NEET MDS Lessons
Pharmacology
Morphine
Morphine is effective orally, but is much less effective than when given parenterally due to first-pass metabolism in the liver. Metabolism involves glucuronide formation, the product of which is excreted in the urine.
1. Central Nervous System Effects
• Morphine has mixed depressant and stimulatory actions on the CNS.
• Analgesia:
• Dysphoria – Euphoria
- morphine directly stimulates the chemoreceptor trigger zone, but later depresses the vomiting center in the brain stem. This center is outside the blood/brain barrier.
- opiates appear to relieve anxiety
• Morphine causes the release of histamine and abolishes hunger.
- causes the body to feel warm and the face and nose to itch.
• Pupils are constricted.- due to stimulation of the nuclei of the third cranial nerves.
- tolerance does not develop to this effect.
• Cough reflex is inhibited. - this is not a stereospecific effect.
- dextromethorphan will suppress cough but will not produce analgesia.
• Respiration is depressed
- due to a direct effect on the brain stem respiratory center.
- death from narcotic overdose is nearly always due to respiratory arrest.
- the mechanism of respiratory depression involves:
• a reduction in the responsiveness of the brain stem respiratory centers to an increase in pCO2.
• depression of brain stem centers that regulate respiratory rhythm.
- hypoxic stimulation of respiration is less affected and O2 administration can produce apnea.
2. Cardiovascular Effects
• Postural orthostatic hypotension.- due primarily to peripheral vasodilation, which may be due in part to histamine release.
• Cerebral circulation is also indirectly influenced by increased pCO2, which leads to cerebral vasodilation and increased cerebrospinal fluid pressure.
• In congestive heart failure, morphine decreases the left ventricular workload and myocardial oxygen demand.
3. Endocrine Effects
• Increases prolactin secretion
• Increases vasopressin (ADH) secretion
• Decreases pituitary gonadotropin (LH & FSH) secretion.
• Decreases stress induced ACTH secretion.
4. Gastrointestinal Tract Effects
• Constipation (tolerance does not develop to this effect).
• Several of these agents can be used in the treatment of diarrhea.
There is an increase in smooth muscle tone and a decrease in propulsive contractions.
Adverse Reactions
Generally direct extensions of their pharmacological actions.
1. respiratory depression, apnea
2. nausea and vomiting
3. dizziness, orthostatic hypotension, edema
4. mental clouding, drowsiness
5. constipation, ileus
6. biliary spasm (colic)
7. dry mouth
8. urine retention, urinary hesitancy
9. hypersensitivity reactions (contact dermatitis, urticaria)
Precautions
1. respiratory depression, particularly in the newborn
3. orthostatic hypotension
4. histamine release (asthma, shock)
5. drug interactions (other CNS depressants)
6. tolerance:
- analgesia, euphoria, nausea and vomiting, respiratory depression
7. physical dependence (psychological & physiological)
PLASMA FRACTIONS:
a) Fresh frozen plasma.
b) Platelets.
c) Plasma concentrates.
d) Non-plasma recombinant factor concentrates.
Factors affecting onset and duration of action of local anesthetics
pH of tissue
pKa of drug
Time of diffusion from needle tip to nerve
Time of diffusion away from nerve
Nerve morphology
Concentration of drug
Lipid solubility of drug
Specific Agents
Hydralazine [orally effective]
MOA: Not completely understood. Seems to be partially dependent on the release of EDRF and perhaps partially due to K+-channel activation
- in clinical doses action is manifest primarily on vascular smooth muscle (non-vascular muscle is not much affected).
- Re: Metabolism & Excretion. In cases of renal failure the plasma half life may be substantially increased (4-5 fold). One mode of metabolism is
via N-Acetylation (problem of slow acetylators)
Side Effects
- those typical of vasodilation = headache, nasal congestion, tachycardia etc.
- chronic treatment with high doses > 200 mg/day may induce a rheumatoid-like state which may resemble lupus erythematosus.
