NEET MDS Lessons
Pharmacology
Clavulanic acid is often combined with amoxicillin to treat certain infections caused by bacteria, including infections of the ears, lungs, sinus, skin, and urinary tract. It works by preventing bacterium that release beta-lactamases from destroying amoxicillin.
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.
Etomidate -Intravenous Anesthetics
- A nonbarbiturate anesthetic used primarily to induce surgical anesthesia.
- It does not produce analgesia.
- Etomidate has minimal effect on the cardiovascular system and respiration during induction of anesthesia.
- Like the barbiturates, etomidate decreases cerebral blood flow, cerebral metabolic rate and intracranial pressure.
- No changes in hepatic, renal or hematologic function have been reported.
- Myoclonic muscle movements are relatively common.
- Postoperative nausea and vomiting are more common with etomidate than with barbiturates.
Selective serotonin reuptake inhibitors (SSRIs)
e.g. fluoxetine, paroxetine, citalopram, and sertraline
- Most commonly used antidepressant category
- Less likely to cause anticholinergic side effects
- Relatively safest antidepressant group in overdose
- Selectively inhibits reuptake of serotonin(5-HT)
Mode of Action;
- Well absorbed when given orally
- Plasma half-lives of 18-24 h allowing once daily dosagedaily dosage
- Metabolised through CYP450 system and most SSRIs inhibit some CYP isoforms
- Therapeutic effect is delayed for 2-4 weeks
ADVERSE DRUG REACTIONS
- Insomnia, increased anxiety, irritability
- Decreased libido
- Erectile dysfunction, anorgasmia, and ejaculatory delay
- Bleeding disorders
- Withdrawal syndrome
Balanced Anesthesia
A barbiturate, narcotic analgesic agent, neuromuscular blocking agent, nitrous oxide and one of the more potent inhalation anesthetic.
EPHEDRINE
It act indirectly and directly on α and β receptors. It increases blood pressure both by peripheral vasoconstriction and by increasing the cardiac output. Ephedrine also relaxes the bronchial smooth muscles.
Ephedrine stimulates CNS and produces restlessness, insomnia, anxiety and tremors.
Ephedrine produces mydriasis on local as well as systemic administration.
Ephedrine is useful for the treatment of chronic and moderate type of bronchial asthma, used as nasal decongestant and as a mydriatic without cycloplegia. It is also useful in preventing ventricular asystole in Stokes Adams syndrome.
Monoamine oxidase inhibitors (MAOIs)
e.g. phenelzine, tranylcypromine, moclobemide
- Belong to first generation antidepressants with TCAs
- Most MAOIs irreversibly inhibit the intraneuronal catabolism of norepinephrine and serotonin by MAO-A and MAO-B
- increase brain levels of noradrenaline and 5-HT
- Moclobemide causes selective, reversible inhibition of MAO-A
DRUG INTERACTIONS
Hypertensive crises similar to cheese reaction with OTC cough/cold preparations containing indirect-sympathomimetics
e.g. ephedrine
- Other antidepressants should not be started at least 2 weeks after stopping MAOIs and vice versa due to risk of serotonin syndrome
- Similar interaction with pethidine
ADVERSE DRUG REACTIONS
- Antimuscarinic side effects (e.g. dry mouth, blurred vision, urinary retention)vision, urinary retention)
- Excessive central stimulation causes tremors, excitement and insomnia
- Postural hypotension
- Increased appetite with weight gain