Cardiovascular Anatomy, Physiology and Pharmacology BS913 Lecture 8: General Pharmacology, Pharmacokinetics and –dynamics, Introduction to cardiovascular drugs … Mücke Leithauser

1)What is Pharmacology? 3)Why is some knowledge in pharmacology important to you? 2)What do you want to know / learn about pharmacology?

Learning objectives „Pharmacology“ -Describe the prescribed usage, alternative nomenclature, dosages, adverse reactions, cautions and common routes of administration -Describe the pharmacological interventions commonly used in the treatment of cardiac disorders -Discuss the effect of common cardiac drugs on the body and their cellular and physiological actions. -Understand the effect of common cardiac drugs on physical activity, and the special considerations related to these drugs.

What is pharmacology? -Pharmacology is the study of drugs and their actions on living organisms -A sound knowledge of basic pharmaceutical principles is essential for professionals who interact with patients who receive medications

1)What is Pharmacology? 3)Why is some knowledge in pharmacology important to you? 2)What do you want to know / learn about pharmacology? 4)Where do we start?

General principles of pharmacology -Drug development -Drug names -Drug categories -Drug actions within the body -Drug reactions -Drug interactions -Factors influencing drug response

Drug development -Long and arduous process -New drugs need to be approved (FDA = Food and Drug Administration and / or similar national organisations) -7 to 12 years or longer -Development of a new drug is a multi- phase process -pre-FDA phase -FDA phase

Drug development -pre-FDA phase: -in-vitro testing using animal and human cells -studies in live animals -FDA-phase: clinical testing -phase I: weeks; individuals (“normal” volunteers or in intended treatment population)

Drug development -FDA-phase: clinical testing -phase II: more people compared to phase I -phase III: more people compared to phase II; generates more info on dosing and safety -Phases I-III last 2-10 years (average 5) -Decision of (dis)approval approx. 2 yr

Phases of drug development

Drug names Drugs are referred to in a number of ways: -By the class or group of drugs -By generic names -By proprietary (or brand) names -Anti-Histamins -Loratadine -Claritin

Drug names GROUPGeneric name Proprietary name Ca-channel blockers VerapamilCordilox VerapamilSecuron ß-blockersPropanololInderal AtenololTenormin

Drug categories -Prespription drugs: -Largest category of drugs -Must be prescribed by licensed health care provider -most drugs taken by cardiac patients need to be prescribed -Non-prescription drugs: -can be obtained without prescription -are drugs; may cause adverse effects -Controlled substances: -high potential for abuse; may cause physical or psych. dependence

Drug actions within the body: -Pharmaceutical phase -Pharmacokinetic phase -Pharmacodynamic phase

Drug actions within the body: -Drugs act in various ways in the body -Solid drugs taken by mouth go through all three phases -Liquid drugs and parenteral drugs (given by injection) go through the latter two phases

Drug actions within the body: -Who has ever taken medication because of horrible headache?

Pharmaceutical phase: -Dissolution of the drug -Drugs must be in solution to be absorbed -Tablets or capsules: disintegrate into small particles and dissolve into body fluids within the gastrointestinal tract -Enteric-coated tablets do not disintegrate until reaching an alkaline environment (small intestine)

Pharmacokinetic phase:

-Refers to activities involving the drug after it is administered -Absorption -Distribution -Metabolism -Excretion -Half-life of a drug: measure of rate at which drug is removed from the body

Absorption -Follows administration -Process by which drug becomes available for use in the body -Occurs after dissolution of solid drug or after administration of a liquid or parenteral drug

Absorption -Drug particles in GIT are moved into body fluids -active absorption (carrier moves drug through membrane) -passive absorption (diffusion) -pinocytosis (cells engulf drug particle causing movement across the cell) -Drug transfer to tissue sites – absorption into body tissues

Absorption -Factors influencing rate of absorption -route of administration -solubility of drug -certain body conditions (e.g. Lipodystrophy)

Absorption -Drugs most rapidly absorbed -intravenous application -intramuscular application -subcutaneous application -oral application

Distribution -Systemic circulation distributes drugs to various body tissues / target sites -Some drugs travel by binding to protein (albumin) -Drugs bound to protein are pharmacologically inactive -There, drugs interact with specific receptors

Distribution -Needs to be released by protein molecules to diffuse into tissue, interact with receptors, produce a therapeutic effect -Certain blood level must be maintained for drug to be effective -If level too low: drug will not produce desired effect -If level too high: toxic symptoms may develop

