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Pharmacology - NEETMDS- courses
NEET MDS Lessons
Pharmacology

Prostaglandines:

Every cell in the body is capable of synthesizing one or more types of PGS. The four major group of PGs are E, F, A, and B.

Pharmacological actions:

stimulation of cyclicAMP production and calcium use by various cells

CVS
PGE2 acts as vasodilator; it is more potent hypotensive than Ach and histamine

Uterous
PGE2 and PGF2α Contract human uterus

Bronchial muscle

PGF2α and thromboxan A2 cause bronchial muscle contraction.

PGE2 & PGI2 cause bronchial muscle dilatation

GIT: PGE2 and PGF2α cause colic and watery diarrhoea

Platelets

Thromboxan A2 is potent induce of platelets aggregation

Kidney

PGE2 and PGI2 increase water, Na ion and K ion excretion (act as diuresis) that cause renal vasodilatation and inhibit
tubular reabsorption

USE
PGI2: Epoprostenol (inhibits platelets aggregation)
PGE1: Alprostadil (used to maintain the potency of arterioles in neonates with congenital heart defects).
PGE2: Dinoproste (used as pessaries to induce labor)
Synthetic analogue of PGE1: Misoprostol (inhibit the secretion of HCl).

Celecoxib

is a highly selective COX-2 inhibitor and primarily inhibits this isoform of cyclooxygenase, whereas traditional NSAIDs inhibit both COX-1 and COX-2. Celecoxib is approximately 10-20 times more selective for COX-2 inhibition over COX-1.

Being a sulphonamide can cause skin rash &  hypersensitivity rxn., occasional oedema& HT.

Indication

Osteoarthritis ( 100‐200mg BID ) , rheumatoid  arthritis, dysmenorrhea, acute gouty attacks,  acute musculoskeletal pain. 

SYMPATHOMIMETICS 

β2 -agonists are invariably used in the symptomatic treatment of asthma. 

Epinephrine and ephedrine are structurally related to the catecholamine norepinephrine, a neurotransmitter of the adrenergic nervous system 

Some of the important β 2 agonists like salmeterol, terbutaline and salbutamol are invariably used as bronchodilators both oral as well as
aerosol inhalants 

SALBUTAMOL
It is highly selective β2 -adrenergic stimulant h-aving a prominent bronchodilator action.
It has poor cardiac action compared to isoprenaline.


TERBUTALINE
It is highly selective β2  agonist similar to salbutamol, useful by oral as well as inhalational route.


SALMETEROL

Salmeterol is long-acting analogue of salbutamol 

BAMBUTEROL

It is a latest selective adrenergic β2 agonist with long plasma half life and given once daily in a dose of 10-20 mg orally.


METHYLXANTHINES (THEOPHYLLINE AND ITS DERIVATIVES)


THEOPHYLLINE
Theophylline has two distinct action:
smooth muscle relaxation (i.e. bronchodilatation) and suppression of the response of the airways to stimuli (i.e. non-bronchodilator prophylactic effects). 

ANTICHOLINERGICS

Anticholinergics, like atropine and its derivative ipratropium bromide block cholinergic pathways that cause airway constriction.

MAST CELL STABILIZERS

SODIUM CROMOGLYCATE

It inhibits degranulation of mast cells by trigger stimuli. 
It also inhibits the release of various asthma provoking mediators e.g. histamine, leukotrienes, platelet activating factor (PAF) and interleukins (IL’s) from mast cell 

KETOTIFEN
It is a cromolyn analogue. It is an antihistaminic (H1  antagonist) and probably inhibits airway inflammation induced by platelet activating factor (PAF) in primate. 
It is not a bronchodilator. It is used in asthma and symptomatic relief in atopic dermatitis, rhinitis, conjunctivitis and urticaria.

LEUKOTRIENE PATHWAY INHIBITORS

MONTELUKAST

It is a cysteinyl leukotriene receptor antagonist indicated for the management of persistent asthma. 

