NEET MDS Lessons
Pharmacology
Gastric acid neutralizers (antacids)
Antacids act primarily in the stomach and are used to prevent and treat peptic ulcer. They are also used in the treatment of Reflux esophagitis and Gastritis.
Mechanism of action:
Antacids are alkaline substances (weak bases) that neutralize gastric acid (hydrochloric acid) they react with hydrochloric acid in the stomach to produce neutral or less acidic or poorly absorbed products and raise the pH of stomach secretion.
Antacids are divided into systemic and non-systemic.
• Systemic antacids (e.g. sodium bicarbonate) are highly absorbed into systemic circulation and enter body fluids. Therefore, they may alter acid–base balance. They can be used in the treatment of metabolic acidosis.
Non-systemic: they do not alter acid–base balance significantly, because they are not well-absorbed into the systemic circulation. They are used as gastric antacids; and include:
• Magnesium compounds such as magnesium hydroxide and magnesium sulphate MgS2O3. They have relatively high neutralizing capacity, rapid onset of action, however, they may cause diarrhoea and hypermagnesemia.
• Aluminium compounds such as aluminium hydroxide. Generally, these have low neutralizing capacity, slow onset of action but long duration of action. They may cause constipation.
• Calcium compounds such as. These are highly effective and have a rapid onset of action but may cause hypersecretion of acid (acid - rebound) and milk-alkali syndrome (hence rarely used in peptic ulcer disease).
Therefore, the most commonly used antacids are mixtures of aluminium hydroxide and magnesium hydroxide .
Seizure classification:
based on degree of CNS involvement, involves simple ( Jacksonian; sensory or motor cortex) or complex symptoms (involves temporal lobe)
1. Generalized (whole brain involved):
a. Tonic-clonic:
Grand Mal; ~30% incidence; unconsiousness, tonic contractions (sustained contraction of muscle groups) followed by clonic contractions (alternating contraction/relaxation); happens for ~ 2-3 minutes and people don’t breathe during this time
Drugs: phenytoin, carbamazepine, Phenobarbital, lamotrigine, valproic acid
Status epilepticus: continuous seizures; use diazepam (short duration) or diazepam + phenytoin
b. Absence:
Petit Mal; common in children; frequent, brief lapses of consciousness with or without clonic motor activity; see spike and wave EEg at 3 Hz (probably relates to thalamocorticoreverburating circuit)
Drugs: ethosuximide, lamotrigine, valproic acid
c. Myoclonic: uncommon; isolated clinic jerks associated with bursts of EEG spikes;
Drugs: lamotrigine, valproic acid
d. Atonic/akinetic: drop seizures; uncommon; sudden, brief loss of postural muscle tone
Drugs: valproic acid and lamotrigine
2. Partial: focal
a. Simple: Jacksonian; remain conscious; involves motor or sensory seizures (hot, cold, tingling common)
Drugs: carbamazepine, phenytoin, Phenobarbital, lamotrigine, valproic acid, gabapentin
b. Complex: temporal lobe or psychomotor; produced by abnormal electrical activity in temporal lobe (involves emotional functions)
Symptoms: abnormal psychic, cognitive, and behavioral function; seizures consist of confused/altered behavior with impaired consciousness (may be confused with psychoses like schizophrenia or dementia)
Drugs: carbamazepine, phenytoin, laotrigine, valproic acid, gabapentin
Generalizations: most seizures can’t be cured but can be controlled by regular administration of anticonvulsants (many types require treatment for years to decades); drug treatment can effectively control seizures in ~ 80% of patients
Properties of inhalation anesthetics
The lower the solubility, the faster the onset and the faster the recoverability.
All general anesthetics:
1. inhibit the brain from responding to sensory stimulation.
2. block the sensory impulses from being recorded in memory.
3. prevent the sensory impulses from evoking “affect”.
Most general anesthetic agents act in part by interacting with the neuronal membranes to affect ion channels and membrane excitability.
