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Pharmacology of

The Pituitary Gland

Basics
A. Exocrine gland – Ducts – Lumen and surfaces B. Endocrine gland – Chemical messengers – Blood stream

Hormones
• Chemical messenger

– –

Secreted by endocrine gland Specific to target Acti ate cellular change

! Classes of Hormones
1. Peptide/ Protein 2. Steroid e.g. estradiol 3. Amine single amino acid! e.g. Catecholamines "P#$ DA! from tyrosine %. "icosanoid from arachidonic acid! e.g. prostaglandins.

Hormone " #eceptor .

Control of Endocrine $unction A. or 'egati&e (eed)ac* mechanisms •. Self+regulating system . Positi&e B.

• is secondarily in charge of almost e&erything else.Hypothalamic%Pituitary Axis • .ost feed)ac* loops run through this a-is • .PA mediates gro/th$ meta)olism$ stress response$ reproduction. .

.

ormone 2elease+#nhi)iting .ormone Target .S0#.ormone! Pituitary Stimulating .1L1S Hypothalamus 2eleasing .ormone Gland .

$ antidiuretic hormone 4&asopressin53 C2.$ gro/th hormone3 6.2.ypothalamic + pituitary endocrine system AC0..$ gro/th hormone+releasing hormone3 6n2.$ gonadotropin+releasing hormone3 L.$ corticotropin+releasing hormone3 DA$ dopamine3 (S.$ thyroid+ stimulating hormone.$ thyrotropin+releasing hormone3 0S. .$ luteini7ing hormone3 P2L$ prolactin3 SS0$ somatostatin3 02.$ adrenocorticotropin3 AD.$ follicle+stimulating hormone3 6.

Anterior pituitary hormones .

'il/ production Egg0sperm prod. Adrenocortico% Tropin +ACTH. $ollicle +$SH.th Cortisol release +androgens. 1uteini2ing +1H. Sex hormones 'any tissues Adrenal cortex Breast Gonads Gonads . Prolactin +Prl.th +GH.H&#'&(E Thyroid +TSH. TA#GET Thyroid gland $)(CT*&( TH synthesis release gro. Stimulating Gro.

Prolactin Structure3 #t is a single polypeptide chain composed of 189 amino acid residues. #t has three sulfide )onds. .

Prolactin mechanism of action Protein tyrosine *inase molecules :A.! 0ranscription S0A0! molecules .

Actions of Prolactin Principal hormone of lactation 4 /ith appropriate le&els of coricosteroids$ estrogen$ progestins and insulin5 .

ypothalamic destruction or < Prolactin+secreting adenomas 'anifestations3 1. Compression symptoms /ith large adenomas. Treatment3 Dopamine agonists .Abnormal prolactin secretion 4eficiency3 Pituitary deficency$ 2are 'anifestations3 (ailure of lactation or a luteal phase defect. *ncreased secretion +Hyperprolactinaemia. 4inhi)ition of 6n2.3 < .5 2. 6alactorrhea and amenorrhea in females = loss of li)ido and infertility in males. Treatment3 no preparation a&aila)le.

$ gro/th hormone3 6.$ antidiuretic hormone 4&asopressin53 C2.AC0.$ adrenocorticotropin3 AD.$ gro/th hormone+releasing hormone3 6n2.$ follicle+stimulating hormone3 6.$ thyroid+ stimulating hormone. .$ luteini7ing hormone3 P2L$ prolactin3 SS0$ somatostatin3 02.2.$ gonadotropin+releasing hormone3 L.$ corticotropin+releasing hormone3 DA$ dopamine3 (S.$ thyrotropin+releasing hormone3 0S.

5inetics3 Oral. vaginal or IM Ergot derivatives: Bromocriptine and Cabergoline Non-ergot agent: Quinagolide t½ 65 h t½ 20 h t½ 7 h . Decrease prolactin and growth hormone.4opamine agonists 'echanisn of action3 Agonist of G-protein coupled receptors.

