A. Alpha -1 blockers
Prazosine
B. Alpha – 2 blockers
Yohimbine
Phenoxybenzamine
Dibenamine
Tolazoline
Phentolamine
Ergot alkaloids
A. Beta -1 blockers
Atenolol
Acebutolol
Metaprolol
B. Beta-2 blockers
Butoxamine
Propranolol
Sotolol
Nodolol
Timolol
62
UNIT - 3
Guanethidine
Guanoxon
Guanachlor
Bethanidine
Debrisoquine sulphate
63
Though the ganglionic stimulating agents have no therapeutic use, they find use as
experimental tools
Classification
1. Natural alkaloids
Nicotine
Lobeline
2. Synthetic compounds
Nicotine
Lobeline
Dim ethyl phenyl piperazinium iodide (DMPP)
Tetra methyl ammonium (TMA)
Acetylcholine
Carbachol
Pilocarpine
Anticholinesterases
65
1. Competitive agents
D- Tunocurarine
Gallamine
Pancuronium
Alcuronium
Atracurium
Vecuronium
2. Depolarizing agents
Succinylcholine
66
Local anesthetics
Def
Local anesthetics are drugs that block nerve conduction when applied locally nerve tissue
in appropriate concentrations
1. Injectable
Procaine
Chlo-procaine
Tetracaine (Amethocaine)
Cinchocaine
Bupivacaine
Ropivacaine
Cocaine
Lignocaine
Tetracaine
B. Insoluble
Benzocaine
Butamben
Oxethazaine
67
They act on every type of nerve fiber and can cause both sensory and motor paralysis in
the innervated area
They act on axons, cell body , dendrites, synapse and other excitable membranes that
utilize sodium channels as the primary means of action potential generation
Cocaine was the first agent to be isolated by Niemann in 1860 and used for 30 years
Procaine was synthesized in 1905 and it rules the field for the next 50 years
In 1943 , Lignocaine was synthesized and it continues to dominate the field till today
Chemistry
Local anesthetics are bases and consist of a hydrophilic amino groups on one side and a
lopophilic aromatic residue on the other side , joined by an intermediate chain through an
ester or amide linkage
Local anesthetics are weak bases and the infected tissues have a low extra cellular PH
Local anesthetics ionize in such medium bases and the infected tissues have a low extra
cellular PH
Local anesthetics ionize in such medium and a very low fraction of non-ionized LAs
available for diffusion into the cell
Action potential
If enough Na channels are opened, then the rate of Na entry into the axon exceeds the rate
of K exit
68
Threshold potential
At the point where the rate of Na entry into the axon exceeds the rate of K exit that point
is called threshold point or threshold point
At the this point, the entry of Na ions further depolarizes the membrane
This opens more Na channels, resulting in further depolarization that opens more Na
channels and so on.
The fast inward Na current quickly depolarizes the membrane towards the Na equilibrium
potential around + 70 m V
Then, Inactivation of the Na channels and the continuing efflux of K ion cause the
repolarization of the membrane
Finally, the Na channels regain their normal excitable state and the Na pump restores the
lost K and removes the gained Na ions
Mechanism of action
Local anesthetics prevent the generation and the conduction of nerve impulses
Local anesthetics directly interact with specific site or receptor on voltage – sensitive Na
channels and gradually raise the threshold for excitation
That is autonomic fibers are blocked first followed by sensory fibers conducting pain,
temperature sense, then touch, pressure and vibration sensations in the same order
Non – myelinated fibers are blocked more readily than the myelinated
Pharmacological actions
69
1. Effect on sensation
They produce blockade of smaller nerve fibers initially followed by large nerve fibers
Recovery occurs in the reverse order
Applied to the tongue, bitter taste is lost firs followed by sweet and sour and salty taste
If it is given with adrenaline through injection route, the adrenaline reduces the systemic
toxicity of local anesthetics because it reduces the rate of absorption and metabolism
keeps the plasma concentration lower and increase the activity when exactly the action is
required
2. CNS
Procaine and lignocaine are synthetic compounds and much less potent in this regard
3. CVS
All LA produces depressant effect on the myocardium, they increase the effective
refractory periods similar effect of the quinidine so used in the arrhythmias
4. Other effects
Pharmacokinetics
These are rapidly absorbed from the mucous membranes and abraded skin
Adverse effects
Hypersensitive reactions like skin rashes, dermatitis , angioedema, asthma and rarely
anaphylaxis
CVS Effects
Like light headedness, dizziness, auditory and visual disturbances , mental confusion,
disorientation, shivering, twitching, tremors, finally convulsions and reparatory arrest
CVS Effects
The effects like bradycardia, hypotension, cardiac arrhythmias and vascular collapse
Rarely cardiac arrest is seen
USES
Some of the important drugs which possess this action are cocaine, procaine.lignocaine,
benzocaine and amethocaine
Cocaine
It is poorly absorbed in the intestines but well absorbed by the mucous membrane and it
can be given as surface anesthetic
Actions
CNS stimulants
Dilates pupil
Rise the BP
Produces euphoria
Toxic effects
Mental excitement
Confusion
Tremors
Convulsions
Respiratory paralysis
Dose
8 – 16 mg by injection
Adrenaline has to be given along with cocaine which produces local vasoconstriction and
prolong the local anesthetic effect
Procaine
It rapidly diffuses from the site of injection and vasoconstrictors like adrenaline as to
given , to prolong the effect of procaine
Dose
0.25 - 2% solution is injected subcutaneously
It is injected into the spinal theca to block spinal nerves and to produce spinal anesthesia
This is more powerful and more stable and longer acting than procaine
Toxicity
Toxicity is very low
I fit is combined with adrenaline the effect will last for about two hours
It can also be used in the treatment of status epilepticus and acute ventricular arrhythmia
Benzocaine
This is a local apathetic employed as an application to various mucous surfaces
It is incorporated in throat lozenges to relieve the local soreness and is used in rectal
suppositories
Amethocaine
UNIT - 4
General anesthetics
73
Def
General anesthetics are drugs which produce reversible loss of all sensation and
consciousness
Abolition of reflexes
1. Inhalation anesthetics
A. Gas
Nitrous oxide
Cyclopropane
Ethylene
B. Liquids
Ether
Chloroform
Halothane
Ethyl chloride
Vinyl ether
Thiopentone
Methohexitone
Ketamine
Paraldehyde
Properties
Actions
5-10% of ether is required in the inspired air to induce anesthetic and at least 3-5% to
maintain it
It irritates respiratory tract leading to efflux secretion of saliva and mucous from the
mouth and respiratory tract
The initial stages are more prolonged with ether in the absence of premeditation
Other actions
Advantages
Dis-advantages
It catches fire
Induction of anesthesia as well as Recovery are slow
Vomiting is likely to occur postoperatively
Generalized convulsions are produced specially in children
Chloroform
Actions
Other action
Advantages
Disadvantages
Chloroform depresses myocardium resulting in slowing down of the heart and even
cardiac arrest
Liver function is affected leading to necrosis and hepatic failure and death
Intestinal motility is diminished
Blood concentration of about 15 mg% is required to maintain anesthesia but about 20-25
mg% is fatal
Halothane
Physical properties
Advantages
Recovery is also fast , smooth with low incidences of nausea and vomiting It is not
inflammable and hence does not irritate respiratory passage inhibits salivary secretion
hence endotracheal intunotion is much easier
It does not produce bronchospasm, and can be used in patients with bronchial asthma
Dis advantages
It is poor analgesic
Nitrous oxide
Properties
It is non inflammable
Advantages
Irritation is less
Disadvantages
Uses
It is used for short duration operations such as tooth extraction or setting right a fracture
It is used along with the oxygen for producing partial anesthesia following basal
anesthetics
Halothane
Physical properties
It effects most of metals including stainless steel, brass, cupper and rubber
78
Advantages
It is not inflammable and hence does irritate respiratory passage inhibits salivary
secretion hence end tracheal intubations is much easier
It does not produce branch spasm, larygospasm, hence can be used in patients with
bronchial asthma
Disadvantage
It is poor analgesic
Intravenous anesthetics
Barbiturates are generally used as intravenous general anesthetics for short term
operations
Of these Thiopentone and hex baritone are the drugs of choice being given by the slow
route to avoid respiratory arrest
Advantages
Easy to administer
Non-expensive
Disadvantages
Poor analgesia
Preparations
Thiopental sodium --- 2.5% solution
Methohexitone --- 1% solution
Propanidid --- 4mg/Kg
Ketamine --- 1.2mg/Kg
General anesthetics
General anesthetics are the drugs which are used to produce complete loss of sensation to
allow the surgical operations to be performed without the sensation of pain to the patient
General anesthetics depress the sensory as well as motor nerves and produce loss of
sensation which is reversible
When discontinued the anesthetic should be eliminated quickly without harming the
tissues
80
It should produce adequate muscular relaxation with complete motor and sensory
paralysis
Stages of anesthesia
Induction of general anesthesia is divided into four stages according to the deapth of CNS
depression
All these stages are continuous but described separately for the sake of clarity
1. Stage of induction
2. Stage of excitement
1. Stages of induction
There is a sensation of warmth and suffocation , reflex secretion of mucous and saliva
with coughing and sneezing are noticed
Muscle are stiff, pupils are dialate and pulse rate is quick
2. Stage of excitement
Sensory nerves cells are paralyzed first but motor reflexes are still present
Here complete paralysis of the enters of cerebral cortex and Spinal reflexes commences
This is reversible
Muscles are relaxed , pulse is slow and regular, respiration becomes slow
This stage is suitable for surgical operations to be performed as all the motor reflexes are
abolished and the muscles are relaxed fully
Pupil are dilated and inactive , pulse becomes weak and blood pressure falls.
