SlideShare a Scribd company logo
1 of 21
Pharmacology Part 1
Themba Hospital FCOG(SA) Part 1 Tutorials
By Dr N.E Manana
INTRODUCTION TO THERAPEUTICS
USE OF DRUGS
ā€¢ A century ago, physicians had only a handful of effective drugs (e.g.
morphia, quinine, ether, aspirin and digitalis leaf) at their disposal.
ā€¢ Thousands of potent drugs have since been introduced, and
pharmaceutical chemists continue to discover new and better drugs.
ā€¢ With advances in genetics, cellular and molecular science, it is likely that
progress will accelerate and huge changes in therapeutics are inevitable.
RISK/BENEFIT
ā€¢ Medicinal chemistry has contributed immeasurably to human health, but
this has been achieved at a price
ā€¢ In the nineteenth century they could safely adhere to the Hippocratic
principle ā€˜first do no harmā€™, because the opportunities for doing good
were so limited.
ā€¢ The discovery of effective drugs has transformed this situation, at the
expense of very real risks of doing harm
ā€¢ All effective drugs have adverse effects, and therapeutic judgements
based on risk/benefit ratio permeate all fields of medicine
Basic duties of prescribers
1. Restrictive use ā€“ is drug therapy warranted?
2. Careful choice of an appropriate drug and dose regimen
3. Consultation and consent
4. Prescription and recording
5. Supervision (including monitoring)
7. Termination, as appropriate
8. Conformity with the law relating to prescribing
Consideration when deciding on a
therapeutic plan
1. Age
2. Coexisting disease, especially renal and or hepatic impairment
3. The possibility of pregnancy
4. Drug history
5. The best that can reasonably be hoped for in this individual patient
6. The patientā€™s beliefs and goals
SCIENTIFIC BASIS OF DRUGS
ā€¢ Clinical pharmacology deals with the effects of drugs in humans.
ā€¢ It entails the study of the interaction of drugs with their receptors, and the
changes that they bring about in cells, organs and the whole organism.
ā€¢ These processes (what the drug does to the body) are called
ā€˜pharmacodynamicsā€™.
ā€¢ The processes of absorption, distribution, metabolism and elimination (what
the body does to the drug) ,These processes comprise ā€˜pharmacokinetics
ā€¢ The use of drugs in society is encompassed by pharmacoepidemiology and
pharmacoeconomics
PHARMACODYNAMICS
ā€¢ Pharmacodynamics is the study of effects of drugs on biological processes.
ā€¢ Many mediators exert their effects as a result of high-affinity binding to
specific receptors in plasma membranes or cell cytoplasm/nuclei,
ā€¢ And many therapeutically important drugs exert their effects by combining
with these receptors and either mimicking the effect of the natural mediator
(in which case they are called ā€˜agonistsā€™) or blocking it
ā€¢ Not all drugs work via receptors for endogenous mediators: many
therapeutic drugs exert their effects by combining with an enzyme or
transport protein and interfering with its function.
ā€¢ Whether the site of action of a drug is a receptor or another macromolecule,
binding is usually highly specific
PHARMACODYNAMICS
ā€¢ Binding is usually reversible. Occasionally, however, covalent bonds are
formed with irreversible loss of function, e.g. aspirin binding to
cyclooxygenase
ā€¢ Most drugs produce graded concentration-/dose-related effects which
can be plotted as a doseā€“response curve
ā€¢ Doseā€“response curves facilitates quantitative analysis of full agonists
(which produce graded responses up to a maximum value), antagonists
(which produce no response on their own, but reduce the response to
an agonist)
ā€¢ And partial agonists (which produce some response, but to a lower
maximum value than that of a full agonist, and antagonize full agonists)
ā€¢ FIGURE 2.2
ā€¢ FIGURE 2.3
RECEPTORS AND SIGNAL TRANSDUCTION
ā€¢ Drugs are often potent (i.e. they produce effects at low concentration)
and specific (i.e. small changes in structure lead to profound changes in
potency).
ā€¢ High potency is a consequence of high binding affinity for specific
macromolecular receptors
ā€¢ Receptors were originally classified by reference to the relative potencies
of agonists and antagonists on preparations containing different receptors
RECEPTORS AND SIGNAL TRANSDUCTION
ā€¢ Receptors fall into only four ā€˜super familiesā€™ each linked to distinct types of
signal transduction mechanism
1. Fast (millisecond responses) neurotransmitters (e.g. nicotinic receptors)-
transmembrane ion channel
2. Slower neurotransmitters and hormones (e.g. muscarinic receptors) -
intracellular G-protein
3. Receptors linked to an enzyme on the inner membrane (e.g. insulin
receptors) are slower still
4. Intra-nuclear receptors (e.g. gonadal and glucocorticosteroid hormones)
ā€¢ FIGURE 2.4
AGONISTS
ā€¢ Agonists activate receptors for endogenous mediators ā€“ e.g. salbutamol is an
agonist at Ī²2-adrenoceptors
ā€¢ The consequent effect may be excitatory (e.g. increased heart rate) or
inhibitory (e.g. relaxation of airway smooth muscle).
ā€¢ Agonists at nicotinic acetylcholine receptors (e.g. suxamethonium, exert an
inhibitory effect (neuromuscular blockade) by causing long-lasting
depolarization at the neuromuscular junction,
ā€¢ And hence inactivation of the voltage-dependent sodium channels that
initiate the action potential.
AGONISTS
ā€¢ Endogenous ligands have sometimes been discovered long after the
drugs that act on their receptors.
ā€¢ Endorphins and enkephalins (endogenous ligands of morphine
receptors) were discovered many years after morphine.
ā€¢ Anandamide is a central transmitter that activates CB (cannabis)
receptors
ANTAGONISM
ā€¢ Competitive antagonists combine with the same receptor as an
endogenous agonist (e.g. ranitidine at histamine H2-receptors), but fail
to activate it.
ā€¢ When combined with the receptor, they prevent access of the
endogenous mediator.
ā€¢ The complex between competitive antagonist and receptor is reversible.
ā€¢ Provided that the dose of agonist is increased sufficiently, a maximal
effect can still be obtained
ā€¢ Physiological antagonism describes the situation where two drugs have
opposing effects (e.g. adrenaline relaxes bronchial smooth muscle,
whereas histamine contracts it).
PARTIAL AGONISTS
ā€¢ Some drugs combine with receptors and activate them, but are incapable
of eliciting a maximal response, no matter how high their concentration
may be.
ā€¢ These are known as partial agonists, and are said to have low efficacy.
ā€¢ Several partial agonists are used in therapeutics, including
buprenorphine (a partial agonist at morphine Ī¼-receptors) and
oxprenolol (partial agonist at Ī²-adrenoceptors).
ā€¢ Full agonists can elicit a maximal response when only a small proportion
of the receptors is occupied (underlying the concept of ā€˜spareā€™
receptors),
ā€¢ But this is not the case with partial agonists, where a substantial
proportion of the receptors need to be occupied to cause a response
SLOW PROCESSES
ā€¢ Prolonged exposure of receptors to agonists, as frequently occurs in
therapeutic use, can cause down-regulation or desensitization.
ā€¢ Desensitization is sometimes specific for a particular agonist (when it is
referred to as ā€˜homologous desensitizationā€™), or there may be cross-
desensitization to different agonists (ā€˜heterologous desensitizationā€™).
ā€¢ Desensitization is probably involved in the tolerance that occurs during
prolonged administration of drugs, such as morphine or benzodiazepines
ā€¢ Therapeutic effects sometimes depend on induction of tolerance.
NON-RECEPTOR MECHANISMS
ā€¢ In contrast to high-potency/high-selectivity drugs which combine with
specific receptors, some drugs exert their effects via simple physical
properties or chemical reactions due to their presence in some body
compartment.
ā€¢ Examples include antacids (which neutralize gastric acid), osmotic
diuretics (which increase the osmolality of renal tubular fluid), and bulk
and lubricating laxatives.
ā€¢ These agents are of low potency and specificity, and hardly qualify as
ā€˜drugsā€™ in the usual sense at all, although some of them are useful
medicines.
THANK YOU

