General Pharmacology part 1 Flashcards
Father of pharmacology
Oswald Schmiedeberg
Define drug
Any substance or product that is used or intended to be used to modify or explore physiological and pathological states for the benefits of the recipient
Two types: pharmacodynamic and chemotherapeutic
Clinical pharmacology
It includes pharmacodynamic and pharmacokinetic investigation in healthy volunteers as well as patients
The molecular weight of most drugs is in the range of ___ and why
100 D -1000 D
Large enough to have specific characteristics
Small enough to pass through membranes
Sources of drugs
- Plants (alkaloids, glycosides, oils,…)
- Animals
- Microbes (antibiotics)
- Minerals
- Synthetic (rational drug designing)
- Biotechnology
Drugs derived from animal sources
Exenatide
Lepirudin (anticoagulant)
Semisynthetic drugs examples
Apomorphine
Modified insulin
Examples Glulisine, lispro, aspart Made by changing the sequence of gene Change in onset and duration of action There are structural changes
What are BAN ,USAN and rINN
These are the naming guidelines for non proprietary names of drugs
For older drugs it was named according to
British Approved Name
US Adopted Name,…
But for newer drugs it is according to recommended International Nonproprietary Name
The first drug discovered to act on the ANS
Reserpine
What are the pros and cons of drugs marketed under brand / proprietary names
Pros
To ensure consistency of product for quality and bioavailability and are not generic like those prescribed on the basis of the generic name
Cons
- More expensive for marketing
- Less uniformity and convenience
- Less better in comprehension as brand names have no relation to each other
Pharmacopoeias and formularies, the types of drug compendias (drug compilations)
Pharmacopoeias contains the description of chemical and physical characteristics of drugs hence useful for drug manufacturers and regulatory authorities
Eg., Indian Pharmacopeia IP
Formularies are easily carried booklets which contains biological properties of drugs useful for doctors
Eg., National Formulary of India NFI
Examples of major unofficial compendiums
- Martindale: The complete drug reference (extrapharmacopoeia) by Britain
From USA: - Physicians desk reference (PDR)
- Drug facts and compilations
Essential drugs
Those which satisfy the priority healthcare needs of the nation that are economical and safe
They should be preferably single compounds
Orphan drugs
Drugs which are not economical and affects less number of people (0.2 million according to USA)
Government incentives are given
Major types of medical powders
Bulk powder: powder for topical application are supplied as bulk powder in metabolic and plastic containers with holes for sprinkling
Effervescent powder contain granulated sod, bicarbonate and citric or tartaric acid. The react when dissolved in water to produce bubbling
Different types of tablets
- Chewable tablets
- Dispersable tablets
- Sublingual tablets
- Enteric coated tablets
- Sustained / Extended release tablets
- Controlled release tablets
Different types of capsules
- Soft gelatin capsules: dissolves rapidly, generally contains a liquid medicament
- Enteric coated capsules
- Spansules: extended release capsules which are packed with granules of the drug having different coatings to dissolve over a period of time
Lozenges
Tablet like bodies containing the drug along with a suitable gum , sweetening and flavouring agents
They are retained in the mouth and allowed to dissolve very slowly, providing local action for mouth and throat
Suppositories and its derivatives
Suppository is a clinical bullet shaped dosage form for insertion in the anal canal, in which the drug is mixed with a mouldable form base that melts at high temperature and releases the stored drug
Pessaries: are oval or suitably shaped bodies for vaginal insertion
Bougies: elongated pencil like cones for insertion into male or female urethra
Syrups and their derivatives
Syrups: Sweet hydro alcoholic derivatives of drugs
Elixirs: less sweet and thick compared to syrups
Dry syrups: for drugs that are unstable in water
They must be reconstituted with water
Linctus: viscous syrupy liquid meant to be licked slowly for soothing the throat
Lotions and their derivatives
Meant for external applications without rubbing
They usually have soothing, cooling, protective or emollient property
Liniments are similar preparations which are usually contain counterirritants and are to be rubbed on the skin to relieve pain and cause rubefaction
Injections are supplied through
Ampoules and vials
Ointments and creams
In ointments, drugs are incorporated in an oily base (wax,…). They are not suitable for oozing surfaces.