Finally respiration stops leading to the arrest of the heart and death
Soon after the removal of the anesthetic the respiration becomes quieter and less
strenuous
Pupils dilate, coughing, acute vomiting may occur just before returning to consciousness
Mechanism of action
This is a complex polysynaptic pathway in the brainstem reticular formation that projects
diffusely to the cortex
The general anesthetics increase the sensitivity of the gamma- amonobutyric acid (GABA
A) receptors to the neurotransmitter, GABA, at clinically effective concentration of the
drug
This causes a prolongation of the inhibitory chloride ion current after a pulse of GABA
release.
Ex
The activity of the inhibitory glycine receptors in the spinal motor neurons is increased
The inhalation anesthetics block the excitatory postsynaptic current of the nicotinic
receptors
Pre-unaesthetic medication
Aim
To induce sedation
To decrease gastric secretion
1.Opiods
Ex
83
Morphine
To produce analgesia
2. Sedatives
Ex
Diazepam or lorazepam
3. Anti-cholinergic
Ex
Atropine
4. Neuroleptics
Ex
Chlorpromazine
5. H2 Blockers
Ex
Ranitidine
6. Anti-emetics
Ex
Metaclopramide
To reduce post operative vomiting
Alcohols
Alcohols are aliphatic hydrocarbons
Classification
1. Mono-hydroxy alcohols
2. Dihydroxy alcohols
3. Tri-hydroxy alcohols
Glycerol or glycerine
4. Poly-hydroxy alcohols
Mannitol, sorbitol
Ethyl alcohol
Ethyl alcohol is commonly used alcohol
Mechanism of action
Alcohol produce CNS depression by a generalized membrane action by altering the state
of membrane lipids
The activity and translocation of channel or enzyme proteins in the membrane could be
affected by alcohol through protein kinase C and protein kinase A mediated alteration in
the state of their phosphorlation
Pharmacological actions
1. Externally
It evaporates quickly and producing cooling effect and is used for reducing the
temperature in fevers
In concentration of 70% , it acts as antiseptic , the action is seen only against vegetative
forms of organism and spores are resistant
2. GIT
It has an irritant action on the gastric mucous membrane and act as appetizer
50 ml of 7-10% alcohol increases the gastric secretion ,by releasing histamine and
gasstrin from the antrum of the stomach
Concentration above 15% inhibit both motility and secretion and effect may persist for
many hours
Concentration above 20% reduce the enzymatic activity of the gastric and the intestinal
juices
Concentration above 40% and over have a direct toxic effect on gastric mucosa and may
precipitate gastritis, giving rise to pain, nausea, vomiting and other symptoms
Many alcoholics suffer from chronic diarrhea as a result of malabsorption from chronic
mucosal damage
3. CNS
It is primarily a CNS depressant and acts by enhancing the inhibitory GABA receptor
activity or inhibiting NMDA receptors
4. CVS
Small dose produce only cutaneous and gastric vasodilatation B.P is not affected
Moderate doses cause tachycardia and a mild rise in BP due to increased muscular
activity and sympathetic stimulation
Large doses cause direct myocardial as well as vasomotor centre depression and there is
fall in BP
Chronic alcoholism may contribute to hypertension and lead to cardiomyopathy
Atrial fibrillation and other cardiac arrhythmias may occur due to conduction defects and
Q-T prolongation
5. On respiration
Moderate doses produce slight stimulation whereas large doses produce respiratory
depression which may be fatal
87
6. Kidney
7. Sax
8. Body temperature
Alcohol produces a sense of warmth due to cutaneous and gastric vasodilatation , but
heat loss is increased in cold surroundings
9. Liver
Alcohol produces little direct effect. Fatigue is produced by small doses, but muscle
work is increases or decreased
11. Blood
Regular intake of small to moderate amounts has been found to raise HDL levels and
decrease LDL oxidation
Megaloblastic anemia has been seen in chronic alcoholism due to interference with
folate metabolism
Alcohol dehydrogenase
Ethyl alcohol -------------------------------------------------------Acetaldehyde
Aldehyde dehydrogenase
Acetaldehyde-------------------------------------------------------------Acetyl CoA
Toxicity
Hypotension
gastritis
hypoglycemia
Collapse, respiratory depression
Coma and death
Treatment
89
Gastric lavage maintain patent airway and take steps to prevent aspiration of vomit us
Most patients will recover with supportive treatment, maintenance of fluid and
electrolyte balance and correction of hypoglycemia by glucose infusion till alcohol is
metabolized
Chronic alcoholism
Physical dependence occurs only on heavy and round the clock drinking
Treatment
Many CNS depressants like barbiturates , phenothiazines, chloral hydrate have been used
as substitution therapy in the past to suppress withdrawal syndrome but benzodiazepines
like chordiazepoxide, diazepam are the preferred drugs now
These have a long duration of action and can be gradually withdrawn later
Disulfiram
It is a drug for the treatment of chronic alcoholism
It is administered at a dose of 500 mg once daily for a week and alter 250 mg daily as
maintenance dose
Flushing
Burning sensation
Throbbing headache
Perspiration
Uneasiness
Tightness in chest
Dizziness
Vomiting
Visual disturbances
Mental confusion and circulatory collapse
Duration of the syndrome (1-4 hours ) depends on the amount of alcohol consumed
Disulfiram is used in chronic alcoholics who are motivated and sincerely desire to leave
the habit
Sensitization to alcohol develops after 2-3 hours of first dose and lasts for 7-14 days after
stopping it ,because inhibition of aldehyde dehydrogenase with disulfiram is irreversible
Synthesis of fresh enzyme is required for return of activity
Unit - 5
91
Qualitatively hypnotics and sedatives produce depression of CNS and the difference
between them is mainly quantitative
1. Barbiturate derivatives
2. Non – barbiturate derivatives
1 .Barbiturate derivatives
Phenobarbitone
Mephobarbitone
Methylphenobarbitone
Barbitone
Amylobarbitone
Butobarbitone
Allobarbitone
Vinbarbitone
Pentobarbitone
Secobarbitone
Cyclobarbitone
Hepatobarbitone
Thiobarbitone
Hexabarbitone
Methobarbitone
A. Benzodiazepines
Diazepam
Oxazepam
B. Aldehydes
Chloral hydrate
Chloral formamide
Paraldehyde
C. Bromides
Potassium bromide
Sodium bromide
Ammonium bromide
D. Alcohols
Ethyl alcohol
Tribromo-ehamol
Amylene hydrate
E. Piperidine derivatives
Glutethimide
Methyprylon
Barbiturates
93
Barbituric acid itself does not possess hypnotic activity but hypnotic activity is produced,
if the hydrogen atoms at position 5 are replaced by alkyl or aryl groups
The barbiturates were formerly the mainstay of treatment used to sedate the patient or to
induce and maintain sleep
Today , they have been largely replaced by the benzodiazepines, primarily because
barbiturates induce tolerance, drug metabolizing enzymes, physical dependence and
severe withdrawal symptoms
The sedative – hypnotic action of the barbiturates is due to their interaction with GABA A
receptors which enhances GABA nergic transmission
Barbiturates potentate GABA Acton on chloride entry into the neuron by prolonging the
duration of the chloride channel openings
Pharmacological actions
On CNS
Barbiturates produce all degrees of CNS depression like mild sedation, hypnosis and
general anesthesia
Sleep
But it decreases the time spent on rapid-eye movement sleep, also there is hangover
effect after awakening
Analgesic effect
94
They enhance the analgesic effect of salicylates and para-amino phenol derivatives
Anesthetic effect