More Related Content

What's hot

What's hot (20)

Infections and pregnancy
Infections and pregnancyInfections and pregnancy
Infections and pregnancy
Ā 
Intrauterine Growth Restriction.pptx
Intrauterine Growth Restriction.pptxIntrauterine Growth Restriction.pptx
Intrauterine Growth Restriction.pptx
Ā 
Intro embryology (1)
Intro embryology (1)Intro embryology (1)
Intro embryology (1)
Ā 
Gametogenesis and ovulation
Gametogenesis and ovulationGametogenesis and ovulation
Gametogenesis and ovulation
Ā 
Abdomen part 3
Abdomen part 3Abdomen part 3
Abdomen part 3
Ā 
7. Amnionic Fluid.pptx
7. Amnionic Fluid.pptx7. Amnionic Fluid.pptx
7. Amnionic Fluid.pptx
Ā 
1. Fetal Assessment.pptx
1. Fetal Assessment.pptx1. Fetal Assessment.pptx
1. Fetal Assessment.pptx
Ā 
Abdomen part 4
Abdomen part 4Abdomen part 4
Abdomen part 4
Ā 
Maternal physiology
Maternal physiologyMaternal physiology
Maternal physiology
Ā 
8. Teratology.pptx
8. Teratology.pptx8. Teratology.pptx
8. Teratology.pptx
Ā 
Pelvic floor and perineal body
Pelvic floor and perineal bodyPelvic floor and perineal body
Pelvic floor and perineal body
Ā 
Second week of development
Second week of developmentSecond week of development
Second week of development
Ā 
The Foetus and Placenta.pptx
The Foetus and Placenta.pptxThe Foetus and Placenta.pptx
The Foetus and Placenta.pptx
Ā 
Abdomen part 1
Abdomen part 1Abdomen part 1
Abdomen part 1
Ā 
Pelvic bones
Pelvic bonesPelvic bones
Pelvic bones
Ā 
Embryonic stage
Embryonic stageEmbryonic stage
Embryonic stage
Ā 
ABNORMALITIES OF LABOUR.pptx
ABNORMALITIES OF LABOUR.pptxABNORMALITIES OF LABOUR.pptx
ABNORMALITIES OF LABOUR.pptx
Ā 
Cardiovascular system physiology
Cardiovascular system physiologyCardiovascular system physiology
Cardiovascular system physiology
Ā 
Abdomen part 2
Abdomen part 2Abdomen part 2
Abdomen part 2
Ā 
2. Fetal Imaging.pptx
2. Fetal Imaging.pptx2. Fetal Imaging.pptx
2. Fetal Imaging.pptx
Ā 

Similar to Pharmacology part 1

Pharmacodynamics
PharmacodynamicsPharmacodynamics
PharmacodynamicsSabaShaikh76
Ā 
pharmacodynamics 1.pdf
pharmacodynamics 1.pdfpharmacodynamics 1.pdf
pharmacodynamics 1.pdfImtiyaz60
Ā 
Pharmacodynamics PPT
Pharmacodynamics PPTPharmacodynamics PPT
Pharmacodynamics PPTDr. Vijay Prasad
Ā 
Mechanism Of Drug Action.pdf
Mechanism Of Drug Action.pdfMechanism Of Drug Action.pdf
Mechanism Of Drug Action.pdfDnyaneshwar Gutale
Ā 
pharmacodynamics 1.pptx
pharmacodynamics 1.pptxpharmacodynamics 1.pptx
pharmacodynamics 1.pptxImtiyaz60
Ā 
Pharmacodynamics
PharmacodynamicsPharmacodynamics
PharmacodynamicsMrunalAkre
Ā 
Receptor - Pharmacology
Receptor - PharmacologyReceptor - Pharmacology
Receptor - PharmacologyHarshit Jadav
Ā 
Pharmacodynamics
PharmacodynamicsPharmacodynamics
PharmacodynamicsSufyan Akram
Ā 
Introduction and sources of drugs, routs of drug administration, principles ...
Introduction and sources of drugs, routs of drug administration,  principles ...Introduction and sources of drugs, routs of drug administration,  principles ...
Introduction and sources of drugs, routs of drug administration, principles ...Subramani Parasuraman
Ā 
Principles of pharmacodynamics
Principles of pharmacodynamicsPrinciples of pharmacodynamics
Principles of pharmacodynamicsJaineel Dharod
Ā 
pharmacodynamics 6.pptx
pharmacodynamics 6.pptxpharmacodynamics 6.pptx
pharmacodynamics 6.pptxImtiyaz60
Ā 
Pharmacology unit I.pptx
Pharmacology unit I.pptxPharmacology unit I.pptx
Pharmacology unit I.pptxAsifAliLashari2
Ā 
2. pharmacodynamics and kinetics
2. pharmacodynamics and kinetics2. pharmacodynamics and kinetics
2. pharmacodynamics and kineticsjhonee balmeo
Ā 
BNSC 1 PHARMACODYNAMICS PART 1.pptx
BNSC 1 PHARMACODYNAMICS PART 1.pptxBNSC 1 PHARMACODYNAMICS PART 1.pptx
BNSC 1 PHARMACODYNAMICS PART 1.pptxNatwijukaAndrew1
Ā 
Pharmacology Unit - 2.pptx
Pharmacology Unit - 2.pptxPharmacology Unit - 2.pptx
Pharmacology Unit - 2.pptxNikita Gupta
Ā 
2022_UMSU PHARMACODYNAMIC 1 2.pptx
2022_UMSU PHARMACODYNAMIC 1  2.pptx2022_UMSU PHARMACODYNAMIC 1  2.pptx
2022_UMSU PHARMACODYNAMIC 1 2.pptxdrRiyan1
Ā 

