Chapter 2 230327072253 9bf1fc09
Chapter 2 230327072253 9bf1fc09
Chapter 2 230327072253 9bf1fc09
The peripheral nervous system consists of the nerves that branch out from the
brain and spinal cord. These nerves form the communication network between the
CNS and the body parts.
The peripheral nervous system is further subdivided into the somatic nervous
system and the autonomic nervous system. The somatic nervous system consists
of nerves that go to the skin andmuscles and is involved in conscious activities.
The autonomic nervous system consists of nervesthat connect the CNS to the
visceral organs such as the heart, stomach, and intestines.
b. Smooth muscle
Smooth muscle in most organs is contracted. Tone and peristalsis in
the
gastrointestinal tract is increased and sphincters relax →abdominal
cramps and evacuationof bowel.
Peristalsis in ureter is increased.
Bronchial muscles constrict, asthmatics are highly sensitive →
bronchospasm, dyspnoea, precipitation of an attack of
bronchial asthma.
c. Glands
d. Eye
Contraction of circular muscle of iris resulting in miosis.
Contraction of ciliary muscle causing spasm of
accommodation,
increased aqueous outflow facility, reduction in intraocular tension
(especially in glaucomatous patients).
B. Nicotinic actions
1. Autonomic ganglia Both sympathetic and parasympathetic ganglia are
stimulated. High dose of ACh given after atropine causes tachycardia and rise
in BP dueto stimulation of sympathetic ganglia and release of
catecholamines.
3. CNS actions
ACh injected i.v. does not penetrate blood-brain barrier and no central effects
are
seen. However, direct injection into the brain produces arousal response followed
by depression.
Uses -
Indirect-acting cholinergic agonists are indicated for the following
medical conditions:
a. Treatment of myasthenia gravis, antidote for nondepolarizing
neuromuscular junction blockers,increased survival after exposure
to nerve gas
b. Treatment of mild to moderate Alzheimer’s disease.
Anti-Cholinergic drugs
(Cholinolytics)
The Anti-Cholinergic drugs is restricted to those which block actions of
ACh on automatic effectors and in the CNS exerted through muscarinic
receptors.
Classification of Anti-Cholinergic drugs
1. Natural alkaloids:- Atropine, Hyoscine (Scopolamine).
3. Synthetic compounds
(a) Mydriatics: Cyclopentolate, Tropicamide.
Quaternary
(b) Antisecretory
(i) compounds: Propantheline, Oxyphenonium,
- antispasmodics:
Clidinium, Pipenzolatemethyl bromide, Isopropamide,
Glycopyrrolate
(ii) Tertiary amines: Dicyclomine, Valethamate, Pirenzepine
(iii) Vasicoselective: Oxybutynin, Flavoxate, Tolterodine
(iv) Antiparkinsonian: Trihexyphenidyl (Benzhexol), Procyclidine,
Biperiden
Atropine
Atropine is a prescription medicine used to treat the symptoms of low heart rate
(bradycardia), reducesalivation and bronchial secretions before surgery or as an
antidote for overdose of cholinergic drugs.
2. Eye:
3. CVS: -
Most prominent effect is to cause tachycardia.
4. Smooth muscles :-
All visceral smooth muscles that receive parasympathetic motor
innervation are relaxed by atropine.
5. Glands :-
Atropine markedly decreases sweat, salivary, tracheobronchial and lacrimal
secretion.
6. Body temperature :-
Rise in body temperature occurs at higher doses. It is due to both inhibition
of sweating as well as stimulation of temperature regulating centre in the
hypothalamus.
7. Localanaesthetic :-
Atropine has a mild anaesthetic action on the cornea.
Uses -
Atropine is used for the treatment of poisoning by susceptible
organophosphorus
nerve agents havinganticholinesterase activity as well as organophosphorus
or carbamate insecticides in adults and pediatric patients.
Contraindications
Fast heartrate
High pressure in the eye (glaucoma)
Abdominal blockage (pyloric obstruction)
Dry mouth
Blurred vision
Sensitivity to light
Lack of sweating
Dizziness
Nausea
Adrenergic Drugs
(Sympathomimetics)
These are drugs with actions similar to that of Adrenaline or of
sympathetic stimulation.
Pharmacological Action -
4. Heart – Adrenaline increases heart rate by enhancing the pacemaker
activity of SA node. Force of cardiac contraction is increased.
Noradrenaline injected i.v. usually elicits bradycardia.