Good for dry chronic lessons
In creams, the base is a water in oil emulsion. The drug is better absorbed and are cosmetically more acceptable
What are PMDIs
Pressurised metered dose inhaler are hand held devices which use a propellant (hydro fluoro alkane) and deliver the specified drug in aerosol form in actuation
Jet nebulisers
Jet nebulisers produce a mist of drug solution generated by pressurised air or oxygen
Rotahaler
Rotahaler is device in which a portable capsule (rotacap) containing very fine powder of drug is punctured during actuation and the released particles are aerosolised by the inspiratory airflow
Particle size of aerosolised drug
1-5 micrometer for effective deposition in the bronchioles
Larger in the oropharynx
Smaller do not settle and are exhaled out
Dosage forms of drugs
- Solid forms (powder, tablets, pills, capsules, lozenges and suppositories)
- Liquid forms (aqueous, suspensions, elixirs, drops, lotions, injections)
- Semisolid forms (ointments, pastes, gels)
- Inhalations
Limitations of oral route of administration
- Slower action
- Unpalatable drugs cannot be used
- May cause nausea and vomiting
- Cannot be used for unconscious, uncooperative or vomiting patient
- Absorption of drug may be variable or erratic (streptomycin)
- Maybe destroyed by liver (first pass metabolism) or by digestive juices
Buccal or sublingual route of administration of drugs
Only lipid soluble and non irritant drugs can be used
Can be spat after the effect has been obtained
Relatively rapid
Liver is bypassed
Examples: GTN, buprenorphine, desamino-oxytocin
Drugs which are sometimes given rectally
Diazepam, paracetamol, indomethacin, ergotamine
50% bypass liver
Advantages of TTS
Transdermal therapeutic patches
- Smooth plasma concentrations
- Decreased inter individual variations, due to little first pass metabolism
- Decreased side effects
But they are costly
Drugs absorbed via nasal route
GnRH agonists, calcitonin, desmopressin
Dermojet
High velocity jet of drug solution is protected from a micro fine orifice using a gun like implement
A type of subcutaneous parental route
Generally painless and suited for mass inoculations
Pellet implantation
Drugs in the form of solid pellet is introduced with a trochar and cannula
Sustained release over weeks or months
Examples: DOCA, testosterone
Sialistic (non biodegradable) and biodegradable implants
Crystalline drug is packed in tubes or capsules made of suitable materials and implanted under the skin
Slow and uniform leaving of drug occurs over months
Examples: hormones and contraceptives (Norplant)
Intramuscular route
Drug is injected into a large muscle (less innervation but more vascular) like …,triceps, rectus femoris,…
Self injection is often impractical because deep penetration is required
Oily or aqueous solutions can be used
Avoided with anticoagulant treated patient since it may cause local haematoma
Intravenous
Advantages and risks
- Highly irritant drugs can be used (insensitive intima and dilution)
- Rapid. Dose is smallest as bioavailability is 100%
- Large volumes can be infused
- Titration with dose can be possible
Risks are:
- Thrombophlebitis of the injected vein
- Necrosis of adjoining tissues of extravasation occurs
IV disadvantages
- Only aqueous solutions can be used
- Risk of air embolism
- Most risky route
Intradermal injection
The drug is injected into the skin causing a bleb (BCG vaccine, sensitivity testing) or scarring/multiple puncture of epidermis through a drop of drug is done
For specific purposes only
Routes of drug administration
A) Local routes: topical, deeper, arterial
B) Systemic routes: oral, buccal, rectal,
cutaneous, inhalation, nasal,
parenteral ;
1. Subcutaneous (dermojet, pellet implantation, implants)
2. Intramuscular i.m.
3. Intravenous
4. Intradermal injection
Filtration is the mechanism of absorption of which type of drugs
Water soluble drugs through aqueous channels
Antimicrobials requiring dosage reduction even in MILD renal failure
Acyclovir Aminoglycosides Amphocetericin B Cephalexin Ethambutol Vancomycin
Relationship between pH and absorption and excretion of drugs
Ion trapping
Generally acidic drugs (aspirin,…) are absorbed from stomach and vice versa
Within the gastric cell, the drug is ionised (pH=7) and then passes only slowly to the extra-cellular fluid (ion trapping)
This may contribute to gastric mucosal cell damage caused by aspirin
Acidic drugs are excreted more in alkaline urine and vice versa
Basic drugs attain higher concentration intercellularly
Drugs which are actively transported
Levodopa and methyl dopa are actively transported by aromatic amino acid transporter
P-glycoprotein to deal with zenobiotics
Significance of redistribution of drugs
Highly lipid soluble drugs undergo more redistribution
They are very short acting (less time in systemic circulation)
Eg., thiopentone
Drug action types
- Stimulant
- Depressant
- Irritant
- Replacement
- Cytotoxic
Mechanism of drug action
- Physical
- Chemical
- Enzymes
- Ion channel
- Transporter
- Receptor
Antimicrobials which need dosage reduction only in severe renal failure
Carbenicillin Cefotaxime Ciprofloxacin Cotrimaxazole Metronidazole Norfloxacin
Drugs having cumulative effect (accumulated in the body)