Similar to Pharmacology part 1 (20)

Pharmacodynamics
PharmacodynamicsPharmacodynamics
Pharmacodynamics
Ā 
pharmacodynamics 1.pdf
pharmacodynamics 1.pdfpharmacodynamics 1.pdf
pharmacodynamics 1.pdf
Ā 
Pharmacodynamics PPT
Pharmacodynamics PPTPharmacodynamics PPT
Pharmacodynamics PPT
Ā 
Mechanism Of Drug Action.pdf
Mechanism Of Drug Action.pdfMechanism Of Drug Action.pdf
Mechanism Of Drug Action.pdf
Ā 
pharmacodynamics 1.pptx
pharmacodynamics 1.pptxpharmacodynamics 1.pptx
pharmacodynamics 1.pptx
Ā 
Pharmacodynamics
PharmacodynamicsPharmacodynamics
Pharmacodynamics
Ā 
Pharmacodynamics
PharmacodynamicsPharmacodynamics
Pharmacodynamics
Ā 
Pharmacodynamics
PharmacodynamicsPharmacodynamics
Pharmacodynamics
Ā 
Receptor - Pharmacology
Receptor - PharmacologyReceptor - Pharmacology
Receptor - Pharmacology
Ā 
medicinal chemistry .pptx
medicinal chemistry .pptxmedicinal chemistry .pptx
medicinal chemistry .pptx
Ā 
General Pharmacology
General PharmacologyGeneral Pharmacology
General Pharmacology
Ā 
Pharmacodynamics
PharmacodynamicsPharmacodynamics
Pharmacodynamics
Ā 
Introduction and sources of drugs, routs of drug administration, principles ...
Introduction and sources of drugs, routs of drug administration,  principles ...Introduction and sources of drugs, routs of drug administration,  principles ...
Introduction and sources of drugs, routs of drug administration, principles ...
Ā 
Principles of pharmacodynamics
Principles of pharmacodynamicsPrinciples of pharmacodynamics
Principles of pharmacodynamics
Ā 
pharmacodynamics 6.pptx
pharmacodynamics 6.pptxpharmacodynamics 6.pptx
pharmacodynamics 6.pptx
Ā 
Pharmacology unit I.pptx
Pharmacology unit I.pptxPharmacology unit I.pptx
Pharmacology unit I.pptx
Ā 
2. pharmacodynamics and kinetics
2. pharmacodynamics and kinetics2. pharmacodynamics and kinetics
2. pharmacodynamics and kinetics
Ā 
BNSC 1 PHARMACODYNAMICS PART 1.pptx
BNSC 1 PHARMACODYNAMICS PART 1.pptxBNSC 1 PHARMACODYNAMICS PART 1.pptx
BNSC 1 PHARMACODYNAMICS PART 1.pptx
Ā 
Pharmacology Unit - 2.pptx
Pharmacology Unit - 2.pptxPharmacology Unit - 2.pptx
Pharmacology Unit - 2.pptx
Ā 
2022_UMSU PHARMACODYNAMIC 1 2.pptx
2022_UMSU PHARMACODYNAMIC 1  2.pptx2022_UMSU PHARMACODYNAMIC 1  2.pptx
2022_UMSU PHARMACODYNAMIC 1 2.pptx
Ā 