2. Blood vessels - Both vasoconstriction (α) and vasodilatation (β2 ) can occur
depending on the drug, its dose and the vascular bed. Constriction
predominates in cutaneous, mucous membrane and renal beds. Vasodilatation
predominates in skeletal muscles, liver and coronaries.
3. BP - NA causes rise in systolic, diastolic and mean BP; it does not cause
vasodilatation (no β2 action), peripheral resistance increases consistently
due to α action.
Adrenaline given by slow i.v. infusion or s.c. injection causes rise in systolic
but fall in diastolic BP; peripheral resistance decreases because vascular β2
receptors are more sensitive than α receptors. Mean BP generally rises.
Pulse
pressure is increased.
10.CNS – Adrenaline does not produce any marked CNS effects because of
poor penetration in brain, but restlessness, apprehension and tremor may
occur.
Activation of α2 receptors in the brainstem results in decreased sympathetic
outflow → fall in BP and bradycardia.
Salbutamol
Salbutamol is a beta-2 adrenergic receptor agonist used to treat asthma,
bronchitis, COPD, as well asprevent exercise induced bronchospasms.
Mechanism of action:
Salbutamol stimulate β2 adrenergic receptors which are predominant
receptors in bronchial smooth muscle.
Stimulation of β2 receptors leads to the activation of enzyme adenyl
cyclase that form cyclic AMP (adenosine-mono-phosphate) from ATP
(adenosine-tri-phosphate).
USES -
Shock/acute hypotension - Shock may be due to haemorrhage, volume
depletion (severe diarrhoea, vomiting, burn, etc.), cardiogenic (myocardial
infarction, arrhythmias, etc.), anaphylactic, neurogenic (in trauma, drug
overdose, etc.) or septic (gram negative bacteraemia, severe infection).
Along with local anaesthetics – Duration of anaesthesia is prolonged
and systemic toxicity of the local anaesthetic is reduced.
Control of local bleeding - Local bleeding is minimised.
Nasal decongestant - In colds, rhinitis, sinusitis, blocked
nose or eustachian tube, α-agonists is used as nasal drops.
Cardiac uses - Cardiac arrest Adrenaline may be used to stimulate the
heart in case of cardiac arrest due to drowning, electrocution,
Stokes-
Adams syndrome, and other causes.
Bronchial asthma and COPD - Adrenergic β2 stimulants are the primary
drugs for relief of reversible airway obstruction.
Allergic disorders - Adrenaline is a physiological antagonist of
histamine which is an important mediator of many acute
hypersensitivity reactions.
It affords quick relief in urticaria, angioedema and is life saving
in laryngeal edema or anaphylaxis.
Ocular uses - Phenylephrine dilates the pupil, and is used to
facilitate
fundus examination, since cycloplegia is not required for this
purpose.
Uterine relaxant - Selective β2 stimulants, especially ritodrine, infused i.v.
has been successfully used to postpone labour but maternal morbidity and
mortality may be increased due to its cardiac and metabolic actions
and incidents of pulmonary edema.
Insulin hypoglycaemia - By its hyperglycaemic action, Adrenaline can
rapidly reverse insulin hypoglycaemia.
Contraindication:
• Caution when used during pregnancy.
Antiadrenergic Drugs
(Sympatholytics)
These are drugs which antagonize the receptor action of adrenaline and related
drugs. They are competitive antagonists at α or β or both α and β adrenergic
receptors and differ from the “adrenergic neurons blocking agents”, which act
by interfering with the release of adrenergictransmitter on nerve stimulation.
Classification of Antiadrenergic Drugs
I. Nonequilibrium type
(i) β-Haloalkylamines—Phenoxybenzamine.
Uses -
8. Pheochromocytoma - It is a tumour of adrenal medullary cells. Excess CAs are
secreted which can cause intermittent or persistent hypertension.
Phenoxybenzamine is indicated for the control of episodes of hypertension
and sweating that occur witha disease called pheochromocytoma.
Contraindication:
Nasal congestion
Dizziness
Upset stomach
Sexual dysfunction (difficulty ejaculating)
Dizziness
Ear term pregnancy, breast feeding
mothers etc.
Pharmacological Action –
1.Skeletal muscles - Intravenous injection of nondepolarizing blockers rapidly
produces muscle weakness followed by flaccid paralysis.
3.Histamine release - d-TC releases histamine from mast cells. Histamine release
contributes to the hypotension produced by d-TC. Flushing, bronchospasm and
increased respiratory secretions are the other effects.
