Bukenya

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PHARMACODYNAMICS

• BUKENYA BONNY
• CCN, CN, BME

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Definition

• This is the study of action of the drug on the
  body, their mechanisms of action i.e. what the
  drug does to the body and how it does it.
• Drugs produce their effects by interacting with
  the physiological systems of the organisms by
  either increasing or decreasing their activity
  but not changing the basic functions of any
  physiological system

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Drugs act by

• Stimulation the increase in activity of the
  specialized cells e.g. adrenaline stimulated the
  heart.
• Depression the decrease in activity of the
  specialized cells e.g. barbiturates depress the
  CNS
• Irritation this can occur on all types of
  tissues in the body and may result in
  inflammation, corrosion and necrosis of cells

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• Replacement drugs may be used for replacement
  incases of deficiency of natural substances like
  hormones, nutrients e.g. insulin in DM, iron in
  anemia, vitamin C in scurvy.
• Anti-infective and cytotoxic action drugs may
  act by specifically destroying infective
  organisms e.g. penicillins and anticancer drugs.
• Modification of immune status vaccines and sera
  act by improving immunity while
  immune-suppressants depress immunity e.g.
  Glucocorticoid

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MECHANISMS OF DRUG ACTION

• Drugs may produce their effects by acting locally
  or systemically
• most drugs produce their effects by binding to
  specific target protein like receptors, enzymes
  and ion chemicals. Therefore, the fundamental
  mechanism of drug action may be

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Through receptors

• Drugs act by interacting with specific receptors
  in the body.
• A receptor is a site on the cell with which an
  agonist binds to bring about a change. They are
  proteins present in the cytoplasm or on the
  nucleus.
• Functions of receptors
• It identifies the compound which will then bind
  to convey the message to bring a response. The
  compound may be

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• An agonist this is a substance that binds to the
  receptor and produce a response
• Antagonist this is a substance that binds to the
  receptor and prevents the action of agonist to
  the receptor
• Partial agonist it binds to the receptor but has
  low intrinsic activity (has partial response).

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Through enzymes and pumps.

• Drugs inhibit various enzymes reactions e.g.
  acetazolamide inhibits carbonic anhydrase.
• Membrane pumps like HK ATPase, Nak ATPase are
  inhibited by drugs like omeprazole, digoxin
  respectively.
• 3. Through ion channels
• They interfere with movement of ions across
  specific channels e.g. calcium channel blockers,
  potassium channel openers, etc.

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• 4. Altering metabolic process.
• Drugs like antimicrobials alter the metabolic
  pathway in the microorganisms resulting in
  destruction of microorganism e.g. sulfonamides
  interfere with bacterial folic acid synthesis.
• 5. Chemical interaction
• Drugs may act by chemical reaction e.g. antacids
  neutralize gastric acids.
• 6. Physical action
• The action of a drug could result from its
  physical properties e.g. absorption by activated
  charcoal in poisoning, radio-opacity by Barium
  sulfate contrast media.

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AGONISTS

• Agonists are the chemicals that interact with a
  receptor, thereby initiate a chemical reaction
  in the cell and produces effect .
  
• ExampleACh is agonist at muscarinic receptor in
  heart cell.
• Will have both Affinity and Intrinsic activity
• Affinity It is the ability of a drug to bind to
  the receptor (just bind)
• Intrinsic activity It is the ability of a drug
  to activate a receptor following receptor
  occupation

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• Any drug that binds to a receptor and stimulates
  the functional activities
• e.g. Ach

Recptor
Some Effect
Acetylcholine
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TYPES OF AGONISTS

• Full agonist A drug capable of fully activating
  the effector system when it binds receptor
• It has a high affinity for the activated receptor
  conformation
• Partial agonist A drug that binds to its
  receptor but produces a smaller effect than a
  full agonist. Therefore, there is an Intermediate
  levels of efficacy, such that even when 100
  receptor occupancy, tissue response is submaxima

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Partial agonist

• Produces a submaximal response

Partial agonist
Oh!!!, I should Have been here
Submaximal effect
True agonist
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• Inverse agonists these are the chemicals that
  interact with a receptor, but produces opposite
  effect of the well-recognized agonist for that
  receptor
• Will have Affinity and negative Intrinsic
  activity e.g. Flumazenil is an inverse agonist of
  Benzodiazepine