Barbiturates like phenobarbitone which have a phenyl group at the 5 th carbon atom have
anticonvulsant effect
Respiration
Large dose administered intravenously may produce death due to central respiratory
paralysis
GIT
Intestinal motility is not affected at a normal dose, but gastric secretion may be depressed
Uterus
Kidney
No effect at normal dose but anesthetic dose decreases urinary output due to decrease in
glomerular filtration and release of Ach
Liver
No effect at normal dose but anesthetic dose may produce hepatic dysfunction
Enzyme induction
ADME
95
They are chiefly metabolized in the liver and to a small extent in kidney and brain
Excretion is through urine both in free form and as glucuronic acid conjugate
Adverse reaction
Therapeutic uses
Benzodiazepines
96
These are very important class of hypnotics and sedatives because of their high
therapeutic index
Diazepam
Flurazepam
Nitrazepam
Lorazepam
Oxazepam
Mechanism of action
The GABA (Gamma amino butyric acid ) is acts as an inhibitory neurotransmitter in the
body
These benzodiazepines acts on GABA and stimulate the GABA receptors , leading to
increase in the GABA activity
GABA activating the chloride channels leading to increase in the Cl conductance and
hence decrease firing of the regions
Therapeutic uses
As a pre-anesthetic medication
Adverse effects
Drowsiness, confusion, impaired motor in co-ordination, tolerance and dependence to the
less extent and reparatory depression
Chloral hydrate
97
The drug is an effective sedative and hypnotic that induces sleep in about thirty minutes
and lasts about six hours
Chloral hydrate is irritating to the gastrointestinal tract and causes epigastric distress
It does not have the analgesic activity but may produce excitement and delirium in
presence of pain
Adverse effects
Nausea, vomiting, gastric irritation, respiratory and vasomotor depression , myocardial
depression and arrhythmia
Paraldehyde
It is nauseating and volatile, liquid hypnotic which is harmless and quick in Acton
During labor it causes analgesic effect but it can cross placenta and may delay respiration
in new born
It reacts with plastic materials so cannot administer with the plastic syringes
Ethyl alcohol
98
It has antianxiety and sedative effects , but its toxic potential outweighs its benfits
Ethanol is a CNS depressant producing sedation and ultimately hypnosis with increasing
dosage
It is readily absorbed orally and has a volume of distrinution close to that of total body
water
Elimination is mostly through the kidney, but a fraction is excreted through the lungs
Ethanol synergizes wit h many other sedative agents and can produce severe CNS
depression with antihistamines or barbiturates
Chronic consumption can lead to severe liver disease, gastritis and nutritional
deficiencies
Antianxiety drugs
99
Def
Antianxiety drugs (anxiolytics) are CNS depressants which control symptom of anxiety
They produce a calming effect in anxiety states
1. Benzodiazepines
Diazepam
Oxazepam
Lorazepam
Alprazolam
2. Azapirones
Buspirone
Gipirone
Benzodiazepines
Mechanism of action
It is believed that these agents facilitate the effects of GABA receptor activation in the
CNS
Side effects
Sedation
Lethargy
Ataxia
Weight gain
Confusion
Tolerance
Dependence
Diazepam
100
Like all other benzodiazepines, it has a hypnotic, anxiolytic, muscle relaxant and
anticonvulsant actions
Uses
Status epileptic us
Dose
2- 5 mg twice a day
Oxazepam
Dis-advantages
It is short acting
Dose
10 mg
Lorazepam
Dose
1-4mg
Alprazolam
USE
Dose
Meprobamate
Adverse reaction
Drowsiness
Angioneurotic edema and other r allergic manifestations
Blood dyscrasias
Disadvantages
102
Tolerance develops
IT produces drug
Dependence
USES
Anxiety
Neurosis
Chlordiazapoxide
It produces calmness
It stimulates appetite
Adverse reaction
Disadvantages
Tolerance develops
Use
As preanaesthestic medication
Buspirones
It does not have sedative, hypnotic, muscle relaxant and anticonvulsant effects as
103
produced by benzodiazepines
It has a slow action and the effect is delayed for even two weeks
Mechanism of action
USE
Dose
Flumazinil
It is a benzodiazepine antagonist
USE
In Benzodiazepine overdose
The classes of drugs which can be used fro skeletal muscle relaxation are centrally acting
drugs and drugs acting peripherally at neuromuscular junction
1. Mephenesin group
Mephenesin
Carisoprodol
Chlorzoxazone
104
Chlormezamone
Methocarbamol
2 .Benzodiazepines
Diazepam and others
3. GABA derivative
Baclofen
Tizanidine
Mepaenesin
It is the first centrally acting muscle relaxant which was introduced in 1946 still being
widely used today
It relaxes normal and spastic skeletal muscles without interfering within neuro-muscular
transmission
The drug is will absorbed orally and parent rally ,but duration of action is short
It is used to treat acute spasm of skeletal muscle in tetanus and status epileptic us
Use to reduce agitation in chronic alcoholism an to relieve muscular rigidity and tremors
in parkinsonism
Dose
Mephenesin carbamate an ester of mephanesin has a longer duration of action and hence
is preferred
Methocarbamol
It is orally active with a longer duration of action and milder side effects
Carisoprodol
Unwanted side effects are drowsiness, vertigo, weakness and allergic reactions on skin
Metaxalone
But there are drugs which block the action f acetyl choline on skeletal muscle receptors
thereby producing muscle relaxation
1. Competitive blockers
2. Depolarization blockers
106
1. Competitive Blockers
The drugs which act by this mechanism are d-tubocurarine and gallamine
D-Tubocurarine
This is the dextro rotatory alkaloid obtained from the strychnos species
It competes with acetyl choline to reach the receptors and thus blocks the action of
acetylcholine at the neuromuscular junction and produces muscle relaxation
The drug is given intravenously for muscle relaxation during operative procedures
Gallamine
Depolarization blockers
Here the drugs act by depolarizing the receptor motor end plate of the muscle which
becomes resistance to further stimulation
The drug which acts by this process and relaxing skeletal muscles is succinyl chloride
Unit - 6
Anti-psychotic drugs
These are the drugs which used in treatment of major psychosis
They are also called a major tranquilizers, since they reduce agitation and disturbed
behavior seen in schizophrenia
1. Phenothiazines
Chlorpromazine
Triflupromazine
Fluphenazine
Thioridazine
2. Butyrophenones
Haloperidol
Trifluperidol
3. Rauwolfia alkaloids
Reserpine
4. Thioxanthines
Chlorprothixene
Thiothixene
5. Indolic derivatives
Molindine
6. Miscellaneous
Oxypertine
Tetrabenazine
Pimozide
109
CHLOPROMAZINE (CPZ)
These are the most widely used compounds in the treatment of major psychoses
Phenothiazines are three ringed structures
In which two benzene rings are linked by a sulphur and a nitrogen atom
Mechanism of action
Phenothiazines and other antipsychotic drugs produce beneficial effects probably by
affecting three of the major integrating systems in the brain
Mesolimbic system
Mesocortical system
Hypothalamus
Pharmacological actions
On CNS
When chlorpromazine is given to patients with psychosis , it produces
Psychomotor slowing
Emotional quietening
Decreased initiative
Decreased anxiety
Behavioral effects
In normal subjects CPZ reduces motor activity, produces drowsiness and indifference to
surroundings
In psychotic agitated patients, it reduce aggression , initiative and motor activity, relieves
anxiety and brings about emotional quietening and drowsiness
Cortex
CPZ lowers seizure threshold and can precipitate convulsions in untreated epileptics
Hypothalamus
Basal ganglia