Hyperprolactinaemia3 2estore o&ulation$ decrease prolactin and decrease tumour si7e. Physiological lactation3 2arely cause stro*e or coronary throm)osis.)ses of dopamine agonists 6. 8. Acromegaly3 #n high doses /ith other treatments radiation$ surgery or octreotides! . 7.

A. Pulmonary infiltrates. Local irritation. Bleeding from peptic ulceration. @. 1ong term3 1. Peripheral &asospasm. e-trapyramidal system! . %. Psychiatric manifestations. 3. ?.Ad erse effects of 4opamine agonist At initiation of therapy3 'ausea$ headache$ fatigue$ postural hypotension and light+headness. Dys*inesias. "rythromelalgia> consists of red$ tender$ painful$ s/ollen feet and$ occasionally$ hands$ at times associated /ith arthralgia3 symptoms and signs clear /ithin a fe/ days of /ithdra/al of the causal drug. 2.

0he ergot+deri&ed agonists are )est a&oided in patients /ith peripheral &ascular disease. 3.Ad erse effects of 4opamine agonists cont. 2. Pregnancy3 safe + .icroadenoma B Discontinue rare increase in tumour si7e! + . 2ecent myocardial infarction. %. Acti&e peptic ulceration. Psychotic illness. Contraindications3 1.acroadenomas B Continue .

Gro. #t has t/o disulfide )onds.th Hormone +GH. Structure3 #t is a single polypeptide chain composed of 181 amino acid residues. .

! 0ranscription S0A0! molecules .GH mechanism of action Protein tyrosine *inase molecules :A.

2. *ndirect3 through #6(+# #nsulin li*e effect on glucose transport Dglycogen and lipid synthesis! E lipolysis $ gluconeogenesis and proteolysis! . Ana)olic effect on muscle increase lean )ody mass!. %. 3. Decrease insulin sensiti&ity. Cata)olic effect on lipids decrease adiposity!.Actions of GH 4irect3 1. Produce #6(+# from L#C"2$ )one$ cartilage$ muscle and *idneys.

g.th hormone deficiency3 + 6enetic or acFuired e.ith short stature3 impro&e gro/th Chronic renal insufficiency 0urner syndrome$ Prader+Gilli syndrome$ 'oonan syndrome$ #diopathic short stature &ther uses3 Short )o/el syndrome impro&e 6#0 function! .)ses of GH Gro. traumatic! Childhood> short stature$ mild adiposity$ hypoglycaemia Adulthood> generali7ed o)esity$ reduced muscle mass$ asthenia and reduced cardiac output.#C infection Anti+aging #ncrease muscle mass athletes! . A child .

%. Peripheral edema$ myalgias$ and arthralgias especially in the hands and /rists!. #ntracranial hypertension. . A. Adults3 ?. Contraindicated in a patient /ith a *no/n malignancyHH 'o increase incidence!. 3. Carpal tunnel syndrome. Proliferati&e retinopathy may rarely occur. Scoliosis during rapid gro/th$ slipped capital femoral epiphysis and edema. Patients /ith Prader+Gilli syndrome ha&e an increased ris* of otitis media. . #ncreases the acti&ity of cytochrome P%?I isoforms. Pancreatitis$ gynecomastia$ and ne&us gro/th. @. #ncrease mortality critically ill patients. 2.Toxicity of GH Children 3 rare 1.ypothyroidism.

KPL6LKCA". #ncreased intracranial tension 3. .*G$%* Agonists *ndication3 (ailure of response to 6.ecasermin rinfa)ate rh#6(+# J rh#(6+# BP+3! D t1/2 Ad erse effects3 1. "le&ation of li&er en7ymes . .#A 2.ecasermin rh#6(+#! .

