NEET MDS Lessons
Pharmacology
Different Systems of the CNS & their functions
These systems are pathways formed of specific parts of the brain and the neurons connecting them.
They include:
1.The pyramidal system
2.The extrapyramidal system
3.The limbic system
4.The reticular formation
5.The tuberohypophyseal system
The pyramidal system:
It originates from the motor area of the cerebral cortex and passes through the spinal cord, therefore it is also known as the “corticospinaltract”.
It is responsible for the regulation of the fine voluntary movements.
The extrapyramidal system:
It also controls the motor functionbut involves areas other than the corticospinal tract.
It is involved in the regulation of gross voluntary movements, thus it complements the function of the pyramidal system.
The “basal ganglia” constitute an essential part of this system.
Degenerative changes in the pathway running from the “substantianigra”to the “corpus striatum”(or nigrostriatal pathway) may cause tremors and muscle rigidity characteristic of “Parkinson’s disease”.
The limbic system:
The major parts of this system are: the hypothalamus, the basal ganglia, the hippocampus(responsible for short term memory), and some cortical areas.
The limbic system is involved in the control of “behavior”& “emotions”.
The reticular formation:
It is composed of interlacing fibers and nerve cells that run in all directions beginning from the upper part of the spinal cord and extending upwards.
It is important in the control of “consciousness” and “wakefulness”.
The tuberohypophyseal system:
It is a group of short neurons running from the hypothalamusto the hypophysis(pituitary gland) regulating its secretions.
Classification
I) Esters
1. Formed from an aromatic acid and an amino alcohol.
2. Examples of ester type local anesthetics:
Procaine
Chloroprocaine
Tetracaine
Cocaine
Benzocaine- topical applications only
2) Amides
1. Formed from an aromatic amine and an amino acid.
2. Examples of amide type local anesthetics:
Articaine
Mepivacaine
Bupivacaine
Prilocaine
Etidocaine
Ropivacaine
Lidocaine
Neuron Basic Structure (How brain cells communicate)
• Synapse:A junction between the terminal button of an axon and the membrane of another neuron
• Terminal button(orbouton):The bud at the end of a branch of an axon; forms synapses with another neuron; sends information to that neuron.
• Neurotransmitter:A chemical that is released by a terminal button; has an excitatory or inhibitory effect on another neuron.
Different types of Synapses
1-Axo-denrdritic
2-Axo-axonal
3-Axo-somatic
Chemical transmission in the CNS
The CNS controls the main functions of the body through the action endogenous chemical substances known as “neurotransmitters”.
These neurotransmitters are stored in and secreted by neurons to “transmit”information to the postsynaptic sites producing either excitatoryor inhibitory responses.
Most centrally acting drugs exert their actions at the synaptic junctions by either affecting neurotransmitter synthesis, release, uptake, or by exerting direct agonistor antagonistaction on postsynaptic sites.
Flucloxacillin, important even now for its resistance to beta-lactamases produced by bacteria such as Staphylococcus species. It is still no match for MRSA (Methicillin Resistant Staphylococcus aureus).
The last in the line of true penicillins were the antipseudomonal penicillins, such as ticarcillin, useful for their activity against Gram-negative bacteria
Tetracycline
Tetracycline is an antibiotic produced by the streptomyces bacterium
Mechanism and Resistance Tetracycline inhibits cell growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. This prevents the addition of amino acids to the elongating peptide chain, preventing synthesis of proteins. The binding is reversible in nature.
Example: Chlortetracycline, oxytetracycline, demethylchlortetracycline, rolitetracycline, limecycline, clomocycline, methacycline, doxycycline, minocycline
Source: Streptomyces spp.; some are also semi-synthetic
Spectrum of activity: Broad-spectrum. Exhibits activity against a wide range of Gram-positive, Gram-negative bacteria, atypical organisms such as chlamydiae, mycoplasmas, rickettsiae and protozoan parasites.
Effect on bacteria: Bacteriostatic
Cells become resistant to tetracyline by at least two mechanisms: efflux and ribosomal protection.
Contraindications Tetracycline use should be avoided during pregnancy and in the very young (less than 6 years) because it will result in permanent staining of teeth causing an unsightly cosmetic result.
Tetracyclines also become dangerous past their expiration dates. While most prescription drugs lose potency after their expiration dates, tetracyclines are known to become toxic over time; expired tetracyclines can cause serious damage to the kidneys.
Miscellaneous: Tetracyclines have also been used for non-antibacterial purposes, having shown properties such as anti-inflammatory activity, immunosuppresion, inhibition of lipase and collagenase activity, and wound healing.
Aspirin
Mechanism of Action
ASA covalently and irreversibly modifies both COX-1 and COX-2 by acetylating serine-530 in the active site Acetylation results in a steric block, preventing arachidonic acid from binding
Uses of Aspirin
Dose-Dependent Effects:
Low: < 300mg blocks platelet aggregation
Intermediate: 300-2400mg/day antipyretic and analgesic effects
High: 2400-4000mg/day anti-inflammatory effects
Often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. It has also an anticoagulant (blood thinning) effect and is used in long-term low-doses to prevent heart attacks
Low-dose long-term aspirin irreversibly blocks formation of thromboxane A2 in platelets, producing an inhibitory affect on platelet aggregation, and this blood thinning property makes it useful for reducing the incidence of heart attacks
Its primary undesirable side effects, especially in stronger doses, are gastrointestinal distress (including ulcers and stomach bleeding) and tinnitus. Another side effect, due to its anticoagulant properties, is increased bleeding in menstruating women.
Sympathomimetics -Adrenergic Agents
The sympathomimetic or adrenergic or adrenomimetic drugs mimic the effects of adrenergic sympathetic nerve stimulation.