Brainstem
Anti-emetic action
On ANS
CPZ also has ant cholinergic properties which leads to side effects like dryness of mouth,
blurred vision, reduced sweating, decreased gastric motility, constipation and urinary
retention
The degree of anti cholinergic activity also varies with each drug
CVS
CPZ produce hypotension due to alpha blockade action and reflex tachycardia
These has local anesthetic properties but is not used for the purpose since in is an irritant
Kidney
Tolerance develops to the sedative and hypertensive actions while no tolerance is seen to
the anti psychotic actions
On endocrine glands
These effect are produced by blocking the action of dopamine on hypothalamus and
pituitary
Other actions
Inhibition of hiccough
The half life period is 20 to 24 hours and is therefore given once a day
It is metabolized in the liver and the metabolic products are excreted in urine s
Adverse reaction
CNS effects
ANS effects
CVS effects
Hemopoietic effects
Endocrine effects
Hypersensinitivity reactions
Drug interactions
CPZ enhance the sedative effects of CNS depressants, alpha blockers and of ant
cholinergic drugs
When combined with these groups of drugs , the effects may be additive
Dose
Uses
In acute psychosis they may be given intramuscularly and response is seen in 24 hrs
While in chronic psychosis it takes 2-3 weeks of treatment to demonstrate the beginning
of obvious response
Drug dependence
They are useful in the management of psychosis associated with chronic alcoholism tbu
are contraindicated in acute withdrawal syndromes for fear of precipitating seizures
Haloperidol
This is a very potent drug, belonging go the class of butyrophenones but with similar
clinical effects as piperzine phenothiazines
It is more effective in highly agitated or manic patients and has less prominent sedative
and autonomic effects than chlorpromazine
It can also be given IM in the dose of 2-10 mg, repeated every hour up to a total of 30
mg, in agitated and violent patients
The incidence of EPS with this drug is high and it dies not seem to be superior to
phenothiazines in the routine treatment of schizophrenia
The irreversible toxic encephalopathy has been reported in patients on lithium if they are
given high doses of haloperidol
The other drugs of this series are trifluperidol and droperidol which are used in
combination with fentamyl for neuroleptanalgesia
Rauwolfia alkaloids
In ancient Ayurvedic medicine, the extract of this plant has been claimed to be useful in
cases of insomnia , insanity and snake bite
Mechanism of action
A single dose of 5 mg / kg body weight is sufficient to cause 90% reduction in brain nor
adrenaline and 5-HT over a period of 10 days
This depletion of cerebral monoamines is believed to be responsible for its central actions
Pharmacological actions of reserpine
CNS
It has central antipsychotic action resembling those of phenothiazines
It differs from the latter compounds in that it has no antihistaminic, cholinergic blocking
or direct adrenergic blocking effects
In man , it produces a similar calming effect as well as extra pyramidal action as those
observed flowing chlorpromazine
CVS
115
Clozapine
Its major advantage is that the drug improves not only the positive symptoms but also the
negative symptoms such as emotional withdrawal, bunted affect, retardation and social
withdrawal
It is started in the dose of 12.5 mg once daily and gradually increased to 200- 450 mg /
day in divided doses
Adverse reactions
These includes nausea, vomiting , sedation , hypotension , severe tachycardia , and
confusion
116
Anti-depressant drugs
These are the drugs used for the treatment of mental depression
Meclobemide
Phenelzine
Isocarboxazid
Nialamide
Imipramine
Desipramine
Amitriptyline
Nortriptyline
Citalopram
Escitalopram
Paroxetine
Sertaline
Phenelzine
Tranylcypromine
117
Monoamine oxidase (MAO) is a mitochondrial enzyme found in nerve , liver and gut
In the neuron, MAO functions is to deaminate and inactivate any excess neurotransmitter
molecules (nor epinephrine, dopamine and serotonin) that may leak out of synaptic
vesicles when the neuron is at test
The MAO inhibitors may irreversibly or reversibly inactivate the enzyme, permitting
neurotransmitter molecules to escape degradation and therefore to both accumulate
within the presysaptic neuron and leak into the synaptic space
This causes activation of nor- epinephrine and serotonin receptors and it may be
responsible for the antidepressant action of these drugs
Two MAO inhibitors are currently available for treatment of depression- Phenelzine and
tranylcypromine
The use of MAO inhibitors is now limited due to the complicated dietary restrictions
required of patients taking MAO inhibitors
Mechanism of action
MAO inhibitors such as phenelzine form stable complex with enzyme, causing
irreversible inactivation
These results in increased stores of nor epinephrine, serotonin and dopamine within the
neuron and subsequent diffusion of excess neurotransmitter into the synaptic space
Pharmacological actions
1.Behavior
In case o f mental depression, these compounds elevate the mood
The patient feels more energetic and fresh
2. On CVS
No effect on heart or circulation at normal dose
Uses
MAO inhibitors are indicated for depressed patients who are un- responsive or allergic to
TCA or who experience strong anxiety
Adverse effects
Behavioral effects
CNS effects
ANS effects
Hypertension
Tyramine is met abolished by the enzyme MAO
These blocks nor epinephrine and serotonin uptake into the neuron
119
These drugs are voluble alternative for patients who do not respond to SSRIs
Mechanism of action
These are potent inhibitors of the neuronal re-uptake of nor epinephrine and serotonin
into presynaptic nerve terminals
TCAs also block serotonergic, alpha adrenergic ,histamine and muscarinic receptors
Pharmacological actions
1. Behavior
The onset of the mood elevation is slow , requiring two weeks or longer
These drugs do not produce CNS stimulation or mood elevation in normal individuals
The drugs can be used for prolonged treatment of depression without loss of effectiveness
2. CVS
3. ANS
Imipramine produces anti cholinergic effects like dry mouth, constipation , palpitation
and blurred vision
ADME
Because of their lipophilic nature ,they are widely distributed and readily penetrate into
the CNS
This lipid solubility also causes these drugs to have long half lives – 4 – 17 hours for
imipramine
120
These drugs are metabolized by the hepatic microsomal system and conjugated with
glucuronic acid
Adverse reactions
CNS effects
ANS effects
CVS effects
Allergic reactions
Uses
Imipramine has been used to control bed- wetting in children by causing contraction of
the internal sphincter of the bladder
These drugs do not produce CNS stimulation or mood elevation in normal individuals
Pharmacological actions
SSRIs block the re-uptake of serotonin , leading to increased concentrations of the
neurotransmitter in the synaptic clefts and to greater postsynaptic neuronal activity
The patients that do not responds to one antidepressant may respond to another and
approximately eithy percent or more will respond to at least one antidepressants drug
Pharmacokinetics
These are well absorbed on oral administration
Fluoxetine and paroxetine are potent inhibitors of a hepatic cytochrome P-450 iso
enzymes responsible for elimination of tricyclic antidepressant drugs
Excretion of the SSRIs is primarily through the kidneys except for paroxetine and
sertraline which also undergo fecal excretion
USES
The primary indication for SSRIs is depression, for which they are as effective as the
