NEET MDS Lessons
Pharmacology
Metabolism
Hepatic Drug-Metabolizing Enzymes: most drug metabolism in the liverperformed by the hepatic microsomal enzyme system.
Therapeutic Consequences of Drug Metabolism
- Accelerated Renal Drug Excretion: The most important consequence of drug metabolism is the promotion of renal drug excretion. Metabolism makes it possible for the kidney to excrete many drugs that it otherwise could not.
- Drug Inactivation
- Increased Therapeutic Action: Metabolism may increase the effectiveness of some drugs.
- Activation of Prodrugs: A prodrug is a compound that is inactive when administered and made active by conversion in the body.
- Increased or Decreased Toxicity
Factors that influence rate of metabolism:
- Age: Hepatic maturation doesn't occur until about a year old.
- Induction of Drug-Metabolizing Enzymes: Some drugs can cause the rate of metabolism to increase, leading to the need for an increased dosage. May also influence the rate of metabolism for other drugs taken at the same time, leading to a need for increased dosages of those drugs as well.
- First-Pass Effect: Hepatic inactivation of certain oral drugs. Avoided by parentaral administration of drugs that undergo rapid hepatic metabolism.
- Nutritional Status
- Competition between Drugs
Glitazones (thiazolidinediones)
Thiazolidinediones, also known as the "-glitazones"
pioglitazone
rosiglitazone
Mechanism
bind to nuclear receptors involved in transcription of genes mediating insulin sensitivity
peroxisome proliferator-activating receptors (PPARs)
↑ insulin sensitivity in peripheral tissue
↓ gluconeogenesis
↑ insulin receptor numbers
↓ triglycerides
Clinical use
type II DM
as monotherapy or in combination with other agents
contraindicated in CHF
associated with increased risk of MI (in particular rosiglitazone)
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.
Helicobacter Pylori Agents
Antimicrobial
• Amoxicillin,
• Clarithromycin,
• Metronidozole
• Tetracycline
Antisecreteory agents accelerates symptom relief and yield healing (omeprozole)
Bismuth subsalicylate
Therapy For H. Pylori
Original
• Tetracycline
• Metronidazole (Flagyl)
• Bismuth subsalicylate
• Given for 14 days
• >90% effective in eradicating microorganisms
New triple therapy
• Amoxicillin
• Clarithromycin
• Omeprazole (Prilosec)
• Given for 7 days
• >90% effective in eradicating microorganisms
Dual Therapy
Amoxicillin or clarithromycin
Omeprazole
Given for 14 days
60-80% effective in eradication of H. Pylori
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
Dental implications of these drugs:
1. Adverse effects: gingival hyperplasia (phenytoin), osteomalacia (phenytoin, Phenobarbital), blood dyscrasias (all but rare)
2. Drug interactions: additive CNS depression (anesthetics, anxiolytics, opioid analgesics), induction of hepatic microsomal enzymes (phenytoin, Phenobarbital, carbamazepine), plasma protein binding (phenytoin and valproic acid)
3. Seizure susceptibility: stress can → seizures
Midazolam -Intravenous Anesthetics
Midazolam is a benzodiazepine used for preoperative sedation, induction of anesthesia, or maintenance of anesthesia in short procedures.