Download - Pharmacodynamics - 3
-
7/27/2019 Pharmacodynamics - 3
1/28
PharmacodynamicsDr.U.P.Rathnakar
MD.DIH.PGDHM
-
7/27/2019 Pharmacodynamics - 3
2/28
Factors modifying fuel efficiency???
Factors modifying drug action
New
Driver
Mfr.defect
Bad road
Over loaded
Engine problem
Traffic congestion
[Age?]
[M or F]
[Genetic?]
[Envn.]
[Obesity?]
[Patho.states]
[DI, polypharmacy]
-
7/27/2019 Pharmacodynamics - 3
3/28
Factors modifying drug action
Quantitative changes-plasma concentration
and the action of drug is altered. This can be
corrected by altering the dose-COMMON
Qualitative-UNCOMMON-Allergy,
idiosyncrasy[response is altered]-drug may
have to be discontinued
-
7/27/2019 Pharmacodynamics - 3
4/28
Factors Modifying Drug Action
Age
Body size
Sex[Gender]
Species & race
Genetics
Route
Environment
Psychological
Diseases[Pathological state]
Other drugs
Cumulation
Tolerance
Drug resistance
-
7/27/2019 Pharmacodynamics - 3
5/28
Factors Modifying Drug Action:
1. Route
Quantitative- Oral dose more than i.v. dose
Qualitative
Mgso4 Locally- Reduces edema
Mgso4 orally - Purgative
Mgso4 i.v. - CNS depressant
-
7/27/2019 Pharmacodynamics - 3
6/28
Presence of other drugs
Combined effect-synergism or antagonism
-
7/27/2019 Pharmacodynamics - 3
7/28
Cumulation:
When elimination is slower- may accumulate
and produce toxic effect- Digoxin
-
7/27/2019 Pharmacodynamics - 3
8/28
Factors Modifying Drug Action:
Age:
Infants & Children: not just small adults!
Low GFR and immature tubular transport
Penicillin G is given BID Inadequate hepatic metabolizing system
Chloramphenicolgray baby syndrome
Blood brain barrier is more permeable -kernicterus
Skin is more permeable
Rectal absorption is faster
-
7/27/2019 Pharmacodynamics - 3
9/28
Factors Modifying Drug Action:Children
Tablets & aerosols difficult to administer
Tetracyclines get deposited in teeth
Drug metabolism may be faster in children-higher dose of digoxin
Children are definitely not Miniature adults
-
7/27/2019 Pharmacodynamics - 3
10/28
Factors Modifying Drug Action:
Children
Youngs formula
Child's Dose = Adult Dose X Age
Age+12 Dillings formula
Child's Dose Adult Dose X Age
20
-
7/27/2019 Pharmacodynamics - 3
11/28
Factors Modifying Drug Action:
Elderly:
- decline in renal function
-reduced hepatic activity
-reduced intestinal motility
-altered volume of distribution
-drug interactions
-prostatic hypertrophy - urinary retention
ADE [Adverse effects] more
Dose to be lowered- Eg.Aminoglycosides
-
7/27/2019 Pharmacodynamics - 3
12/28
Body Wt. And Surface Area
Body weight:
Individual = Body weight (kg) X Adult dose
Dose 70
BSA
Individual = BSA x Adult doseDose 1.7
-
7/27/2019 Pharmacodynamics - 3
13/28
7. Sex[gender]
Females-smaller size
Androgens[Females] & estrogens[Males]
Betablockers-affect sexual function only in males
Ketaconozloe-libido in men, gynecomastia
Pregnancy:
GI motility low-delayed absorption
Renal blood flow increases-Fast elimination of drugs
Terratogenic
-
7/27/2019 Pharmacodynamics - 3
14/28
Environment and time of
administration
Environment:
Pollutants like DDT, Cigarette smoke,
Insecticides, Alcohol-Enzyme inducers- Eg.