tricyclic antidepressants
Adverse reaction
SSRIs have fewer and less severe adverse effects than the tricyclic antidepressant and
MAOI
1. Sleep disturbances
Paroxetine and fluvoxamine are sedating and may useful in patients who have difficulty
sleeping
2. Sexual dysfunction
Loss of libido, delayed ejaculation and anorgasmia are underreported side effects often
noted by clinicians but not prominently featured in list of standard side effects
Anti depressants should be used cautiously in children and teenagers , because about one
out of fifty children become more suicidal as result of SSRI treatment
Pediatric patients should be observed for worsening depression and suicidal thinking
whenever one of these drugs is started or their dose is increased or decreased
4. Overdoses
Large intakes of SSRIs do not cause cardiac arrhythmias, but fluoxetine may cause
seizures
All SSRIs have the potential to cause a serotonin syndrome characterized by
hyperthermia , muscle rigidity , clonic muscle twitching and changes in mental status and
vital signs when used in the presence of a monoamine oxidase inhibitor
Lithium salts
Carbamazepine
Valproic acid
Lithium carbonates
In 1949 it was found to be sedative in animals and to exert beneficial effects in manic
patients
123
Mechanism of action
Lithium partly replaces body Na and is nearly equally distributed in and outside the cells
( contrast Na and K ) , this may affect ionic fluxes across brain cells or modify the
property of cellular membranes
Lithium has been found to decrease the release of Na and DA in t he brain of treated
animals without affecting 5 –HT release
Pharmacological actions
On CNS
Lithium has practically no acute effects in normal individuals as well as in MDI patients
Given to patients in acute mania, it gradually suppresses the episode taking 1-2 weeks
Other actions
Lithium inhibits action of ADH on distal tubules and causes a diabetes like state
Pharmacokinetics
It first distributes in the extra cellular water and then gradually enters cells and slowly
penetrates into the CNS , ultimately attaining a rather uniform distribution in total body
water , apparent volume of distribution at steady- state averages 0.8 L/kg
After a single dose of li urinary excretion of rapid for 10- 12 hours followed by a much
slower phase is 16- 30 hours
Levels are higher in older patients and in those with renal insufficiency
Peaks in plasma lithium level over and above the steady-state level occur after every
dose and produce episodes of toxicity if steady-state level if high or the dose is large
Adverse reaction
Nausea, vomiting and mild diarrhea occur initially, can be minimized by starting at lower
doses
Thirst and polyuria are experienced by most, some fluid retention may occur initially but
clears later
Fine tremors and rarely seizures are seen even at therapeutic concentrations
On long term use some patients develop renal diabetes and goiter has been reported in
about 4 %
Interactions
Tetracycline’s , indomethacin and ACE inhibitors can also cause lithium retention
125
Haloperidol have been frequently used along with lithium without problem , sometimes ,
the combination of haloperidol and lithium produces marked tremor and rigidity
Dose
Lithium used as its carbonate salt because this is less hygroscopic and less gastric irritant
than lithium chloride or other salts
It is generally stared at 600 mg/day and gradually increased to yields therapeutic plasma
levels, mostly 600-1200 mg /day is required
Hallucinogens
These are drugs which alter mood, behavior, thought and perception in a manner similar
to that seen in psychosis
In appropriate doses these produce changes in visual, auditory perception, in smell and
taste , broadly illusions and hallucinations
There will be alteration of the sense of time and space with personality changes
Cannabis
Flowering tops (ganja), the leaves (bhang) , the resinous exudation (Charas) or the
whole drug ( Hashish)
Cannabinal (chemically an alcohol) a red syrapy oil is said to be the active principle
Mescaline
When given orally the drug produces sympathomimetic effects and visual hallucinations
and a sense of floating in space
It induces psychotic states in which repressed memories form the subconscious mind are
brought of light
It stimulates emotional activity producing the sense of lightness and withdrawal from
reality
It is noticed that it can induce chromosomal abnormalities and fetal malformation and
possibly leukemia and hence it I withdrawn even form research
Other minor hallucinogens like bufetinine, psilocybin and harmolin produce similar
psychic effects but not used therapeutically
127
Unit - 7
Anti- Epileptic drugs
It is a collective term applied for a group of convulsive disorders
CLASSIFICATION
1. Hydantoins
Phenytoin
2. Barbiturates
Phenobarbitone
Primidone
3. Iminostilbbenes
Carbamazepine
4. Succinimides
Ethosuximided
Sodium valproate
6. Benzodiazepines
Clonazepam
Clobazam
Diazepam
7. Newer antiepileptic
Lamotrigine
Gbapentine
8. Miscellaneous
Trimethadione
Acetazolamide
128
Phenytoin
Phenytoin was synthesized in 1908, but its anticonvulsant property was discovered only
in 1938
It is effective in suppressing tonic-clinic and partial seizures and is a drug of choice for
initial therapy, particularly in treating adults
Mechanism of action
Pharmacological action
Phenytoin exerts antiseizure activity without causing general depression of the CNS
It is one of the most effective drugs against generalized tonic-clonic seizures and partial
seizures
Pharmacokinetics
It is metabolized in liver
Therapeutic uses
Phenytoin is highly effective for all partial seizures ( simple and complex), for tonic-
chronic seizures and in the treatment of status epileptics
Phenytoin is not effective for absence seizures, which often may worsen if treated with
this drug
129
Adverse effects
Peripheral neuropathy
Teratogenicity
When taken by the pregnant lady, phenytion produces fetal hydantion syndrome
characterized by hypo plastic phalanges, cleft palate, and harelip
Drug interactions
Phenobarbitone
Phenobartitone was the first effective antiepileptic drug to be introduced in 1912. It still
remains one of the widely used drugs
Mechanism of action
Pharmacokinetics
It is a potent inducer of the cytochrome P450 system and when given chronically, it
enhances the metabolism of their agents
Therapeutic uses
It provides favorable response for simple partial seizures, but it is not very effective for
complex partial seizures
The drug had been regarded as the first choice in treating recurrent seizures in children,
including febrile seizures
It also used to treat recurrent tonic-clonic seizures, especially in patients who donot
respond to diazepam plus phenytoin
It also used as a mild sedative to relieve anxiety, nervous tension and insomnia
Adverse effects
Primdone
It has more efficacy due to the its metabolites Phenobarbital and phenyl-ethyl-
malonamide which have longer half- lives than the parent drug
These drug has the same adverse effects as those seen with Phenobarbital
132
Benzodiazepines
Clonazepam
It suppresses seizure spread from the epileptogenic focus and is effective in absence and
myoclonic seizures , but tolerance develops
Clonazepate
Clorazepate is effective in partitial seizures when used in conjunction with other drugs
Diazepam
It is effective against
Pedestal epilepsy
Mylclonic seizures
Status epilepsy
It is drug of choice for status epilepticus
Lorazepam
Lorazepam and diazepam are both effective in interrupting the repetitive seizures of
status epilepticus.