More from NkosinathiManana2

HIV AND TUBERCULOSIS IN PREGNANCY.pptx
HIV AND TUBERCULOSIS IN PREGNANCY.pptxHIV AND TUBERCULOSIS IN PREGNANCY.pptx
HIV AND TUBERCULOSIS IN PREGNANCY.pptxNkosinathiManana2
Ā 
Caesarean delivery.pptx
Caesarean delivery.pptxCaesarean delivery.pptx
Caesarean delivery.pptxNkosinathiManana2
Ā 
INDUCTION OF LABOUR.pptx
INDUCTION OF LABOUR.pptxINDUCTION OF LABOUR.pptx
INDUCTION OF LABOUR.pptxNkosinathiManana2
Ā 
Infections in pregnancy and the puerperium.pptx
Infections in pregnancy and the puerperium.pptxInfections in pregnancy and the puerperium.pptx
Infections in pregnancy and the puerperium.pptxNkosinathiManana2
Ā 
MEDICAL DISORDERS IN PREGNANCY.pptx
MEDICAL DISORDERS IN PREGNANCY.pptxMEDICAL DISORDERS IN PREGNANCY.pptx
MEDICAL DISORDERS IN PREGNANCY.pptxNkosinathiManana2
Ā 
TUBERCULOSIS (TB) IN PREGNANCY.pptx
TUBERCULOSIS (TB) IN PREGNANCY.pptxTUBERCULOSIS (TB) IN PREGNANCY.pptx
TUBERCULOSIS (TB) IN PREGNANCY.pptxNkosinathiManana2
Ā 
Bleeding in early pregnancy (miscarriage).pptx
Bleeding in early pregnancy (miscarriage).pptxBleeding in early pregnancy (miscarriage).pptx
Bleeding in early pregnancy (miscarriage).pptxNkosinathiManana2
Ā 
COVID-19 in pregnant and postpartum women.pptx
COVID-19 in pregnant and postpartum women.pptxCOVID-19 in pregnant and postpartum women.pptx
COVID-19 in pregnant and postpartum women.pptxNkosinathiManana2
Ā 
ANTEPARTUM HAEMORRHAGE.pptx
ANTEPARTUM HAEMORRHAGE.pptxANTEPARTUM HAEMORRHAGE.pptx
ANTEPARTUM HAEMORRHAGE.pptxNkosinathiManana2
Ā 
Hypertensive Disorders in Pregnancy.pptx
Hypertensive Disorders in Pregnancy.pptxHypertensive Disorders in Pregnancy.pptx
Hypertensive Disorders in Pregnancy.pptxNkosinathiManana2
Ā 
Gender Based Violence.pptx
Gender Based Violence.pptxGender Based Violence.pptx
Gender Based Violence.pptxNkosinathiManana2
Ā 
Fetus as an allograft.pptx
Fetus as an allograft.pptxFetus as an allograft.pptx
Fetus as an allograft.pptxNkosinathiManana2
Ā 
6. Fetal Disorders.pptx
6. Fetal Disorders.pptx6. Fetal Disorders.pptx
6. Fetal Disorders.pptxNkosinathiManana2
Ā 
4. Immunological Aspects of Infection.pptx
4. Immunological Aspects of Infection.pptx4. Immunological Aspects of Infection.pptx
4. Immunological Aspects of Infection.pptxNkosinathiManana2
Ā 
2. Immune Regulation.pptx
2. Immune Regulation.pptx2. Immune Regulation.pptx
2. Immune Regulation.pptxNkosinathiManana2
Ā 

More from NkosinathiManana2 (20)

Fetal monitoring.pptx
Fetal monitoring.pptxFetal monitoring.pptx
Fetal monitoring.pptx
Ā 
ANTENATAL CARE.pptx
ANTENATAL CARE.pptxANTENATAL CARE.pptx
ANTENATAL CARE.pptx
Ā 
HIV AND TUBERCULOSIS IN PREGNANCY.pptx
HIV AND TUBERCULOSIS IN PREGNANCY.pptxHIV AND TUBERCULOSIS IN PREGNANCY.pptx
HIV AND TUBERCULOSIS IN PREGNANCY.pptx
Ā 
Caesarean delivery.pptx
Caesarean delivery.pptxCaesarean delivery.pptx
Caesarean delivery.pptx
Ā 
INDUCTION OF LABOUR.pptx
INDUCTION OF LABOUR.pptxINDUCTION OF LABOUR.pptx
INDUCTION OF LABOUR.pptx
Ā 
Infections in pregnancy and the puerperium.pptx
Infections in pregnancy and the puerperium.pptxInfections in pregnancy and the puerperium.pptx
Infections in pregnancy and the puerperium.pptx
Ā 
MEDICAL DISORDERS IN PREGNANCY.pptx
MEDICAL DISORDERS IN PREGNANCY.pptxMEDICAL DISORDERS IN PREGNANCY.pptx
MEDICAL DISORDERS IN PREGNANCY.pptx
Ā 
TUBERCULOSIS (TB) IN PREGNANCY.pptx
TUBERCULOSIS (TB) IN PREGNANCY.pptxTUBERCULOSIS (TB) IN PREGNANCY.pptx
TUBERCULOSIS (TB) IN PREGNANCY.pptx
Ā 
Bleeding in early pregnancy (miscarriage).pptx
Bleeding in early pregnancy (miscarriage).pptxBleeding in early pregnancy (miscarriage).pptx
Bleeding in early pregnancy (miscarriage).pptx
Ā 
COVID-19 in pregnant and postpartum women.pptx
COVID-19 in pregnant and postpartum women.pptxCOVID-19 in pregnant and postpartum women.pptx
COVID-19 in pregnant and postpartum women.pptx
Ā 
ANTEPARTUM HAEMORRHAGE.pptx
ANTEPARTUM HAEMORRHAGE.pptxANTEPARTUM HAEMORRHAGE.pptx
ANTEPARTUM HAEMORRHAGE.pptx
Ā 
Hypertensive Disorders in Pregnancy.pptx
Hypertensive Disorders in Pregnancy.pptxHypertensive Disorders in Pregnancy.pptx
Hypertensive Disorders in Pregnancy.pptx
Ā 
Gender Based Violence.pptx
Gender Based Violence.pptxGender Based Violence.pptx
Gender Based Violence.pptx
Ā 
Fetus as an allograft.pptx
Fetus as an allograft.pptxFetus as an allograft.pptx
Fetus as an allograft.pptx
Ā 
6. Fetal Disorders.pptx
6. Fetal Disorders.pptx6. Fetal Disorders.pptx
6. Fetal Disorders.pptx
Ā 
4. prenatal dx.pptx
4. prenatal dx.pptx4. prenatal dx.pptx
4. prenatal dx.pptx
Ā 
3. 3D U.pptx
3. 3D U.pptx3. 3D U.pptx
3. 3D U.pptx
Ā 
4. Immunological Aspects of Infection.pptx
4. Immunological Aspects of Infection.pptx4. Immunological Aspects of Infection.pptx
4. Immunological Aspects of Infection.pptx
Ā 
3. Autoimmunity.pptx
3. Autoimmunity.pptx3. Autoimmunity.pptx
3. Autoimmunity.pptx
Ā 
2. Immune Regulation.pptx
2. Immune Regulation.pptx2. Immune Regulation.pptx
2. Immune Regulation.pptx
Ā 