These are the important group of therapeutic agents which may be used to maintain blood pressure and in certain cases of severe bronchial asthma.
Mechanism of Action and Adrenoceptors
The catecholamines produce their action by direct combination with receptors located on the cell membrane. The adrenergic receptors are divided into two main groups – alpha and beta.
alpha receptor - stimulation produces excitatory effect and
beta receptor -stimulation usually produces inhibitory effect.
Alpha receptors: There are two major groups of alpha receptors, α1 and α2.
Activation of postsynaptic α1 receptors increases the intracellular concentration of calcium by activation of a phospholipase C in the cell membrane via G protein.
α2 receptor is responsible for inhibition of renin release from the kidney and for central aadrenergically mediated blood pressure depression.
Beta receptors:
a. Beta 1 receptors have approximately equal affinity for adrenaline and noradrenaline and are responsible for myocardial stimulation and renin release.
b. Beta 2 - receptors have a higher affinity for adrenaline than for noradrenaline and are responsible for bronchial muscle relaxation, skeletal muscle vasodilatation and uterine relaxation.
c. Dopamine receptors: The D1 receptor is typically associated with the stimulation of adenylyl cyclase. The important agonist of dopamine receptors is fenoldopam (D1) and bromocriptine (D2) and antagonist is clozapine (D4) .
Adrenergic drugs can also be classified into:
a. Direct sympathomimetics: These act directly on a or/and b adrenoceptors e.g. adrenaline, noradrenaline, isoprenaline, phenylephrine, methoxamine salbutamol etc.
b. Indirect sympathomimetics: They act on adrenergic neurones to release noradrenaline e.g. tyramine.
c. Mixed action sympathomimetics: They act directly as well as indirectly e.g. ephedrine, amphetamine, mephentermine etc.
Pharmacological Action of Sympathomimetics
Heart: Direct effects on the heart are determined largely by β1 receptors.
Adrenaline increases the heart rate, force of myocardial contraction and cardiac output
Blood vessels: Adrenaline and noradrenaline constrict the blood vessels of skin and mucous membranes.
Adrenaline also dilates the blood vessels of the skeletal muscles on account of the preponderance of β2 receptor
Blood pressure: Because of vasoconstriction (α1) and vasodilatation (β2) action of adrenaline, the net result is decrease in total peripheral resistance.
Noradrenaline causes rise in systolic, diastolic and mean blood pressure and does not cause vasodilatation (because of no action on β2 receptors) and increase in peripheral resistance due to its a action.
Isoprenaline causes rise in systolic blood pressure (because of β1 cardiac stimulant action) but marked fall in diastolic blood pressure (because of b2 vasodilatation action) but mean blood pressure generally falls.
GIT: Adrenaline causes relaxation of smooth muscles of GIT and reduce its motility.
Respiratory system: The presence of β2 receptors in bronchial smooth muscle causes relaxation and activation of these receptors by β2 agonists cause bronchodilatation.
Uterus: The response of the uterus to the atecholamines varies according to species
Eye: Mydriasis occur due to contraction of radial muscles of iris, intraocular tension is lowered due to less production of the aqueous humor secondary to vasoconstriction and conjunctival ischemia due to constriction of conjunctival blood vessels.
a. Urinary bladder: Detrusor is relaxed (b) and trigone is constricted (a) and both the actions tend to inhibit
micturition.
b. Spleen: In animals, it causes contraction (due to its a action) of the splenic capsule resulting in increase in number of RBCs in circulation.
c. It also cause contraction of retractor penis, seminal vesicles and vas deferens.
d. Adrenaline causes lacrimation and salivary glands are stimulated.
e. Adrenaline increases the blood sugar level by enhancing hepatic glycogenolysis and also by decreasing the uptake of glucose by peripheral tissues.
Adrenaline inhibits insulin release by its a-receptor stimulant action whereas it stimulates glycogenolysis by its b receptor stimulant action.
f. Adrenaline produces leucocytosis and eosinopenia and accelerates blood coagulation and also stimulates platelet aggregation.
Adverse Effects
Restlessness, anxiety, tremor, headache.
Both adrenaline and noradrenaline cause sudden increase in blood pressure, precipitating sub-arachnoid haemorrhage and occasionally hemiplegia, and ventricular arrhythmias.
May produce anginal pain in patients with ischemic heart disease.
Contraindications
a. In patients with hyperthyroidism.
b. Hypertension.
c. During anaesthesia with halothane and cyclopropane.
d. In angina pectoris.
Therapeutic Uses
Allergic reaction: Adrenaline is drug of choice in the treatment of various acute allergic disorders by acting as a physiological antagonist of histamine (a known mediator of many hypersensitivity reactions). It is used in bronchial asthma, acute angioneurotic edema, acute hypersensitivity reaction to drugs and in the treatment of anaphylactic shock.
Bronchial asthma: When given subcutaneously or by inhalation, adrenaline is a potent drug in the treatment of status asthmaticus.
Cardiac uses: Adrenaline may be used to stimulate the heart in cardiac arrest.
Adrenaline can also be used in Stokes-Adam syndrome, which is a cardiac arrest occurring at the transition of partial to complete heart block. Isoprenaline or orciprenaline may be used for the temporary treatment of partial or complete AV block.
Miscellaneous uses:
a. Phenylephrine is used in fundus examination as mydriatic agent.
b. Amphetamines are sometime used as adjuvant and to counteract sedation caused by antiepileptics.
c. Anoretic drugs can help the obese people.
d. Amphetamine may be useful in nocturnal enuresis in children.
e. Isoxsuprine (uterine relaxant) has been used in threatened abortion and dysmenorrhoea.