NEET MDS Lessons
Pharmacology
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.
Characteristics of Opioid Receptors
mu1
Agonists : morphine phenylpiperidines
Actions: analgesia bradycardia sedation
mu2
Agonists : morphine phenylpiperidines
Actions: respiratory depression euphoria physical dependence
delta
Actions: analgesia-weak, respiratory depression
kappa
Agonists: ketocyclazocine dynorphin nalbuphine butorphanol
Actions: analgesia-weak respiratory depression sedation
Sigma
Agonists: pentazocine
Action: dysphoria -delerium hallucinations tachycardia hypertension
epsilon:
Agonists: endorphin
Actions: stress response acupuncture
Meperidine (Demerol)
Meperidine is a phenylpiperidine and has a number of congeners. It is mostly effective in the CNS and bowel
- Produces analgesia, sedation, euphoria and respiratory depression.
- Less potent than morphine, 80-100 mg meperidine equals 10 mg morphine.
- Shorter duration of action than morphine (2-4 hrs).
- Meperidine has greater excitatory activity than does morphine and toxicity may lead to convulsions.
- Meperidine appears to have some atropine-like activity.
- Does not constrict the pupils to the same extent as morphine.
- Does not cause as much constipation as morphine.
- Spasmogenic effect on GI and biliary tract smooth muscle is less pronounced than that produced by morphine.
- Not an effective antitussive agent.
- In contrast to morphine, meperidine increases the force of oxytocin-induced contractions of the uterus.
- Often the drug of choice during delivery due to its lack of inhibitory effect on uterine contractions and its relatively short duration of action.
- It has serotonergic activity when combined with monoamine oxidase inhibitors, which can produce serotonin toxicity (clonus, hyperreflexia, hyperthermia, and agitation)
Ketorolac
Mechanism of action
primary action responsible for its anti-inflammatory/antipyretic/analgesic effects is inhibition of prostaglandin synthesis through inhibition of the enzyme cyclooxygenase (COX). Ketorolac is not a selective inhibitor of COX enzymes
Indications: short-term management of pain
Contraindications
hypersensitivity to ketorolac, and against patients with the complete or partial syndrome of nasal polyps, angioedema, bronchospastic reactivity or other allergic manifestations to aspirin or other non-steroidal anti-inflammatory drugs (due to possibility of severe anaphylaxis).
Classification Based on
a. Chemical structure
I. Sulphonamidcs.and others - c.g.. sulphadiazine. etc.
2. Beta-lactum ring - e.g.. penicillin
3. Tetracycline - e.g.. Oxytetracycline,.doxycycline.etc.
b. Mechanism of action
1. Inhibits cell-wall synthesis - penicillin. cephalosporin..cycloserine. etc.
2. Cause leakage from cell-membrane – polypeptides (polymyxin, Bacitracin), polyenes (Nystatin)
3. Inhibit protein synthesis - tetracyclines. chloramphenicols. erythromycin.
4. Cause mis-reading of mRNA code - aminoglycosides
5. Interfere with DNA function - refampicin.. metronidazole
6. Interfere with intermediary metabolism - sulphonamides. ethambutole
c. Type of organism against which it is primarily activate
I. Antibacterial - penicillin.
2. Antifungal - nystatin.
d. Spectrum of activity
1. Broad spectrum - tetracylines .
2. Narrow spectrum - penicillin G (penG). streptomycin.erythromycin
e. Type of action
I. Bacteriostatic - sulphonamides, erythromycin.tertracyclines
2. Bacteriocidal - penicillin. aminoglycoside
f. Source
I. Fungi - penicillin. cephalosporins
2. Bacteria - Polymyxin B
On the basis of Receptors, drugs can be divided into four groups,
a. agonists
b. antagonists
c. agonist-antagonists
d. partial agonists
a. Agonist
morphine fentanyl pethidine
Action : activation of all receptor subclasses, though, with different affinities
b. Antagonist
Naloxone , Naltrexone
Action : Devoid of activity at all receptor classes
c. Partial Agonist: (Mixed Narcotic Agonists/Antagonists)
Pentazocine, Nalbuphine, Butorphanol , Buprenorphine
Action: activity at one or more, but not all receptor types
With regard to partial agonists, receptor theory states that drugs have two independent properties at receptor sites,
a. affinity
The ability, or avidity to bind to the receptor
Proportional to the association rate constant, Ka
b. efficacy
or, intrinsic activity, and is the ability of the D-R complex to initiate a pharmacological effect
Drugs that produce a less than maximal response and, therefore, have a low intrinsic activity are called partial agonists.
These drugs display certain pharmacological features,
a. the slope of the dose-response curve is less than that of a full agonist
b. the dose response curve exhibits a ceiling with the maximal response below that obtainable by a full agonist
c. partial agonists are able to antagonise the effects of large doses of full agonists
Indomethacin
commonly used to reduce fever, pain, stiffness, and swelling. It works by inhibiting the production of prostaglandins, molecules known to cause these symptoms.
Indications
ankylosing spondylitis, rheumatoid arthritis, osteoarthritis, juvenile arthritis, psoriatic arthritis, Reiter's disease, Paget's disease of bone, Bartter's disease, pseudogout, dysmenorrhea (menstrual cramps), pericarditis, bursitis, tendonitis, fever, headaches, nephrogenic , diabetes insipidus (prostaglandin inhibits vasopressin's action in the kidney)
Indomethacin has also been used clinically to delay premature labor, reduce amniotic fluid in polyhydramnios, and to treat patent ductus arteriosus.
Mechanism of action
Indomethacin is a nonselective inhibitor of cyclooxygenase (COX) 1 and 2, enzymes that participate in prostaglandin synthesis from arachidonic acid. Prostaglandins are hormone-like molecules normally found in the body, where they have a wide variety of effects, some of which lead to pain, fever, and inflammation.
Prostaglandins also cause uterine contractions in pregnant women. Indomethacin is an effective tocolytic agent, able to delay premature labor by reducing uterine contractions through inhibition of PG synthesis in the uterus and possibly through calcium channel blockade.
Indomethacin easily crosses the placenta, and can reduce fetal urine production to treat polyhydramnios. It does so by reducing renal blood flow and increasing renal vascular resistance, possibly by enhancing the effects of vasopressin on the fetal kidneys.
Adverse effects
Since indomethacin inhibits both COX-1 and COX-2, it inhibits the production of prostaglandins in the stomach and intestines which maintain the mucous lining of the
gastrointestinal tract. Indomethacin, therefore, like other nonselective COX inhibitors, can cause ulcers.
Many NSAIDs, but particularly indomethacin, cause lithium retention by reducing its excretion by the kidneys.
Indomethacin also reduces plasma renin activity and aldosterone levels, and increases
sodium and potassium retention. It also enhances the effects of vasopressin. Together these may lead to:
edema (swelling due to fluid retention)
hyperkalemia (high potassium levels)
hypernatremia (high sodium levels)
hypertension (high blood pressure)
Sulindac: Is a pro‐drug closely related to Indomethacin.
Converted to the active form of the drug.
Indications and toxicity similar to Indomethacin