Recently uploaded

Vip Call Girls Anna Salai Chennai šŸ‘‰ 8250192130 ā£ļøšŸ’Æ Top Class Girls Available
Vip Call Girls Anna Salai Chennai šŸ‘‰ 8250192130 ā£ļøšŸ’Æ Top Class Girls AvailableVip Call Girls Anna Salai Chennai šŸ‘‰ 8250192130 ā£ļøšŸ’Æ Top Class Girls Available
Vip Call Girls Anna Salai Chennai šŸ‘‰ 8250192130 ā£ļøšŸ’Æ Top Class Girls AvailableNehru place Escorts
Ā 
Call Girls Service Jaipur Grishma WhatsApp ā¤8445551418 VIP Call Girls Jaipur
Call Girls Service Jaipur Grishma WhatsApp ā¤8445551418 VIP Call Girls JaipurCall Girls Service Jaipur Grishma WhatsApp ā¤8445551418 VIP Call Girls Jaipur
Call Girls Service Jaipur Grishma WhatsApp ā¤8445551418 VIP Call Girls Jaipurparulsinha
Ā 
Russian Escorts Girls Nehru Place ZINATHI šŸ”9711199012 ā˜Ŗ 24/7 Call Girls Delhi
Russian Escorts Girls  Nehru Place ZINATHI šŸ”9711199012 ā˜Ŗ 24/7 Call Girls DelhiRussian Escorts Girls  Nehru Place ZINATHI šŸ”9711199012 ā˜Ŗ 24/7 Call Girls Delhi
Russian Escorts Girls Nehru Place ZINATHI šŸ”9711199012 ā˜Ŗ 24/7 Call Girls DelhiAlinaDevecerski
Ā 
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort ServicePremium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Servicevidya singh
Ā 
VIP Call Girls Indore Kirti šŸ’ššŸ˜‹ 9256729539 šŸš€ Indore Escorts
VIP Call Girls Indore Kirti šŸ’ššŸ˜‹  9256729539 šŸš€ Indore EscortsVIP Call Girls Indore Kirti šŸ’ššŸ˜‹  9256729539 šŸš€ Indore Escorts
VIP Call Girls Indore Kirti šŸ’ššŸ˜‹ 9256729539 šŸš€ Indore Escortsaditipandeya
Ā 
VIP Call Girls Pune Vrinda 9907093804 Short 1500 Night 6000 Best call girls S...
VIP Call Girls Pune Vrinda 9907093804 Short 1500 Night 6000 Best call girls S...VIP Call Girls Pune Vrinda 9907093804 Short 1500 Night 6000 Best call girls S...
VIP Call Girls Pune Vrinda 9907093804 Short 1500 Night 6000 Best call girls S...Miss joya
Ā 
Call Girls Horamavu WhatsApp Number 7001035870 Meeting With Bangalore Escorts
Call Girls Horamavu WhatsApp Number 7001035870 Meeting With Bangalore EscortsCall Girls Horamavu WhatsApp Number 7001035870 Meeting With Bangalore Escorts
Call Girls Horamavu WhatsApp Number 7001035870 Meeting With Bangalore Escortsvidya singh
Ā 
Bangalore Call Girls Hebbal Kempapura Number 7001035870 Meetin With Bangalor...
Bangalore Call Girls Hebbal Kempapura Number 7001035870  Meetin With Bangalor...Bangalore Call Girls Hebbal Kempapura Number 7001035870  Meetin With Bangalor...
Bangalore Call Girls Hebbal Kempapura Number 7001035870 Meetin With Bangalor...narwatsonia7
Ā 
(Rocky) Jaipur Call Girl - 9521753030 Escorts Service 50% Off with Cash ON De...
(Rocky) Jaipur Call Girl - 9521753030 Escorts Service 50% Off with Cash ON De...(Rocky) Jaipur Call Girl - 9521753030 Escorts Service 50% Off with Cash ON De...
(Rocky) Jaipur Call Girl - 9521753030 Escorts Service 50% Off with Cash ON De...indiancallgirl4rent
Ā 
Call Girls Cuttack Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Cuttack Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Cuttack Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Cuttack Just Call 9907093804 Top Class Call Girl Service AvailableDipal Arora
Ā 
Best Rate (Hyderabad) Call Girls Jahanuma āŸŸ 8250192130 āŸŸ High Class Call Girl...
Best Rate (Hyderabad) Call Girls Jahanuma āŸŸ 8250192130 āŸŸ High Class Call Girl...Best Rate (Hyderabad) Call Girls Jahanuma āŸŸ 8250192130 āŸŸ High Class Call Girl...
Best Rate (Hyderabad) Call Girls Jahanuma āŸŸ 8250192130 āŸŸ High Class Call Girl...astropune
Ā 
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...Miss joya
Ā 
Kesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls Service
Kesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls ServiceKesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls Service
Kesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls Servicemakika9823
Ā 
Call Girls Service Navi Mumbai Samaira 8617697112 Independent Escort Service ...
Call Girls Service Navi Mumbai Samaira 8617697112 Independent Escort Service ...Call Girls Service Navi Mumbai Samaira 8617697112 Independent Escort Service ...
Call Girls Service Navi Mumbai Samaira 8617697112 Independent Escort Service ...Call girls in Ahmedabad High profile
Ā 
Aspirin presentation slides by Dr. Rewas Ali
Aspirin presentation slides by Dr. Rewas AliAspirin presentation slides by Dr. Rewas Ali
Aspirin presentation slides by Dr. Rewas AliRewAs ALI
Ā 
VIP Call Girls Pune Vani 9907093804 Short 1500 Night 6000 Best call girls Ser...
VIP Call Girls Pune Vani 9907093804 Short 1500 Night 6000 Best call girls Ser...VIP Call Girls Pune Vani 9907093804 Short 1500 Night 6000 Best call girls Ser...
VIP Call Girls Pune Vani 9907093804 Short 1500 Night 6000 Best call girls Ser...Miss joya
Ā 
VIP Service Call Girls Sindhi Colony šŸ“³ 7877925207 For 18+ VIP Call Girl At Th...
VIP Service Call Girls Sindhi Colony šŸ“³ 7877925207 For 18+ VIP Call Girl At Th...VIP Service Call Girls Sindhi Colony šŸ“³ 7877925207 For 18+ VIP Call Girl At Th...
VIP Service Call Girls Sindhi Colony šŸ“³ 7877925207 For 18+ VIP Call Girl At Th...jageshsingh5554
Ā 
Bangalore Call Girls Majestic šŸ“ž 9907093804 High Profile Service 100% Safe
Bangalore Call Girls Majestic šŸ“ž 9907093804 High Profile Service 100% SafeBangalore Call Girls Majestic šŸ“ž 9907093804 High Profile Service 100% Safe
Bangalore Call Girls Majestic šŸ“ž 9907093804 High Profile Service 100% Safenarwatsonia7
Ā 
Bangalore Call Girls Marathahalli šŸ“ž 9907093804 High Profile Service 100% Safe
Bangalore Call Girls Marathahalli šŸ“ž 9907093804 High Profile Service 100% SafeBangalore Call Girls Marathahalli šŸ“ž 9907093804 High Profile Service 100% Safe
Bangalore Call Girls Marathahalli šŸ“ž 9907093804 High Profile Service 100% Safenarwatsonia7
Ā 

