Pharmacodynamics (pharmacology), Slides of Pharmacology

Download Pharmacodynamics (pharmacology) and more Slides Pharmacology in PDF only on Docsity! Pharmacodynamics Contents ⚫ The pharmacodynamic process ⚫ Types of Pharmacological Actions of Drugs ⚫ Therapeutic response ⚫ Classification of adverse drug reactions ⚫ Tolerance ⚫ Withdrawal symptoms ⚫ Drug interactions Types of Pharmacological Actions of Drugs 1. Drug action via a receptor Receptors are specific proteins situated in either cell membranes or in some cases inside the cell. For each type of receptor, there are specific group of drugs or endogenous substances (known as ligands), which are capable of binding to the receptor and thereby producing pharmacological effect. There are 3 types of ligands which can act by binding to a receptor- ❖ Agonists- Ligands which bind to a receptor and produce an appropriate response are called agonists. For e.g. adrenaline is an agonist at β-adrenoreceptors. When it binds to β-adrenoreceptors in the heart it increases the blood pressure. ❖Antagonists- Ligands which prevent an agonist from blinding to a receptor, and thus prevent its effects are called antagonists. However, antagonists do not themselves have any pharmacological actions mediated by receptors. For e.g. propranolol is a β-adrenoreceptor antagonist. When it binds to β-adrenoreceptors in the heart, it decreases the blood pressure. ❖ Partial Agonists/Antagonists- A full agonist is one which is capable of producing a maximal response, when it binds to a sufficient number of receptors. In contrast, a partial agonist cannot produce the maximal response, even when it binds to the same number of receptors as a full agonist binds to when it produces a maximal response. For e.g. Oxprenolol which is a β-adrenoreceptor antagonist is also a partial agonist Types of Pharmacological Actions of Drugs 2. Drug action via the alteration of endogenous substance ❖ Physiological antagonism- A drug can produce the opposite physiological effect of an endogenous substance. For e.g. glucagon is a physiological antagonist of the actions of insulin. ❖ Increase in endogenous release- The action of an endogenous substance may be enhanced if its release is increased. For e.g. amphetamines increase the release of dopamine from nerve endings. Types of Pharmacological Actions of Drugs Inhibition of Endogenous Re-uptake Types of Pharmacological Actions of Drugs 3. Drug action via the modification of transport process ❖ Calcium antagonists- The calcium antagonists, such as verapamil, diltiazem, nifedipine etc. act by inhibiting the transport of calcium through specific calcium channels. Thus a decrease in the level of calcium occurs in the myocardial cell and results in vasodilation. ❖ Insulin- One of the many actions of insulin is to increase the inward flux of glucose into cells by an action mediated by insulin receptors. In the treatment of hyperglycemia in diabetes the rapid fall of blood glucose produced by insulin is undoubtedly due to this action. ❖ Probenecid- Probenecid is an organic acid which blocks the reabsorption of uric acid and thus used as a uricosuric agent in gout. Modification of transport process by Calcium antagonists USS ee US: USS Sa AY insbatby | Gandnithie Types of Pharmacological Actions of Drugs 4. Drug action via enzyme inhibition ❖ Allopurinol- Xanthines are oxidized to uric acid by the enzyme xanthine oxidase, which is inhibited by allopurinol. Allopurinol therefore decreases the synthesis of uric acid and reduces the risk of gout. ❖ MAO Inhibitors- MAO inhibitors (selegiline, rasagiline, phenelzine etc.) inhibit the activity of monoamine oxidases and thus reduces the oxidative deamination of monoamines such as epinephrine, norepinephrine, dopamine etc. Thus MAO inhibitors are used in CNS disorders like depression, schizophrenia and others. Drug action via enzyme inhibition Allopurinol Medications to Prevent Gout Attacks Hypouremic agents  ® ® Drug action via enzyme inhibition MAO Inhibitors Practice Problems 5. Nicotine stimulates receptors to start a reaction that results in further release of neurotransmitters 6. Morphine, works just like natural opioids (e.g endorphins) of our body. It binds to opioid receptors located in pain signaling cells of the nervous system and slows down the pain response. 7. Fluoxetine elicits antidepressant effect by inhibiting serotonin re-uptake in the synapse by binding to the re-uptake pump on the neuronal membrane to increase its availability and enhance neurotransmission. 