Oral Contarceptive Pills
Hypnotics more effective at night
Glucocorticoids given in mornings-Least HPAaxis
-
7/27/2019 Pharmacodynamics - 3
15/28
Genetic factors
Pharmacogenetics- Study of genetic basis for
variability of drug response
Pharmacogenomics- Use of this information
for the choice of drugs in an individual
INH [Isoniazid]-Fast and slow acetylators Succinylcholine-Apnoea [Atypical
pseudocholinesterase]
-
7/27/2019 Pharmacodynamics - 3
16/28
Emotional factors
Placebo [I will please] [Nocebo-I will harm]
Dummy medicine without Pharmacological effect [Psychodynamiceffect]
Some may have endogenous activity [Naloxone blocks analgesic effect of
placebo] Placebo reactors
Uses
1. Relief of subjective symptoms- Eg .Anxiety
2. In Clinical trials to reduce bias Factors affecting placebo action
Pt factors-With neurotic symptoms
Drug factor-Injection, Capsules, colored tablets
Doctor factor-Personality, Fame, Dr - Pt relationship
-
7/27/2019 Pharmacodynamics - 3
17/28
Pathological states
Gastrointestinal diseases:
Malabsorption syndrome:
Achlorhydria: Decreases aspirin absorption
Liver disease:
First pass metabolism
B.A of Lidocaine, Propranalol
Kidney disease
Clearance of drugs that are excreted in unchanged
form.
Aminoglycosides
-
7/27/2019 Pharmacodynamics - 3
18/28
Kidney disease[Aminoglycosides, Digoxin, Phenobarbitone]
-
7/27/2019 Pharmacodynamics - 3
19/28
Tolerance
Tolerance occurs when the person no longer
responds to the drug in the way that person
initially responded.
A state in which higher dose is required to
achieve the same effect
Eg.
Nitrates in Angina
Morphine in pain relief
-
7/27/2019 Pharmacodynamics - 3
20/28
Types of Tolerance
AcquiredToleranceNatural
SPECIES
Rabbits
are
resistant toAtropine
RACE
In Afro
Carribeans
blockers
Less
effective
On
repeated
exposure
May be
only tosome
effects of
a drug
Morphine
Not to
Constipation
and
Miotic actions
-
7/27/2019 Pharmacodynamics - 3
21/28
Tolerance: Mechanism
Pharmacokinetic:
Increased Metabolism, reduced absorption
[Barbiturates]
Pharmacodynamic
Cells of the target organ become less sensitive
Morphine, Barbiturates, Nitrates,Alcohol
-
7/27/2019 Pharmacodynamics - 3
22/28
Tachyphylaxis
(acute tolerance)
Rapid development of tolerance, can not be overcome
by increasing the dose
Ephedrine, Amphetamine, Nicotine
Cross tolerance:
Development of tolerance to pharmacologically
related drugs
Eg. Alcohol and Barbiturates
Morphine and Barbiturates
Morphine and Pethidine
-
7/27/2019 Pharmacodynamics - 3
23/28
Others
Antipyeretics lower body temp.-Fever
Thiazides marked diuresis-Edema
Myesthenics-sensitive to curare Hypnotics in a pt. with pain-mental confusion
and delirium
-
7/27/2019 Pharmacodynamics - 3
24/28
12. Drug interactions
When the action of one drug is affected by another
Drug interactions may be defined as an
Alteration in duration and/or onset of action or
effect
Of one drug produced by another drug.
Beneficial or harmful
Polypharmacy may be a necessity!
-
7/27/2019 Pharmacodynamics - 3
25/28
Drug interactions may be
unavoidable Hypertension Congestive cardiac failure
Multiple diseases
-
7/27/2019 Pharmacodynamics - 3
26/28
Drug interactions classification
Pharmacokinetic,which occur at the level of
Absorption,
Distribution,
Metabolism and
Excretion of one drug by another. Pharmacodynamic:
Response of a drug target is modified by asecond drug
Eg. NSAIDs and ACE inhibitorsNitrates and Sildenafil
-
7/27/2019 Pharmacodynamics - 3
27/28
PD interactions
The direct pharmacodynamic interactions Antagonism or synergism
The indirect pharmacodynamic interactions
Digoxin and spironolactone
Salicylates and warfarin
-
7/27/2019 Pharmacodynamics - 3
28/28
Drug interactions
Beneficial or harmful [Make a listfrom text book]
Common with drugs exhibiting
Steep DRC Low TIEnzyme induction / inhibition
Zero order kineticsSeverely ill patientsImpaired renal / liver function