All of the antiepileptics, the benzodiazepines are the safest and most free from severe
side effects
Side effects
Drowsiness,
Somnolence,
Fatigue,
Ataxia,
Dizziness and behavioral changes
Respiratory depression and cardiac depression may occur when given intravenously in
acute situations
133
Ethosuximide
About 25% of the drug is excreted unchanged in the urine and 75% is converted to
inactive metabolites in the liver by the microsomal cytochrome P450 system
The drug is irritating to the stomach and nausea and vomiting may occur on chronic
administration
Valproic Acid
It also diminishes absence seizures, but because of its hepatotixic potential, it is a second
choice
About 90% is bound to the plasma proteins ,only 3% of the drug is excreted unchanged,
the rest is converted into active metabolites by the liver
It can cause nausea, vomiting ,sedation, ataxia and tremor are common
Carbamaepines
Actions
ADME
The enhanced hepatic cytochrome p450 system activity also increases the metabolism of
many drugs including other antiepileptic drugs
Therapeutic uses
Trigeminal neuralgia
Adverse effects
The drug is irritating to the stomach and nausea and vomiting may occur
Drug interaction
Anti - parkinsonism
It was described b James Parkinson in 1817 and is therefore named after him
Characterized by
Akinesia
Muscular rigidity
Tremors
Other symptoms
Excessive salivation
Seborrhea
Mood changes
The balance between inhibitory dopaminergic neurons and excitatory cholinergic neurons
is disturbed
Antiparkinsonian drugs
It can only help to alleviate the symptoms and improve the quality of life
A. Dopamine precursor
Levodo[a
Amantidine
C. Dopaminergic agonists
Bromocryptine
Lisuride
A. Central anticholinergics
Bintropine
Benzhexol
Biperidine
B. Antihistamines
Diphenhydramine
Promethazine
137
Levodopa
Acetylcholin and dopamine are excitatory and inhibitory neurotransmitters in the corpus
striatum
Dopamine is of no therapeutic value because it dies not cross the blood- brain barrier
It crosses the Blood- Brain-Barrier and is taken up by the surviving nigrostriatal neurons
Decarboxylase
Levodopa ------------------------------------------- Dopamine
Actions
Other actions
Pharmacokinetics
Some amino acids in the food compete with levodopa for the absorption and transport to
the brain
Adverse reactions
Behavioral effects like anxiety, depression , hallucinations and sometimes psychosis can
occur
Use
Levodopa is the most effective drug in idiopathic parkinsonism but is not useful in drug
induced parkinsonism
Drug interactions
When carbidopa or bensrazide are given with levodopa, they prevent the formation of
dopamine in the periphery
They do not cross the BBB and hence allow levodopa to reach the CNS
The combination is synergistic and therefore levodopa is always given with carbidopa or
benserazide
Advantages of combination
Amantadine
It is an antiviral drug
It enhances the release of dopamine in the brain and diminishes the re-uptake of DA
The response starts early and its adverse effects are minor
Bromocriptine
It is an ergot derivative having dopamine agonistic activity at D2 receptors
It is used as
An adjunct to levodopa in the management of on- off phenomenon
It include vomiting , postural hypotension, hallucinations, skin eruptions and first dose
phenomenon - sudden cardiovascular collapse
140
Seleglline
It is a selective MAO- B inhibitor
Uses - Mild cases of parkinsonism are started on selegiline’It is also used as an adjunct
to levodopa
Anti- cholinergic
Atropine like side effects such as dry mouth , constipation, blurred vision may be
encountered
Uses
Anticholinergics are used as
Adjunct to levodopa
Drugs of choice in drug induced parkinsonism
Unit - 8
Analgesics and Anti-pyretics
These drugs relieve pain of lesser intensity like tooth-ache and muscle pain
But they do not relieve severe pain like visceral pain which is relieved by opioid
analgesics. These drugs do not produce addiction
All these drugs produce an anti-inflammatory effect, so these are called as non-steroidal
anti-inflammatory drugs ( NSAID )
These are weak analgesics as compared to narcotic analgesics and have primary action on
peripheral pain mechanism
They act without interacting with opioid receptors, they are called as non- opioid
Analgesics
These drugs have three main function – Analgesics , Anti-pyretic and Anti-inflammatory
action
1.Salicylates
Acetyl-salicylic acid
Sodium salicylate
Methyl salycilate
Salicylic acid
Paracetamol
Phenacetin
3. Pyrazolon derivatives
Phenyl butazone
Oxypehenbutazone
Aminopyrine
Antipyrine
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5. Indole derivatives
Indomethacin
8. Oxicam derivatives
Poroxicam, Tenoxicam
Mechanism of action
Phospholipase A2
Membrane -- Phospholipids--- ------------------------------------- Arachidonic acid
Cyclo- oxygenase
------------------------------------- Prostaglandins
The arachidonic acid is liberated from damaged cells during an inflammatory reaction
Prostaglandins and other mediators of inflammation are formed from Arachidonic acid
with the help of an enzyme Cyclo-oxygemase
The prostaglandin formed are responsible for many of the features of inflammation I.e. –
swelling, redness and pain )
These prostaglandins produce hyperalgesia -- They sensitize the nerve endings to pain
and other mediators of inflammation like bradykinin and histamine
The NSAID block the action of enzyme cyclo-oxygenase and thus prevent or reduces the
production of prostaglandins and other mediators of inflammation
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Asprin
It is a acetyl salicylic acid
It is rapidly converted in the body to salicylic acid which is responsible for most of the
actions
Other actions are the result of acetylation of certain macromolecules including COX
Mechanism of action
Pharmacological actions
1. Analgesic action
Mechanism
A. The hypothalamic heat regulating center ( thermostat of the body) is set for a higher
temperature in fever
This is reset for a lower temperature by salicylates
4. On respiration
5. Cardiovascular system
No effect at normal dose
Large doses increase cardiac output to meet increased peripheral O2 demand and cause
direct vasodilatation
6. GI Tract
Salicylates produce nausea and vomiting due to
Direct stimulation
Stimulation of chemoreceptor trigger zone
Salicylates can also cause gastric ulceration and hemorrhage
8. Blood
Salicylates lower the erythrocyte sedimentation rate (ESR) which is high in rheumatic
fever
Uricosuric effect
This effect is produced by inhibiting the reabsorption of uric acid in the proximal tubule
Immunological effect
Salicylates inhibit antigen- antibody reaction and so prevent the release of histamine
9. Metabolic effects
They inhibit the synthesis but enhance the breakdown of fatty acids
10. Hormones
This free thyroxin depresses the secretion of thyroid stimulating hormone (TSH)
Salicylates , especially salicylic acid and methyl salicylate have antiseptic, fungi static
and keratolytic effects
ADME
They are mainly concentrated in the liver, heart, muscle, and brain
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They are metabolized in liver by conjugation with glycine and glucuronic acid
Adverse reactions
Uses
It is used as analgesic for light and moderate pain
It is used as anti-rheumatic
It also used as antiseptic , anti-fungal and keratolytic
Pracetamol
Paracetamol is active on cyclo-oxygenase in the brain which accounts for its antipyretic
action
In presence of peroxides present at the site of inflammation , it has poor ability too inhibit
cyclo-oxygenase
It has no action on acid- base balance , cellular metabolism , cardiovascular system and
platelet function
Mechanism of action
ADME
Treatment
(150 mg/kg IV infusion over 15 min followed by 70 mg/kg every 4 hours -17 doses)