8. Activated charcoal adsorbs ingested toxins within the gastrointestinal tract preventing the systemic absorption of that toxin. Therapeutic Response of Digoxin e Bi ee Te Action PTT tT  Therapeutic Response of Digoxin The concentration of intracellular Na* 2 Increases, and the concentration gradient across the membrane decreases, Increased Na* decreases the driving force for the 3 Na’/Ca? "exchanger, so there is decreased extrusion of Ca** into the extracellular space. Therapeutic Response of Digoxin Molecular pharmacology Cell pharmacology Cell physiology Tissue physiology Organ physiology Pharmacological effect Inhibition of Na+K+ ATPase Inhibition of transport of Na+ /K+ Increase in intracellular Ca2+ Alteration of action potential Increased myocardial contractility Increased cardiac output Relief of signs and symptoms of heart failure Fig- The chain of events leading to the pharmacological effect of digoxin Level of Effects Results Adverse Effects *Here, adverse effects that are solely harmful for patients and requires dose adjustments or withdrawal of drugs are discussed. 1. Dose related adverse effects: Dose related adverse reactions may occur because of variations in the pharmaceutical, pharmacokinetic or pharmacodynamics properties of a drug. ❖ Pharmaceutical Variations: For e.g. phenytoin intoxication occurred in the late 1960s in Australia because one of the excipients was changed from calcium sulphate to lactose. This caused an increase in the systemic availability of phenytoin. Sometimes an adverse reaction occurs in a patient because of the presence of a contaminant, for e.g. pyrogens or even bacteria in intravenous formulations, if quality control is poor. Pharmaceutical Variations 2. Non-dose related adverse effects: These types of adverse reactions can not necessarily be reduced by dose-minimization. Several immunological reactions may occur such as allergy, asthma, hypersensitivity etc. due to some drugs in susceptible individuals. Such as penicillin hypersensitivity, allergic reactions due to some protein and polypeptide drugs (insulin), increased photosensitivity by sulphonamides, thiazide diuretics, tetracyclines etc. Adverse Effects A simple example of a delayed adverse effect of drug is that of hypothyroidism occurring years after the treatment of hyperthyroidism with radioactive iodine. Some drugs may cause carcinogenesis as a delayed adverse effect, for e.g. incidence of vaginal and uterine cancers in women taking diethylstilbestrol or daughters of women taking diethylstilbestrol during pregnancy. Impairment of male fertility maybe caused by sulphasalazine, MAO inhibitors and cytotoxic drugs in long term use. Teratogenesis occurs when a drug taken during early stages of pregnancy causes a developmental abnormality in a fetus. Such as- ACE inhibitors, some anticancer drugs, thalidomide etc. Delayed Adverse Effects Tolerance Drug tolerance is a state of decreased responsiveness to a drug, brought about by previous exposure to that drug or to a drug with similar effects. Tolerance to organic nitrates can occur with the workers handling nitroglycerine in munitions factories. In these workers, organic nitrate drugs are needed to be used at higher doses for the treatment of angina. Again in the severe chronic pain, tolerance may occur to the analgesic effect of morphine and other narcotic analgesics and increased doses may be required to alleviate the pain. Despite the discovery of opioid receptors and their subtypes along with the interrelation between pain relief and opioid drugs, the precise mechanism by which tolerance develops is still not understood. Drug Interactions The interaction of allopurinol with azathioprine and 6-mercaptopurine is an important example of the effect of inhibition of a specific metabolic pathway. During allopurinol therapy xanthine oxidase activity is inhibited. Both azathioprine and 6-mercaptopurine are metabolized by xanthine oxidase. Thus the metabolisms of these drugs are inhibited by allopurinol and their dose requirements are reduced. This bears great clinical significance in patients with both hyperuricemia and leukemia. Drug Interactions Drug-Food Interactions: ACE inhibitors can increase the amount of potassium in body. Too much potassium can be harmful and can cause an irregular heartbeat and heart palpitations (rapid heart beats). Foods high in potassium, such as bananas, oranges, green leafy vegetables, and salt substitutes that contain potassium should be avoided. They can raise the level of potassium even higher. Vitamin K in food can make some medicines less effective, such as warfarin and other anticoagulant drugs. Foods high in vitamin K include broccoli, cabbage, spinach, turnip etc. should be avoided. Drug Interactions Taking alcohol with the antibiotic metronidazole can cause headache, palpitations, and nausea and vomiting. The fiber in oatmeal and other cereals, when consumed in large amounts, can interfere with the absorption of digoxin. Calcium or foods containing calcium, such as milk and other dairy products can reduce the absorption of tetracycline which should be taken 1 hour before or 2 hours after eating.