NEET MDS Lessons
Pharmacology
RENIN-ANGIOTENSIN SYSTEM INHIBITORS
The actions of Angiotensin II include an increase in blood pressure and a stimulation of the secretion of aldosterone (a hormone from the adrenal cortex) that promotes sodium retention. By preventing the formation of angiotensin II, blood pressure will be reduced. This is the strategy for development of inhibitors. Useful inhibitors of the renin-angiotensin system are the Angiotensin Converting Enzyme Inhibitors
First line treatment for: Hypertension , Congestive heart failure [CHF]
ACE-Inhibitor’s MOA (Angiotensin Converting Enzyme Inhibitors)
Renin-Angiotensin Aldosterone System:
. Renin & Angiotensin = vasoconstrictor
. constricts blood vessels & increases BP
. increases SVR or afterload
. ACE Inhibitors blocks these effects decreasing SVR & afterload
. Aldosterone = secreted from adrenal glands
. cause sodium & water reabsorption
. increase blood volume
. increase preload
. ACE I blocks this and decreases preload
Types
Class I: captopril
Class II (prodrug) : e.g., ramipril, enalapril, perindopril
Class III ( water soluble) : lisinopril.
Mechanism of Action
Inhibition of circulating and tissue angiotensin- converting enzyme.
Increased formation of bradykinin and vasodilatory prostaglandins.
Decreased secretion of aldosterone; help sodium excretion.
Advantages
- Reduction of cardiovascular morbidity and mortality in patients with atherosclerotic vascular disease, diabetes, and heart failure.
- Favorable metabolic profile.
- Improvement in glucose tolerance and insulin resistance.
- Renal glomerular protection effect especially in diabetes mellitus.
- Do not adversely affect quality of life.
Indications
- Diabetes mellitus, particularly with nephropathy.
- Congestive heart failure.
- Following myocardial infraction.
Side Effects
- Cough (10 - 30%): a dry irritant cough with tickling sensation in the throat.
- Skin rash (6%).
- Postural hypotension in salt depleted or blood volume depleted patients.
- Angioedema (0.2%) : life threatening.
- Renal failure: rare, high risk with bilateral renal artery stenosis.
- Hyperkalaemia
- Teratogenicity.
Considerations
- Contraindications include bilateral renal artery stenosis, pregnancy, known allergy, and hyperkalaemia.
- High serum creatinine (> 3 mg/dl) is an indication for careful monitoring of renal function, and potassium. Benefits can still be obtained in spite of renal insufficiency.
- A slight stable increase in serum creatinine after the introduction of ACE inhibitors does not limit use.
- ACE-I are more effective when combined with diuretics and moderate salt restriction.
ACE inhibitors drugs
Captopril 50-150 mg
Enalapril 2.5-40 mg
Lisinopril 10-40 mg
Ramipril 2.5-20 mg
Perindopril 2-8 mg
Angiotensin Receptor Blocker
Losartan 25-100 mg
Candesartan 4-32 mg
Telmisartan 20-80 mg
Mechanism of action
They act by blocking type I angiotensin II receptors generally, producing more blockade of the renin -angiotensin - aldosterone axis.
Advantages
• Similar metabolic profile to that of ACE-I.
• Renal protection.
• They do not produce cough.
Indications
Patients with a compelling indication for ACE-I and who can not tolerate them because of cough or allergic reactions.
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
DIAGNOSIS
Affective disorders:
I. unipolar depression – depression alone
bipolar affective disorder – alternating II. bipolar affective disorder – alternating depression and mania
Diagnosis is based on
At least five of the following for 2 weeks
I. Depressed mood most of the day
II. Markedly diminished interest or pleasureII. Markedly diminished interest or pleasure
III. Significant weight loss or weight
IV. Insomnia or hypersomnia
V. Psychomotor agitation or retardation
VI. Fatigue or loss of energy
VII. Feelings of worthlessness or excessive guilt
VIII. Diminished ability to think or concentrate,
IX. Recurrent thoughts of death
Underlying biological basis for depression is a deficiency of the monoamine neurotransmitters norepinephrine and/or serotonin in the brain.
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)
Phenoxymethylpenicillin (penicillin V) Phenoxymethylpenicillin, commonly known as penicillin V, is the orally-active form of penicillin. It is less active than benzylpenicillin
Indications:
infections caused by Streptococcus pyogenes, tonsillitis, pharyngitis, skin infections, prophylaxis of rheumatic fever, moderate-to-severe gingivitis (with metronidazole)
Pharmacokinetics
Pharmacokinetics is the way that the body deals with a drug - how that drug moves throughout the body, and how the body metabolizes and excretes it. The factors and processes involved in pharmacokinetics must be considered when choosing the most effective dose, route and schedule for a drug's use.
The four processes involved in pharmacokinetics are:
Absorption: The movement of a drug from its site of administration into the blood.
Several factors influence a drug's absorption:
- Rate of Dissolution: the faster a drug dissolves the faster it can be absorbed, and the faster the effects will begin.
- Surface Area: Larger surface area = faster absorption.
- Blood Flow: Greater blood flow at the site of drug administration = faster absorption.
- Lipid Solubility: High lipid solubility = faster absorption
- pH Partitioning: A drug that will ionize in the blood and not at the site of administration will absorb more quickly.
Distribution: The movement of drugs throughout the body.
Metabolism: (Biotransformation) The enzymatic alteration of drug structure.
Excretion: The removal of drugs from the body.
As a drug moves through the body, it must cross membranes. Some important factors to consider here then are:
Body's cells are surrounded by a bilayer of phospholipids (cell membrane).
There are three ways that a substance can cross cell membranes:
- Passing through channels and pores: only very small molecules can cross cell membranes this way.
- Transport Systems: Selective carriers that may or may not use ATP.
- Direct Penetration of the Cell Membrane:
Operator position
For the right-handed operator, the 8 and 10 o’clock position and for left-handed operators, the corresponding 2 and 4 o’clock position almost always allows for optimal visualization of the injection field.