- Full loading dose of digoxin should not be given to the patient if he has received it within the past week
- A course of emetine should not be repeated within 6 weeks
Placebo reactors
Examples of placebos
People who will easily respond to placebo
Examples: lactose tablets/ capsules, distilled water injection, multi vitamin preparations
(Nocebo is the negative psychodynamic effect)
Factors affecting absorption of drug
- Aqueous solubility
- Concentration
- Area of absorbing surface
- Vascularity
- Route of administration
- Bioavailability
Does faster gastric emptying accelerate drug absorption? Why
Yes The absorption of almost all drugs is low (even for acidic drugs) in stomach because of: 1. Thick mucosa 2. Covered with mucus 3. Low surface area
Drugs and food
Food dilutes the drug and generally reduces absorption
Certain drugs form poorly absorbed complexes (tetracycline with Ca of milk)
One exception is the absorption of lumefantrine with fatty food
P-gp
The oral absorption of certain drugs is reduced by the efflux transporter (actively) P-gp of intestinal lumen
Free systemic elimination (part of first pass metabolism)
May be developed by tumour cells
Examples: digoxin , cyclosporine which are metabolised by CYPA4
Inhibitors of P-gp
Verapamil (used to reverse anti cancer resistance )
Amiodarone
Cyclosporine
Itraconazole
Nifedipine
Erythromycin and Quinidine
These inhibitors increases the oral bioavailability of certain drugs
P-gp inducers
Phenobarbitone
Rifampin
The reduce the oral bioavailability of certain drugs
Luminal effect of drugs
Formation of insoluble complexes due to the interaction between drugs which decreases absorption
Examples:
1. tetracyclines and iron preparations with calcium salts and antacids
2. Phenytoin with sucralfate
This can be minimised by administering the drugs at 2-3 hour intervals
Examples of urine acidifiers for removing toxicity of alkaline drugs
Ammonium chloride
Vitamin C
Cranberry juice
(Bicarbonate for alkalinisation)
Henderson Hasselbach’s equation
For an acidic drug:
Log(u/i) = pKa - pH
For basic unionised and ionised trade places
pKa is the pH of the medium at which 50% of drugs is ionised and 50% is unionised.
Drugs which affect gut wall motility
Anticholinergics, tricyclic depressants and opioids retard motility
while metoclopramide increases it
Drugs which cause mucosal damage
Neomycin
Methotrexate
Vinblastine
Drugs which penetrate intact skin
Hyoscine Fentanyl GTN Nicotine Testosterone Estradiol
Cornea as a drug route
It is permeable to lipid soluble unionised physostigmine but not to highly ionised neostigmine
Timolol eye drops get absorbed through nasolacrimal duct to produce bradycardia and asthma
Bioavailability (f)
It is the fraction of unchanged drug which reaches the systemic circulation
It depends on absorption and first- pass metabolism
Calculation of bioavailability
Bioavailability = AUC_oral/ AUC_iv * 100
Area under the curve which is trapezoid for oral and hyperbolic for IV
Cross tolerance
Development of tolerance to pharmacologically related drugs
Closer, the more complete the cross tolerance
Examples:
Alcoholics are tolerant to barbiturates and general anaesthetics
Mechanisms of tolerance of drugs
- Pharmacokinetic/ drug disposition tolerance:
The effective concentration of the drug is decreased, mostly due to enhancement of drug elimination on chronic use
Barbiturates and carbamazepine induce their own metabolism
Amphetamine accelerate its own renal elimination - Pharmacodynamic/ cellular tolerance:
Cells become less responsive
Tachyphylaxis
Rapid development of tolerance when doses of drug repeated in rapid succession.
Usually seen in indirectly acting drugs like ephedrine, tyramine, nicotine,… These drugs act by releasing the catecholamines of the body which can get depleted soon. This is one mechanism
Corticosteroids should be taken at what time of the day and why
Single morning dose
Due to more pituitary-adrenal suppression at night
Statins are more effective at what time of the day
Late evening
HMG CoA is reductase is more active in the evening
But statins have longer half lives when taken at the day time
But atorvostatin and rosuvastatin have half lives of 20-30 hours so it can be taken at any part of the day
For which type of drugs are loading dose required
For drugs with long t1/2
Since several days would be wasted to acquire the required therapeutic effect, an initial loading dose is given followed by maintenance doses
Example: chloroquine
How does probenecid increase the duration of action of penicillin
Probenecid is an organic acid which has high affinity for tubular OATP (organic anion transporting polypeptides)
It blocks active transport of penicillin and decreases tubular secretion of penicillin
Examples of hit and run drugs
Organophosphate and anticholinesterases
Reserpine drugs with irreversible action
Clopidogrel
Bioequivalence of drugs
Two pharmaceuticals equivalent compounds that are similar in rate and extent of absorption
FDA criteria for approval of generic drug
Bioequivalence = +- 20% of the existing (branded) drug
Pharmacognosy
The study of extraction, purification and analysis of drugs obtained from plants.
Ethnopharmacology
The interdisciplinary scientific exploration of biologically active agents traditionally employed or observed by man