4. C.V.S. - d-Tubocurarine produces significant fall in BP.
This is due to—
(a) ganglionic blockade
(b) histamine release and
(c) reduced venous return—a result of paralysis of limb and respiratory muscles.
Heart rate may increase due to vagal ganglionic blockade.
Uses –
7. The most important use of neuromuscular blockers is as adjuvants to
general anaesthesia.
8. Assisted ventilation: Critically ill patients in intensive care units often need
ventilatory support. This can be facilitated by continuous infusion of
subparalysing doses of a competitive neuromuscular blocker which reduces
the
chest wall resistance to inflation. Vecuronium is most commonly used.
3. Convulsions and trauma from electroconvulsive therapy can be avoided by the
use of muscle relaxants without decreasing the therapeutic benefit. SCh is
most commonly used for this purpose.
4. Tetanus and status epilepticus, who are not controlled by diazepam or other
drugs, may be paralysed by a neuromuscular blocker.
Myasthenia Gravis
It is an autoimmune disorder affecting about 1 in 10,000 population, due to
development of antibodies directed to the nicotinic receptors (NR) at the
muscle endplate. The number of free Nm cholinoceptors may be reduced to 1/3
of normal or less and structural damage to the neuromuscular junction.
Symptoms - weakness and easy fatigability on repeated activity, with recovery after
rest. The eyelid, external ocular, facial and pharyngeal muscles are generally
involved first. Later, limb and respiratory muscles get affected.
Neostigmine:
Neostigmine is a cholinesterase inhibitor, prescribed for Myasthenia Gravis.
Neostigmine and its congeners are the first line drugs used to restore
muscle strength. They improve muscle contraction by allowing ACh
released from prejunctional endings to accumulate and act on the receptors
over a larger area, as well as by directly depolarizing the endplate.
Treatment is usually started with neostigmine 15 mg orally 6 hourly; dose
and frequency is then adjusted to obtain optimum relief from weakness.
Treatment –
Thymectomy is now generally advised for patients with generalized
weakness, particularly for those with a thymoma and for younger patients.
Thymus may contain modified muscle cells with NRs on their surface,
which may be the source of the antigen for production of anti-NR antibodies
in myasthenic patients.
Corticosteroids afford improvement in myasthenia gravis by their
immunosuppressant action. They inhibit production of antibodies to NR,
and
may increase synthesis of new NRs.
Immunosuppressants like azathioprine and cyclosporine are also
beneficial. Both inhibit NR-antibody synthesis by affecting T-cells.
Removal of antibodies by plasmapheresis (plasma exchange) is another
approach. It may produce dramatic but often short-lived improvement
in myasthenic crisis.
Local anesthetics
Local anaesthetics (LAS) are drugs which upon topical application or
local injection cause reversible loss of sensory perception, especially of
pain, in a restricted area of thebody.
Classification:
Mechanism of Action - The LAs block nerve conduction by decreasing the entry
of Na+ ions during upstroke of action potential (AP). As the concentration of the
LA is increased, the rate of rise of AP and maximum depolarization decreases
causing slowing of conduction. Finally, local depolarization fails to reach the
threshold potential and conduction block ensues.
Local Actions - The clinically used LAs have no/minimal local irritant action and
block sensory nerve endings, nerve trunks, neuromuscular junction, ganglionic
synapse and receptors (non-selectively), i.e. those structures which function
through increased Na+ permeability. They also reduce release of acetylcholine
from motor nerve endings. Injected around a mixed nerve they cause anaesthesia
of skin and paralysis of the voluntary muscle supplied by that nerve.
Uses:
Local anesthesia is given to reduce the stress associated with surgery, and to
provide pain relief after surgery.
More commonly, it is used for pain caused by hemorrhoids, fissures,
insect bites, andminor burns.
It is applied topically for these conditions. It is also indicated
for vaginal, rectal and otological examinations, cystoscopy, and
catheterization.
Systemic Action –
1. C.N.S. - All LAs are capable of producing a sequence of stimulation
followed by depression. Cocaine is a powerful CNS stimulant causing
in sequence euphoria—excitement—mental confusion—restlessness—
tremor and twitching of muscles— convulsions—unconsciousness—
respiratory depression—death, in a dose-dependent manner.
2. C.V.S. –
Heart - LAs are cardiac depressants, but no significant effects are
observed at conventional doses. At high doses or on inadvertent i.v. injection,
they decrease automaticity, excitability, contractility, conductivity and prolong
effective refractory period (ERP).
Blood vessels - LAs tend to produce fall in BP. At high concentrations,
locally at the site of injection, do cause direct relaxation of arteriolar smooth
muscle.