Recently uploaded (20)

Vip Call Girls Anna Salai Chennai šŸ‘‰ 8250192130 ā£ļøšŸ’Æ Top Class Girls Available
Vip Call Girls Anna Salai Chennai šŸ‘‰ 8250192130 ā£ļøšŸ’Æ Top Class Girls AvailableVip Call Girls Anna Salai Chennai šŸ‘‰ 8250192130 ā£ļøšŸ’Æ Top Class Girls Available
Vip Call Girls Anna Salai Chennai šŸ‘‰ 8250192130 ā£ļøšŸ’Æ Top Class Girls Available
Ā 
Call Girls Service Jaipur Grishma WhatsApp ā¤8445551418 VIP Call Girls Jaipur
Call Girls Service Jaipur Grishma WhatsApp ā¤8445551418 VIP Call Girls JaipurCall Girls Service Jaipur Grishma WhatsApp ā¤8445551418 VIP Call Girls Jaipur
Call Girls Service Jaipur Grishma WhatsApp ā¤8445551418 VIP Call Girls Jaipur
Ā 
Russian Escorts Girls Nehru Place ZINATHI šŸ”9711199012 ā˜Ŗ 24/7 Call Girls Delhi
Russian Escorts Girls  Nehru Place ZINATHI šŸ”9711199012 ā˜Ŗ 24/7 Call Girls DelhiRussian Escorts Girls  Nehru Place ZINATHI šŸ”9711199012 ā˜Ŗ 24/7 Call Girls Delhi
Russian Escorts Girls Nehru Place ZINATHI šŸ”9711199012 ā˜Ŗ 24/7 Call Girls Delhi
Ā 
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort ServicePremium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
Ā 
VIP Call Girls Indore Kirti šŸ’ššŸ˜‹ 9256729539 šŸš€ Indore Escorts
VIP Call Girls Indore Kirti šŸ’ššŸ˜‹  9256729539 šŸš€ Indore EscortsVIP Call Girls Indore Kirti šŸ’ššŸ˜‹  9256729539 šŸš€ Indore Escorts
VIP Call Girls Indore Kirti šŸ’ššŸ˜‹ 9256729539 šŸš€ Indore Escorts
Ā 
VIP Call Girls Pune Vrinda 9907093804 Short 1500 Night 6000 Best call girls S...
VIP Call Girls Pune Vrinda 9907093804 Short 1500 Night 6000 Best call girls S...VIP Call Girls Pune Vrinda 9907093804 Short 1500 Night 6000 Best call girls S...
VIP Call Girls Pune Vrinda 9907093804 Short 1500 Night 6000 Best call girls S...
Ā 
Call Girls Horamavu WhatsApp Number 7001035870 Meeting With Bangalore Escorts
Call Girls Horamavu WhatsApp Number 7001035870 Meeting With Bangalore EscortsCall Girls Horamavu WhatsApp Number 7001035870 Meeting With Bangalore Escorts
Call Girls Horamavu WhatsApp Number 7001035870 Meeting With Bangalore Escorts
Ā 
Bangalore Call Girls Hebbal Kempapura Number 7001035870 Meetin With Bangalor...
Bangalore Call Girls Hebbal Kempapura Number 7001035870  Meetin With Bangalor...Bangalore Call Girls Hebbal Kempapura Number 7001035870  Meetin With Bangalor...
Bangalore Call Girls Hebbal Kempapura Number 7001035870 Meetin With Bangalor...
Ā 
(Rocky) Jaipur Call Girl - 9521753030 Escorts Service 50% Off with Cash ON De...
(Rocky) Jaipur Call Girl - 9521753030 Escorts Service 50% Off with Cash ON De...(Rocky) Jaipur Call Girl - 9521753030 Escorts Service 50% Off with Cash ON De...
(Rocky) Jaipur Call Girl - 9521753030 Escorts Service 50% Off with Cash ON De...
Ā 
Call Girls Cuttack Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Cuttack Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Cuttack Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Cuttack Just Call 9907093804 Top Class Call Girl Service Available
Ā 
sauth delhi call girls in Bhajanpura šŸ” 9953056974 šŸ” escort Service
sauth delhi call girls in Bhajanpura šŸ” 9953056974 šŸ” escort Servicesauth delhi call girls in Bhajanpura šŸ” 9953056974 šŸ” escort Service
sauth delhi call girls in Bhajanpura šŸ” 9953056974 šŸ” escort Service
Ā 
Best Rate (Hyderabad) Call Girls Jahanuma āŸŸ 8250192130 āŸŸ High Class Call Girl...
Best Rate (Hyderabad) Call Girls Jahanuma āŸŸ 8250192130 āŸŸ High Class Call Girl...Best Rate (Hyderabad) Call Girls Jahanuma āŸŸ 8250192130 āŸŸ High Class Call Girl...
Best Rate (Hyderabad) Call Girls Jahanuma āŸŸ 8250192130 āŸŸ High Class Call Girl...
Ā 
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
Ā 
Kesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls Service
Kesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls ServiceKesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls Service
Kesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls Service
Ā 
Call Girls Service Navi Mumbai Samaira 8617697112 Independent Escort Service ...
Call Girls Service Navi Mumbai Samaira 8617697112 Independent Escort Service ...Call Girls Service Navi Mumbai Samaira 8617697112 Independent Escort Service ...
Call Girls Service Navi Mumbai Samaira 8617697112 Independent Escort Service ...
Ā 
Aspirin presentation slides by Dr. Rewas Ali
Aspirin presentation slides by Dr. Rewas AliAspirin presentation slides by Dr. Rewas Ali
Aspirin presentation slides by Dr. Rewas Ali
Ā 
VIP Call Girls Pune Vani 9907093804 Short 1500 Night 6000 Best call girls Ser...
VIP Call Girls Pune Vani 9907093804 Short 1500 Night 6000 Best call girls Ser...VIP Call Girls Pune Vani 9907093804 Short 1500 Night 6000 Best call girls Ser...
VIP Call Girls Pune Vani 9907093804 Short 1500 Night 6000 Best call girls Ser...
Ā 
VIP Service Call Girls Sindhi Colony šŸ“³ 7877925207 For 18+ VIP Call Girl At Th...
VIP Service Call Girls Sindhi Colony šŸ“³ 7877925207 For 18+ VIP Call Girl At Th...VIP Service Call Girls Sindhi Colony šŸ“³ 7877925207 For 18+ VIP Call Girl At Th...
VIP Service Call Girls Sindhi Colony šŸ“³ 7877925207 For 18+ VIP Call Girl At Th...
Ā 
Bangalore Call Girls Majestic šŸ“ž 9907093804 High Profile Service 100% Safe
Bangalore Call Girls Majestic šŸ“ž 9907093804 High Profile Service 100% SafeBangalore Call Girls Majestic šŸ“ž 9907093804 High Profile Service 100% Safe
Bangalore Call Girls Majestic šŸ“ž 9907093804 High Profile Service 100% Safe
Ā 
Bangalore Call Girls Marathahalli šŸ“ž 9907093804 High Profile Service 100% Safe
Bangalore Call Girls Marathahalli šŸ“ž 9907093804 High Profile Service 100% SafeBangalore Call Girls Marathahalli šŸ“ž 9907093804 High Profile Service 100% Safe
Bangalore Call Girls Marathahalli šŸ“ž 9907093804 High Profile Service 100% Safe
Ā 