Metabolism -Sometimes called biotransformation -Process of chemical reactions by which the liver converts the drug to inactive compounds -Important: patients with liver disease may require lower dosage; frequent liver function tests are necessary -Kidneys, lungs, plasma and intestinal mucosa aid in metabolism of drugs

Excretion -Elimination of drugs from the body -After liver renders a drug inactive, kidneys excrete inactive compounds from the body in the urine -Some drugs are excreted unchanged by the kidney without liver involvement

Excretion -Important: Patients with kidney disease may require a lower dosage; careful monitoring of kidney function -Special case “children”: immature kidney function -Special case “older adults”: reduced kidney function -Other ways of elimination: breast milk, breathing, faeces

Half life -Time required for the body to eliminate 50% of the drug -It takes five to six half-lives to eliminate approximately 98% of a drug -Half-life of a drug is the same in most people -Reduced liver and kidney function can increase half-life and by this the risk of toxicity

Pharmacodynamic phase -The drug’s action and effects within the body -After administration most drugs enter the systemic circulation and expose almost all body tissue to their potential effects -All drugs produce more than one effect in the body -The primary effect is the desired or therapeutic effect

Pharmacodynamic phase -Secondary effects are all other effects (desirable or undesirable) produced by the drug -Most drugs have an affinity for certain organs or tissues -They exert greatest action at the cellular level in those specific areas -Main mechanisms of action: -alteration in cellular environment -alteration in cellular function

Pharmacodynamic phase -Physical alterations in cellular environment, e.g. -Changes in osmotic pressure -Absorption (activ. charcoal) -Conditions on surface of cell membrane (stool softener) -Chemical alterations in cellular environment, e.g. -alteration of chemical components of body fluid (ph-change; antacids)

Pharmacodynamic phase -Most drugs act on body by altering cellular function -increase or decrease of certain physiologic function, e.g. -heart rate -blood pressure -urine output

Pharmacodynamic phase -Receptor-mediated drug action -Cell function alters when drug interacts with receptor -Agonists: drugs bind with receptor to produce a therapeutic response -Antagonists: drugs bind with receptor and thereby prevent the action of an agonist

Pharmacodynamic phase -Receptor-mediated drug effects -Number of available receptor sites influences effects of a drug -If drug occupies only few receptors when many are available: small effect

Drugs : a variety of reactions -Adverse drug reactions -Allergic drug reactions -Drug idiosyncrasy -Drug tolerance -Cumulative drug effect -Toxic reactions

Adverse Drug reactions: -Adverse drug reactions -Undesirable drug effects -May be mild, severe, life-threatening -Occur after first dose, several doses, many doses -Sometimes predictable -In many cases without warning

Adverse effects:

Allergic Drug reactions: -Hypersensivity -Occurs usually after more than one dose has been given -Immune system views drug as a foreign substance (antigen) -Initiates antibody production -Allergic reaction must be reported to health care provider

Allergic Drug reactions: -Symptoms -Itching skin -Rash -Breathing difficulties -Wheezing -swelling of the eyes, lips

Anaphylactic Shock:

Drug idiosyncrasy: -Unusual or abnormal reaction to a drug Drug tolerance -Decreased response to a drug -After taking the drug for long time -increase in dosage to maintain effect

Cumulative Drug effect: -In patients with liver / kidney problems - Can lead to toxic reactions Toxic reaction -If administered in large dosages -When blood concentration level exceeds therapeutic level -sometimes antidote available

Drug interactions: -Drug-drug interactions -Drug-food interactions

Drug interactions: -Drug-drug interactions -Additive drug reaction: = 2 -Synergistic drug reaction: = (>2) -Antagonistic drug reaction:

Drug interactions: -Drug-Food interactions -Drug taken on empty stomach: Faster absorbed -Full stomach: Slower absorbed -Drug-food complex (tetracycline) -food as “antagonist” (vit. K and warfarin)

Factors influencing drug response: -Age -Weight -Gender -Disease -Route of administration

Factors influencing drug response: -Age: -immature organ function in kids -reduced function in elderly -Disease: liver, kidney; -Route of administration -Weight: reference weight 75 lb -Gender: higher fat/water ratio in F

Factors influencing drug response: -Route of administration - some drugs can onlygiven by one route -differences in appearance of drug action

Factors influencing drug response:

Drugs used to treat cardiac conditions: