Introduction to Pharmacology Flashcards
WHAT IS PHARMACOLOGY
- The study of effects of drugs on the function of living systems
PHARMACODYNAMICS
- Where a drug acts in the body (site of action)
- Biochemical, physiological and behavioral effects of drug (mode of action)
PHARMACOKINETICS
- The way in which the drug concentration changes over time
- How drugs get into the body, move around the body and leave the body, or, (Absorption, Distribution, Metabolism, Excretion)
- Quantitative pharmacokinetics (measure concentration of drug at various times)
- Allows one to make intelligent decisions regarding dose and frequency of drug administration
ORAL ROUTE OF ADMINISTRATION
- Enteral , p.o (per os)
- Most common route
- Usually safet
- Most convenient
- Most economical
- Because of its natural physiology and function, the intestine is the major site of drug absorption following oral administration
DIFFICULTIES WITH ORAL ROUTE
- First pass metabolism
- Before entering the systemic circulation, blood leaving the GI tract passes through the liver→ drugs that are highly metabolised by liver may attain very low circulating levels relative to those obtained after parenteral administration
SUMMARY OF ROUTES OF ADMINISTRATION AND DRUG DISTRIBUTION IN THE BLOOD
- With most routes of administration the drug will enter the bloodstream and be taken round the body BEFORE passing through the liver
- For example if a drug is given by intramuscular injection it gets absorbed through small blood vessels in the muscle and gets taken directly to the heart and pumped around the body
- First pass metabolism
- Drugs taken orally are absorbed in the stomach and small intestine
- Blood vessels take the drug directly to the liver
- Drug passes through liver before being distributed round the body
Oral bioavailability
The fraction of orally administered drug that reaches the systemic circulation
Bioequivalence
2 drugs with identical chemical composition that yield different blood concentration and different effectiveness, differ in bioavailability (and are not bioequivalent)
Intravenous: Absorption pattern
- Precise, accurate and potentially immediate effects (absorption phase is bypassed)
- Suitable for large volumes and mixtures
Intravenous: Special Unity
- Valuable for emergency use, permits titration of dose
- Usually required for high molecular weight protein and peptide drug
Intravenous: Limitations and precautions
- Greater risk of adverse effects (high concentration attained rapidly, risk of embolism)
- Must inject solutions slowly as a rule
- Not suitable for oil solutions or poorly soluble drugs
THERAPEUTICS
Use of drugs used to cure, treat or prevent disease and in the alleviation of pain and suffering
CHEMOTHERAPY
Use of drugs to kill or weaken invading cells or organisms
TOXICOLOGY
Study of poisons and the treatment of poisoning
HOW DRUGS WORK
- The majority of drugs interact with specific molecule s involved in regulatory functions (e.g. a receptor or drug receptors active site on an enzyme (drug target ))
- A small number of drugs interact with chemicals in the body but are not bound to a tissue component
- Osmotic diuretics (mannitol) or osmotic laxatives (sorbitol) will bind to water in the kidney
- Antacids will bind to acid in the stomach
ORIGINS OF DRUGS
- Some drugs are synthesised within the body (e.g. hormones, autacoids, neurotransmitters) this includes insulin, oestradiol, adrenaline and testosterone
- Most drugs are not synthesized within the body
- Xenobiotics (e.g. synthetic or semisynthetic drugs)
- Posions
- Toxins (poisons of biologic origin)
PHYSICAL NATURE OF DRUGS
- Solid (aspirin, paracetamol)
- Liquid (ethanol)
- Gaseous (Nitrous Oxide)
- These factors often determine route of administration
- Some liquid drugs are easily vapourised and can be inhaled
DRUG NOMENCLATURE 1
- Chemical name- N-acetyl-p- aminophenol (identifies chemical structure)
- Generic name- official name (lower case) (e.g. paracetamol)
- Trade name- Proprietary/brand name (first letter capitalised) (E.g. Panadol)
DRUG NOMENCLATURE 2
- Generic drugs belonging to the same drug group (often) have the same suffix
- Most antianxiety drugs (benzodiazepines) ‘-azepam’ e.g. diazepam,
- Local anaesthetics ‘-caine’ (e.g. lignocaine, cocaine)
- Mot beta-receptor antagonists ‘-olol’ (e.g. propranolol, metoprolol)
THE THERAPEUTIC DRUG MARKET 1
- 700 active ingredients
Multiple combinations (e.g.)
- Panadeine= codeine + paracetamol
- Tylenol Sinus= Paracetamol + pseudoephedrine
Delivery forms (e.g.)
