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Advanced Pharmacology Test 1 (1).
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Advanced Pharmacology Test 1 (1).
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Advanced Pharmacology Test 1Target tissue interactions: Structurally non-specific - ANS-Physical presense of drug in tissue
creates effect
Target tissue interactions: structurally specific: - ANS-Chemical structure of drug essential for
biological act reversible chemical bonds with some component of target tissue.
Target Tissue Sites: Membrane components binding sites. - ANS-Hormone or neurotransmitter
receptor channels (Ca channel blockers), transport proteins (sodium ATPase inhibitors:
amiloride)
Target tissue sites: Cellular organelles: - ANS-Chromosomes/DNA target for cyclophosamide,
ribosomes target for some antibiotics like tetracycline, microtubules target for vincristine.
Target Tissue Sites: Enxymes - ANS-Some drugs are substrates for selective enzymes, LDOPA:
other drugs are enzyme inhibitors
Drug - Receptor Binding - ANS-Drug+ Receptor>> (Affinity) DR (Drug Receptor Complex)> ST
(signal transduction) > Biological response. "When membrane binds to drug or hormone there's
biological response. Primary messenger is the hormone or drug, binds to receptor, causing
activation of 2nd messengers, that triggers regulatory proteins leading, that triggers response
proteins.
Signal Transduction - ANS-Transfer of info from the bound receptor to the response proteins.
2nd messengers - ANS-cAMP/cGMP, Calcium, NO
Regulatory Proteins - ANS-Protein Kinases
ResponseProteins - ANS-Contractile Proteins.
Affinity - ANS-Needed for drug to bind to receptor. Measure of the drug concentration needed to
bind to receptor. Concentration of drugs that saturates 50% of the receptors in ta target tissue.
HigherVsLowerAffinity - ANS-Lower the concentration of the drug that saturates 50% of the
receptors the HIGHER the affinity. Here concentration to saturate = LOWER affinity.
Potency RT Affinity - ANS-Partly explained by affinity of a drug for receptor. Lower concentration
of a drug, which is high affinity, that binds to the receptor, the lower the ED50= higher potency.
Lower concentration needed + both higher affinity and high potency.
, Efficacy - ANS-Ability of the occupied receptor to trigger ST events that leads to biological
response. Used to explain intrinsic activity values. Classifies agonist (high efficacy) partial
agonist and antagonist.
Efficacy RT Intrinsic activity - ANS-Low efficacty= low intrinsic activity and vice versa.
Conformational changes - ANS-Changes shape of the receptor that leads to ST and response -
efficacy depends on this
Other types of drug antagonism - ANS-Chemical: protamine is an antagonist to heparin. Positive
electrical charge allows it to bind to negative heparin, preventing heparin binding to clotting
factors.
Physiological: glucocorticoid therapy may cause hyperglycemia that can compromise
hypoglycemic effects produced by insulin.
Classification of toxic side-effects(SE)-ClassA - ANS-About 80% of SE produced by drugs.
PREDICTABLE and DOSE-DEPENDENT. Either they cant be avoided RT nature of drug
response or they are from poor pt compliance or medical care.
Classification of toxic side-effects(SE)-Class B - ANS-About 20%. Not dose-dependent and
often characterized as IDIOSYNCTRATIC. eg anaphylactic shock produced by PCN.
Exaggerated therapeutic effects - ANS-Warfarin can cause uncontrolled hemorrhaging
Rebound Responses - ANS-Induced by abrupt drug withdrawal. Taper drug dosage over time
recommended for many classes of drugs. Eg Propranolol can induced rebound HTN.
Propranolol Treatment - ANS-Beta receptor antagonist. Normally epinephrine bind to receptors
on the heart giving the biological response htn. Treat with propranolol, a b receptor antagonist
produces an antihypertensive effect. Lack of stimulus in some target tissues induces a
compensatory UP REGULATION of receptors. With abrupt withdrawal of an antagonist
receptors become unoccupied creating a REBOUND RESPONES htn crisis - abrupt withdrawal.
Teratogens - ANS-Stages of gestation/risks:
-Conception to formation of the 3 germ layers (0-2 weeks)
-Embryogenesis (3-8wks) formation of major organ systems MOST SUSCEPTIBLE STAGE TO
TERATOGENS
-Fetogenesis (9-38 wks) enlargement of all major systems.
Pregnancy categories - ANS--A: vita B6 - Drugs appear to be safe when taken during
pregnancy.
-B: Cimetidine - Drugs tested in animals appear safe, safety in humans not established.
-C: Codeine - Drugs produce malformations in animals, drug safety in humans not established.
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