Drugs Flashcards
What are the aims of drug therapy?
Get the drug into the patient
Get the drug to the site of action
Produce the correct pharmacological effect
Produce the correct therapeutic effect
What 4 basic factors define pharmacokinetics?
Absorption
Distribution
Metabolism
Elimination
What does ADME enable us to understand?
Dosage Drug administration Drug handling Patient variability Potential for harm
Why must drugs be absorbed?
To become biologically active most drugs need to be absorbed by the bloodstream so they can target the specific site.
What are some methods of administering drugs?
Oral Intravenous Subcutaneous - injection into skin Intramuscular Other GI - Sublingual, rectal Inhalation Nasal Transdermal - patch
What is absorption?
The process of movement of unchanged drug from the site of administration to the systemic circulation.
What is a therapeutic range?
The range of concentrations a drug is active across.
What happens if drug absorption is above or below the therapeutic range?
Above - Toxicity
Below- insufficient or no pharmaceutical action.
What is bioavailability?
The amount of drug which reaches the circulation and which is available for action. Intravenous drugs have 100% bioavailability.
What are some factors that affect bioavailability?
Formulation- slow release preparations
Ability of drug to pass physiological barriers - particle size, lipid solubility, pH and ionisation.
Gastrointestinal effects- gut motility, food, illness.
First pass metabolism
Describe drug ionisation?
Most drugs do not completely ionise in water.
Most drugs are weak acids or bases so the degree of ionisation depends on the pH of the environment.
The ionised drug will not pass through the membrane.
What does the Henderson-Hasselbalch equation portray?
The relationship between the local pH and the degree of drug ionisation.
In what state must a drug be to pass across a lipid bi-layer?
Drug must be in solution and be lipid soluble.
What is active absorption?
Energy dependent transport across membranes against a concentration gradient.
To undergo active transport drugs must resemble naturally occurring compounds.
The drug is reversibly bound to a carrier system.
Relatively unusual.
Where are most drugs absorbed?
Small intestine.
What does First Past Metabolism mean?
Metabolism of drug prior to reaching systemic circulation.
When is rectal administration used?
Drugs given via the rectum bypass first pass metabolism.
Absorption tends to be slow.
The rectum is often used for drugs which cause irritation of the stomach.
What are the considerations for the mode of administration chosen?
Purpose and site of drug action- local absorption, avoid first pass metabolism Disease effects Patients ability to take medicine Speed of action Reliability of absorption
How does a drug become distributed?
A drug must then leave the blood stream and enter the inter or intracellular spaces.
What is drug distribution?
The reversible transfer of a drug between the blood and the extra vascular fluids and tissues of the body (for example, fat, muscle, and brain tissue).
What are some mechanisms for distributing drugs throughout tissues?
Plasma protein binding Tissue perfusion Membrane characteristics Transport mechanisms Elimination
Describe some features of plasma protein binding?
Bind to proteins like albumin and alpha1-glycoprotein.
Only the unbound drug is active.
Binding is reversible
How can the amount of bound drug be changed?
Renal failure Hypoalbuminaemia Pregnancy Other drugs Saturability of binding
What is the volume of distribution?
The volume of plasma that would be necessary to account for the total amount of drug in a patient’s body, if that drug were present throughout the body at the same concentration as found in the plasma.
What happens to the ability of the drug to diffuse through membranes if the volume of distribution increases?
The ability of the drug to diffuse through membranes also increases.
What is clearance?
The theoretical volume from which a drug is completely removed over a period of time.
What is clearance dependant on?
Dependent on concentration and urine flow rate for renal clearance.
Dependent on metabolism and biliary excretion for hepatic clearance.
What is half life?
The time taken for the drug concentration in the blood to decline to half of the current value.
What are the advantages of knowing a drug’s half life?
Helps us work out how often a drug needs to administered. Prolongation of the half life will increase the toxicity of the drug.
Generally how many doses of a drug need to be administered before plasma levels stabilise?
Usually 4-5 half-lives.
What is drug elimination?
The removal of the active drug and metabolites from the body. It determines the length of action of the drug. Made up of 2 parts: metabolism and excretion.
What is the primary organ for excretion?
Kidneys
What are the kidney’s 3 principle mechanisms used for excretion?