· If the concentration given is too low:
1. Movement may occur
2. Reflex activity present (laryngeal spasm)
3. Hypertension
4. Awareness
Premedication of analgesic drugs and muscle relaxants are designed to minimise these effects
· If the concentration given is too high:
1. Myocardial depression
2. Respiratory depression
3. Delayed recovery
Hypothalamic - Pituitary Drugs
Somatropin
Growth hormone (GH) mimetic
Mechanism
agonist at GH receptors
increases production of insulin growth factor-1 (IGF-1)
Clinical use
GH deficiency
increase adult height for children with conditions associated with short stature
Turner syndrome
wasting in HIV infection
short bowel syndrome
Toxicity
scoliosis
edema
gynecomastia
increased CYP450 activity
Octreotide
Somatostatin mimetic
Mechanism
agonist at somatostatin receptors
Clinical use
acromegaly
carcinoid
gastrinoma
glucagonoma
acute esophageal variceal bleed
Toxicity
GI upset
gallstones
bradycardia
Oxytocin
Mechanism
agonist at oxytocin receptor
Clinical use
stimulation of labor
uterine contractions
control of uterine hemorrhage after delivery
stimulate milk letdown
Toxicity
fetal distress
abruptio placentae
uterine rupture
Desmopressin
ADH (vasopressin) mimetic
Mechanism
agonist at vasopressin V2 receptors
Clinical use
central (pituitary) diabetes insipidus
hemophilia A (factor VIII deficiency)
increases availability of factor VIII
von Willebrand disease
increases release of von Willebrand factor from endothelial cells
Toxicity
GI upset
headache
hyponatremia
allergic reaction
Barbiturates (BARBS):
were used for antianxiety, sedation but now replaced by BZs; for IV sedation & oral surgery
Advantages: effective and relatively inexpensive (common in third world countries), extensively studied so have lots of information about side effects/toxicity
Peripheral effects: respiratory depression (with ↑ dose), CV effects (↓ BP and HR at sedative-hypnotic doses), liver effects (bind CYP450 → induction of drug metabolism and other enzymes → ↑ metabolism of steroids, vitamins K/D, cholesterol, and bile salts)
General mechanisms: potently depress neuron activity in the reticular formation (pons, medulla) and cortex
o Bind barbiturate site on GABAA receptor → enhanced inhibitory effect and ↑ Cl influx; → ↓ frequency of Cl channel opening but ↑ open time of Cl channels (in presense of GABA) so more Cl enters channel (at high [ ] they directly ↑ Cl conductance in absence of GABA- act as GABA mimetics)
Metabolism: liver microsomal drug metabolizing enzymes; most are dealkylated, conjugated by glucoronidation; renal excretion
Uses: anticonvulsant, preoperative sedation, anesthesia
Side effects: sedation, confusion, weight gain, N/V, skin rash
Contraindications: pain (can ↑ sensitivity to painful situations → restlessness, excitement, and delirium) and pulmonary insufficiency (since BARBS → respiratory depression)
Drug interactions: have additive depressant affects when taken with other CNS depressants, enhance depressive effects (of antipsychotics, antihistamines, antiHTNs, ethanol, and TCAs), and accelerates metabolism (of β blockers, Ca-channel blockers, corticosteroids, estrogens, phenothiazines, valproic acid, and theophylline; occurs with chronic BARB ingestion)
Acute toxicity: lower therapeutic index; can be fatal if OD; BARB poisoning a major problem (serious toxicity at only 10x hypnotic dose; → respiratory depression, circulatory collapse, renal failure, pulmonary complications which can be life-threatening)
Symptoms: severe respiratory depression, coma, severe hypotension, hypothermia
Treatment: support respiration and BP, gastric lavage (if recent ingestion)
Tolerance: metabolic (induce hepatic metabolic enzymes, occurs within a few days), pharmacodynamic (↓ CNS response with chronic exposure occurs over several weeks; unknown mechanism), and cross tolerance (tolerance to other general CNS depressants)
Physical dependence: develops with continued use; manifest by withdrawal symptoms (mild = anxiety, insomnia, dizziness, nausea; severe = vomiting, hyperthermia, tremors, delirium, convulsions, death)
Other similar agents: meprobamate (Equanil; pharmacological properties like BZs and barbiturates but mechanism unknown) and chloral hydrate (common sedative in pediatric dentistry for diagnostic imaging; few adverse effects but low therapeutic index)
Other drugs for antianxiety: β-adrenoceptor blockers (e.g., propranolol; block autonomic effects- palpitations, sweating, shaking; used for disabling situational anxiety like stage fright), buspirone (partial agonist at serotonin 1A receptor, produces only anxiolytic effects so no CNS depression, dependence, or additive depression with ethanol but onset of action is 1-3 weeks), lodipem (not a BZ but does act at BZ receptors)
Angiotensin
It is generated in the plasma from a precursor plasma globulin. It is involved in the electrolyte balance, plasma
volume and B.P
Angiotensin I:
Renin is an enzyme produced by the kidney in response to a number of factors including adrenergic activity (β1-
receptor) and sodium depletion. Renin converts a circulating glycoprotein (angiotensinogen) into an inactive material angiotensin-I. It gets activation during passage through pulmonary circulation to angiotensin II by (ACE). ACE is located on the luminal surface of capillary endothelial cells, particularly in the lungs & also present in many organ (e.g brain).
Angiotensin II:
Is an active agent, has a vasoconstrictor action on blood vessels & sodium and water retention
Procoagulant Drugs:
Desmospressin Acetate
• Is a synthetic analogue of the pituitary antidiuretic hormone (ADH).
• Stimulates the activity of Coagulation Factor VIII
• Use for treatment of hemophilia A with factor VIII levels less than or equal to 5%, treatment of hemophilia B or in clients who have factor VIII antibodies. Treatment of severe classic von Willebrand's disease (type I) and when an abnormal molecular form of factor VIII antigen is present. Use for type IIB von Willebrand's disease.