Introduction to Pharmacology (Maria Concepcion Sison, MD) Flashcards
Body of knowledge concerned with the action of chemicals on biologic systems
Pharmacology
A substance that brings about a change in biologic function through chemical actions
Drug
A substance intended for use in the modification or exploration of the physiological system or pathological states for the benefit of the recipient
Drug (WHO definition)
T/F: Drugs can cause anaphylactic shock
True
Medical pharmacology is concerned with the use of chemicals in the (1), (2), and (3) of disease especially in humans.
(1) Prevention
(2) Diagnosis
(3) Treatment
What substances are used in pharmacologic prevention?
- Vitamins
- Vaccines
- Antibiotics
Concerned with the undesirable effects of chemicals on the living system
Toxicology
According to Paracelsus, what makes the poison?
The dose
The field concerned with the mechanisms of action and therapeutic and toxic effects of drugs. It describes the relationship between the concentration and pharmacological response.
Pharmacodynamics
REMEMBER: “D” for drug on body
Deals with the absorption, distribution, and elimination of drugs
Pharmacokinetics
REMEMBER: “K” for katawan on drug
A discipline that involves all aspects of the relationship between drugs and humans. Its ultimate goal is safe and effective prescribing.
Clinical Pharmacology
Reasons why drug therapy has changed over the last 4 decades
- Potency and diversity of drugs available
- Number of diseases that can be treated
- Impact of molecular biology on the development of drugs
- Pharmacological principles that underpin the rational use of medicines
What diseases have been eradicated in wealthier nations due to drug therapy?
- Pertussis
- Poliomyelitis
- Diphtheria
What common chronic diseases have benefited from the evolution of drug therapy?
- Asthma
- Hypertension
- Hypercholesterolemia
When did pharmacology start?
When the process of purification was introduced in the field of chemistry
What is the primitive form of the pharmacy?
Apothecary system
The person who discovered digoxin
Dr. William Wuthering of Scotland
What plant is digoxin derived from?
Purple foxglove (Digitalis purpurea)
What were the practical uses of digoxin prior to Wuthering’s discovery?
- Poison
- Healing of wounds (topical)
- Treatment of edema
When was digoxin officially introduced by Wuthering?
1785
What other diseases was digoxin used for for which it was unsuccessful in treating?
Adenitis, bronchitis, tuberculosis, typhoid, asthma, epilepsy, hydrocephalus, insanity and others
Describe the therapeutic index of digoxin
Narrow
The Father of Pharmacology
Oswald Schmiedeberg of France
What did Schmiedeberg isolate from the foxglove?
Digitoxin, the first pure glycoside
Who is the French pharmacist who isolated “digitalin” from foxglove 6 years before Schmiedeberg?
Nativelle, a French pharmacist
Who else discovered glycosides?
Mannheim and Kraft
What was digoxin marketed as in 1957?
Lanicor
Who said “Facts and facts alone are the basis of science.”?
Francois Magendie of France
What did Claude Bernard of France do?
Studied curare and CO gas on animals
What did Rudolph Buchheim of Germany do?
He established the first laboratory for experimental pharmacology in his basement.
Who coined the term “chemotherapy” and launched the antimicrobial era?
Paul Ehrlich of Germany
Who were the two notable individuals that contributed to the development of pharmacology in England?
John Newport Langley and Sir Henry Hallett Dale
Who introduced histamine as a receptor substance?
John Newport Langley of England
Who identified acetylcholine as a possible neurotransmitter?
Sir Henry Hallett Dale of England
The Father of American Pharmacology
John Jacob Abel
The Father of Philippine Pharmacology
Dr. Daniel De La Paz
Progress in physiology, biochemistry and molecular biology led to a more (1) approach to drug designs.
(1) Targeted
What were the first anti-hypertensive drugs to be developed?
Angiotensin Converting Enzyme (ACE) inhibitors
What are the different kinds of anti-hypertensive drugs?
- ACE inhibitors
- Angiotensin Receptor Blockers (ARBs)
- Renin inhibitors
What is the mechanism of action of an ACE inhibitor?
Prevents the conversion of AI to AII and bradykinin to inactive metabolites
Properties of Angiotensin II
- Potent vasoconstrictor
2. Promotes release of aldosterone
What is the equation for blood pressure?
BP = Cardiac Output x Peripheral Vascular Resistance
ACE inhibitors are also known as?
Kininases
What is the most common side effect of taking ACE inhibitors?
Cough due to decreased breakdown of bradykinins
What is the mechanism of action of renin inhibitors?
They prevent the conversion of angiotensinogen to angiotensin I.
What is the mechanism of action of angiotensin receptor blockers?
They prevent the conversion of angiotensin II to AT1 and AT2.
What converts kininogen to bradykinin?
Kallikrein
What is an example of a direct renin inhibitor?