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Inverse agonist

• Any drug that binds to a receptor and produces an
  opposite effect as that of an agonist

Effect opposite to that of the true agonist
A Cell
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DRUG SYNERGISM AND ANTAGONISM

• When two or more drugs are given concurrently the
  effect may be additive, synergistic or
  antagonistic.
• Additive effect the effect of two or more drugs
  get added up and the total effect is equal to the
  sum of their individual actions e.g. ephedrine
  with theophylline in bronchial asthma.
• Synergism the action of one drug is enhanced by
  another drug and the effect of the combination is
  greater than the sum of their independent effects
  (supra additive effect).
• Antagonism one drug opposing or inhibiting the
  action of another drug.

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ANTAGONISTS

• ANTAGONISTS
• This is a drug that binds to the receptor and
  blocks the effect of an agonist for that receptor
• Atropine is antagonist of ACh at Muscarinic
  receptors.
• Will have only Affinity but no Intrinsic activity

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So, what is a receptor antagonist?

• Any drug that prevents the binding of an agonist
• eg Atropine (an anticholinergic drug)

Atropine
Dude, youre in my way!
Acetylcholine
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TYPES OF ANTAGONISTS

• 1. Competitive antagonism/reversible
• Describes a situation where a drug binds
  selectively to a particular type of receptor
  without activating it, but in such a way as to
  prevent the binding of an agonist.
• At a given agonist, the agonist occupancy will be
  reduced in the presence of the antagonist.
  because the two are in competition, raising the
  agonist can restore the tissue occupancy.

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Irreversible competitive antagonism

• Competitive antagonism occurs when the antagonist
  dissociates very slowly or not at all.
• No change in the antagonist occupancy takes place
  when the agonist is applied.
• Occurs with drugs that possess reactive groups
  which form covalent bonds with the receptors.

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Noncompetitive antagonism

• Antagonist block at some point the chain of
  events that leads to the production of a response
  by the agonist. E.g. Ca2 blockers prevent the
  influx of Ca2 through the cell membrane and thus
  block nonspecifically the contraction of smooth
  muscle produced by other drugs.

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 FACTORS THAT MODIFY THE ACTION OF DRUGS

• Body weight the dose of a drug has to be
  calculated according to the Kg body weight of the
  patient that is dose body weight
  (kg)/70average adult dose.
• Age body response to drugs change with age
  resulting in altered response in extremes of age
  e.g. in newborns the liver and kidney are
  immature to handle drugs like chloramphenicol
  that cause gray baby syndrome. Therefore, correct
  doses should be calculated for children. E.g.
  childs dose age (years)/age12 adult dose.

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• Sex hormonal differences and smaller body size
  in women may influence drug response. Therefore,
  special care is necessary while prescribing for
  pregnant and lactating women.
• Diet and environment food interferes with
  absorption of many drugs e.g. tetracyclines form
  complexes with calcium in food which affects
  absorption.
• Route of administration e.g. magnesium sulfate
  when given orally is a purgative, given IV. It
  depresses CNS and has anticonvulsant effects,
  topically it reduces edema and hypertonic
  magnesium sulfate retention enema reduces
  intracranial tension

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• Diseases
• Malabsorption drugs are poorly absorbed
• Liver diseases metabolism is reduced and reduced
  protein binding
• Cardiac diseases in CCF, edema of the gut mucosa
  and decreases perfusion of liver and kidney.
• Renal dysfunction drugs accumulate and cause
  toxicity due to reduced excretion.

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• Presence of other drugs concurrent use of two or
  more drugs can influence the response of each
  other.
• Psychological factors doctor patient
  relationship and nursing care influence the
  response to a drug by acting on the patients
  psychology.
• Dose as the dose is increased, the magnitude of
  the response also increases till the maximum is
  reached. E.g. in myasthenia gravis, neostigmine
  enhances muscle power in therapeutic doses but in
  high doses it causes muscle paralysis

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Thank You!