N- cetylcysteine partly replenishes the glutathione stores of the liver and prevents binding
of toxic metabolites to the cellular constituents
Adverse effects
But when large doses are taken, acute paracetamol poisoning results
Children are more susceptible due to their ability to conjugate by glucuronidation to poor
Symptoms
Nausea
Vomiting
anorexia
Abdominal pain
Uses
Paracetamol is used as an analgesic in painful conditions like toothache, headache and
myalgia
As an antipyretic
Its analgesic activity is independent of anti- inflammatory activity and has both central
and peripheral effect
Adverse effects
Nausea
Vomiting
Gastric discomfort
CNS effects
Hypersensitivity reactions
Dose
400- 800 mg TDS
Uses
Indomethacin
It relieves pain and reduces temperature in febrile patients reduces pain and joint swelling
in rheumatoid arthritis but does not modify progress
It is well absorbed, 90% bound to plasma proteins & half life is 4 – 6 hours
Dose
25 -30 mg BD-TDS
Adverse effects
Gastrointestinal irritation with nausea, GI bleeding , vomiting , diarrhea and peptic ulcers
can occur
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Hypersensitivity reactions like skin rashes, leucopenia and asthma in aspirin sensitive
individuals
Drug interactions
Indomethacin blunts the diuretic action of furosemide and the anti-hypertensive action of
thiazides, furosemide, beta blockers and ACE inhibitors by causing salt and water
retention
Uses
Rheumatoid arthritis
Gout
Ankylosing sodalities
Nimesulide
It inhibits leukocyte function, prevents the release of mediators and in addition has
antihistaminic and ant allergic properties
May also inhibit release of tumor necrosis factor alpha and thus reduce the formation of
cytokines
It is well absorbed orally, extensively bound to plasma proteins and has a half life is 3
hours
It is excreted by kidney
Dose
50 -100 mg BD
Adverse reaction
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Nausea
Diarrhea,
Vomiting
Rash
Dizziness
Somnolence
Headache
Uses
It is used as an analgesic, antipyretic and anti- inflammatory agent for short periods as in
headache, toothache, myalgia, dysmenorrheal, sinusitis, post-operative pain and arthritis
It has good anti- inflammatory activity, is more potent but has poorer analgesic and
antipyretic effects
I is an urocosuric agent
It causes retention of Na and water. Thus after 1-2 weeks of use edema results It can also
precipitate CHF
Pharmacokinetics
It is completely absorbed from orally
IM injection is not recommended because its absorption is slow as it binds to local tissue
proteins and also causes local tissue damage
Dose
100 – 200 mg , BD
Small doses may be given 3-4 times a day to avoid gastric irritation
Adverse effects
Phenyl butazone is more toxic than aspirin and is poorly tolerated – dyspepsia, epigastric
distress nausea and vomiting . Peptic ulceration and diarrhea may occur
It may inhibit iodine uptake by thyroid resulting in hypothyroidism and goiter on lojg
term use
CNS effects like insomnia vertigo, optic neuritis, blurring of vision and convulsions may
be encountered
Uses
Rheumatoid arthritis
Ankylosing sodalities
Osteoarthritis
Gout
Other musculoskeletal disorders
Oxyphenbutazone
It is a major metabolite of phenylbutazone, similar in pharmacodynamic,
pharmacokinetic, toxic and drug interaction profile
Dose
100 – 200 mg BD
Diclofenac sodium
Diclofenac is an analgesic, antipyretic and anti-inflammatory agent
It is tissue penetrability is good and attains good concentration n synovial fluid which is
maintained for a long time
Mechanism if action
The potassium salts are absorbed rapidly and action sets in much earlier
Dose
50 mg BD- TDS
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Uses
Treatment of chromic inflammatory conditions like rheumatoid arthritis and osteoarthritis
Severely painful conditions live acute pulpits and acute periapical abscess
Mephenamic acid
An analgesic, antipyretic and anti-inflammatory drug which inhibits COX as will as
antagonists certain actions of PGS
Pharmacokinetics
Oral absorption is slow but almost complete
Adverse effects
Diarrhea is the most important dose related side effect
Dose
250 – 500 mg TDS
Uses
Mephenamic acid is indicated primarily as analgesic in muscle, joint and soft tissue pain
where strong anti-inflammatory action is not needed
It may be useful in some cases of rheumatoid and osteoarthritis but has mo distinct
advantage
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Opioid analgesics
Analgesics
These are drugs which relieve pain without causing loss of consciousness
Opioid analgesics
These are the natural accruing, semi-synthetic and synthetic drugs which have morphine
like action
i.e. relief of pain and depression of CNS
A . Phenanthrene derivatives
Morphine
Codeine
Thebaine
B . Benzo-isoquinoline derivatives
Papaverine
Noscapine
Morphine
Codeine
Heroine
Pholcodeine
C. Synthetic opiods
Pethidine
Methadine
Tramadol
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Morphine
Morphine is a natural opium alkaloid
It is a dried extract obtained from the capsules of the poppy plant known as papaver
somniferum
Mechanism of action
Opioids exert their major effects by interacting with opioid receptors in the CNS
Opioids causes hyper polarization of nerve eells , inhibition of nerve firing and
presynaptic inhibition of transmitter release
Morphine acts at kappa receptors in lamina 1 and 11 of the substantia gelatinosa of the
spinal cord and decreases the release of substance p, which is modulates pain perception
in the spinal cord
Pharmacological actions
1. Analgesia
Mechanisms
Opioids relieve pain both by raising the pain threshold at the spinal cord level and more
importantly by altering the brains perception of pain
2.CNS
4. Anti-tussive property
5. Emesis
In small doses, morphine directly stimulates the chemoreceptor trigger zone in the area
postrema that causes vomiting
6. Pupil
The pinpoint pupil, characteristic of morphine use, results from stimulation of u and k
receptors
7. Gastro-intestinal tract
8. Billary tract
Morphine increase billiary tract pressure due to contraction of the gallbladder and
9. Cardiovascular system
Normal dose of morphine produces no effect on heart rate , blood pressure or circulation
Because of respiratory depression and carbon dioxide retention, cerebral vessels dilate
and increase the cerebrospinal fluid pressure
Morphine releases histamine from mast cells, causing urticaria, seating and vasodilatation
Morphine can cause the bronco-constriction , asthmatics should not receive the drug
Morphine inhibits release of GRH and corticotrophic releasing hormone and it decreases
the concentration of luteinizing hormone, FSH, ACTH
ADME
Dose
Morphine sulphate
or
Morphine hydrochloride
158
Adverse reactions
Drug interactions
Repeated use produces tolerance to the respiratory depressant, analgesic, euphoric ,and
sedative effects of morphine
Uses
Used as anti-tussive
Codeine
It is a phenanthrene alkaloid of opium
It is methyl- morphine
The other action like spasmogenic effect, nausea and vomiting , miosis and addiction are
less with codeine
In most non – prescription cough preparations , codeine has been replaced by drugs such
as dextro- methorphan - a synthetic cough depressant that has mo analgesic action and a
low potential for abuse
Heroin
It is a diamorphine, or diacetylmorphine
Due to its greater lipid solubility allows it to cross the blood- brain barrier more rapidly
than morphine
The sedative, emetic and hypertensive actions are said to be less prominent
It has mo outstanding therapeutic advantage over morphine and has been banned in most
countries except U.K
Pethidine
It is a synthetic compound
Mechanism of action
Pharmacological actions
Respiratory depression
Analgesic effect