Stimulants: 

Amphetamines: amphetamine is a substrate of serotonin and NE uptake transporters so in cytoplasm, it competes for transport into storage vesicles → ↑ [ ] in cytoplasm then excess amines bind to membrane transporter and are transported out of cell

Drugs: 
a.    Dextroamphetamine: psychomotor stimulant (↓ fatigue), short-term weight loss, prevents narcolepsy
b.    Methylphenidate (Ritalin): prevents narcolepsy, treatment for ADD and ADHD
c.    Methamphetamine: psychomotor stimulant, abused widely (cheap, easy to make)

Side effects: 
a.    CNS: euphoria, anxiety, agitation, delirium, paranoia, panic, suicidal/homicidal impulses, psychoses, tolerance (develops rapidly to most CNS effects), physical dependence (not clinically relevant)
b.    CV: headache, chills, arrhythmias and HTN (may be fatal)

DIURETICS

The basis for the use of diuretics is to promote sodium depletion (and thereby water) which leads to a decrease in extracellular fluid volume.
An important aspect of diuretic therapy is to prevent the development of tolerance to other antihypertensive drugs.

TYPES OF DIURETICS
A. Thiazide Diuretics examples include     chlorothiazide 
hydrochlorothiazide 
a concern with these drugs is the loss of potassium as well as sodium

B. Loop Diuretics (High Ceiling Diuretics) examples include 
furosemide (Lasix)
bumetanide
these compounds produce a powerful diuresis and are capable of producing severe derangements of electrolyte balance

C. Potassium Sparing Diuretics examples include
triamterene
amiloride 
spironolactone 
unlike the other diuretics, these agents do not cause loss of potassium

Mechanism of Action

Initial effects: through reduction of plasma volume and cardiac output.
Long term effect: through decrease in total peripheral vascular resistance.

Advantages

Documented reduction in cardiovascular morbidity and mortality.
Least expensive antihypertensive drugs.
Best drug for treatment of systolic hypertension and for hypertension in theelderly.
Can be combined with all other antihypertensive drugs to produce synergetic effect.

Side Effects
Metabolic effects (uncommon with small doses): hypokalemia,hypomagnesemia, hyponatremia, hyperuricemia, dyslipidemia (increased total
and LDL cholesterol), impaired glucose tolerance, and hypercalcemia (with thiazides).
Postural hypotension.
Impotence in up to 22% of patients.  

 Considerations
- Moderate salt restriction is the key for effective antihypertensive effect of diuretics and for protection from diuretic - induced hypokalaemia. 
- Thiazides are not effective in patients with renal failure (serum creatinine > 2mg /dl) because of reduced glomerular filtration rate.
- Frusemide needs frequent doses ( 2-3 /day ).Thiazides can be given once daily or every other day.
- Potassium supplements should not be routinely combined with thiazide or loop diuretics. They are indicated with hypokalemia (serum potassium < 3.5 mEq/L) especially with concomitant digitalis therapy or left ventricular hypertrophy.
- Nonsteroidal antiinflammatory drugs can antagonize diuretics effectiveness.

Special Indications

Diuretics should be the primary choice in all hypertensives.

They are indicated in:
- Volume dependent forms of hypertension: blacks, elderly, diabetic, renal and obese hypertensives.
- Hypertension complicated with heart failure.
- Resistant hypertension: loop diuretics in large doses are recommended.
- Renal impairment: loop diuretics

CNS acting drugs are of major therapeutic and clinical importance. 

They can produce diverse physiologicaland psychologicaleffects such as:

•Induction of Anesthesia 
•Relief of Pain 
•Prevention of Epileptic seizures 
•Reduction of Anxiety 
•Treatment of Parkinsonism 
•Treatment of Alzheimer's disease 
•Treatment of Depression 
•Centrally acting drugs also include drugs that are administered without medical intervention like tea, coffee, nicotine, and opiates.
 

Antidiarrheal

 Antidiarrheal drugs may be given to relieve the symptom (non-specific therapy) or may be given to treat the underlying cause of the symptom (specific therapy). 


Ι. Drugs used for the symptomatic (non-specific) treatment of diarrhoea include: 


• Opiates and opiate derivatives are the most effective (such as morphine), but it is not used because of potentially serious adverse effects. Other agents, such as diphenoxylate and loperamide, are commonly used.

• Adsorbent – demulcent products such as kaolin – pectin preparation may be included in antidiarrheal preparations. Unfortunately, they may adsorb nutrients and other drugs, including the antidiarrheal agents if given concurrently.

• Anticholinergic agents e.g. atropine is occasionally used to decrease abdominal cramping and pain associated with diarrhoea.

ΙΙ. Specific therapy may include the use of antibacterial agents that are recommended for use in carefully selected cases of bacterial enteritis. For example, severe diarrhoea by salmonella, shigella, campylobacter and clostridia species can be treated by antibiotics (ampicillin, chloramphenicol, co-trimoxazole). 

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