Glomerular filtration
Passive tubular reabsorption
Active tubular secretion
What are some key facts about glomerular filtration?
All unbound drugs will be filtered at the glomerulus as long as their molecular size, charge or shape are not excessively large.
Factors that affect the glomerular filtration rate will reduce the clearance of a drug.
Describe active tubular secretion?
Tubular secretion is the transfer of materials from peritubular capillaries to the renal tubular lumen and occurs mainly by active transport.
This is the most important system for eliminating protein bound cationic and anionic drugs.
Describe passive tubular reabsorption?
Passive diffusion occurs in the distal tubule and collecting duct.
Only un-ionised drugs such as weak acids are reabsorbed. Move back via the concentration gradient.
What is biliary secretions role within drug excretion?
The liver secretes 1 litre of bile a day.
Drugs may be passively or actively secreted into the bile.
Biliary secretion accounts for 5-95% of drug elimination for many drugs.
Many drugs are then reabsorbed from the bile into the circulation. This is called entero-hepatic circulation.
It continues until the drug is metabolised in the liver or excreted by the kidneys. E.g morphine, Adriamycin
Metronidazole
What is drug metabolism?
Biochemical modification of pharmaceutical substances by living organisms usually through specialized enzymatic activity.
Rendering lipid soluble and non-polar compounds to water soluble and polar compounds so that they can be excreted.
Where are the important sites in the body for drug metabolism?
Liver,
Lining of the gut,
Kidneys
Lungs
What are the effects of metabolism?
Loss of pharmacological activity.
Production of toxic metabolites
Increase in metabolic activity - activation of a prodrug.
What is the process of metabolism?
2 phase process
1 - Oxidation, Reduction, Hydrolysis
2- Glucuronidation
What occurs during phase 1 metabolism?
Polar groups are on their molecule or introduced to molecules. Provides an active site for phase 2.
What enzymes are most important in drug metabolism?
cytochrome P-450 enzymes
What occurs during phase 2 metabolism?
Involves conjugation which increases the water solubility and enhances excretion of the metabolised compound..
It involves the attachment of glucuronic acid, glutathione, sulphate or acetate to the metabolite generated by Phase 1 metabolism. Leads to inactivation.
What are some factors that affect metabolism?
Other drugs/herbals/natural substances Genetics Hepatic blood flow Liver disease Age Sex Ethnicity Pregnancy
What is enzyme induction?
Its activity is stimulated by an outlying source e.g alcohol, smoking. Increased metabolism of drugs metabolised by that enzyme.
Resulting in decreased drug effect.
What does lack or decreased enzyme activity lead to?
Increased drug toxicity.
What is a drug interaction?
The modification of a drugs effect by prior or concomitant administration of another Drug, Herb, Foodstuff, Drink.
Not just a direct function of their individual effects.
What is an object drug?
The drug whose activity is effected by such an interaction.
What is the precipitant?
The agent which causes such an interaction.
Are there any circumstances when drug interactions aren’t detrimental?
Hypertension treatment
Treatment of Parkinson’s disease.
Give some examples of drugs that are involved in serious interactions?
Lithium Warfarin Cyclosporin Fluconazole Erythromicin Linezolid
What is meant by saying drugs are potent with a narrow therapeutic index?
This means that a small change in blood levels can induce profound toxicity.
Give some examples of foods that interact with Warfarin?
Broccoli Cabbage Brussel sprouts Green tea Liver Fish oils Avocado
What patients are increasingly susceptible to drug to drug interactions?
Elderly.
Young children.
Critically ill- liver disease, renal impairment, diabetes m, epilepsy, asthma.
Patients undergoing complicated surgical procedures.
Name some drugs which delay gastric emptying?
Anticholinergics,
Tricyclic anti-depressants,
Opiates
What is an example of direct antagonism?
An antagonist blocks the action of an agonist drug.
E.g Beta-blockers such as atenolol will block the actions of agonists e.g. bronchodilators such as salbutamol.
What is a synergistic interaction?
When two drugs with the same pharma-cological effect acting on the same receptor are given concurrently.
What is an example of indirect agonism?
Central Nervous System Depression
Benzodiazepines and tricyclics or alcohol
Warfarin and NSAIDs (Indomethacin)
Atenolol and verapamil.