It dilates cerebral vessels, increases CSF pressure and contracts smooth muscle
It does not cause pinpoint pupil but rather causes the pupils to dilate because of an
atropine like action
Pharmacokinetics
It is well absorbed from the GIT when given orally and parental administration
T he drug has a duration of action of two to four hours which shorter than that of
morphine
Adverse reactions
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Uses
As pre-anesthetic medication
Methadone
Mechanism of action
Pharmacological actions
Pharmaco-kinetic actions
Adverse effects
Uses
Tramadol
It is a centrally acting analgesic that binds to the u – opioid receptor
Its analgesic action is only partially reversed by opioid antagonist known as naloxone
It is well tolerated
Pharmaco-kinetics
The half life is 3-5 hrs and effects last 4-6 hrs
Adverse effects
Dizziness
Nausea
Sleepiness
Dry mouth
Sweating
Drug interaction
Tramadol should also be avoided in patients taking mono amine oxidase inhibitors
Dose
Opioid antagonists
1. Naloxone
2. Naltrexone
3. Nalmefene
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1. Naloxone
It is N- alyl-nor- oxy- morphone and a competitive antagonist on all types of opioid receptors
It blocks u receptors at much lower doses than those needed to block k or delta receptors
Naloxone is a competitive antagonist at u, k and delta receptors with a ten- fold higher affinity
for u receptors than for k
Naloxone is used to reverse the coma and respiratory depression of opioid overdose
It rapidly displaces all receptor- bound opioid molecules and is able to reverse the effect of a
heroin overdose
Within 30 sec of iv injection of naloxone, the respiratory depression and come characteristic of
high doses of heroin are reversed, causing the patient to be revived and alert
USES
Naloxine is the drug of choice for morphine poisoning ( 0.4 mg iv every 2 -3 min,
maximum 10 mg)
2. Naltrexone
It is chemically related to naloxone and is anther pure opioid antagonist
Naltrexone differs from naloxone in being orally active and having a long duration of
action (1 – 2 days)
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It has a longer duration of action than naloxone and a single oral dose of naltrexone
blocks the effect of injected heroin for up to 48 hours
Naltrexone is hepatotoxic
Dose
50 mg tab
Side effects
Nausea
Headache
3. Nalmefene
This is recently developed pure opioid antagonist lacks
No hepatotoxicity
CNS Stimulants
These are brain stimulants which markedly stimulate the respiration and circulation
These in large doses acts as convulsants’The;y are useful in the following conditions
A. Cortical stimulants
1. Xanthene alkaloids
Caffeine
Theophylline
Theo-bromine
Aminophylline
2. Sympathomimetics
Amphetamine
Methyl phenidate
B. Medularly stimulants
Picrotoxin
Pentylene-tetrazol
Nikethamide
Doxapram
C. Spinal stimulants
Strychnine
Lobeline
Nicotine
Veratrine
Ammonia
Xanthene alkaloids
Methyl xanthenes includes theophyline found in tea and Theo bromine found in cocoa
Caffeine , the most widely consumed stimulant in the world, is found in highest
concentration in coffee, but is also present in tea, cola drinks , chocolate candy and cocoa
Mechanism of action
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Pharmacological actions
On CNS
The caffeine contained in one to two cups of coffee (100 – 200mg) causes a decrease
fatigue and increased mental alertness as a result of stimulating t he cortex and other
areas of the brain
On CVS
A high dose of caffeine has positive inotropic and chronotropic effects on the heart
Xanthenes produce a direct stimulant effect on the myocardium, also they produces
dilatation of coronary and pulmonary blood vessels due to the stimulation of vagal nerve
On bronchioles
Caffeine and its derivatives relax the smooth muscles of the bronchioles
Decrease in fatigue of smooth muscles
Diuretic action
Caffeine has a mild diuretic action that increases urinary output of sodium, chloride and
potassium
169
GIT
Pharmacokinetics
The drugs cross the placenta to the fetus and are secreted into the mothers milk
All the methylxanthines are metabolized in the liver and the metabolites are then
excreted in the urine
Adverse effects
The lethal dose is about 10 grams of caffeine about 100 cups of coffee which induce
cardiac arrhythmias
Lethargy, irritability and headache occur in users who have routinely consumed more
than 600 mg of caffeine per day roughly six cups of coffee per day and then suddenly
stop
Therapeutic uses
Caffeine and its derivatives relax the smooth muscles of the bronchioles
Antidepressants
Coronary vasodilators
Diuretics
Nicotine
Nicotine represents a serious risk factor for lung and cardiovascular disease and various
cancers
Mechanism of action
Pharmacological actions
On CNS
Nicotine is highly soluble in lipid and readily crosses the blood-brain barrier
High doses of nicotine result in central respiratory paralysis and severe hypotension
caused by modularly paralysis
Peripheral effects
At higher doses , blood pressure falls and activity ceases in both the GIT and bladder
musculature
Pharmacokinetics
Absorption readily occurs via the oral mucosa, lungs, gastrointestinal mucosa and skin
Nicotine crosses the placental membrane and is secreted in the milk if lactating women
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Clearance if nicotine involves metabolism in the lung and the liver and urinary excretion
Adverse effects
Nicotine may also cause intestinal cramps, diarrhea and increased heart rate and blood
pressure
Withdrawal syndrome
Cocaine
Cocaine is an inexpensive , widely available and highly addictive drug that is currently
abused daily by more than three million people in the USA
It is poorly absorbed in the intestines but well absorbed by the mucous membrane and it
can be given as surface anesthetic
Mechanism of action
Pharmacological actions
On CNS
CNS stimulant
Cocaine acutely increases mental awareness and produces a feeling of well being and
euphoria similar to that caused by amphetamine
Cocaine increases motor activity and at high doses m it causes tremors and convulsions,
followed by respiratory and vasomotor depression
Peripherally, cocaine potentates the action of nor-adrenaline and produces the fight or
flight syndrome characteristic of adrenergic stimulation
Dilates pupil
Rise the BP
Produces euphoria
Pharmacokinetics
The peak effect occurs at fifteen to twenty minutes after intra-nasal intake of cocaine
powder
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Toxic effects
Mental excitement
Confusion
Tremors
Convulsions
Respiratory paralysis
Dose
8 – 16 mg by injection
Adrenaline has to be given along with cocaine which produces local vasoconstriction and
prolong the local anesthetic effect
Uses
Cocaine is applied topically as a local anesthetic during eye, ear ,nose and throat surgery
The anesthetic action of cocaine is due to a block of voltage – activated sodium channels
An interaction with potassium channels may contribute to the ability of cocaine to cause
cardiac arrhythmias
Drug Abuse
The use of drugs for non-therapeutic purposes and mainly the drugs acting on CNS is
termed as misuse or drug abuse.
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They may be misused for the production of dangerous and thrilling effects for escaping
from physical discomforts like hunger, fatigue, pain or mental discomforts like
boredom ,frustration and anxiety.
Generally the drugs which are abused are – ethanol, diazepam, morphine, heroin,
pethidine, methadone, methaqualon, LSD-25 , cannabis and mescaline.
Public must be given drug education on the harmful physical and mental effects of drug
dependence and abuse
Legal prohibition of possession and transportation in these drugs which may be abused
for non-medical purposes