Pharmacology part 1

  • 1. Pharmacology Part 1 Themba Hospital FCOG(SA) Part 1 Tutorials By Dr N.E Manana
  • 3. USE OF DRUGS ā€¢ A century ago, physicians had only a handful of effective drugs (e.g. morphia, quinine, ether, aspirin and digitalis leaf) at their disposal. ā€¢ Thousands of potent drugs have since been introduced, and pharmaceutical chemists continue to discover new and better drugs. ā€¢ With advances in genetics, cellular and molecular science, it is likely that progress will accelerate and huge changes in therapeutics are inevitable.
  • 4. RISK/BENEFIT ā€¢ Medicinal chemistry has contributed immeasurably to human health, but this has been achieved at a price ā€¢ In the nineteenth century they could safely adhere to the Hippocratic principle ā€˜first do no harmā€™, because the opportunities for doing good were so limited. ā€¢ The discovery of effective drugs has transformed this situation, at the expense of very real risks of doing harm ā€¢ All effective drugs have adverse effects, and therapeutic judgements based on risk/benefit ratio permeate all fields of medicine
  • 5. Basic duties of prescribers 1. Restrictive use ā€“ is drug therapy warranted? 2. Careful choice of an appropriate drug and dose regimen 3. Consultation and consent 4. Prescription and recording 5. Supervision (including monitoring) 7. Termination, as appropriate 8. Conformity with the law relating to prescribing
  • 6. Consideration when deciding on a therapeutic plan 1. Age 2. Coexisting disease, especially renal and or hepatic impairment 3. The possibility of pregnancy 4. Drug history 5. The best that can reasonably be hoped for in this individual patient 6. The patientā€™s beliefs and goals
  • 7. SCIENTIFIC BASIS OF DRUGS ā€¢ Clinical pharmacology deals with the effects of drugs in humans. ā€¢ It entails the study of the interaction of drugs with their receptors, and the changes that they bring about in cells, organs and the whole organism. ā€¢ These processes (what the drug does to the body) are called ā€˜pharmacodynamicsā€™. ā€¢ The processes of absorption, distribution, metabolism and elimination (what the body does to the drug) ,These processes comprise ā€˜pharmacokinetics ā€¢ The use of drugs in society is encompassed by pharmacoepidemiology and pharmacoeconomics
  • 8. PHARMACODYNAMICS ā€¢ Pharmacodynamics is the study of effects of drugs on biological processes. ā€¢ Many mediators exert their effects as a result of high-affinity binding to specific receptors in plasma membranes or cell cytoplasm/nuclei, ā€¢ And many therapeutically important drugs exert their effects by combining with these receptors and either mimicking the effect of the natural mediator (in which case they are called ā€˜agonistsā€™) or blocking it ā€¢ Not all drugs work via receptors for endogenous mediators: many therapeutic drugs exert their effects by combining with an enzyme or transport protein and interfering with its function. ā€¢ Whether the site of action of a drug is a receptor or another macromolecule, binding is usually highly specific
  • 9. PHARMACODYNAMICS ā€¢ Binding is usually reversible. Occasionally, however, covalent bonds are formed with irreversible loss of function, e.g. aspirin binding to cyclooxygenase ā€¢ Most drugs produce graded concentration-/dose-related effects which can be plotted as a doseā€“response curve ā€¢ Doseā€“response curves facilitates quantitative analysis of full agonists (which produce graded responses up to a maximum value), antagonists (which produce no response on their own, but reduce the response to an agonist) ā€¢ And partial agonists (which produce some response, but to a lower maximum value than that of a full agonist, and antagonize full agonists)
  • 12. RECEPTORS AND SIGNAL TRANSDUCTION ā€¢ Drugs are often potent (i.e. they produce effects at low concentration) and specific (i.e. small changes in structure lead to profound changes in potency). ā€¢ High potency is a consequence of high binding affinity for specific macromolecular receptors ā€¢ Receptors were originally classified by reference to the relative potencies of agonists and antagonists on preparations containing different receptors
  • 13. RECEPTORS AND SIGNAL TRANSDUCTION ā€¢ Receptors fall into only four ā€˜super familiesā€™ each linked to distinct types of signal transduction mechanism 1. Fast (millisecond responses) neurotransmitters (e.g. nicotinic receptors)- transmembrane ion channel 2. Slower neurotransmitters and hormones (e.g. muscarinic receptors) - intracellular G-protein 3. Receptors linked to an enzyme on the inner membrane (e.g. insulin receptors) are slower still 4. Intra-nuclear receptors (e.g. gonadal and glucocorticosteroid hormones)
  • 15. AGONISTS ā€¢ Agonists activate receptors for endogenous mediators ā€“ e.g. salbutamol is an agonist at Ī²2-adrenoceptors ā€¢ The consequent effect may be excitatory (e.g. increased heart rate) or inhibitory (e.g. relaxation of airway smooth muscle). ā€¢ Agonists at nicotinic acetylcholine receptors (e.g. suxamethonium, exert an inhibitory effect (neuromuscular blockade) by causing long-lasting depolarization at the neuromuscular junction, ā€¢ And hence inactivation of the voltage-dependent sodium channels that initiate the action potential.
  • 16. AGONISTS ā€¢ Endogenous ligands have sometimes been discovered long after the drugs that act on their receptors. ā€¢ Endorphins and enkephalins (endogenous ligands of morphine receptors) were discovered many years after morphine. ā€¢ Anandamide is a central transmitter that activates CB (cannabis) receptors
  • 17. ANTAGONISM ā€¢ Competitive antagonists combine with the same receptor as an endogenous agonist (e.g. ranitidine at histamine H2-receptors), but fail to activate it. ā€¢ When combined with the receptor, they prevent access of the endogenous mediator. ā€¢ The complex between competitive antagonist and receptor is reversible. ā€¢ Provided that the dose of agonist is increased sufficiently, a maximal effect can still be obtained ā€¢ Physiological antagonism describes the situation where two drugs have opposing effects (e.g. adrenaline relaxes bronchial smooth muscle, whereas histamine contracts it).
  • 18. PARTIAL AGONISTS ā€¢ Some drugs combine with receptors and activate them, but are incapable of eliciting a maximal response, no matter how high their concentration may be. ā€¢ These are known as partial agonists, and are said to have low efficacy. ā€¢ Several partial agonists are used in therapeutics, including buprenorphine (a partial agonist at morphine Ī¼-receptors) and oxprenolol (partial agonist at Ī²-adrenoceptors). ā€¢ Full agonists can elicit a maximal response when only a small proportion of the receptors is occupied (underlying the concept of ā€˜spareā€™ receptors), ā€¢ But this is not the case with partial agonists, where a substantial proportion of the receptors need to be occupied to cause a response
  • 19. SLOW PROCESSES ā€¢ Prolonged exposure of receptors to agonists, as frequently occurs in therapeutic use, can cause down-regulation or desensitization. ā€¢ Desensitization is sometimes specific for a particular agonist (when it is referred to as ā€˜homologous desensitizationā€™), or there may be cross- desensitization to different agonists (ā€˜heterologous desensitizationā€™). ā€¢ Desensitization is probably involved in the tolerance that occurs during prolonged administration of drugs, such as morphine or benzodiazepines ā€¢ Therapeutic effects sometimes depend on induction of tolerance.
  • 20. NON-RECEPTOR MECHANISMS ā€¢ In contrast to high-potency/high-selectivity drugs which combine with specific receptors, some drugs exert their effects via simple physical properties or chemical reactions due to their presence in some body compartment. ā€¢ Examples include antacids (which neutralize gastric acid), osmotic diuretics (which increase the osmolality of renal tubular fluid), and bulk and lubricating laxatives. ā€¢ These agents are of low potency and specificity, and hardly qualify as ā€˜drugsā€™ in the usual sense at all, although some of them are useful medicines.