'ausea$ &omiting$ a)dominal cramps$ flatulence$ and steatorrhea /ith )ul*y )o/el mo&ements. %. Dra/)ac*s> tM 1+3 minutes and multiple effects.ypothalamus$ pancreas #nhi)it release of 6.$ 0S. 2. Somatostatin Analogs3 Lctreotide> Lanreotide 1ses> acromegaly$ hormone secreted tumur and control of )leeding oesophageal &arices. Citamin B12 deficiency may occur /ith long+term use of octreotide.GH Antagonists Somatostatin .$ glucagon$ insulin and gastrin. Pain at the site of inNection is common$ especially /ith the long+acting octreotide suspension. 3. Sinus )radycardia and conduction distur)ances. Biliary sludge and gallstones. . Ad erse effects3 1.

)ses3 Acromegaly Ad erse effects3 ele&ated li&er en7ymes .GH #eceptor Antagonists Peg&isomant> . /hich allo/s dimeri7ation of the receptor )ut )loc*s the conformational changes reFuired for signal transduction.utant form of 6.

L'LK> 1rofollitropin$ follitropin alfa and )eta L. L'LK> Lutropin alfa )ses3 L&ulation induction .emoperitoneum$ fe&er and throm)oem)olism amy occur! 2. .enotropins from urine of menupausal /omen! (S.ale infertility. Ad erse effects3 1.$SH and 1H 4ynamics3 6+protein coupled receptors Preparations3 .ultiple pregnancies.! (S. . and L. L&arian hyperstimulation 4o&arian enlargment$ ascites$ hydrothora-$ hypo&olaemia and shoc*5 .

Posterior pituitary hormones .

&xytocin Structure3 A 8+amino acid peptide. .

.&xytocin mechanism of action 6 protein+coupled receptors and the phosphoinositide+calcium second+ messenger system to contract uterine smooth muscle. L-ytocin also stimulates the release of prostaglandins and leu*otrienes that augment uterine contraction.

#n small doses> increases )oth the freFuency and the force of uterine contractions. . 2. 1actation3 Contraction of myoepithelial cells surrounding mammary al&eoli$ /hich leads to mil* eNection. Antidiuretic and pressor acti ity3 /ea* At high concentrations$ due to acti&ation of &asopressin receptors.Actions of &xytocin &n uterine muscles3 1. At higher doses> it produces sustained contraction.

Post partum haemorrhage. 8. . *nduction of labour. 7. )ses of &xytocin 6. )terine inertia.> for control of postpartum )leeding.C. Elimination3 By the *idneys and li&er$ /ith tM ? minutes. #.. L-ytocin is not )ound to plasma proteins.&xytocin 5inetics Administration3 #..> for initiation and augmentation of la)our.

Contraindications3 (etal distress$ prematurity$ a)normal fetal Presentation$ cephalopel&ic disproportion$ and other predispositions for uterine rupture. Hypotension3 Bolus inNections. . Acti ation of asopressin receptors3 (luid retention$ or /ater into-ication$ leading to hyponatremia$ heart failure$ sei7ures$ and death.Ad erse effects of &xytocin Excessi e stimulation of uterine contractions before deli ery3 (etal distress$ placental a)ruption$ or uterine rupture.

released in response to rising plasma tonicity or falling )lood pressure. . Structure3 A 8+amino acid peptide.9AS&P#ESS*( +A(T*4*)#ET*C H&#'&(E: A4H.

A4H mechanism of action 6 protein+coupled receptors .

Pituitary diabetes insipidus... Control of bleeding of oesophageal arices. 8.$ #. .. Paralytic ileus. !. Desmopressin> 4long acting synthetic analog /ith minimal pressor effect5 #.$ intranasally$ or orally )ses of A4H 6. or #. Before radiography.A4H 5inetics Adminstration3 Casopressin #.. Elimination3 By the *idneys and li&er$ /ith tM 1? minutes.C.C. 7.

9asoconstriction3 asopressin only. 7. (ausea: abdominal cramps: agitation.Ad erse effects of A4H 6. Allergic reactions. . 8. !. & erdosage3 hyponatremia and sei2ures.