Pharmacodynamics PDF

PHARMACODYNAMICS It is the study of drug action or effect on the body tissues and system and the mechanism of this action. The effects: are the signs in the body resulting from drug administration. The mechanism of action: is the way the drug produces its effects on the cell func...

PHARMACODYNAMICS It is the study of drug action or effect on the body tissues and system and the mechanism of this action. The effects: are the signs in the body resulting from drug administration. The mechanism of action: is the way the drug produces its effects on the cell function.  The Pharmacodynamic Effects 1- Pharmacotherapeutic effects The desired therapeutic effects of the drug which is either: a. Local effect (topical) at the site of application. b. Reflex effect: which is a remote action by a reflex response to a local application of a drug c. Systemic effect: which is a generalized action or response to a drug after absorption and distribution. 2- Side effects: these are the undesirable effects of the drug. ex: salivation inhibition during the treatment with atropine. 3- Toxic effects: these are the untoward bad effects of the drug. ex: nephritis due to gentamicin administration excessive. - Exaggerated response - Allergic response - Intolerance - Secondary effects as diarrhea with antibiotics - Iatrogenic effects or production of disease by drugs - Teratogenic effect - Drug/drug interactions  DOSE-RESPONSE RELATIONSHIP It is a relation between the dose of the drug and induced response  Factors affecting body response to the drugs Dose of the drug Presence of another drug (Drug interaction) Species variation Individual variation  1- Dose of the drug Dose response curve It is either a graded response curve or quantal dose response curve The graded response curve ►Indicating a graded increased response with increasing doses ( continuous scale) i.e. dose-effect ► Relates dose to the intensity of effect ‫► ﯾﺮﺑﻂ اﻟﺠﺮﻋﺔ ﺑﻜﺜﺎﻓﺔ اﻟﺘﺄﺛﯿﺮ‬ ► Measured in a single biological unit or animal ► Including the following parameters - Magnitude of response is graded - Intrinsic activity is the ability of the drug to elicit a response  - Agonist = binds and activates the receptor * i.e. Efficacy is 1 - Antagonist = binds to the receptor without causing activation * i.e. Efficacy is zero - Partial agonist = Drugs with intermediate level of efficacy, such that response is submaximal even with 100% receptor occupancy  100 Agonist 80 60 Response 40 Partial agonist 20 Antagonist 0 1 10 100 1000 Dose  Efficacy = The tendency of a drug to activate the receptors once it binds to the receptors * i.e. the height of the dose-response curve Affinity = The tendency of a drug to bind to the receptors * i.e. relates to the slope of the dose-response curve Potency = the dose that produce 50% of the maximal response = The lower the dose that is required to produce 50% of the maximal response, the more potent the drug is  Quantal dose response curve ► The relation between the dose and the percentage of response (It represents the % response of animals in a group of population to the doses of a drug). ► Each animal receiving a dosage is characterized as responding or non- responding. (The percentages responding to each dose are recorded (i.e. 0% dead, 0% alive, % responded or % not responded etc.). ► Usually follow the all- or- non low of pharmacological effect ► population studies ► relates dose to frequency of effect ‫► ﯾﺮﺑﻂ اﻟﺠﺮﻋﺔ ﺑﺘﻜﺮار اﻟﺘﺄﺛﯿﺮ‬ ► This type of curve is used for estimating ED50 , LD50 and TI= LD50/ED50  LD50: It is called median lethal dose, which is defined as the dose which would be expected to kill 50% of the exposed population. ED50: It is called median effective dose, which is defined as the dose which would be expected to produce a desired therapeutic response among 50% of the exposed population.  100 Therapeutic Toxic 80 % Responding 60 40 20 0 70 80 90100 200 300 Dose  2- Presence of another drugs (Drug/ drug interaction) e.g. synergism, addition, potentiation and antagonism which may be: - Physiological, - chemical, - pharmacological (competitive or non competitive).  COMPETETIVE ANTAGONISM Antagonists combine with the same site on the receptor as the agonist but have little or no efficacy and an intrinsic response of 0. It is may be reversible or irreversible. Reversible competitive antagonisms are not covalently bound, shift the dose- response curve of the agonist to the right, increase the ED50 and the maximum response unchanged ‫اﻟﻔﺎﻋل ‪+‬اﻟﺿﺎد ﻏﯾر اﻟﻌﻛﺳﻰ‬  Noncompetitive antagonism Bind to the receptor at a site other than the agonist- binding site and either prevent the agonist from binding correctly or prevent it from activating the receptor. Consequently, the effective amount of receptor is reduced. The maximum response decreased and the ED50 is unchanged. 100 80 60 40 20 0 1 10 100 1000  * Mechanism of action of drug occurs through one or more of following: 1- Physical: a- adsorption: As kaolin on diarrhea, charcoal. b- Osmosis: As osmotic diuretics 2- Chemical: a- Neutralization as NaHCO3. In hyper acidity b- chelation as BAL in case of arsenic poisoning  3- Interference with cell division: As cytotoxic drugs. 4- Action on enzymes: As cholinesterase inhibitors drugs and carbonic anhydrase inhibitor drugs Examples include: Neostigmine inhibits acetyl cholinesterase reversibly Aspirin inhibits cyclooxygenase irreversibly ACE inhibitors inhibits angiotensin-converting enzyme 5- Interference with normal Metabolic pathway as sulphonamides competing with PABA essential for Bacterial growth 6- Action on cell membrane Make stabilization of cell mem. (no entrance of Ca, Na) As local anesthetic action 7- action on receptors  * Membrane receptors: Present on the cell membrane and can occupied by both agonist and antagonist drugs 1- Adrenergic receptors: They are typed into: α- receptors ß - receptors 2- Cholinergic receptors: 1- Nicotinic receptors in nerves, skeletal Ms, myoneural function a motor end plate and on ganglia 2- Muscarinic receptors  3- Histaminic= histaminergic receptors: H1 in skin, GIT, lung H2 on stomach H3 in CNS 4- Dopamine receptors 5- Opioid receptors 6- GABA receptors ''Gama amino bertyric acid'‘ 7- SHT receptors ''serotonine receptors'' '' 5- Hydroxy tryptamine''