Aliskiren
Define: Chemotherapy
Use of chemotherapeutic agents to destroy microbes, parasites or cancer cells with minimal effect on healthy living tissues
Define: Pharmacogenetics
It deals with genetically mediated variations in drug responses.
Define: Pharmacogenomics
Use of genetic information to guide choice of drug therapy and/or dosage given to patient
Define: Biopharmaceutics
It deals with the development of new drug delivery systems and dosage forms.
What is the study of drug effects at the population level?
Pharmacoepidemiology
Described in quantitative terms (i.e. sigmoid dose-response curves)
Pharmacodynamics
What is the basis of development of most drugs?
Drug-receptor binding
Example of a non-receptor mediated drug
Maalox or AlMgOH
Explain: “Specificity is reciprocal.”
Certain classes of drugs bind only to certain targets. Conversely, certain targets only recognise certain classes of drugs.
T/F: There are drugs that are completely specific in their actions.
False
What side effects can penicillin cause?
Hypersensitivity and renal failure
What are the different receptor conformations?
- Active
2. Inactive
Define: Agonist
It favours the active receptor conformation.
Define: Antagonist
It favours the inactive receptor conformation.
What is an exception to the drug-receptor interaction?
Blood vessels
They maintain their tone despite absence of a ligand.
Describe the mechanism of action of digoxin
Inhibits Na+/K+ ATPase -> lowers Na+ ingress -> increases Ca2+ -> increases contractility
What enzyme inhibition effects does digoxin have on non cardiac tissue?
- Decreased sympathetic outflow from CNS
- Sensitization of the cardiac baroreceptors
- Reduction of renal tubular reabsorption of Na+
- Suppression of renin release from kidney
What conditions can digoxin be used for?
- Congestive heart failure
- Atrial fibrillation
- Flutter
Digitalis affects which parts of the body?
All excitable tissues including smooth muscle and CNS
What does digitalis do to the heart?
Causes arrythmia
What does digitalis do to the GI tract?
Causes anorexia, nausea, vomiting and diarrhea
What effects can digitalis have on the nervous system?
Disorientation, hallucination and visual disturbances
What is the therapeutic range of digitalis?
0.5 - 2.0 ng/mL (narrow)
What is elimination?
Metabolism and excretion
Deals with mathematical description of drug movement into, within and exit from the body
Pharmacokinetics
Describe drug in the blood
Either free or protein-bound
Which compartment model does digoxin follow?
Two-compartment model
What is a very important assumption in pharmacokinetics regarding drug intake?
Once it is taken it, it is distributed uniformly.
What is the formula for initial concentration?
Initial Concentration = Loading Dose/Volume of Distribution
What is the formula for volume of distribution?
Volume of Distribution = Loading Dose/Initial Concentration
Define: Steady-state condition
Rate of drug elimination equals rate of administration
What is the formula for steady-state concentration?
Cpss = (fraction absorbed x maintenance dose)/(dosing interval x clearance)
Define: Clearance
Ratio of the rate of elimination of drug to the concentration of drug in the plasma
What is the relationship between of half-life, volume of distribution and clearance?
Half-life is directly proportional to volume of distribution and inversely proportional to clearance.
What is the formula for half-life?
Half-life = (0.693)(Volume of Distribution)/Clearance
What is the relationship between half-life and rate of action of the drug?
A shorter half-life means faster action, while a longer half-life means slower action.
What are the values for F, Vd, half-life, percent metabolized and plasma protein binding of digoxin?
F = 0.75 Vd = 6.3 L/kg Half-life = 40 hrs Plasma protein binding = 20 - 40% Percent metabolized = <40%
What circulation contributes to the long half-life of digoxin?
Enterohepatic circulation
What substance binds toxic drugs in the intestines?
Activated charcoal
What proportion of digoxin is excreted unchanged in the kidney?
2/3
What are the recommendations for digoxin use?
- Not a first-line drug
- Used only for symptom control
- To be used in patients with heart failure and atrial fibrillation
What is rational drug use?
- Therapeutic efficacy
- Avoidance of toxicity
- Socially-responsible prescribing behaviour
How many percent of doctor visits end in prescription writing?
70 - 90%
How much does drug development cost on average?
$1.7 B
What is the danger in patients taking multiple drugs?
Drug interactions may occur.
What is the danger in elderly taking drugs?
There is more potential for adverse drug reactions.
What aspect of pharmaceutical companies remain a threat to cost-effective prescribing decisions?
Direct-to-consumer advertising
Enumerate the Rule of Rights
- Right indication
- Right drug
- Right route, dosage and duration
- Right patient
- Right patient information
- Right evaluation
- Right price
I Do Right for Patients. Patients Enable Practice.
Define: Efficacy
How it can bring about what you want for the patient
Define: Safety
Weighing benefits vs. risks and checking for contraindications and adverse effects