Uses –
1. Surface anaesthesia - This is produced by topical application of a
surface anaesthetic to mucous membranes or abraded skin. Only the
superficial layer is anaesthetised and there is no loss of motor
function.
2. Infiltration anaesthesia - Infiltration is used for minor operations,
e.g. incisions, excisions, hydrocele, herniorrhaphy, etc.
3. Conduction block - The LA is injected around nerve trunks so that
the area distal to injection is anaesthetised and paralysed.
4. Spinal anaesthesia - Lower abdomen and hind limbs are anaesthetised
and paralysed.
5. Epidural anaesthesia - The spinal dural space is filled with semiliquid
fat through which nerve roots travel. The LA injected in this space acts
primarily on the nerve roots (in the epidural as well as subarachnoid
spaces to which it diffuses) and small amount permeates through
intervertebral foramina to produce multiple paravertebral
blocks.
6. Intravenous regional anaesthesia (Intravascular infiltration anaesthesia,
or Bier’s block) - It is mainly used for the upper limb and for
orthopaedic procedures.
Contraindications:
Classification:
Aspirin
Aspirin is acetylsalicylic acid. It is rapidly converted in the body to
salicylic acid which isresponsible for most of the action.
It used to treat pain, fever, inflammation, migraines, and reducing the risk of
major adversecardiovascular events.
Mechanism of Action:
Pharmacological Actions -
1. Analgesic, antipyretic, anti-inflammatory actions - Aspirin is a weaker
analgesic (has lower maximal efficacy) than morphine type drugs. However, it
effectively relieves inflammatory, tissue injury related, connective tissue and
integumental pain, but is relatively ineffective in severe visceral and
ischaemic pain.
Aspirin resets the hypothalamic thermostat and rapidly reduces fever by
promoting heat loss (sweating, cutaneous vasodilatation), but does not
decrease heat production.
Anti-inflammatory action is exerted at high doses. Signs of inflammation like
pain, tenderness, swelling, vasodilatation and leucocyte infiltration are
suppressed.
2. GIT - Aspirin, as well as salicylic acid released from it irritate gastric
mucosa, cause epigastric distress, nausea and vomiting. At high doses, it
stimulates CTZ. Vomiting caused by aspirin has a central component as well.
3. Blood - Aspirin, even in small doses, irreversibly inhibits TXA2 synthesis
by platelets. Thus, it interferes with platelet aggregation and bleeding time
is prolonged to nearly twice the normal value.
4. Cellular metabolism is enhanced, especially in skeletal muscles, due
to uncoupling of oxidative phosphorylation.
5. Glucose utilization is increased resulting in fall in blood glucose
level (especially in diabetics); liver glycogen is depleted.
6. Respiration is stimulated by direct action on respiratory centre as well as due
to increased CO2 production.
7. Respiratory stimulation tends to washout CO2 and produce
respiratory alkalosis.
8. This is compensated by enhanced HCO3 – excretion by kidney. Most adults
receiving 3–5 g/day stay in a state of compensated respiratory alkalosis. Still
higher doses depress respiration while excess CO2 production continues to
cause respiratory acidosis. Increased production of metabolic acids (lactic,
pyruvic, acetoacetic) and dissociated salicylic acid may contribute to
uncompensated metabolic acidosis, since plasma HCO3 – is already low.
Dehydration occurs due to excess water loss in urine, sweating and
hyperventilation. Most children menifest this phase during salicylate
poisoning, while in adults it is seen only in late stages of poisoning. • Aspirin
has no direct effect on heart or circulation, but doses which enhance metabolic
rate, increase cardiac output indirectly. Toxic doses depress vasomotor centre,
so that blood pressure may fall. CHF may be precipitated if cardiac reserve is
low. SECTION 3 214 AUTACOIDS AND RELATED DRUGS • Aspirin
interferes with urate excretion and antagonises the uricosuric effect of
probenecid. However, at high doses (≥ 5 g/day) it may block urate
reabsorption and increase its excretion, but aspirin is not a reliable uricosuria
Uses :
Pain, fever, and inflammation cold, neck and back pain, dysmenorrhea,
headache, tooth pain,sprains, fractures, myositis, neuralgia, synovitis,
arthritis, bursitis, burns, and various injuries.
Contraindication:
Sensitive Persons
Children with viral diseases
Peptic ulcer disease and bleeding disorders
Chronic liver diseases
Diabetes, CHF and juvenile Rh. Arthritis
G-6-PD deficient persons
Stop prior to surgery