- Adalat Oros= Slow release nifedipine tablets (once daily)
- Adalat= nifedipine tablets (twice daily)
Over 30,000 different medicinal drug products on Australian market
THE THERAPEUTIC DRUG MARKET 2
- The availability of potentially dangerous drugs and chemicals needs to be restricted to enable their safe and effective use
- Scheduling is the legal process used to achieve this (Therapeutic Goods Act 1989)
- Medicinal drugs (therapeutic goods) includes:
- Prescription and non-prescription products from synthetic and biological sources, herbal products, vitamin and mineral supplements, sunscreens and homeopathic products
- Unscheduled drugs can be sold through other retail outlets such as supermarkets (e.g. paracetamol)
S8- Controlled drug
- Available only on separate prescription form; prior authority of Department of Health required. E.g. Morphine, amphetamine/methylphenidate
S7- Dangerous Poisons
Contains many substances requiring Department of Health authority to obtain, use or supply
S6- Industrial and Ag. poisons
No restriction on sale; special packaging and storage requirements with warnings and first aid directions
S5- Domestic type poisons
No restriction on sale or storage; special packaging requirements with warnings and first aid directions
S4- Prescription Only
Drugs available only from pharmacists on prescription
S3- Pharmacist Only Medicine
Drugs available without prescription only from a pharmacist who must hand product to customer
S2- Pharmacy Medicine
Drugs available without prescription from pharmacists or poisons licence holders only
WHAT IS AN AGONIST?
- Drug, hormone or neurotransmitter that elicits a biological effect when it interacts with receptors- e.g. bethanechol (used for urinary retention) combines with muscarinic receptor
- Bethanechol mimics action of ACh (the neurotransmitter at these receptors)
- Magnitude of signal depends on number of receptors occupied and/or rate of formation of drug-receptor complexes
- An agonist that can bind to a receptor has an AFFINITY for that receptor
- When an agonist binds to a receptor it can produce a pharmacological response. The agonist therefore has INTRINSIC ACTIVITY
WHAT IS AN ANTAGONIST?
- A drug which interacts with a receptor, does not elicit a biological effect and blocks or reverses effect of an agonist-
E.g. atropine (muscarinic receptor- antagonist-smooth muscle relaxant) - An antagonist that can bind to a receptor has an AFFINITY for that receptor
- When an antagonist binds to a receptor it does not produce a pharmacological response, the agonist therefore has NO INTRINSIC ACTIVITY
- An antagonist however, can prevent agonists from binding to the receptor
What is affinity
Relative tendency of a drug to combine with its receptors
The response of the cell is a product of affinity and intrinsic activity
What is intrinsic activity of efficacy
- Capacity of a drug to produce a pharmacological effect after binding to its receptor (ie.e the maximal possible effect that can be produced by the drug) (E-max)
- The response of the cell is due to affinity and intrinsic activity
Agonists possess?
Affinity and intrinsic activity
Antagonists possess
Affinity but lack intrinsic activity
Partial agonist
Compound which interacts with a receptor but produces less than the maximum effect- less intrinsic activity or efficacy
Potency
- Inherent ability of a drug to combine with receptors
- Depends on drug affinity
- Important for dosage but unimportant characteristic of a drug for clinical purposes as long as it can be administered conveniently
- No justification that the more potent of 2 drugs is clinically superior (toxicity is also important)
- Usually stated in absolute terms (e,g 10mg/kg)
Maximal effect (Emax)
- Maximal efficacy- plateau in the dose response (DR) - curve
- Dependent on intrinsic activity of the drug
- Potency vs efficacy- whereas potency refers to the concentration of drug required to produce a particular effect, efficacy refers to the maximal possible effect that can be produced by the drug
DRUG TOXICITY
- Potency provides little info about the dose of a drug at which toxic effects manifest themselves
- Determined from the LD50 (median lethal dose) (dose of drug that is lethal to 50% of subjects)
- Thus therapeutic index (LD50/ED50) gives an idea of the relative margin of safety of a drug
- Greater this ratio, the safer the drug
- Must be greater than 1.0 to be therapeutic agent, less than 2.0 typically see toxicity at therapeutic dose
DESENSITISATION AND TACHYPHYLAXIS 1
- Synonymous terms- a drug effect which gradually diminishes over a few seconds to minutes
Causes:
- Change in receptors→ receptor resulting in tight binding of agonist without opening of ion channel
- Loss of receptors- Endocytosis during prolonged exposure
- Exhaustion of mediators- Depletion of neurotransmitters or second messengers
TOLERANCE
- Takes days or weeks to develop
- Need to increase dosage in order to achieve same therapeutic response (e.g. morphine)
Causes:
- Increased metabolic degradation→ induction of metabolic enzymes
- Physiological adaptation → e.g. side effects, (nausea, sleepiness) sometimes tend to subside