Minoxidil (Loniten) [orally effective]
MOA: K+-channel agonist
- very effective antihypertensive. Used primarily to treat life-threatening hypertension or hypertension resistant to other agents.
Side effects - growth of hair
Diazoxide (Hyperstat) [used only IV]
MOA: K+-channel agonist
- Administered by rapid IV injection; action appearing after 3-5 min; action may last from 4 to 12 hours.
Nitroprusside (Nipride) [used only IV]
MOA: increase in cGMP
- unlike the other vasodilators, venous tone is substantially reduced by nitroprusside.
- rapid onset of action (.30 sec); administered as an IV-infusion.
- particularly useful for hypertension associated with left ventricular failure.
Antimania Drugs
MANIC SYMPTOMSMANIC SYMPTOMS
Elevated or irritable mood
Increased activity or psychomotor agitation
Reduced need for sleep
Inflated self esteem or grandiosity
Increased or pressure of speech
Flight of ideas
These drugs are used to treat manic-depressive illness.
1. Lithium
2. Carbamazepine
3. Valproic acid
Mechanisms of action
1. Lithium works inside the cell to block conversion of inositol phosphate to inositol.
2. Carbamazepine blocks sodium channels
3. Valproic acid blocks sodium and calcium channels
PHARMACOKINETICS
Absorbed readily and almost completely from the GI tract; peak concentrations in 1-2 hrs
Lithium toxicity
1. Nausea, diarrhea, convulsions, coma, hyperreflexia, cardiac arrhythmias, hypotension.
2. Thyroid enlargement; increases thyroid stimulating hormone (TSH) secretion; may cause hypothyroidism.
3. Polydipsia, polyuria (lithium inhibits the effect of antidiuretic hormone on the kidney).
Clinical applications concerning lithium
- Patients must be warned against sodium-restricted diets because sodium restriction leads to greater retention of lithium by the kidney.
- Patients must have regular (e.g., monthly) blood checks because the margin of safety is narrow.
Endocrine Effects – Goitre and hypothyroidism commonly
Cardiac Effects:– ECG changes(common) - T-wave flattening/inversion and appearance of U wavesflattening/inversion and appearance of U waves
Li and Pregnancy -1st Trimester:Cardiovascular anomalies of the newborn, especially Ebstein's malformation
- 3rd Trimester: Neonatal goiter, CNS depression, hypotonia ("floppy baby" syndrome)
Drug–drug interactions of lithium
Diuretics and newer nonsteroidal anti-inflammatory drugs (NSAIDs) reduce lithium excretion and may cause lithium toxicity.
Kinins
Peptide that are mediated in the inflammation.
Action of kinin:
On CVS: vasodilatation in the kidneys, heart, intestine, skin, and liver. It is 10 times active than histamine as vasodilator.
On exocrine and endocrine glands: kinin modulate the tone of pancreas and salivery glands and help regulate GIT motility, also affect the transport of water and electrolytes, glucose and amino acids through epithelial cell transport.
Pharmacology is the study of drugs and the way they interact with living systems. Clinical pharmacology is the study of drugs in humans.
A drug is any chemical that can effect living processes.
Therapeutics: the medical use of drugs.
An ideal drug has several important properties. Three of these properties are of utmost importance: effectiveness, safety and selectivity.
Effectiveness: This is the most important quality that a drug can have. Effectiveness refers to the drug's ability to do what it is supposed to do.
Safety: Although no drug can be totally safe, proper usage can lessen the risks of adverse effects.
Selectivity: A truly selective drug would have no side effects, and would effect only the body process' for which it is designed and given. Therefore, there is no such thing as a selective drug.
Pharmacokinetics: The way the body deals with a drug. Pharmacokinetics is concerned with the processes of absorption, distribution, metabolism and excretion.
Pharmacodynamics: What a drug does to the body.
Pharmacokinetics and pharmacodynamics are two of the processes that determine how a person will respond to a drug. Other factors include how a drug is administered (dose, route, and timing of administration), interactions with other drugs, and individual physiological variables (weight, age, function of body systems).