Editor's Notes

  1. For example, cures of leukaemias, Hodgkinā€™s disease and testicular carcinomas have been achieved through a preparedness to accept a degree of containable harm. Similar considerations apply in other disease areas Drugs are the physicianā€™s prime therapeutic tools, and just as a misplaced scalpel can spell disaster, so can a thoughtless prescription. Some of the more dramatic instances make for gruesome reading in the annual reports of the medical defence societies, but perhaps as important is the morbidity and expense caused by less dramatic but more common errors
  2. An example is shown in Figure 2.1, demonstrating and comparing the effects of a proton pump inhibitor and of a histamine H2 receptor antagonist (both drugs used for the treatment of peptic ulceration and other disorders related to gastric hyperacidity) on gastric Ph Examples include inhibitors of angiotensin converting enzyme and serotonin reuptake. These sites of drug action are not ā€˜receptorsā€™ in the sense of being sites of action of endogenous mediators.
  3. The order of potency of isoprenaline adrenaline noradrenaline on tissues rich in Ī²-receptors, such as the heart, contrasts with the reverse order in Ī±-receptormediated responses, such as vasoconstriction in resistance arteries supplying the skin. Quantitative potency data are best obtained from comparisons of different competitive antagonists, as explained below.
  4. This has two clinical consequences. First, partial agonists antagonize the effect of a full agonist, because most of the receptors are occupied with low-efficacy partial agonist with which the full agonist mustcompete. Second, it is more difficult to reverse the effects of a partial agonist, such as buprenorphine, with a competitive antagonist such as naloxone, than it is to reverse the effects of a full agonist such as morphine. A larger fraction of the receptors is occupied by buprenorphine than by morphine, and a much higher concentration of naloxone is required to compete successfully and displace buprenorphine from the receptors
  5. Membrane receptors may become internalized. Alternatively, G-protein mediated linkage between receptors and effector enzymes (e.g. adenylyl cyclase) may be disrupted For example, analogues of gonadotrophin-releasing hormone (GnRH), such as goserelin or buserelin, are used to treat patients with metastatic prostate cancer (Chapter 48). Gonadotrophin-releasing hormone is released physiologically in a pulsatile manner. During continuous treatment with buserelin, there is initial stimulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release, followed by receptor desensitization and suppression of LH and FSH release. This results in regression of the hormone-sensitive tumour. Conversely, reduced exposure of a cell or tissue to an agonist (e.g. by denervation) results in increased receptor numbers and supersensitivity. Prolonged use of antagonists may produce an analogous effect. One example of clinical importance is increased Ī²-adrenoceptor numbers following prolonged use of beta-blockers. Abrupt drug withdrawal can lead to tachycardia and worsening angina in patients who are being treated for ischaemic heart disease